Phase Ib study of the mitochondrial inhibitor ME-344 plus topotecan in patients with previously treated, locally advanced or metastatic small cell lung, ovarian and cervical cancers.

PubMed

Diamond, Jennifer R; Goff, Barbara; Forster, Martin D; Bendell, Johanna C; Britten, Carolyn D; Gordon, Michael S; Gabra, Hani; Waterhouse, David M; Poole, Mark; Ross Camidge, D; Hamilton, Erika; Moore, Kathleen M

2017-10-01

Background This multicenter, open-label, phase Ib study was designed to assess the safety, pharmacokinetics and preliminary efficacy of ME-344, a mitochondrial inhibitor, administered in combination with the topoisomerase I inhibitor, topotecan, in patients with previously treated, locally advanced or metastatic small cell lung (SCLC), ovarian and cervical cancers. Patients and methods In Part 1, patients received ME-344 10 mg/kg intravenously weekly on days 1, 8, 15 and 22 in combination with topotecan 4 mg/m 2 on days 1, 8, and 15 of a 28 day cycle. Cycles were repeated until disease progression or unacceptable toxicity. Patients were evaluated for dose-limiting toxicity (DLT) in cycle 1 and ME-344 pharmacokinetic samples were obtained. In Part 2, patients with locally advanced or metastatic SCLC and ovarian cancer were enrolled in expansion cohorts treated at the recommended phase II dose (RP2D) determined in Part 1. Results Fourteen patients were enrolled in Part 1 and no DLTs were observed. The RP2D of ME-344 in combination with topotecan was established as 10 mg/kg. In Part 2, 32 patients were enrolled. The most common treatment-emergent all-grade and grade 3/4 toxicities included fatigue (65.2%, 6.5%), neutropenia (56.5%, 43.5%) and thrombocytopenia (50%, 23.9%). One patient with recurrent ovarian cancer experienced a partial response by RECIST 1.1 and 21 patients achieved stable disease as best response. Conclusions The combination of ME-344 10 mg/kg weekly and topotecan 4 mg/m 2 was tolerable, however, the degree of anti-cancer activity does not support further investigation of the combination in unselected patients with SCLC, ovarian and cervical cancers.

Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis.

PubMed

Benza, Raymond L; Miller, Dave P; Foreman, Aimee J; Frost, Adaani E; Badesch, David B; Benton, Wade W; McGoon, Michael D

2015-03-01

Data from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) were used previously to develop a risk score calculator to predict 1-year survival. We evaluated prognostic implications of changes in the risk score and individual risk-score parameters over 12 months. Patients were grouped by decreased, unchanged, or increased risk score from enrollment to 12 months. Kaplan-Meier estimates of subsequent 1-year survival were made based on change in the risk score during the initial 12 months of follow-up. Cox regression was used for multivariable analysis. Of 2,529 patients in the analysis cohort, the risk score was decreased in 800, unchanged in 959, and increased in 770 at 12 months post-enrollment. Six parameters (functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide levels, and pericardial effusion) each changed sufficiently over time to improve or worsen risk scores in ≥5% of patients. One-year survival estimates in the subsequent year were 93.7%, 90.3%, and 84.6% in patients with a decreased, unchanged, and increased risk score at 12 months, respectively. Change in risk score significantly predicted future survival, adjusting for risk at enrollment. Considering follow-up risk concurrently with risk at enrollment, follow-up risk was a much stronger predictor, although risk at enrollment maintained a significant effect on future survival. Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival. Thus, serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.

Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam.

PubMed

Phuong, N T M; Nhung, N V; Hoa, N B; Thuy, H T; Takarinda, K C; Tayler-Smith, K; Harries, A D

2016-03-21

The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010-2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010-2012. A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection-currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation.

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial.

PubMed

Atkins, Michael B; Plimack, Elizabeth R; Puzanov, Igor; Fishman, Mayer N; McDermott, David F; Cho, Daniel C; Vaishampayan, Ulka; George, Saby; Olencki, Thomas E; Tarazi, Jamal C; Rosbrook, Brad; Fernandez, Kathrine C; Lechuga, Mariajose; Choueiri, Toni K

2018-03-01

Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma. In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma. Eligible patients received axitinib plus pembrolizumab in a dose-finding phase to estimate the maximum tolerated dose, and additional patients were enrolled into a dose-expansion phase to further establish safety and determine preliminary efficacy. Axitinib 5 mg was administered orally twice per day with pembrolizumab 2 mg/kg given intravenously every 3 weeks. We assessed safety in all patients who received at least one dose of axitinib or pembrolizumab; antitumour activity was assessed in all patients who received study treatment and had an adequate baseline tumour assessment. The primary endpoint was investigator-assessed dose-limiting toxicity during the first two cycles (6 weeks) to estimate the maximum tolerated dose and recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02133742. Between Sept 23, 2014, and March 25, 2015, we enrolled 11 patients with previously untreated advanced renal cell carcinoma to the dose-finding phase and between June 3, 2015, and Oct 13, 2015, we enrolled 41 patients to the dose-expansion phase. All 52 patients were analysed together. No unexpected toxicities were observed. Three dose-limiting toxicities were reported in the 11 patients treated during the 6-week observation period (dose-finding phase): one patient had a transient ischaemic attack and two patients were only able to complete less than 75% of the planned axitinib dose because of treatment-related toxicity. At the data cutoff date (March 31, 2017), 25 (48%) patients were still receiving study treatment. Grade 3 or worse treatment-related adverse events occurred in 34 (65%) patients; the most common included hypertension (n=12 [23%]), diarrhoea (n=5 [10%]), fatigue (n=5 [10%]), and increased alanine aminotransferase concentration (n=4 [8%]). The most common potentially immune-related adverse events (probably related to pembrolizumab) included diarrhoea (n=15 [29%]), increased alanine aminotransferase concentration (n=9 [17%]) or aspartate aminotransferase concentration (n=7 [13%]), hypothyroidism (n=7 [13%]), and fatigue (n=6 [12%]). 28 (54%) patients had treatment-related serious adverse events. At data cutoff, 38 (73%; 95% CI 59·0-84·4) patients achieved an objective response (complete or partial response). The treatment combination of axitinib plus pembrolizumab is tolerable and shows promising antitumour activity in patients with treatment-naive advanced renal cell carcinoma. Whether or not the combination works better than a sequence of VEGF pathway inhibition followed by an anti-PD-1 therapy awaits the completion of a phase 3 trial comparing axitinib plus pembrolizumab with sunitinib monotherapy (NCT02853331). Pfizer Inc. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effects of previous open renal stone surgery types on PNL outcomes.

PubMed

Ozgor, Faruk; Kucuktopcu, Onur; Ucpinar, Burak; Sarilar, Omer; Erbin, Akif; Yanaral, Fatih; Sahan, Murat; Binbay, Murat

2016-01-01

Our aim was to demonstrate the effect of insicion of renal parenchyma during open renal stone surgery (ORSS) on percutaneous nephrolithotomy (PNL) outcomes. Patients with history of ORSS who underwent PNL operation between June 2005 and June 2015 were analyzed retrospectively. Patients were divided into two groups according to their type of previous ORSS. Patients who had a history of ORSS with parenchymal insicion, such as radial nephrotomies, anatrophic nephrolithotomy, lower pole resection, and partial nephrectomy, were included in Group 1. Other patients with a history of open pyelolithotomy were enrolled in Group 2. Preoperative characteristics, perioperative data, stone-free status, and complications were compared between the groups. Stone-free status was defined as complete clearance of stone(s) or presence of residual fragments smaller than 4 mm. The retrospective nature of our study, different experience level of surgeons, and lack of the evaluation of anesthetic agents and cost of procedures were limitations of our study. 123 and 111 patients were enrolled in Groups 1 and 2, respectively. Preoperative characteristics were similar between groups. In Group 1, the mean operative time was statistically longer than in Group 2 (p=0.013). Stone-free status was significantly higher in Group 2 than in Group 1 (p=0.027). Complication rates were similar between groups. Hemorrhage requiring blood transfusion was the most common complication in both groups (10.5% vs. 9.9%). Our study demonstrated that a history of previous ORSS with parenchymal insicion significantly reduces the success rates of PNL procedure.

What The Oregon Health Study Can Tell Us About Expanding Medicaid

PubMed Central

Allen, Heidi; Baicker, Katherine; Finkelstein, Amy; Taubman, Sarah; Wright, Bill J.

2012-01-01

The recently enacted Patient Protection and Affordable Care Act includes a major expansion of Medicaid to low-income adults in 2014. This paper describes the Oregon Health Study, a randomized controlled trial that will be able to shed some light on the likely effects of such expansions. In 2008, Oregon randomly drew names from a waiting list for its previously closed public insurance program. Our analysis of enrollment into this program found that people who signed up for the waiting list and enrolled in the Oregon Medicaid program were likely to have worse health than those who did not. However, actual enrollment was fairly low, partly because many applicants did not meet eligibility standards. PMID:20679654

Efficacy and safety of nab-paclitaxel in patients with previously treated metastatic colorectal cancer: a phase II COLO-001 trial.

PubMed

Ducreux, Michel; Bennouna, Jaafar; Adenis, Antoine; Conroy, Thierry; Lièvre, Astrid; Portales, Fabienne; Jeanes, Julie; Li, Li; Romano, Alfredo

2017-01-01

This single-arm, phase II trial evaluated nab-paclitaxel monotherapy in pretreated patients with metastatic colorectal cancer (mCRC). Patients with mCRC (RAS wild-type and RAS mutant cohorts) received nab-paclitaxel 125 mg/m 2 days 1, 8, and 15 (28-day cycle). The primary endpoint was investigator-assessed progression-free survival (PFS) rate at week 8; secondary endpoints included overall survival, overall response rate, and safety. Stage 1 planned enrollment was 15 patients per cohort per Simon 2-stage design. Stage 2 enrollment was to continue unless ≤8 of the first 15 patients per cohort achieved PFS at 8 weeks. Stage 1 enrolled 41 patients (RAS wild type: n = 18; RAS mutant: n = 23). In both RAS cohorts, 3 of 15 patients initially enrolled were progression-free at week 8 (20%; 95% CI 4.0-48.0). Median PFS was 8.1 weeks (95% CI 7.7-8.6) and 7.9 weeks (95% CI 7.6-8.0) for RAS wild-type and RAS mutant cohorts, respectively. There were no complete or partial responses. The overall disease control rate was 16% (95% CI 6.0-32.0), and rates were similar in the RAS wild-type and RAS mutant cohorts (18 and 15%, respectively). No new safety signals were reported; the most common grade ≥3 adverse events included neutropenia, asthenia, and peripheral neuropathy. This study did not progress to stage 2 per the preplanned statistical stopping rule. In patients with heavily pretreated mCRC, nab-paclitaxel did not demonstrate promising antitumor activity; further assessment of nab-paclitaxel monotherapy in this population of patients is not supported. NCT02103062.

OpT2mise: a randomized controlled trial to compare insulin pump therapy with multiple daily injections in the treatment of type 2 diabetes-research design and methods.

PubMed

Aronson, Ronnie; Cohen, Ohad; Conget, Ignacio; Runzis, Sarah; Castaneda, Javier; de Portu, Simona; Lee, Scott; Reznik, Yves

2014-07-01

In insulin-requiring type 2 diabetes patients, current insulin therapy approaches such as basal-alone or basal-bolus multiple daily injections (MDI) have not consistently provided achievement of optimal glycemic control. Previous studies have suggested a potential benefit of continuous subcutaneous insulin infusion (CSII) in these patients. The OpT2mise study is a multicenter, randomized, trial comparing CSII with MDI in a large cohort of subjects with evidence of persistent hyperglycemia despite previous MDI therapy. Subjects were enrolled into a run-in period for optimization of their MDI insulin regimen. Subjects showing persistent hyperglycemia (glycated hemoglobin [HbA1c] ≥8% and ≤12%) were then randomly assigned to CSII or continuing an MDI regimen for a 6-month phase followed by a single crossover of the MDI arm, switching to CSII. The primary end point is the between-group difference in mean change in HbA1c from baseline to 6 months. Secondary end points include change in mean 24-h glucose values, area under the curve and time spent in hypoglycemia and hyperglycemia, measures of glycemic excursions, change in postprandial hyperglycemia, and evaluation of treatment satisfaction. Safety end points include hypoglycemia, hospital admissions, and emergency room visits. When subject enrollment was completed in May 2013, 495 subjects had been enrolled in the study. The study completion for the primary end point is expected in January 2014. OpT2mise will represent the largest studied homogeneous cohort of type 2 diabetes patients with persistent hyperglycemia despite optimized MDI therapy. OpT2mise will help define the role of CSII in insulin intensification and define its safety, rate of hypoglycemia, patient adherence, and patient satisfaction.

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial.

PubMed

Suzuki, Kazuyuki; Endo, Ryujin; Takikawa, Yasuhiro; Moriyasu, Fuminori; Aoyagi, Yutaka; Moriwaki, Hisataka; Terai, Shuji; Sakaida, Isao; Sakai, Yoshiyuki; Nishiguchi, Shuhei; Ishikawa, Toru; Takagi, Hitoshi; Naganuma, Atsushi; Genda, Takuya; Ichida, Takafumi; Takaguchi, Koichi; Miyazawa, Katsuhiko; Okita, Kiwamu

2018-05-01

The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH 3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH 3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia. © 2017 The Japan Society of Hepatology.

A study of prospective surveillance for inhibitors among persons with haemophilia in the United States.

PubMed

Soucie, J M; Miller, C H; Kelly, F M; Payne, A B; Creary, M; Bockenstedt, P L; Kempton, C L; Manco-Johnson, M J; Neff, A T

2014-03-01

Inhibitors are a rare but serious complication of treatment of patients with haemophilia. Phase III clinical trials enrol too few patients to adequately assess new product inhibitor risk. This project explores the feasibility of using a public health surveillance system to conduct national surveillance for inhibitors. Staff at 17 U.S. haemophilia treatment centres (HTC) enrolled patients with haemophilia A and B into this prospective study. HTC staff provided detailed historic data on product use and inhibitors at baseline, and postenrolment patients provided monthly detailed infusion logs. A central laboratory performed inhibitor tests on blood specimens that were collected at baseline, annually, prior to any planned product switch or when clinically indicated. The central laboratory also performed genotyping of all enrolled patients. From January 2006 through June 2012, 1163 patients were enrolled and followed up for 3329 person-years. A total of 3048 inhibitor tests were performed and 23 new factor VIII inhibitors were identified, 61% of which were not clinically apparent. Infusion logs were submitted for 113,205 exposure days. Genotyping revealed 431 distinct mutations causing haemophilia, 151 of which had not previously been reported elsewhere in the world. This study provided critical information about the practical issues that must be addressed to successfully implement national inhibitor surveillance. Centralized testing with routine monitoring and confirmation of locally identified inhibitors will provide valid and representative data with which to evaluate inhibitor incidence and prevalence, monitor trends in occurrence rates and identify potential inhibitor outbreaks associated with products. © 2013 John Wiley & Sons Ltd.

Fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) combination therapy for elderly acute myeloid leukemia patients.

PubMed

Kim, Inho; Koh, Youngil; Yoon, Sung-Soo; Park, Seonyang; Kim, Byoung Kook; Kim, Dae-Young; Lee, Jung-Hee; Lee, Kyoo-Hyung; Cheong, June-Won; Lee, Hong-Kee; Kim, Sung-Hyun; Kim, Hyuk; Joo, Young Don; Lee, Sang-Min; Won, Jong-Ho; Park, Sung-Kyu; Hong, Dae-Sik; Kim, Se-Hyung; Sohn, Sang Kyun; Kim, Chul-Soo; Park, Eunkyung; Kim, Min Kyoung; Park, Moo Rim; Lee, Je-Hwan; Min, Yoo Hong

2013-01-01

We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (≥60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m(2) , days 1-4), cytarabine (1,000 mg/m(2) , days 1-4), and attenuated-dose idarubicin (5 mg/m(2) , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F = 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493). Copyright © 2012 Wiley Periodicals, Inc.

Using the Theory of Planned Behaviour to examine enrolled nursing students' intention to care for patients with alcohol dependence: A survey study.

PubMed

Talbot, Anna-Lisa; Dorrian, Jillian; Chapman, Janine

2015-11-01

Nurses are often the first point of contact for patients hospitalized due to alcohol-related causes. Alcohol dependence is highly stigmatized and as a result healthcare professionals often have low behavioural intentions, meaning low willingness to care for these patients. This can have a direct influence on quality of care. The purpose of this study was to explore enrolled nursing students' intention to care for patients with alcohol dependence and the antecedents, preliminary factors, that predict this within the Theory of Planned Behaviour; specifically attitudes, subjective norms, self-efficacy and controllability. The study was a cross-sectional survey using the Theory of Planned Behaviour. Two Technical and Further Education South Australia campuses across metropolitan Adelaide. n=86 enrolled nursing students completed the survey (62% response rate). Enrolled nursing students' intention, attitudes, subjective norms, self-efficacy and controllability were measured using a Theory of Planned Behaviour Questionnaire. The Short Alcohol and Alcohol Problems Perception Questionnaire investigated attitudes in more detail and a short knowledge scale assessed alcohol-related knowledge. Subjective norms and attitudes had a significant, positive effect on intention to care within the final model, accounting for 22.6% of the variance, F2,83=12.12, p<0.001. Subjective norms were the strongest predictor. External factors such as age, previous alcohol training and alcohol-related knowledge held direct paths to antecedents of intention. Subjective norms were the strongest predictor of intention to care for patients with alcohol dependence, followed by attitudes. The study provides an understanding of enrolled nursing students' intention to care for alcohol dependent patients. These findings can assist in developing tailored alcohol training for students, to increase attitudes and foster behavioural change, in order to improve the quality of care for these patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam

PubMed Central

Nhung, N. V.; Hoa, N. B.; Thuy, H. T.; Takarinda, K. C.; Tayler-Smith, K.; Harries, A. D.

2016-01-01

Setting: The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. Objectives: To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010–2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010–2012. Design: A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. Results: The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. Conclusion: Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection—currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation. PMID:27051608

The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study

PubMed Central

Shi, Yuankai; Zhou, Caicun; Liu, Xiaoqing; Wang, Dong; Song, Yong; Li, Qiang; Feng, Jifeng; Qin, Shukui; Xv, Nong; Zhou, Jianying; Zhang, Li; Hu, Chunhong; Zhang, Shucai; Luo, Rongcheng; Wang, Jie; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2015-01-01

Background Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Methods Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. Results From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9–6.6 m) and 5.4 months (95%CI 3.1–7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). Conclusions In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. Trial Registration ClinicalTrials.gov NCT02486354 PMID:26599904

The effects of previous open renal stone surgery types on PNL outcomes

PubMed Central

Ozgor, Faruk; Kucuktopcu, Onur; Ucpinar, Burak; Sarilar, Omer; Erbin, Akif; Yanaral, Fatih; Sahan, Murat; Binbay, Murat

2016-01-01

Introduction: Our aim was to demonstrate the effect of insicion of renal parenchyma during open renal stone surgery (ORSS) on percutaneous nephrolithotomy (PNL) outcomes. Methods: Patients with history of ORSS who underwent PNL operation between June 2005 and June 2015 were analyzed retrospectively. Patients were divided into two groups according to their type of previous ORSS. Patients who had a history of ORSS with parenchymal insicion, such as radial nephrotomies, anatrophic nephrolithotomy, lower pole resection, and partial nephrectomy, were included in Group 1. Other patients with a history of open pyelolithotomy were enrolled in Group 2. Preoperative characteristics, perioperative data, stone-free status, and complications were compared between the groups. Stone-free status was defined as complete clearance of stone(s) or presence of residual fragments smaller than 4 mm. The retrospective nature of our study, different experience level of surgeons, and lack of the evaluation of anesthetic agents and cost of procedures were limitations of our study. Results: 123 and 111 patients were enrolled in Groups 1 and 2, respectively. Preoperative characteristics were similar between groups. In Group 1, the mean operative time was statistically longer than in Group 2 (p=0.013). Stone-free status was significantly higher in Group 2 than in Group 1 (p=0.027). Complication rates were similar between groups. Hemorrhage requiring blood transfusion was the most common complication in both groups (10.5% vs. 9.9%). Conclusions: Our study demonstrated that a history of previous ORSS with parenchymal insicion significantly reduces the success rates of PNL procedure. PMID:28255416

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study.

PubMed

Patterson, Marc C; Mengel, Eugen; Vanier, Marie T; Schwierin, Barbara; Muller, Audrey; Cornelisse, Peter; Pineda, Mercè

2015-05-28

Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit. In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years.

Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

PubMed Central

Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

2013-01-01

Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

Phase I trial of a yeast-based therapeutic cancer vaccine (GI-6301) targeting the transcription factor brachyury

PubMed Central

Heery, Christopher R.; Singh, B. Harpreet; Rauckhorst, Myrna; Marté, Jennifer L.; Donahue, Renee N.; Grenga, Italia; Rodell, Timothy C.; Dahut, William; Arlen, Philip M.; Madan, Ravi A.; Schlom, Jeffrey; Gulley, James L.

2015-01-01

The nuclear transcription factor brachyury has previously been shown to be a strong mediator of the epithelial-to-mesenchymal transition (EMT) in human carcinoma cells and a strong negative prognostic factor in several tumor types. Brachyury is overexpressed in a range of human carcinoma as well as in chordoma, a rare tumor for which there is no standard systemic therapy. Preclinical studies have shown a recombinant Saccharomyces cerevisiae (yeast) vaccine encoding brachyury (GI-6301) can activate human T cells in vitro. A Phase I dose escalation (3+3 design) trial enrolled 34 patients at 4 dose levels (3, 3, 16, and 11 patients, respectively, at 4, 16, 40, and 80 yeast units (YU)). Expansion cohorts were enrolled at 40 and 80 YU dose levels for analysis of immune response and clinical activity. We observed brachyury-specific T-cell immune responses in the majority of evaluable patients despite most having been heavily pretreated. No evidence of autoimmunity or other serious adverse events were observed. Two chordoma patients showed evidence of disease control (one mixed response and one partial response). A patient with colorectal carcinoma, who enrolled on study with a large progressing pelvic mass and rising CEA, remains on study for greater than 1 year with stable disease, evidence of decreased tumor density and decreased serum CEA. This study is the first-in-human to demonstrate the safety and immunogenicity of this therapeutic cancer vaccine and provides rationale for exploration in Phase II studies. A randomized Phase II chordoma study is enrolling. PMID:26130065

Parameters influencing the physical activity of patients with a history of coronary revascularization.

PubMed

Acar, Burak; Yayla, Cagri; Gucuk Ipek, Esra; Unal, Sefa; Ertem, Ahmet Goktug; Burak, Cengiz; Senturk, Bihter; Bayraktar, Fatih; Kara, Meryem; Demirkan, Burcu; Guray, Yesim

2017-10-01

Coronary artery disease is the leading cause of mortality worldwide. Regular physical activity is part of a comprehensive management strategy for these patients. We investigated the parameters that influence physical activity in patients with a history of coronary revascularization. We included outpatients with a history of coronary revascularization at least six months prior to enrollment. Data on physical activity, demographics, and clinical characteristics were collected via a questionnaire. A total of 202 consecutive outpatients (age 61.3±11.2 years, 73% male) were enrolled. One hundred and four (51%) patients had previous percutaneous coronary intervention, 67 (33%) had coronary bypass graft surgery, and 31 (15%) had both procedures. Only 46 patients (23%) engaged in regular physical activity. Patients were classified into two subgroups according to their physical activity. There were no significant differences between subgroups in terms of age, comorbid conditions or revascularization type. Multivariate regression analysis revealed that low education level (OR=3.26, 95% CI: 1.31-8.11, p=0.01), and lack of regular follow-up (OR=2.95, 95% CI: 1.01-8.61, p=0.04) were independent predictors of non-adherence to regular physical activity among study subjects. Regular exercise rates were lower in outpatients with previous coronary revascularization. Education level and regular follow-up visits were associated with adherence to physical activity in these patients. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.

PubMed

Kawai, Akira; Umeda, Toru; Wada, Takuro; Ihara, Koichiro; Isu, Kazuo; Abe, Satoshi; Ishii, Takeshi; Sugiura, Hideshi; Araki, Nobuhito; Ozaki, Toshifumi; Yabe, Hiroo; Hasegawa, Tadashi; Tsugane, Shoichiro; Beppu, Yasuo

2005-05-01

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.

Comparing decision making between cancer patients and the general population: thoughts, emotions, or social influence?

PubMed

Yang, Z Janet; McComas, Katherine A; Gay, Geri K; Leonard, John P; Dannenberg, Andrew J; Dillon, Hildy

2012-01-01

This study extends a risk information seeking and processing model to explore the relative effect of cognitive processing strategies, positive and negative emotions, and normative beliefs on individuals' decision making about potential health risks. Most previous research based on this theoretical framework has examined environmental risks. Applying this risk communication model to study health decision making presents an opportunity to explore theoretical boundaries of the model, while also bringing this research to bear on a pressing medical issue: low enrollment in clinical trials. Comparative analysis of data gathered from 2 telephone surveys of a representative national sample (n = 500) and a random sample of cancer patients (n = 411) indicated that emotions played a more substantive role in cancer patients' decisions to enroll in a potential trial, whereas cognitive processing strategies and normative beliefs had greater influences on the decisions of respondents from the national sample.

Case-based learning and simulation: useful tools to enhance nurses' education? Nonrandomized controlled trial.

PubMed

Raurell-Torredà, Marta; Olivet-Pujol, Josep; Romero-Collado, Àngel; Malagon-Aguilera, Maria Carmen; Patiño-Masó, Josefina; Baltasar-Bagué, Alícia

2015-01-01

To compare skills acquired by undergraduate nursing students enrolled in a medical-surgical course. To compare skills demonstrated by students with no previous clinical practice (undergraduates) and nurses with clinical experience enrolled in continuing professional education (CPE). In a nonrandomized clinical trial, 101 undergraduates enrolled in the "Adult Patients 1" course were assigned to the traditional lecture and discussion (n = 66) or lecture and discussion plus case-based learning (n = 35) arm of the study; 59 CPE nurses constituted a comparison group to assess the effects of previous clinical experience on learning outcomes. Scores on an objective structured clinical examination (OSCE), using a human patient simulator and cases validated by the National League for Nursing, were compared for the undergraduate control and intervention groups, and for CPE nurses (Student's t test). Controls scored lower than the intervention group on patient assessment (6.3 ± 2.3 vs 7.5 ± 1.4, p = .04, mean difference, -1.2 [95% confidence interval (CI) -2.4 to -0.03]) but the intervention group did not differ from CPE nurses (7.5 ± 1.4 vs 8.8 ± 1.5, p = .06, mean difference, -1.3 [95% CI -2.6 to 0.04]). The CPE nurses committed more "rules-based errors" than did undergraduates, specifically patient identifications (77.2% vs 55%, p = .7) and checking allergies before administering medication (68.2% vs 60%, p = .1). The intervention group developed better patient assessment skills than the control group. Case-based learning helps to standardize the process, which can contribute to quality and consistency in practice: It is essential to correctly identify a problem in order to treat it. Clinical experience of CPE nurses was not associated with better adherence to safety protocols. Case-based learning improves the patient assessment skills of undergraduate nursing students, thereby preparing them for clinical practice. © 2014 Sigma Theta Tau International.

Left Ventricular Retraining and Late Arterial Switch for D-Transposition of the Great Arteries.

PubMed

Watanabe, Naruhito; Mainwaring, Richard D; Carrillo, Sergio A; Lui, George K; Reddy, V Mohan; Hanley, Frank L

2015-05-01

For many decades, patients with d-transposition of the great arteries underwent an atrial switch procedure. Although many of these patients have continued to do well, a subset experience profound right ventricular failure. Some may be candidates for left ventricular (LV) retraining and late arterial switch. The purpose of this study was to review our experience with LV retraining and late arterial switch. This was a retrospective review of 32 patients with d-transposition. Thirty patients underwent a previous atrial switch and subsequently experienced right ventricular failure, whereas 2 presented late (8 months and 6 years) without previous intervention. The median age at the time of enrollment in this program was 15 years. Seven patients proceeded directly to late arterial switch owing to systemic LV pressures. The remaining 25 underwent a pulmonary artery band for LV retraining. Twenty of the 32 (63%) patients enrolled in this program were able to undergo a late arterial switch. There were 2 operative mortalities (10%). Two additional patients survived surgery but died in the early outpatient time period. There has been no late mortality after the arterial switch with a median follow-up of 5 years. Twelve patients underwent one or more pulmonary artery band procedures without evidence of effective LV retraining. There have been 2 early and 3 late (42%) deaths in this subgroup. The outcomes after arterial switch are encouraging and suggest that LV retraining and late arterial switch provide a viable option for this complex group of patients. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Primary care appointment availability and nonphysician providers one year after Medicaid expansion.

PubMed

Tipirneni, Renuka; Rhodes, Karin V; Hayward, Rodney A; Lichtenstein, Richard L; Choi, HwaJung; Reamer, Elyse N; Davis, Matthew M

2016-06-01

With insurance enrollment greater than expected under the Affordable Care Act, uncertainty about the availability and timeliness of healthcare services for newly insured individuals has increased. We examined primary care appointment availability and wait times for new Medicaid and privately insured patients before and after Medicaid expansion in Michigan. Simulated patient ("secret shopper") study. Extended follow-up of a previously reported simulated patient ("secret shopper") study assessing accessibility of routine new patient appointments in a stratified proportionate random sample of Michigan primary care practices before versus 4, 8, and 12 months after Medicaid expansion. During the study period, approximately 600,000 adults enrolled in Michigan's Medicaid expansion program, representing 57% of the previously uninsured nonelderly adult population. One year after expansion, we found that appointment availability remained increased by 6 percentage points for new Medicaid patients (95% CI, 1.6-11.1) and decreased by 2 percentage points for new privately insured patients (95% CI, -0.5 to -3.8). Over the same period, the proportion of appointments scheduled with nonphysician providers (nurse practitioners or physician assistants) increased from 8% to 21% of Medicaid appointments (95% CI, 5.6-20.2) and from 11% to 19% of private-insurance appointments (95% CI, 1.3-14.1). Median wait times remained stable for new Medicaid patients and increased slightly for new privately insured patients, both remaining within 2 weeks. During the first year following Medicaid expansion in Michigan, appointment availability for new Medicaid patients increased, a greater proportion of appointments could be obtained with nonphysician providers, and wait times remained within 2 weeks.

Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial.

PubMed

Jones, Jeffrey A; Mato, Anthony R; Wierda, William G; Davids, Matthew S; Choi, Michael; Cheson, Bruce D; Furman, Richard R; Lamanna, Nicole; Barr, Paul M; Zhou, Lang; Chyla, Brenda; Salem, Ahmed Hamed; Verdugo, Maria; Humerickhouse, Rod A; Potluri, Jalaja; Coutre, Steven; Woyach, Jennifer; Byrd, John C

2018-01-01

Therapy targeting Bruton's tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia. However, patients who are refractory to or relapse after ibrutinib therapy have poor outcomes. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 active in previously treated patients with relapsed or refractory chronic lymphocytic leukaemia. In this study, we assessed the activity and safety of venetoclax in patients with chronic lymphocytic leukaemia who are refractory to or relapse during or after ibrutinib therapy. In this interim analysis of a multicentre, open-label, non-randomised, phase 2 trial, we enrolled patients aged 18 years or older with a documented diagnosis of chronic lymphocytic leukaemia according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and an Eastern Cooperative Oncology Group performance score of 2 or lower. All patients had relapsed or refractory disease after previous treatment with a BCR signalling pathway inhibitor. All patients were screened for Richter's transformation and cases confirmed by biopsy were excluded. Eligible patients received oral venetoclax, starting at 20 mg per day with stepwise dose ramp-up over 5 weeks to 400 mg per day. Patients with rapidly progressing disease received an accelerated dosing schedule (to 400 mg per day by week 3). The primary endpoint was overall response, defined as the proportion of patients with an overall response per investigator's assessment according to IWCLL criteria. All patients who received at least one dose of venetoclax were included in the activity and safety analyses. This study is ongoing; data for this interim analysis were collected per regulatory agencies' request as of June 30, 2017. This trial is registered with ClinicalTrials.gov, number NCT02141282. Between September, 2014, and November, 2016, 127 previously treated patients with relapsed or refractory chronic lymphocytic leukaemia were enrolled from 15 sites across the USA. 91 patients had received ibrutinib as the last BCR inhibitor therapy before enrolment, 43 of whom were enrolled in the main cohort and 48 in the expansion cohort recruited later after a protocol amendment. At the time of analysis, the median follow-up was 14 months (IQR 8-18) for all 91 patients, 19 months (9-27) for the main cohort, and 12 months (8-15) for the expansion cohort. 59 (65%, 95% CI 53-74) of 91 patients had an overall response, including 30 (70%, 54-83) of 43 patients in the main cohort and 29 (60%, 43-72) of 48 patients in the expansion cohort. The most common treatment-emergent grade 3 or 4 adverse events were neutropenia (46 [51%] of 91 patients), thrombocytopenia (26 [29%]), anaemia (26 [29%]), decreased white blood cell count (17 [19%]), and decreased lymphocyte count (14 [15%]). 17 (19%) of 91 patients died, including seven because of disease progression. No treatment-related deaths occurred. The results of this interim analysis show that venetoclax has durable clinical activity and favourable tolerability in patients with relapsed or refractory chronic lymphocytic leukaemia whose disease progressed during or after discontinutation of ibrutinib therapy. The durability of response to venetoclax will be assessed in the final analysis in 2019. AbbVie, Genentech. Copyright © 2018 Elsevier Ltd. All rights reserved.

The increased risk of globus pharyngeus in patients with chronic thyroiditis: a case control study.

PubMed

Karahatay, S; Ayan, A; Aydin, U; Ince, S; Emer, O; Alagoz, E

2015-12-01

A correlation between globus pharyngeus and thyroid gland inflammation has been mentioned in previous studies. However, the potential risk of globus pharyngeus in chronic thyroiditis patients has not been shown so far. The aim of this study is to investigate a possible association between chronic thyroiditis and globus pharyngeus. The study was performed in an ultrasound (US) center of a tertiary health care institution. Ninety-two patients who were under examination for suspected thyroid pathologies or undergoing follow-up for a previously diagnosed thyroid disease were enrolled in the study. The patients were divided into two groups according to the existence of globus symptoms. Subsequently, all patients underwent high-resolution thyroid ultrasounds. The patients whose ultrasound findings were suggestive of chronic thyroiditis constituted the second subgroup. The demographic data of the patients and other ultrasound findings including the volume of the thyroid glands and nodules, if any, were noted as well. Sixty-seven female (73%) and 25 male (27%) patients were enrolled in the study. Thirty-two (35%) of the 92 patients constituted the globus pharyngeus group according to their responses to the questionnaire and the US findings were concordant with chronic thyroiditis in 36 (39%) patients. The correlation between chronic thyroiditis and globus sensation was significant (p = 0.004), and the odds ratio was calculated as 3.7 (95% CI = 1.5-9.11). Other parameters including age, sex, thyroid volume and nodule status were not significantly related to globus pharyngeus in this particular patient series. In the presented study, the risk of globus pharyngeus occurrence was calculated as 3.7-fold higher in patients with chronic thyroiditis. Being a preliminary report, it is necessary to confirm this finding and understand the pathophysiological mechanism via further investigations with a larger patient series.

A SAS-based solution to evaluate study design efficiency of phase I pediatric oncology trials via discrete event simulation.

PubMed

Barrett, Jeffrey S; Jayaraman, Bhuvana; Patel, Dimple; Skolnik, Jeffrey M

2008-06-01

Previous exploration of oncology study design efficiency has focused on Markov processes alone (probability-based events) without consideration for time dependencies. Barriers to study completion include time delays associated with patient accrual, inevaluability (IE), time to dose limiting toxicities (DLT) and administrative and review time. Discrete event simulation (DES) can incorporate probability-based assignment of DLT and IE frequency, correlated with cohort in the case of DLT, with time-based events defined by stochastic relationships. A SAS-based solution to examine study efficiency metrics and evaluate design modifications that would improve study efficiency is presented. Virtual patients are simulated with attributes defined from prior distributions of relevant patient characteristics. Study population datasets are read into SAS macros which select patients and enroll them into a study based on the specific design criteria if the study is open to enrollment. Waiting times, arrival times and time to study events are also sampled from prior distributions; post-processing of study simulations is provided within the decision macros and compared across designs in a separate post-processing algorithm. This solution is examined via comparison of the standard 3+3 decision rule relative to the "rolling 6" design, a newly proposed enrollment strategy for the phase I pediatric oncology setting.

Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study

PubMed Central

Bible, Keith C; Suman, Vera J; Molina, Julian R; Smallridge, Robert C; Maples, William J; Menefee, Michael E; Rubin, Joseph; Sideras, Kostandinos; Morris, John C; McIver, Bryan; Burton, Jill K; Webster, Kevin P; Bieber, Carolyn; Traynor, Anne M; Flynn, Patrick J; Goh, Boon Cher; Tang, Hui; Ivy, Susan Percy; Erlichman, Charles

2011-01-01

Summary Background Chemotherapy has historically proven ineffective in advanced differentiated thyroid cancers, but the realisation that various tyrosine kinases are activated in the disease suggested a potential therapeutic role for tyrosine-kinase inhibitors. We investigated the safety and efficacy of pazopanib. Methods This phase 2 trial was done from Feb 22, 2008, to Jan 31, 2009, in patients with metastatic, rapidly progressive, radioiodine-refractory differentiated thyroid cancers. Each patient received 800 mg continuous pazopanib daily in 4-week cycles until disease progression, drug intolerance, or both occurred. Up to two previous therapies were allowed, and measurable disease with radiographic progression in the 6-month period before enrolment was a requirement for inclusion. The primary endpoint was any tumour response, according to the Response Evaluation Criteria in Solid Tumors 1.0. This study is registered with ClinicalTrials.gov, number NCT00625846. Findings 39 patients were enrolled. One patient had received no previous radioiodine therapy and another withdrew consent before treatment. Clinical outcomes could, therefore, be assessed in 37 patients (19 [51%] men, median age 63 years). The study is closed to accrual of new patients, but several enrolled patients are still being treated. Patients received a median of 12 cycles (range 1 to >23, total >383). Confirmed partial responses were recorded in 18 patients (response rate 49%, 95% CI 35–68), with likelihood of response lasting longer than 1 year calculated to be 66%. Maximum concentration of pazopanib in plasma during cycle one was significantly correlated with radiographic response (r=−0·40, p=0·021). 16 (43%) patients required dose reductions owing to adverse events, the most frequent of which (any grade) were fatigue (29 patients), skin and hair hypopigmentation (28), diarrhoea (27), and nausea (27). Two patients who died during treatment had pre-existing contributory disorders. Interpretation Pazopanib seems to represent a promising therapeutic option for patients with advanced differentiated thyroid cancers. The correlation of the patient’s response and pazopanib concentration during the first cycle might indicate that treatment can be individualised to achieve optimum outcomes. Assessment of pazopanib in an expanded cohort of patients with differentiated thyroid cancer, as well as in cohorts of patients with medullary and anaplastic thyroid cancers, is presently being done. Funding National Cancer Institute, supported in part by NCI CA15083 and CM62205. PMID:20851682

Prospective, non-interventional, multicenter study of the intraocular pressure-lowering effects of prostaglandin analog/prostamide-containing therapies in previously treated patients with open-angle glaucoma or ocular hypertension

PubMed Central

Tamçelik, Nevbahar; Izgi, Belgin; Temel, Ahmet; Yildirim, Nilgun; Okka, Mehmet; Özcan, Altan; Yüksel, Nurşen; Elgin, Ufuk; Altan, Çiğdem; Ozer, Baris

2017-01-01

Objective The objective of this study was to assess the intraocular pressure (IOP)-lowering efficacy, tolerability, safety, and usage patterns of prostaglandin analog/prostamide (PGA/P)-containing topical ocular hypotensives in ocular hypertension (OHT) and primary open-angle glaucoma in the Turkish clinical setting. Methods This non-interventional, multicenter study enrolled previously treated patients who failed to achieve target IOP (or experienced unacceptable adverse events [AEs]) and were prescribed a PGA/P-containing IOP-lowering agent. Treatment was initiated at baseline (V1), and patients returned at weeks 4–6 (V2) and 8–12 (V3). The primary efficacy measure was the change in IOP from baseline at V3 in each eye. The secondary measures were physician’s assessment of IOP-lowering efficacy, patients (%) reaching target IOP determined at V1, hyperemia score, physician and patient assessment of study treatment tolerability at V3, and AE frequency/severity. A subgroup analysis of patients receiving the most common study treatment was conducted. All analyses were performed using the safety population (patients who received one or more doses and had any data available). Results Of 358 enrolled patients, 60.6% had primary open-angle glaucoma, 29.9% had secondary open-angle glaucoma (protocol amendment), and 13.1% had OHT; 13 patients had multiple diagnoses. At V3, the mean IOP change from baseline was ≥−4.2 mmHg (≥21.1%). IOP met or was lower than the target in 81.7% of patients, 95% exhibited none to mild conjunctival hyperemia (most common AE), and tolerability was rated good/very good by >91.1% of patients and physicians. The results were similar in patients who received the most common study treatment, bimatoprost 0.03%/timolol 0.5% (bim/tim; n=310). Conclusion PGA/P-containing medications, including bim/tim, significantly reduced IOP in previously treated patients with open-angle glaucoma or OHT; most reached their target IOP or an IOP even lower than their target and reported good/very good tolerability. PGA/P-containing medications such as bim/tim should be considered as a safe, effective therapeutic option for Turkish patients who exhibit poor response, tolerance, or adherence to their previous therapy. PMID:28458511

Course of Cytomegalovirus Retinitis in the Era of Highly Active Antiretroviral Therapy: Five-year Outcomes

PubMed Central

Jabs, Douglas A.; Ahuja, Alka; Van Natta, Mark; Lyon, Alice; Srivastava, Sunil; Gangaputra, Sapna

2010-01-01

Purpose To describe the five-year outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS in the era of highly active antiretroviral therapy (HAART). Design Prospective, multicenter, observational study Participants 503 patients with AIDS and CMV retinitis Methods Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and retinal photographs. Participants were classified as having previously-diagnosed CMV retinitis and immune recovery (CD4+ T cells >100 cells/µL), previously-diagnosed retinitis and immune compromise, and newly-diagnosed CMV retinitis (diagnosis < 45 days prior to enrollment). Main outcome measures Mortality, retinitis progression (movement of the border of a CMV lesion ≥ ½ disc diameter or occurrence of a new lesion), retinal detachment, immune recovery uveitis (IRU), and visual loss (to worse than 20/40 and to 20/200 or worse), Results Overall mortality was 9.8 deaths/100 person-years (PY). Rates varied by group at enrollment from 3.0/100 PY for those with previously-diagnosed retinitis and immune recovery to 26.1/100 PY for those with newly-diagnosed retinitis. The rate of retinitis progression was 7.0/100 PY and varied from 1.4/100 PY for those with previously-diagnosed retinitis and immune recovery to 28.0/100 PY for those with newly-diagnosed retinitis. The rate of retinal detachment was 2.3/100 eye-years (EY) and varied from 1.2/100 EY for those with previously-diagnosed retinitis and immune recovery to 4.9/100 EY for those with newly-diagnosed retinitis. The rate of IRU was 1.7/100 PY and varied from 1.3/100 PY for those with previously-diagnosed retinitis and immune recovery at enrollment to 3.6/100 PY for those with newly-diagnosed retinitis who subsequently experienced immune recovery. The rates of visual loss to worse than 20/40 and to 20/200 or worse were 7.9/100 EY and 3.4/100 EY, respectively; they varied from 6.1/100 EY and 2.7/100 EY for those with previously-diagnosed retinitis and immune recovery to 11.8/100 EY and 5.1/100 EY for those with newly-diagnosed retinitis. Although the event rates tended to decline with time, in general, at no time did they reach zero. Conclusions Despite the availability of HAART, patients with AIDS and CMV retinitis remain at increased risk for mortality, retinitis progression, complications of the retinitis, and visual loss over a 5-year period. PMID:20673591

Preoperative Obstructive Sleep Apnea Screening in Gynecologic Oncology Patients.

PubMed

Harrison, Ross F; Medlin, Erin E; Petersen, Chase B; Rose, Stephen L; Hartenbach, Ellen M; Kushner, David M; Spencer, Ryan J; Rice, Laurel W; Al-Niaimi, Ahmed N

2018-05-21

Women with a gynecologic cancer tend to be older, obese, and postmenopausal, characteristics that are associated with an increased risk for obstructive sleep apnea. However, there is limited investigation regarding the condition's prevalence in this population or its impact on postoperative outcomes. In other surgical populations, patients with obstructive sleep apnea have been observed to be at increased risk for adverse postoperative events. To estimate the prevalence of obstructive sleep apnea among gynecologic oncology patients undergoing elective surgery and to investigate for a relationship between obstructive sleep apnea and postoperative outcomes. Patients referred to an academic gynecologic oncology practice were approached for enrollment in this prospective, observational study. Patients were considered eligible for study enrollment if they were scheduled for a non-emergent inpatient surgery and could provide informed consent. Enrolled patients were evaluated for a preexisting diagnosis of obstructive sleep apnea. Those without a prior diagnosis were screened using the validated, 4-item STOP [i.e. Snore loudly, daytime Tiredness, Observed apnea, elevated blood Pressure] questionnaire. All patients who screened positive for obstructive sleep apnea were referred for polysomnography. The primary outcome was the prevalence of women with obstructive sleep apnea or those who screened at high risk for the condition. Secondary outcomes examined the correlation between body mass index (kg/m 2 ) with obstructive sleep apnea and assessed for a relationship between obstructive sleep apnea and postoperative outcomes. Over a 22-month accrual period, 383 eligible patients were consecutively approached to participate in the study. A cohort of 260 patients were enrolled. A total of 33/260 patients (13%) were identified as having a previous diagnosis of obstructive sleep apnea. An additional 66/260 (25%) screened at risk for the condition using the STOP questionnaire. Of the patients who screened positive, 8/66 (12%) completed polysomnography, all of whom (8/8 [100%]) were found to have obstructive sleep apnea. The prevalence of previously-diagnosed obstructive sleep apnea or screening at risk for the condition increased as body mass index increased (p < 0.001). Women with untreated obstructive sleep apnea and those who screened at risk for the condition were found to have an increased risk for postoperative hypoxemia (OR = 3.5 [1.8-4.7]; p = 0.011) and delayed return of bowel function (OR = 2.1 [1.3-4.5]; p = 0.009). The prevalence of obstructive sleep apnea or screening at risk for the condition is high among women presenting for surgery with a gynecologic oncologist. Providers should consider evaluating a patient's risk for obstructive sleep apnea in the preoperative setting, especially when risk factors for the condition are present. Copyright © 2018. Published by Elsevier Inc.

Anti-tuberculosis drug resistance in Bangladesh: reflections from the first nationwide survey.

PubMed

Kamal, S M M; Hossain, A; Sultana, S; Begum, V; Haque, N; Ahmed, J; Rahman, T M A; Hyder, K A; Hossain, S; Rahman, M; Ahsan, Chowdhury R; Chowdhury, R A; Aung, K J M; Islam, A; Hasan, R; Van Deun, A

2015-02-01

To determine the prevalence of tuberculosis (TB) drug resistance in Bangladesh. Weighted cluster sampling among smear-positive cases, and standard culture and drug susceptibility testing on solid medium were used. Of 1480 patients enrolled during 2011, 12 falsified multidrug-resistant TB (MDR-TB) patients were excluded. Analysis included 1340 cases (90.5% of those enrolled) with valid results and known treatment antecedents. Of 1049 new cases, 12.3% (95%CI 9.3-16.1) had strains resistant to any of the first-line drugs tested, and 1.4% (95%CI 0.7-2.5) were MDR-TB. Among the 291 previously treated cases, this was respectively 43.2% (95%CI 37.1-49.5) and 28.5% (95%CI 23.5-34.1). History of previous anti-tuberculosis treatment was the only predictive factor for first-line drug resistance (OR 34.9). Among the MDR-TB patients, 19.2% (95%CI 11.3-30.5; exclusively previously treated) also showed resistance to ofloxacin. Resistance to kanamycin was not detected. Although MDR-TB prevalence was relatively low, transmission of MDR-TB may be increasing in Bangladesh. MDR-TB with fluoroquinolone resistance is rapidly rising. Integrating the private sector should be made high priority given the excessive proportion of MDR-TB retreatment cases in large cities. TB control programmes and donors should avoid applying undue pressure towards meeting global targets, which can lead to corruption of data even in national surveys.

Executive Function, Survival, and Hospitalization in Chronic Obstructive Pulmonary Disease. A Longitudinal Analysis of the National Emphysema Treatment Trial (NETT).

PubMed

Dodd, James W; Novotny, Paul; Sciurba, Frank C; Benzo, Roberto P

2015-10-01

Cognitive dysfunction has been demonstrated in chronic obstructive pulmonary disease (COPD), but studies are limited to cross-sectional analyses or incompletely characterized populations. We examined longitudinal changes in sensitive measures of executive function in a well-characterized population of patients with severe COPD. This study was performed on patients enrolled in the National Emphysema Treatment Trial. To assess executive function, we analyzed trail making (TM) A and B times at enrollment in the trial (2,128 patients), and at 12 (731 patients) and 24 months (593 patients) after enrollment, adjusted for surgery, marriage status, age, education, income, depression, PaO2, PaCO2, and smoking. Associations with survival and hospitalizations were examined using Cox regression and linear regression models. The average age of the patients was 66.4 years, and the average FEV1 was 23.9% predicted. At the time of enrolment, 38% had executive dysfunction. Compared with those who did not, these patients were older, less educated, had higher oxygen use, higher PaCO2, worse quality of life as measured by the St. George's Respiratory Quotient, reduced well-being, and lower social function. There was no significant change over 2 years in TM A or B times after adjustment for covariables. Changes in TM B times were modestly associated with survival, but changes in TM B-A times were not. Changes in TM scores were not associated with frequency of hospitalization. Lung function, PaO2, smoking, survival, and hospitalizations were not significantly different in those with executive dysfunction. In this large population of patients with severe emphysema and heavy cigarette smoking exposure, there was no significant decline over 2 years in cognitive executive function as measured by TM tests. There was no association between executive function impairment and frequency of hospitalization, and there was a possible modest association with survival. It is plausible that cerebrovascular comorbidities explain previously described cognitive pathology in COPD.

“Caseness” for Depression and Anxiety in a Depressed Outpatient Population: Symptomatic Outcome as a Function of Baseline Diagnostic Categories

PubMed Central

Verhaeghen, Anne; Dantchev, Nicolas; Grassi, Luigi; Montejo, Angel L.; Perahia, David G. S.; Quail, Deborah; Reed, Catherine; Tylee, Andre; Bauer, Michael

2009-01-01

Objective: To examine the diagnostic status of patients enrolled in the Factors Influencing Depression Endpoints Research (FINDER) study and symptomatic outcomes and baseline characteristics associated with remission 6 months after commencing antidepressant therapy. Method: Status of clinically diagnosed depressed patients was based on self-rated Hospital Anxiety and Depression Scale (HADS) scores. Five diagnostic categories were defined: noncaseness, mixed anxiety-depression (subthreshold depressive and anxious symptomatology), caseness for depression, caseness for anxiety, and caseness for comorbid anxiety-depression. Assessments included the Somatic Symptom Inventory and health-related quality of life (HRQoL) using the Medical Outcomes Study 36-item Short-Form Health Survey. Remission rates (based on HADS noncaseness for both depression and anxiety) and their associations with baseline characteristics were investigated. Patients were enrolled between May 2004 and September 2005. Results: Of the 3,353 patients enrolled, 66.4% met the HADS criteria for probable depressive disorder and 74.1% met the HADS criteria for probable anxiety disorder. Somatic symptom severity (painful and nonpainful) was highest and HRQoL was lowest in the comorbid anxiety-depression group. After 6 months, remission rates were 50.2% for caseness for depression, 40.4% for caseness for anxiety, and 40.6% for caseness for comorbid anxiety-depression. A lower number of previous depressive episodes, shorter current episode duration, lower painful and nonpainful somatic symptom scores, being married, a higher educational level, and working for pay were most consistently associated with higher remission rates. Conclusions: Physicians do not always differentiate between anxiety and depressive symptoms when making a clinical diagnosis of depression. At baseline, most enrolled patients had significant emotional depressive and anxious symptoms, as well as significant nonpainful and painful somatic symptomatology, and these factors were associated with outcome. PMID:20098522

Lactate clearance in septic shock is not a surrogate for improved microcirculatory flow

PubMed Central

Puskarich, Michael A.; Shapiro, Nathan I.; Massey, Michael J.; Kline, Jeffrey A.; Jones, Alan E.

2016-01-01

Introduction Failure to normalize lactate is associated with poor outcomes in septic shock. It has been suggested that persistently elevated lactate may result from regional ischemia due to disturbed and/or heterogenous microcirculatory blood flow. Objectives The goal of this study was to determine if lactate clearance may serve as a surrogate marker for changes in microcirculatory blood flow in patients with septic shock. Methods This was a prospective observational study performed within a previously published clinical trial of L-carnitine for the treatment of vasopressor-dependent septic shock. Intravital video microscopy was performed at enrollment and 12 hours later, and microcirculatory flow index (MFI) was assessed. Associations between enrollment MFI, lactate, and SOFA score were determined, in addition to associations between ΔMFI, lactate clearance, and ΔSOFA. A preplanned subgroup analysis of only patients with an elevated initial lactate was performed. Results We enrolled a total of 31 patients, 23 with survival to and sufficient quality videos both at enrollment and 12 hours. ΔMFI, lactate clearance, and ΔSOFA were 0.1 (IQR 0, 0.3), 18% (IQR −10%, 46%), and −2 (IQR −4, 0). Both ΔMFI and lactate clearance were associated with ΔSOFA (β = −5.3, p = 0.01 and β = −3.5, 0.047), but not with each other, even in the subgroup of patients with an initially elevated lactate. Conclusion We observed no association between degree of lactate clearance and change in microcirculatory blood flow in patients with septic shock. These data suggest against the hypothesis that lactate clearance may be used as a surrogate marker of microcirculatory blood flow. PMID:26825368

Cost of rotavirus diarrhea for programmatic evaluation of vaccination in Vietnam.

PubMed

Riewpaiboon, Arthorn; Shin, Sunheang; Le, Thi Phuong Mai; Vu, Dinh Thiem; Nguyen, Thi Hien Anh; Alexander, Neal; Dang, Duc Anh

2016-08-11

Rotavirus is the most common etiology of diarrhea-associated hospitalizations and clinic visits in Vietnamese children < 5 years old. To estimate the economic burden of rotavirus-associated formal healthcare encounters, an economic study was conducted. A cost-of-illness study was performed from a societal perspective. Data were collected from children below the age of five years who presented to a clinic or hospital with symptoms of acute gastroenteritis (AGE). Patient-specific information on resource use and cost was obtained through caregiver interviews and medical chart review. Costs are presented in 2014 US dollar ($). A total of 557 children with symptoms of AGE were enrolled from March through June 2009, with mean age of 16.5 months. Of the 340 outpatients and 217 admitted patients enrolled, 41 % tested rotavirus positive. It was found that, from a societal perspective, the mean total cost of AGE was $175. Costs of patients with and without rotavirus were $217 and $158, respectively. From multiple regression analysis, it was found that rotavirus infection, patient age and receiving oral rehydration solution before visiting health facility had significant effect on the costs. This study clearly demonstrated substantial economic burden of AGE including rotavirus disease. They were significantly greater than the previously reported cost estimates in Vietnam. These updated costs of illness result in more favorable vaccine cost-effectiveness than in previous economic evaluations.

Real-world Experience With a Decellularized Dehydrated Human Amniotic Membrane Allograft.

PubMed

Smiell, Janice M; Treadwell, Terry; Hahn, Helen D; Hermans, Michel H

2015-06-01

While randomized controlled trials (RCTs) are designed to evaluate efficacy and/or safety under controlled conditions, use of strict inclusion/ exclusion criteria are noted to exclude more than 50% of wound populations. Applicability of RCT outcomes to performance expectations in real-world wound populations raises questions about generalizing their results. The primary aim of this decellularized, dehydrated human amniotic membrane (DDHAM) Use Registry Study was to gain experience and observe outcomes with use of a DDHAM in uninfected, full-thickness, or partial-thickness wounds that, in the investigators' opinions, would benefit from such treatment. Investigators were instructed to provide usual care regarding visit and application frequencies, concomitant therapies, and change in wound-care regimens. The only exclusions were patients with actively infected wounds or known hypersensitivity to DDHAM. Fifteen sites with practicing wound care clinicians of various specialties participated in this review, enrolling chronic wounds including venous, diabetic, pressure, collagen vascular, and arterial ulcers-all of various severities, durations, sizes, and previous treatments. Twenty-eight ulcers studied had failed 32 previous treatments with advanced biologic therapies. A total of 244 wounds were observed in this study, however, this review is limited to the 179 chronic wounds in 165 patients that were enrolled at 15 of the 19 participating centers. The 4 centers that enrolled acute wounds only were excluded. Results from the analysis of this very heterogeneous population demonstrated that during the usual course of an average of 8 weeks of wound management, patients experienced factors that significantly affected wound closure. These factors included wound infections, noncompliance with prescribed treatments (eg, compression, off-loading, and wound care), re-injury of the wound, and systemic comorbidities. Nearly 50% of chronic wounds (including those that failed previous therapy with advanced biologics) with an average baseline area of 3.1 cm2 achieved complete closure within a median of 6.3 weeks without product-related adverse experiences. Despite the challenges of uncontrolled factors that affect healing, this registry study demonstrated the safety and clinical benefit of DDHAM to support wound closure across a variety of chronic wound types and patient conditions in real-world environments.

1981 Follow-Up Study of Students Enrolled and Previously Enrolled in the Michigan School for the Blind and the Michigan School for the Deaf.

ERIC Educational Resources Information Center

Livingston-White, Deborah J. H.

A followup study of currently and previously enrolled students of the Michigan School for the Blind (MSB) and the Michigan School for the Deaf (MSD) is reported. Eligibility guidelines, services, enrollment, costs, and nature of the student body at each institution are described. Development and use of four questionnaires to evaluate eight…

Association between previous spontaneous abortion and pre-eclampsia during a subsequent pregnancy.

PubMed

Sepidarkish, Mahdi; Almasi-Hashiani, Amir; Maroufizadeh, Saman; Vesali, Samira; Pirjani, Reihaneh; Samani, Reza O

2017-01-01

To determine the impact of a history of spontaneous abortion on pre-eclampsia during a subsequent pregnancy. A cross-sectional study enrolled pregnant women admitted to obstetrics and gynecology wards at 103 hospitals in Tehran, Iran for delivery between July 6 and July 21, 2015. Consenting participants were interviewed by midwives; data were collected using a five-part questionnaire and patients' medical records were retrieved. Patient data were analyzed by multiple logistic regression to identify variables associated with increased odds of pre-eclampsia. In total, 5170 patients were interviewed and 252 had experienced pre-eclampsia. The number of previous spontaneous abortions was found to be associated with pre-eclampsia, and a higher number of previous spontaneous abortions was associated with increased odds of patients having experienced pre-eclampsia (adjusted odds ratio 1.28, 95% confidence interval 1.03-1.59; P=0.025). A history of spontaneous abortion was associated with increased odds of pre-eclampsia during a subsequent pregnancy. © 2016 International Federation of Gynecology and Obstetrics.

A Japanese Post-marketing Surveillance of Cetuximab (Erbitux®) in Patients with Metastatic Colorectal Cancer

PubMed Central

Ishiguro, Megumi; Watanabe, Toshiaki; Yamaguchi, Kensei; Satoh, Taroh; Ito, Hideyuki; Seriu, Taku; Sakata, Yuh; Sugihara, Kenichi

2012-01-01

Objective Cetuximab (Erbitux®) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval. Methods All patients to be treated with cetuximab were enrolled by the central enrolment method. Data on treatment status, and incidence and severity of adverse drug reactions were collected. The target number of patients was 1800. Results A total of 2126 patients were enrolled from 637 institutions. Among 2006 patients analysed, 93.2% received cetuximab as third-line or later treatment. The median duration of treatment was 15.3 weeks, and 11.1% of patients received treatment for >48 weeks. The incidence of adverse drug reactions was 89.6%, of which ≥grade 3 was 21.5%. The incidence of infusion reactions was 5.7% (any grade), with 83.3% of them occurring at the first administration. The incidence of skin disorders was 83.7% (any grade), and the time to event varied for each skin disorder. The incidence of interstitial lung diseases was 1.2% (any grade). Diarrhoea and haematotoxicity scarcely occurred with cetuximab alone. Conclusions In this surveillance, the incidence and categories of adverse drug reactions are not distinct from previous reports. Although most patients received cetuximab as third-line or later treatment, treatment was maintained with a median duration of 15 weeks. Cetuximab treatment in practical use is considered to be well tolerated and clinically useful in Japanese patients with metastatic colorectal cancer. PMID:22327124

Frequency, Prognosis and Surgical Treatment of Structural Abnormalities Seen with Magnetic Resonance Imaging in Childhood Epilepsy

ERIC Educational Resources Information Center

Berg, Anne T.; Mathern, Gary W.; Bronen, Richard A.; Fulbright, Robert K.; DiMario, Francis; Testa, Francine M.; Levy, Susan R.

2009-01-01

The epidemiology of lesions identified by magnetic resonance imaging (MRI), along with the use of pre-surgical evaluations and surgery in childhood-onset epilepsy patients has not previously been described. In a prospectively identified community-based cohort of children enrolled from 1993 to 1997, we examined (i) the frequency of lesions…

Healthcare provision for HIV co-infected tuberculosis patients in rural Zambia: an observational cohort study at primary care centers

PubMed Central

2013-01-01

Background Linkage of healthcare services for tuberculosis (TB) and human immunodeficiency virus (HIV) remains a major challenge in resource-limited settings. Our operational research aimed to evaluate the linkage between TB and HIV services in a rural area of Zambia, and to explore factors associated with the enrolment of TB/HIV co-infected patients in HIV care services. Methods All TB patients newly diagnosed as HIV-positive in Chongwe district, Zambia between 2009 and 2010 were included. Data from TB registers and medical records were reviewed. Patient referral to HIV services and provision of antiretroviral therapy (ART) were further examined through HIV registers and records. Results Of 621 patients (median age 33.0 years, female 42.4%) who started anti-TB treatment, clinic records indicated that 297 patients were newly diagnosed as HIV-positive, and 176 (59.3%) of these were referred to an ART clinic. Analysis of records at the ART clinic found that only 85 (28.6%) of TB/HIV patients had actually been enrolled in HIV care, of whom only 58 (68.2%) had commenced ART. Logistic regression analyses demonstrated the following factors associated with lower enrolment: “male” sex (aOR, 0.45; 95% CI 0.26-0.78), “previous TB treatment” (aOR, 0.29; 95% CI, 0.11-0.75), “registration at sites that did not provide ART services (non-ART site)” (aOR, 0.10; 95% CI, 0.01-0.77) and “death on TB treatment outcome (aOR, 0.20; 95% CI, 0.06-0.65). However, patient registration at TB clinics in 2010 was associated with markedly higher enrolment in HIV care as compared to registration in 2009 (aOR, 2.80; 95% CI, 1.53-5.12). Conclusions HIV testing for TB patients has been successfully scaled up. However referrals of co-infected patients still remain a challenge due to poor linkage between TB and HIV healthcare services. Committed healthcare workers, a well-organized health services system and patient education are urgently required to ensure a higher rate of referral of TB/HIV co-infected patients for appropriate care. PMID:24103082

A novel diagnostic tool for detecting functional patency of the small bowel: the Given patency capsule.

PubMed

Spada, C; Spera, G; Riccioni, M; Biancone, L; Petruzziello, L; Tringali, A; Familiari, P; Marchese, M; Onder, G; Mutignani, M; Perri, V; Petruzziello, C; Pallone, F; Costamagna, G

2005-09-01

The current visualization of small-bowel strictures using traditional radiological methods is associated with high radiation doses and false-negative results. These methods do not always reveal small-bowel patency for solids. The aim is to assess the safety of the Given patency system and its ability to detect intestinal strictures in patients with strictures that are known or suspected radiologically. The Given patency capsule is composed of lactose, remains intact in the gastrointestinal tract for 40-100 hours post ingestion, and disintegrates thereafter. A total of 34 patients with small-bowel stricture were prospectively enrolled; 30 had a previous diagnosis of Crohn's disease, three had adhesion syndrome and in one ischemic enteritis was suspected. Of the patients, 15 (44.1 %) had previously undergone surgery. Following ingestion, the capsule was monitored for integrity and transit time, using a specially designed Given scanner and also radiologically. Seventeen patients had been enrolled with the intent of using the patency capsule as a preliminary test in patients with small-bowel strictures before undergoing video capsule endoscopy. 30 patients (88.2 %) retrieved the capsule in the stool; it was intact in 20 (median transit time 22 hours), and disintegrated in 10 patients (median transit time 53 hours). Six patients complained of abdominal pain which disappeared within 24 hours. The scanner successfully indicated the presence of the capsule in 94 % of cases. Ten patients underwent video capsule endoscopy following the patency capsule examination; in all of these the video capsule passed through the small-bowel stricture. This feasibility study has shown that the Given patency capsule is a safe, effective, and convenient tool for assessment of functional patency of the small bowel. It can indicate functional patency even in cases where traditional radiology indicates stricture.

Risk Factors Associated with Default from Multi- and Extensively Drug-Resistant Tuberculosis Treatment, Uzbekistan: A Retrospective Cohort Analysis

PubMed Central

Lalor, Maeve K.; Greig, Jane; Allamuratova, Sholpan; Althomsons, Sandy; Tigay, Zinaida; Khaemraev, Atadjan; Braker, Kai; Telnov, Oleksander; du Cros, Philipp

2013-01-01

Background The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010. Methods A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression. Results 20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6–9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31–0.86), previous default (2.38, 1.09–5.24) and age >45 years (1.77, 1.10–2.87). The default rate was 14% (42/294) for patients enrolled 2003–2006 and 24% (100/416) for 2007–2008 enrolments (p = 0.001). Conclusions Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted health education and support for at-risk patients after 5 months of treatment when many begin to feel better may decrease default. PMID:24223148

Risk factors associated with default from multi- and extensively drug-resistant tuberculosis treatment, Uzbekistan: a retrospective cohort analysis.

PubMed

Lalor, Maeve K; Greig, Jane; Allamuratova, Sholpan; Althomsons, Sandy; Tigay, Zinaida; Khaemraev, Atadjan; Braker, Kai; Telnov, Oleksander; du Cros, Philipp

2013-01-01

The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010. A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression. 20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6-9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31-0.86), previous default (2.38, 1.09-5.24) and age >45 years (1.77, 1.10-2.87). The default rate was 14% (42/294) for patients enrolled 2003-2006 and 24% (100/416) for 2007-2008 enrolments (p = 0.001). Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted health education and support for at-risk patients after 5 months of treatment when many begin to feel better may decrease default.

Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.

PubMed

Lawitz, Eric; Sulkowski, Mark S; Ghalib, Reem; Rodriguez-Torres, Maribel; Younossi, Zobair M; Corregidor, Ana; DeJesus, Edwin; Pearlman, Brian; Rabinovitz, Mordechai; Gitlin, Norman; Lim, Joseph K; Pockros, Paul J; Scott, John D; Fevery, Bart; Lambrecht, Tom; Ouwerkerk-Mahadevan, Sivi; Callewaert, Katleen; Symonds, William T; Picchio, Gaston; Lindsay, Karen L; Beumont, Maria; Jacobson, Ira M

2014-11-15

Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir. We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790. 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12. Combined simeprevir and sofosbuvir was efficacious and well tolerated. Janssen. Copyright © 2014 Elsevier Ltd. All rights reserved.

Linking the Congenital Heart Surgery Databases of the Society of Thoracic Surgeons and the Congenital Heart Surgeons’ Society: Part 2—Lessons Learned and Implications

PubMed Central

Jacobs, Jeffrey P.; Pasquali, Sara K.; Austin, Erle; Gaynor, J. William; Backer, Carl; Hirsch-Romano, Jennifer C.; Williams, William G.; Caldarone, Christopher A.; McCrindle, Brian W.; Graham, Karen E.; Dokholyan, Rachel S.; Shook, Gregory J.; Poteat, Jennifer; Baxi, Maulik V.; Karamlou, Tara; Blackstone, Eugene H.; Mavroudis, Constantine; Mayer, John E.; Jonas, Richard A.; Jacobs, Marshall L.

2014-01-01

Purpose A link has been created between the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) and the Congenital Heart Surgeons’ Society Database (CHSS-D). Five matrices have been created that facilitate the automated identification of patients who are potentially eligible for the five active CHSS studies using the STS-CHSD. These matrices are now used to (1) estimate the denominator of patients eligible for CHSS studies and (2) compare “eligible and enrolled patients” to “potentially eligible and not enrolled patients” to assess the generalizability of CHSS studies. Methods The matrices were applied to 40 consenting institutions that participate in both the STS-CHSD and the CHSS to (1) estimate the denominator of patients that are potentially eligible for CHSS studies, (2) estimate the completeness of enrollment of patients eligible for CHSS studies among all CHSS sites, (3) estimate the completeness of enrollment of patients eligible for CHSS studies among those CHSS institutions participating in each CHSS cohort study, and (4) compare “eligible and enrolled patients” to “potentially eligible and not enrolled patients” to assess the generalizability of CHSS studies. The matrices were applied to all participants in the STS-CHSD to identify patients who underwent frequently performed operations and compare “eligible and enrolled patients” to “potentially eligible and not enrolled patients” in following five domains: (1) age at surgery, (2) gender, (3) race, (4) discharge mortality, and (5) postoperative length of stay. Completeness of enrollment was defined as the number of actually enrolled patients divided by the number of patients identified as being potentially eligible for enrollment. Results For the CHSS Critical Left Ventricular Outflow Tract Study (LVOTO) study, for the Norwood procedure, completeness of enrollment at centers actively participating in the LVOTO study was 34%. For the Norwood operation, discharge mortality was 15% among 227 enrolled patients and 16% among 1768 nonenrolled potentially eligible patients from the 40 consenting institutions. Median postoperative length of stay was 31 days and 26 days for these enrolled and nonenrolled patients. For the CHSS anomalous aortic origin of a coronary artery (AAOCA)study, for AAOCA repair, completeness of enrollment at centers actively participating in the AAOCA study was 40%. Conclusion Determination of the denominator of patients eligible for CHSS studies and comparison of “eligible and enrolled patients” to “potentially eligible and not enrolled patients” provides an estimate of the extent to which patients in CHSS studies are representative of the overall population of eligible patients; however, opportunities exist to improve enrollment. PMID:24668975

The relationship between health plan advertising and market incentives: evidence of risk-selective behavior.

PubMed

Mehrotra, Ateev; Grier, Sonya; Dudley, R Adams

2006-01-01

Medicare beneficiaries are now facing advertising from an unprecedented number of health plans that are offering prescription drug coverage. Previous Medicare managed care efforts have been undermined by risk selection, the practice of enrolling healthier and therefore less costly patients. In this study we explore how the content of health plan advertising is related to the competitiveness of the health plan market. We find that increased competition is associated with greater use of advertising that targets healthier patients.

The impact of tiered physician networks on patient choices.

PubMed

Sinaiko, Anna D; Rosenthal, Meredith B

2014-08-01

To assess whether patient choice of physician or health plan was affected by physician tier-rankings. Administrative claims and enrollment data on 171,581 nonelderly beneficiaries enrolled in Massachusetts Group Insurance Commission health plans that include a tiered physician network and who had an office visit with a tiered physician. We estimate the impact of tier-rankings on physician market share within a plan of new patients and on the percent of a physician's patients who switch to other physicians with fixed effects regression models. The effect of tiering on consumer plan choice is estimated using logistic regression and a pre-post study design. Physicians in the bottom (least-preferred) tier, particularly certain specialist physicians, had lower market share of new patient visits than physicians with higher tier-rankings. Patients whose physician was in the bottom tier were more likely to switch health plans. There was no effect of tier-ranking on patients switching away from physicians whom they have seen previously. The effect of tiering appears to be among patients who choose new physicians and at the lower end of the distribution of tiered physicians, rather than moving patients to the "best" performers. These findings suggest strong loyalty of patients to physicians more likely to be considered their personal doctor. © Health Research and Educational Trust.

The RIVUR Trial: Profile and Baseline Clinical Associations of Children With Vesicoureteral Reflux

PubMed Central

Hoberman, Alejandro; Mattoo, Tej K.; Mathews, Ranjiv; Keren, Ron; Chesney, Russell W.; Moxey-Mims, Marva; Greenfield, Saul P.

2013-01-01

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is diagnosed in ∼30% to 40% of children who have imaging studies after urinary tract infections (UTIs). Our goal is to characterize children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial and to compare our study cohort with those from previously published studies. METHODS: RIVUR investigators from 19 pediatric sites in the United States recruited 607 children with grade I through IV VUR. Children were enrolled after a first or second UTI. This cross-sectional report of baseline data includes extensive clinical, parental report, and imaging study results. RESULTS: RIVUR recruited 607 children (558 girls, 49 boys) with grade I (11%), II (42%), III (38%), or IV (8%) reflux. The median age was 12 months, and most children (91%) were enrolled after their first UTI. The UTI leading to enrollment was both febrile and symptomatic for 323 children, febrile only in 197 children, and symptomatic only in 86. Renal involvement at baseline as documented by a 99mTc dimercaptosuccinic acid scan was uncommon with cortical defects identified in 89 (15%) children. Bladder and bowel dysfunction was identified in 71 (56%) of 126 toilet-trained subjects assessed. CONCLUSIONS: RIVUR is the largest prospective, randomized trial for children with primary VUR to date, comparing prophylaxis with placebo. The study sample comprises patients from 19 pediatric clinical sites in the United States, whose demographic and clinical characteristics may differ from those of children enrolled in previous trials from other countries. PMID:23753091

Eluxadoline Efficacy in IBS-D Patients Who Report Prior Loperamide Use.

PubMed

Lacy, Brian E; Chey, William D; Cash, Brooks D; Lembo, Anthony J; Dove, Leonard S; Covington, Paul S

2017-06-01

Irritable bowel syndrome with diarrhea (IBS-D) is often managed with over-the-counter therapies such as loperamide, though with limited success. This analysis evaluated the efficacy of eluxadoline in patients previously treated with loperamide in two phase 3 studies. Adults with IBS-D (Rome III criteria) were enrolled and randomized to placebo or eluxadoline (75 or 100 mg) twice daily for 26 (IBS-3002) or 52 (IBS-3001) weeks. Patients reported loperamide use over the previous year and recorded their rescue loperamide use during the studies. The primary efficacy end point was the proportion of patients with a composite response of simultaneous improvement in abdominal pain and reduction in diarrhea. A total of 2,428 patients were enrolled; 36.0% reported prior loperamide use, of whom 61.8% reported prior inadequate IBS-D symptom control with loperamide. Among patients with prior loperamide use, a greater proportion treated with eluxadoline (75 and 100 mg) were composite responders vs. those treated with placebo with inadequate prior symptom control, over weeks 1-12 (26.3% (P=0.001) and 27.0% (P<0.001) vs. 12.7%, respectively); similar results were observed over weeks 1-26. When daily rescue loperamide use was imputed as a nonresponse day, the composite responder rate was still higher in patients receiving eluxadoline (75 and 100 mg) vs. placebo over weeks 1-12 (P<0.001) and weeks 1-26 (P<0.001). Adverse events included nausea and abdominal pain. Eluxadoline effectively and safely treats IBS-D symptoms of abdominal pain and diarrhea in patients who self-report either adequate or inadequate control of their symptoms with prior loperamide treatment, with comparable efficacy and safety irrespective of the use of loperamide as a rescue medication during eluxadoline treatment.

The AFFORD clinical decision aid to identify emergency department patients with atrial fibrillation at low risk for 30-day adverse events.

PubMed

Barrett, Tyler W; Storrow, Alan B; Jenkins, Cathy A; Abraham, Robert L; Liu, Dandan; Miller, Karen F; Moser, Kelly M; Russ, Stephan; Roden, Dan M; Harrell, Frank E; Darbar, Dawood

2015-03-15

There is wide variation in the management of patients with atrial fibrillation (AF) in the emergency department (ED). We aimed to derive and internally validate the first prospective, ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events. We performed a prospective cohort study at a university-affiliated tertiary-care ED. Patients were enrolled from June 9, 2010, to February 28, 2013, and followed for 30 days. We enrolled a convenience sample of patients in ED presenting with symptomatic AF. Candidate predictors were based on ED data available in the first 2 hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We used an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation. Of 497 patients enrolled, stroke and AF-related death occurred in 13 (3%) and 4 (<1%) patients, respectively. The decision aid included the following: age, triage vitals (systolic blood pressure, temperature, respiratory rate, oxygen saturation, supplemental oxygen requirement), medical history (heart failure, home sotalol use, previous percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms), and ED data (2 hours heart rate, chest radiograph results, hemoglobin, creatinine, and brain natriuretic peptide). The decision aid's c-statistic in predicting any 30-day adverse event was 0.7 (95% confidence interval 0.65, 0.76). In conclusion, in patients with AF in the ED, Atrial Fibrillation and Flutter Outcome Risk Determination provides the first evidence-based decision aid for identifying patients who are at low risk for 30-day adverse events and candidates for safe discharge. Copyright © 2015 Elsevier Inc. All rights reserved.

Procalcitonin fails to predict bacteremia in SIRS patients: a cohort study.

PubMed

Hoenigl, M; Raggam, R B; Wagner, J; Prueller, F; Grisold, A J; Leitner, E; Seeber, K; Prattes, J; Valentin, T; Zollner-Schwetz, I; Schilcher, G; Krause, R

2014-10-01

Procalcitonin (PCT) has previously been proposed as useful marker to rule out bloodstream-infection (BSI). The objective of this study was to evaluate the sensitivity of different PCT cut-offs for prediction of BSI in patients with community (CA)- and hospital-acquired (HA)-BSI. A total of 898 patients fulfilling systemic-inflammatory-response-syndrome (SIRS) criteria were enrolled in this prospective cohort study at the Medical University of Graz, Austria. Of those 666 patients had positive blood cultures (282 CA-BSI, 384 HA-BSI, enrolled between January 2011 and December 2012) and 232 negative blood cultures (enrolled between January 2011 and July 2011 at the emergency department). Blood samples for determination of laboratory infection markers (e.g. PCT) were collected simultaneously with blood cultures. Procalcitonin was significantly (p < 0.001) higher in SIRS patients with bacteremia/fungemia than in those without. Receiver operating characteristic curve analysis revealed an area under the curve (AUC) value of 0.675 for PCT (95% CI 0.636-0.714) for differentiating patients with BSI from those without. AUC for IL-6 was 0.558 (95% CI 0.515-0.600). However, even at the lowest cut-off evaluated (i.e. 0.1 ng/ml) PCT failed to predict BSI in 7% (n = 46) of patients. In the group of patients with SIRS and negative blood culture 79% (n = 185) had PCT levels > 0.1. Procalcitonin was significantly higher in patients with BSI than in those without and superior to IL-6 and CRP. The clinical importance of this is questionable, because a suitable PCT threshold for excluding BSI was not established. An approach where blood cultures are guided by PCT only can therefore not be recommended. © 2014 John Wiley & Sons Ltd.

Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer.

PubMed

Beaugerie, Laurent; Carrat, Fabrice; Colombel, Jean-Frédéric; Bouvier, Anne-Marie; Sokol, Harry; Babouri, Abdenour; Carbonnel, Franck; Laharie, David; Faucheron, Jean-Luc; Simon, Tabassome; de Gramont, Aimery; Peyrin-Biroulet, Laurent

2014-09-01

To explore the risk of new or recurrent cancer among patients with IBD and previous cancer, exposed or not to immunosuppressants. Among the 17 047 patients of the CESAME prospective observational cohort who were enrolled from May 2004 to June 2005, and followed-up until December 2007, we identified 405 patients with cancer diagnosed previous to study entry. We calculated the rates of incident cancer in patients with or without previous cancer, and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer. The rate of incident cancer was 21.1/1000 patient-years (PY) and 6.1/1000 PY in patients with and without previous cancer, respectively. The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 (95% CI 1.2 to 3.0, p=0.003). Among patients with previous cancer, the rates of new and recurrent cancers were, respectively, 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry, and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry. There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer. Patients with IBD with a history of cancer are at increased risk of developing any (new or recurrent) cancer, with a predominant incidence of new cancers. Treatment with immunosuppressants has no overall major impact per se on this risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical and Demographic Profile of Patients Receiving Fingolimod in Clinical Practice in Germany and the Benefit-Risk Profile of Fingolimod After 1 Year of Treatment: Initial Results From the Observational, Noninterventional Study PANGAEA.

PubMed

Ziemssen, Tjalf; Lang, Michael; Tackenberg, Björn; Schmidt, Stephan; Albrecht, Holger; Klotz, Luisa; Haas, Judith; Lassek, Christoph; Medin, Jennie; Cornelissen, Christian

2018-01-01

The population with multiple sclerosis receiving treatment in clinical practice differs from that in randomized controlled trials (RCTs). An assessment of the real-world benefit-risk profile of therapies is needed. This analysis used data from the large, noninterventional, observational German study Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) to assess prospectively baseline characteristics and outcomes after 12 months (± 90 days) of fingolimod treatment. Patients were divided into 2 cohorts: fingolimod starter [first received fingolimod in PANGAEA (n = 3315)] and previous study [received fingolimod before enrollment in PANGAEA in RCTs (n = 875), some of whom also had baseline data at entry into RCTs (n = 505)]. At PANGAEA baseline, patients in the fingolimod starter versus the previous study cohort had a higher annualized relapse rate [ARR (95% confidence interval): 1.79 (1.75-1.83) vs 1.32 (1.25-1.40)] and Expanded Disability Status Scale score [3.11 (3.04-3.17) vs 2.55 (2.44-2.66)]. A greater proportion in the fingolimod starter versus previous study cohort had diabetes (2.0% vs 0.7%). After 12 months of fingolimod, ARRs were lower than in the 12 months before PANGAEA enrollment in the fingolimod starter [0.386 (0.360-0.414)] and previous study [0.276 (0.238-0.320)] cohorts. Expanded Disability Status Scale scores were stable versus baseline. Adverse events were experienced by similar proportions in both cohorts during fingolimod treatment. Relevant differences exist in disease activity and comorbidities between patients receiving fingolimod in clinical practice versus RCTs. Irrespective of baseline differences indicating a higher proportion at an advanced stage of multiple sclerosis in the real world versus RCTs, fingolimod remains effective, with a manageable safety profile.

Phase I study of 3-weekly combination chemotherapy using epirubicin, oxaliplatin, and S-1 (EOS) in patients with previously untreated advanced gastric cancer.

PubMed

Sym, Sun Jin; Hong, Junsik; Jung, Minkyu; Park, Jinny; Cho, Eun Kyung; Lee, Woon Ki; Chung, Min; Kim, Hyung-Sik; Lee, Jae Hoon; Shin, Dong Bok

2012-08-01

This study was performed to determine the recommended dose (RD) and dose-limiting toxicity (DLT) associated with epirubicin, oxaliplatin, and S-1 (EOS) combination therapy in patients with previously untreated advanced gastric cancer (AGC). Previously untreated patients with histologically proven metastatic AGC, with an ECOG performance status of 0-2, were enrolled in this study. A fixed dose of epirubicin (50 mg/m(2)) and oxaliplatin (130 mg/m(2)) was intravenously administered on day 1 of treatment, followed by oral S-1 administration twice daily on days 1-14. The S-1 dose was escalated according to the following schedule: level I, 35 mg/m(2); level II, 40 mg/m(2); level III, 45 mg/m(2); Level IV, 50 mg/m(2). Each cycle was repeated every 21 days. DLTs were evaluated during the first two cycles of treatment. Nineteen patients with a median age of 53 years (range, 40-71 years) were enrolled in this study. One case of DLT (grade 4 neutropenia lasting more than 5 days) developed from among the six dose level II patients, while 2 DLTs (grade 3 diarrhea and nausea) were observed among the 4 dose level III patients. Based on these results, dose level II was determined as the RD. Of the 13 patients with measurable lesions, eight achieved partial response, three showed stable disease, and the objective response rate was 61.5 % (95 % confidence interval (CI), 13.3-66.6 %). The median progression-free survival and overall survival of all patients was 6.8 months (95 % CI, 1.4-9.5 months) and 13.3 months (95 % CI, 1.9-24.6 months), respectively. The RD of the EOS regimen in patients with previously untreated AGC was 50 mg/m(2) of epirubicin and 130 mg/m(2) of oxaliplatin on day 1, with administration of 40 mg/m(2) of S-1 twice a day on days 1-14 for each 21-day cycle. The EOS regimen described produced promising results.

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial.

PubMed

O'Brien, Susan; Furman, Richard R; Coutre, Steven E; Sharman, Jeff P; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Richards, Donald A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Izumi, Raquel; Hamdy, Ahmed; Chang, Betty Y; Graef, Thorsten; Clow, Fong; Buggy, Joseph J; James, Danelle F; Byrd, John C

2014-01-01

Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65-84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1-2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one developed grade 4 thrombocytopenia. After a median follow-up of 22.1 months (IQR 18.4-23.2), 22 (71%) of 31 patients achieved an objective response (95% CI 52.0-85.8); four patients (13%) had a complete response, one patient (3%) had a nodular partial response, and 17 (55%) patients had a partial response. The safety and activity of ibrutinib in elderly, previously untreated patients with symptomatic chronic lymphocytic leukaemia, or small lymphocytic lymphoma is encouraging, and merits further investigation in phase 3 trials. Pharmacyclics, Leukemia and Lymphoma Society, D Warren Brown Foundation, Mr and Mrs Michael Thomas, Harry Mangurian Foundation, P50 CA140158 to Prof J C Byrd MD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Baseline Demographics, Safety, and Patient Acceptance of an Insertable Cardiac Monitor for Atrial Fibrillation Screening: The REVEAL-AF Study.

PubMed

Conti, Sergio; Reiffel, James A; Gersh, Bernard J; Kowey, Peter R; Wachter, Rolf; Halperin, Jonathan L; Kaplon, Rachelle E; Pouliot, Erika; Verma, Atul

2017-01-01

Given the high prevalence and risk of stroke associated with atrial fibrillation (AF), detection strategies have important public health implications. The ongoing prospective, single-arm, open-label, multicenter REVEAL AF trial is evaluating the incidence of previously undetected AF using an insertable cardiac monitor (ICM) in patients without prior AF or device implantation, but who could be at risk for AF due to their demographic characteristics, +/- non-specific but compatible symptoms. Enrollment required an elevated AF risk profile defined as CHADS2≥3 or CHADS 2 =2 plus one or more of the following: coronary artery disease, renal impairment, sleep apnea or chronic obstructive pulmonary disease. Exclusions included stroke or transient ischemic attack occurring in the previous year. Of 450 subjects screened, 399 underwent a device insertion attempt, and 395 were included in the final analysis (Reveal XT: n=122; Reveal LINQ: n=273; excluded: n=4). Participants were primarily identified by demographic characteristics and the presence of nonspecific symptoms, but without prior documentation of "overt" AF. The most common symptoms were palpitations (51%), dizziness/lightheadedness/pre-syncope (36%), and shortness of breath (36%). Over 100 subjects were enrolled in each pre-defined CHADS2 subgroup (2, 3 and ≥4). AF risk factors not included in the CHADS2 score were well represented (prevalence≥15%). Procedure and/or device related serious adverse events were low, with the miniaturized Reveal LINQ ICM having a more favorable safety profile than the predicate Reveal XT (all: n=13 [3.3%]; LINQ: n=6 [2.2%]; XT: n=7 [5.7%]). These data demonstrate that REVEAL AF was successful in enrolling its target population, high risk patients were willing to undergo ICM monitoring for AF screening, and ICM use in this group is becoming increasingly safe with advancements in technology. A clinically meaningful incidence of device detected AF in this study will inform clinical decisions regarding ICM use for AF screening in patients at risk.

Efficacy and Safety of Uninterrupted Low-Intensity Warfarin for Radiofrequency Catheter Ablation of Atrial Fibrillation in the Elderly.

PubMed

Xing, Yangbo; Xu, Buyun; Xu, Chao; Peng, Fang; Yang, Biao; Qiu, Yufang; Sun, Yong; Wang, Shengkai; Guo, Hangyuan

2017-09-01

No previous studies exist investigating the optimal intensity of uninterrupted anticoagulation with warfarin during radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in the elderly. Evaluate the efficacy and safety of continuous low-intensity warfarin therapy throughout the periprocedural period of RFCA for AF in the elderly. This is a prospective randomized study. We enrolled AF patients (age ≥ 70 years) who underwent first-time RFCA for AF. Enrolled patients were randomized to group A and group B. The international normalized ratios before ablation were maintained at 1.5 to 2.0 and 2.0 to 2.5 in group A and B, respectively. Primary end points were periprocedural thromboembolic complications and major bleeding. Secondary end points included periprocedural asymptomatic cerebral emboli (ACE) and minor bleeding. A total of 101 patients were enrolled in our study (group A: 52; group B: 49). Baseline characteristics were well balanced between the 2 groups. Only 1 patient suffered from stroke in group B. No major bleeding events occurred in either group. The incidence of new ACE lesions was comparable between the 2 groups (11.5% vs 8.2%, P = 0.82). Minor bleeding occurred in 1 of 52 (1.9%) patients in group A and in 5 of 49 (10.2%) patients in group B ( P = 0.10). Uninterrupted low-intensity warfarin for RFCA of AF might be as effective as standard-intensity warfarin in preventing periprocedural thromboembolic complications and might be associated with fewer bleeding events in the elderly.

ANDRO-IVF: a novel protocol for poor responders to IVF controlled ovarian stimulation

PubMed Central

Bercaire, Ludmila; Nogueira, Sara MB; Lima, Priscila CM; Alves, Vanessa R; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Fanchin, Renato

2018-01-01

Objective This study aimed to assess a novel protocol designed to improve poor ovarian response through intra-ovarian androgenization. The endpoints were: number of oocytes and mature oocytes retrieved, fertilization, cancellation and pregnancy rates. Methods This prospective crossover study enrolled poor responders from previous ovarian stimulation cycles submitted to a novel protocol called ANDRO-IVF. The protocol included pretreatment with transdermal AndroGel(r) (Besins) 25 mg, oral letrozole 2.5 mg and subcutaneous hCG 2500 IU; cycle control was performed with estradiol valerate and micronized progesterone; ovarian stimulation was attained with gonadotropins FSH/LH 450 IU, GnRH antagonist and hCG 5000 IU. Results Fourteen poor responders were enrolled. One patient did not meet the inclusion criteria. Thirteen patients previously summited to the standard protocol were offered the ANDRO-IVF Protocol.-Standard Protocol: Mean age: 35.30 years; cancellation rate: 61.53%; mean number of MII oocytes retrieved per patient: 1.8; fertilization rate: 33.33%. Only two patients had embryo transfers, and none got pregnant.-ANDRO-IVF Protocol: Mean age: 35.83 years; cancellation rate: 7.69%; mean number of oocytes retrieved per patient: 5.58, MII oocytes: 3.91. ICSI was performed in 84.61% of the patients and a mean of 1.5 embryos were transferred per patient. Fertilization rate: 62.5%; cumulative pregnancy rate: 16.66%; mean duration of stimulation: 9.77 days. Conclusion ANDRO-IVF allows intra-ovarian androgenization by increasing serum and intra-follicular androgen levels and preventing androgen aromatization. This protocol apparently improved clinical outcomes of poor responders in parameters such as number of oocytes retrieved and clinical pregnancy rates. Further randomized controlled trials are needed to confirm these findings. PMID:29303236

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa

PubMed Central

Lewandowski, Laura B; Schanberg, Laura E; Thielman, Nathan; Phuti, Angel; Kalla, Asgar A; Okpechi, Ikechi; Nourse, Peter; Gajjar, Priya; Faller, Gail; Ambaram, Priya; Reuter, Helmuth; Spittal, Graeme; Scott, Christiaan

2016-01-01

Background Systemic Lupus Erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE (pSLE) on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa (SA). Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serologic characteristics was extracted from medical records. Results were compared to a well-described North American pSLE cohort. Results Seventy-two SA patients were enrolled in the study; mean age 11.5 years, 82% female. The racial distribution was 68% Coloured, 24% Black, 5% White, and 3% Asian/Indian. Most patients presented with severe lupus nephritis (LN) documented by renal biopsy (61%). Of patients with LN, 63% presented with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate, and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K [SLEDAI-2K] 20.6). The SLEDAI-2K at enrollment in the PULSE cohort (5.0) did not differ from the North American pSLE cohort (4.8). Sixty three % of PULSE cohort had end organ damage with System Lupus International Collaborating Clinic-Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, 9 (13%) developed ESRD with 6 (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrollment in the SA registry. SA patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study reveals a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population. PMID:27488473

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

PubMed

Lewandowski, L B; Schanberg, L E; Thielman, N; Phuti, A; Kalla, A A; Okpechi, I; Nourse, P; Gajjar, P; Faller, G; Ambaram, P; Reuter, H; Spittal, G; Scott, C

2017-02-01

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

[Development of Peptide Vaccines for Triple-Negative Breast Cancer Treatment].

PubMed

Toh, Uhi; Saku, Shuko; Okabe, Mina; Iwakuma, Nobutaka; Kimitsuki, Yuko; Akashi, Momoko; Ogo, Etsuyo; Yamada, Akira; Shichijo, Shigeki; Itoh, Kyogo; Akagi, Yoshito

2016-10-01

Our previous phase II clinical trial showed that therapeutically selected personalized peptide vaccines(PPVs)were effective at boosting anticancer immunity; the immune response after PPV was associated with a clinical outcome as a prognostic factor for metastatic breast cancer(mBC). We conducted an early phase II study to evaluate the safety and efficacy of a new regimen using multiple peptide vaccines(KRM-19)for patients with metastatictriple -negative breast cancer. KRM-19 consisted of 19 mixed peptides chosen from the previously reported 31 PPVs according to their anti-tumor immunologiceffec ts and safety profiles for patients with mBC. All patients had histologically confirmed measurable ER-PgR-HER2- mBC and their human leukocyte antigen(HLA) / -A molecules were A2, A3, A11, A24, A26, A31, or A33. KRM-19(19mg/mL)was administrated subcutaneously every week for a total of 6 doses. Concurrent conventional chemo- and/or endocrine therapy were not permitted during treatment. This was an open-label, early phase II study. The primary endpoint was safety and anti-tumor immunologic effect, while the secondary endpoints were clinical responses and progression-free survival(PFS). The estimated enrollment was 10-15 and 8 patients were enrolled(Clinical trial registry number: UMIN000014616). Measurement of peptide-specific cytotoxic T lymphocyte and IgG responses were conducted before and after vaccination. The correlation between PFS and the increased IgG response and/or CTL levels were investigated.

What happens to patients when we do not repair their cuff tears? Five-year rotator cuff quality-of-life index outcomes following nonoperative treatment of patients with full-thickness rotator cuff tears.

PubMed

Boorman, Richard S; More, Kristie D; Hollinshead, Robert M; Wiley, James P; Mohtadi, Nicholas G; Lo, Ian K Y; Brett, Kelly R

2018-03-01

The purpose of this study was to examine 5-year outcomes in a prospective cohort of patients previously enrolled in a nonoperative rotator cuff tear treatment program. Patients with chronic (>3 months), full-thickness rotator cuff tears (demonstrated on imaging) who were referred to 1 of 2 senior shoulder surgeons were enrolled in the study between October 2008 and September 2010. They participated in a comprehensive, nonoperative, home-based treatment program. After 3 months, the outcome in these patients was defined as "successful" or "failed." Patients in the successful group were essentially asymptomatic and did not require surgery. Patients in the failed group were symptomatic and consented to undergo surgical repair. All patients were followed up at 1 year, 2 years, and 5 or more years. At 5 or more years, all patients were contacted for follow-up; the response rate was 84%. Approximately 75% of patients remained successfully treated with nonoperative treatment at 5 years and reported a mean rotator cuff quality-of-life index score of 83 of 100 (SD, 16). Furthermore, between 2 and 5 years, only 3 patients who had previously been defined as having a successful outcome became more symptomatic and underwent surgical rotator cuff repair. Those in whom nonoperative treatment had failed and who underwent surgical repair had a mean rotator cuff quality-of-life index score of 89 (SD, 11) at 5-year follow-up. The operative and nonoperative groups at 5-year follow-up were not significantly different (P = .11). Nonoperative treatment is an effective and lasting option for many patients with a chronic, full-thickness rotator cuff tear. While some clinicians may argue that nonoperative treatment delays inevitable surgical repair, our study shows that patients can do very well over time. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

PubMed

Magee, M J; Bloss, E; Shin, S S; Contreras, C; Huaman, H Arbanil; Ticona, J Calderon; Bayona, J; Bonilla, C; Yagui, M; Jave, O; Cegielski, J P

2013-06-01

Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing

Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials inmore » NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.« less

Which veterans enroll in a VA health information exchange program?

PubMed

Dixon, Brian E; Ofner, Susan; Perkins, Susan M; Myers, Laura J; Rosenman, Marc B; Zillich, Alan J; French, Dustin D; Weiner, Michael; Haggstrom, David A

2017-01-01

To characterize patients who voluntarily enrolled in an electronic health information exchange (HIE) program designed to share data between Veterans Health Administration (VHA) and non-VHA institutions. Patients who agreed to participate in the HIE program were compared to those who did not. Patient characteristics associated with HIE enrollment were examined using a multivariable logistic regression model. Variables selected for inclusion were guided by a health care utilization model adapted to explain HIE enrollment. Data about patients' sociodemographics (age, gender), comorbidity (Charlson index score), utilization (primary and specialty care visits), and access (distance to VHA medical center, insurance, VHA benefits) were obtained from VHA and HIE electronic health records. Among 57 072 patients, 6627 (12%) enrolled in the HIE program during its first year. The likelihood of HIE enrollment increased among patients ages 50-64, of female gender, with higher comorbidity, and with increasing utilization. Living in a rural area and being unmarried were associated with decreased likelihood of enrollment. Enrollment in HIE is complex, with several factors involved in a patient's decision to enroll. To broaden HIE participation, populations less likely to enroll should be targeted with tailored recruitment and educational strategies. Moreover, inclusion of special populations, such as patients with higher comorbidity or high utilizers, may help refine the definition of success with respect to HIE implementation. Published by Oxford University Press on behalf of the American Medical Informatics Association 2016. This work is written by US Government employees and is in the public domain in the United States.

Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

PubMed

Mori, Takehiko; Yamazaki, Rie; Aisa, Yoshinobu; Nakazato, Tomonori; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Ikeda, Yasuo; Okamoto, Shinichiro

2006-04-01

We previously reported the efficacy of oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate whether the further shortening of the duration of oral cryotherapy could minimize its side effects while sparing its efficacy. Seventeen consecutive recipients of allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan in combination with fludarabine alone or with fludarabine and additional radiation were enrolled in the study. The severity of stomatitis was graded according to the National Cancer Institute-Common Toxicity Criteria. Patients were kept on oral cryotherapy shortly before, during, and for additional 30 min after the completion of melphalan administration (60-min oral cryotherapy). Patients who were also enrolled in our previous study received the same type of oral cryotherapy but for additional 90 min after the completion of melphalan administration (120-min oral cryotherapy), and they served as controls. Only 2 (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18 patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis, respectively. The difference between groups was not statistically significant (P = 0.677). The incidence of unpleasant symptoms such as chills and nausea during oral cryotherapy decreased significantly with 60-min oral cryotherapy, as compared with that associated with 120-min oral cryotherapy (P < 0.01). These results suggest that 60-min oral cryotherapy is as effective as 120-min oral cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter treatment might have contributed to relieve patient discomfort during oral cryotherapy.

Newly diagnosed and previously known diabetes mellitus and short-term outcomes in patients with acute myocardial infarction.

PubMed

Tian, Li; Wei, Chang; Zhu, Jun; Liu, Lisheng; Liang, Yan; Li, Jiandong; Yang, Yanmin

2013-12-01

The prognostic value of diabetes mellitus (DM) on the long-term outcomes of patients after myocardial infarction has been well established. The correlation between DM, including newly diagnosed DM, and short-term outcomes needs to be validated. A total of 5410 ST-segment elevation myocardial infarction (STEMI) patients with typical chest pain onset in the past 12 h were enrolled. Follow-ups were carried out on days 7 and 30 after hospital admission. According to 2013 Standards of Medical Care in Diabetes, the study population was stratified into the following three groups: no diabetes, newly diagnosed diabetes, and previously known diabetes. The primary outcomes of our study were mortality from all causes and major adverse cardiac events (MACE) at days 7 and 30. Patients with previously known diabetes were older and had a higher incidence of previous history of cardiovascular disease compared with the other groups. The 7-day and 30-day mortality was similar between patients without DM and patients with newly diagnosed DM. For both groups, this was significantly lower than that in patients with DM. Similar results were observed for 7-day and 30-day MACE. Multivariable Cox regression analysis indicated that newly diagnosed diabetes did not correlate with 30-day MACE (hazard ratio, 0.901; 95% confidence interval, 0.759-1.069), but that previously known DM correlated with short-term MACE (hazard ratio, 1.211; 95% confidence interval, 1.009-1.453). Previously known DM, but not newly diagnosed DM, was an independent predictor for short-term MACE in patients with STEMI. To reduce the incidence of short-term MACE and the detrimental effects of stress hyperglycemia after STEMI, intensive insulin therapy should be provided to diabetic patients with STEMI.

Executive Function, Survival, and Hospitalization in Chronic Obstructive Pulmonary Disease. A Longitudinal Analysis of the National Emphysema Treatment Trial (NETT)

PubMed Central

Dodd, James W.; Novotny, Paul; Sciurba, Frank C.

2015-01-01

Rationale: Cognitive dysfunction has been demonstrated in chronic obstructive pulmonary disease (COPD), but studies are limited to cross-sectional analyses or incompletely characterized populations. Objectives: We examined longitudinal changes in sensitive measures of executive function in a well-characterized population of patients with severe COPD. Methods: This study was performed on patients enrolled in the National Emphysema Treatment Trial. To assess executive function, we analyzed trail making (TM) A and B times at enrollment in the trial (2,128 patients), and at 12 (731 patients) and 24 months (593 patients) after enrollment, adjusted for surgery, marriage status, age, education, income, depression, PaO2, PaCO2, and smoking. Associations with survival and hospitalizations were examined using Cox regression and linear regression models. Measurements and Main Results: The average age of the patients was 66.4 years, and the average FEV1 was 23.9% predicted. At the time of enrolment, 38% had executive dysfunction. Compared with those who did not, these patients were older, less educated, had higher oxygen use, higher PaCO2, worse quality of life as measured by the St. George’s Respiratory Quotient, reduced well-being, and lower social function. There was no significant change over 2 years in TM A or B times after adjustment for covariables. Changes in TM B times were modestly associated with survival, but changes in TM B − A times were not. Changes in TM scores were not associated with frequency of hospitalization. Lung function, PaO2, smoking, survival, and hospitalizations were not significantly different in those with executive dysfunction. Conclusions: In this large population of patients with severe emphysema and heavy cigarette smoking exposure, there was no significant decline over 2 years in cognitive executive function as measured by TM tests. There was no association between executive function impairment and frequency of hospitalization, and there was a possible modest association with survival. It is plausible that cerebrovascular comorbidities explain previously described cognitive pathology in COPD. PMID:26288391

Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study.

PubMed

Shilyansky, Carrie; Williams, Leanne M; Gyurak, Anett; Harris, Anthony; Usherwood, Timothy; Etkin, Amit

2016-05-01

Antidepressant treatment failure is a common problem worldwide. In this study, we assess whether or not an important aspect of depression, cognitive impairment, is untreated by antidepressants by studying the effect of acute antidepressant treatment on a range of cognitive domains. In this randomised longitudinal study, which is part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trial, we assessed the effects of acute antidepressant treatment in a large patient population, across clinical remission outcomes, on a range of cognitive domains: attention, response inhibition, executive function during visuospatial navigation, cognitive flexibility, verbal memory, working memory, decision speed, information processing speed, and psychomotor response speed. We enrolled patients from primary or specialty care clinics in a multicentre, international, open-label, randomised, prospective trial. Eligible patients (aged 18-65 years) were previously untreated or were willing to undergo a 1-week medication washout before the study start, and could not have had inadequate response to study medications in the past. We enrolled a large population of medication-free (ie, untreated) outpatients in a depressive episode and assessed them for cognitive function at enrolment (pre-treatment), and again after 8 weeks of treatment with one of three antidepressant drugs (escitalopram, sertraline, or venlafaxine extended-release). Patients were randomly assigned (1:1:1) to one of the three antidepressants using a blocked randomisation procedure (block size of 12). As a comparison group, we also simultaneously enrolled matched healthy participants. Healthy participants received no medication or intervention, but were assessed for change in cognitive and clinical measures during the same interval and testing protocol. Therefore, this group acts as a test-retest control for the primary outcome measure examined in this study, change in cognitive measures over 8 weeks of treatment in depressed patients. This study is registered with ClinicalTrials.gov, number NCT00693849. Between Dec 8, 2008, and Sept 30, 2011, we enrolled 1008 eligible people into the study. Impairment in five domains-attention, response inhibition, verbal memory, decision speed, and information processing-showed no relative improvement with acute treatment (controlling for time or repeated testing), irrespective of antidepressant treatment group, even in patients whose depression remitted acutely according to clinical measures. Broader cognitive impairment was associated with greater illness chronicity (earlier illness onset) but not with symptom severity or previous antidepressant failures. Depression is associated with impairments in higher-order cognitive functions and information processing, which persist independently of clinical symptom change with treatment. We recorded no difference between the three antidepressants tested, with none showing efficacy for these impairments. Although the 8-week treatment period limits interpretation to acute treatment effects, it does highlight cognitive impairment as an untargeted contributor to incomplete treatment success. Brain Resource Company Operations Pty Ltd and NIH. Copyright © 2016 Elsevier Ltd. All rights reserved.

New clinical decision rule to exclude subarachnoid haemorrhage for acute headache: a prospective multicentre observational study.

PubMed

Kimura, Akio; Kobayashi, Kentaro; Yamaguchi, Hitoshi; Takahashi, Takeshi; Harada, Masahiro; Honda, Hideki; Mori, Yoshio; Hirose, Keika; Tanaka, Noriko

2016-09-09

To ensure good outcomes in the management of subarachnoid haemorrhage (SAH), accurate prediction is crucial for initial assessment of patients presenting with acute headache. We conducted this study to develop a new clinical decision rule using only objectively measurable predictors to exclude SAH, offering higher specificity than the previous Ottawa SAH Rule while maintaining comparable sensitivity. Multicentre prospective cohort study. Tertiary-care emergency departments of five general hospitals in Japan from April 2011 to March 2014. Eligible patients comprised 1781 patients aged >15 years with acute headache, excluding trauma or toxic causes and patients who presented in an unconscious state. Definitive diagnosis of SAH was based on confirmation of SAH on head CT or lumbar puncture findings of non-traumatic red blood cells or xanthochromia. A total of 1561 patients were enrolled in this study, of whom 277 showed SAH. Using these enrolled patients, we reached a rule with mainly categorical predictors used in previous reports, called the 'Ottawa-like rule', offering 100% sensitivity when using any of age ≥40 years, neck pain or stiffness, altered level of consciousness or onset during exertion. Using the 1317 patients from whom blood samples were obtained, a new rule using any of systolic blood pressure >150 mm Hg, diastolic blood pressure >90 mm Hg, blood sugar >115 mg/dL or serum potassium <3.9 mEq/L offered 100% sensitivity (95% CI 98.6% to 100%) and 14.5% specificity (12.5% to 16.9%), while the Ottawa-like rule showed the same sensitivity with a lower specificity of 8.8% (7.2% to 10.7%). While maintaining equal sensitivity, our new rule seemed to offer higher specificity than the previous rules proposed by the Ottawa group. Despite the need for blood sampling, this method can reduce unnecessary head CT in patients with acute headache. UMIN 00004871. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Outcomes of Patients With Relapsed Hepatoblastoma Enrolled on Children's Oncology Group (COG) Phase I and II Studies.

PubMed

Trobaugh-Lotrario, Angela D; Meyers, Rebecka L; Feusner, James H

2016-04-01

Data are limited regarding outcomes of patients treated for relapsed hepatoblastoma. We reviewed enrollment patterns and outcomes of patients with hepatoblastoma on Children's Oncology Group (COG) phase I/II studies. The medical literature was searched for reports of COG phase I/II studies using PUBMED as well as an inventory from the COG publications office searching manuscripts published from 2000 to 2014. Seventy-one patients with relapsed hepatoblastoma were enrolled on 23 separate COG phase I/II studies. Four studies collected α-fetoprotein (AFP) data, but none utilized AFP decline in assessing response. Most studies enrolled few patients with relapsed hepatoblastoma: 7 studies enrolled 1 patient, and another 7 studies enrolled 2 patients each. Only 9 studies enrolled 3 or more patients with relapsed hepatoblastoma. Four responses were reported. Dedicated strata and/or focus on 1 or 2 studies with compelling biological or clinical rationale for hepatoblastoma may improve accrual (and statistical significance of response data) of patients with relapsed hepatoblastoma. Prospective study of AFP decline versus RECIST response could help determine the optimal method of assessing response to identify potentially beneficial treatments in hepatoblastoma.

Enrollment in Distance Education Classes Is Associated with Fewer Enrollment Gaps among Nontraditional Undergraduate Students in the US

ERIC Educational Resources Information Center

Pontes, Manuel C. F.; Pontes, Nancy M. H.

2012-01-01

The purpose of this research is to determine whether nontraditional undergraduate students in the US who enroll in distance education classes are less likely to have an enrollment gap (enrollment gap=part year enrollment). Previous research has shown that preference for distance education classes is significantly greater among nontraditional than…

Co-enrollment of critically ill patients into multiple studies: patterns, predictors and consequences

PubMed Central

2013-01-01

Introduction Research on co-enrollment practices and their impact are limited in the ICU setting. The objectives of this study were: 1) to describe patterns and predictors of co-enrollment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of co-enrollment on clinical and trial outcomes. Methods In an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the co-enrollment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among co-enrolled and non-co-enrolled patients. Results Among 3,746 patients enrolled in PROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial), 713 (19.0%) were co-enrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study and 9.4% in both). Six factors independently associated with co-enrollment (all P < 0.001) were illness severity (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.19 to 1.53 for each 10-point Acute Physiology and Chronic Health Evaluation (APACHE) II score increase), substitute decision-makers providing consent, rather than patients (OR 3.31, 2.03 to 5.41), experience of persons inviting consent (OR 2.67, 1.74 to 4.11 for persons with > 10 years' experience compared to persons with none), center size (all ORs > 10 for ICUs with > 15 beds), affiliation with trials groups (OR 5.59, 3.49 to 8.95), and main trial rather than pilot phase (all ORs > 8 for recruitment year beyond the pilot). Co-enrollment did not influence clinical or trial outcomes or risk of adverse events. Conclusions Co-enrollment was strongly associated with features of the patients, research personnel, setting and study. Co-enrollment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis and further research are needed on the complex topic of co-enrollment during critical illness. PMID:23298553

Co-enrollment of critically ill patients into multiple studies: patterns, predictors and consequences.

PubMed

Cook, Deborah; McDonald, Ellen; Smith, Orla; Zytaruk, Nicole; Heels-Ansdell, Diane; Watpool, Irene; McArdle, Tracy; Matte, Andrea; Clarke, France; Vallance, Shirley; Finfer, Simon; Galt, Pauline; Crozier, Tim; Fowler, Rob; Arabi, Yaseen; Woolfe, Clive; Orford, Neil; Hall, Richard; Adhikari, Neill K J; Ferland, Marie-Clauide; Marshall, John; Meade, Maureen

2013-01-08

Research on co-enrollment practices and their impact are limited in the ICU setting. The objectives of this study were: 1) to describe patterns and predictors of co-enrollment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of co-enrollment on clinical and trial outcomes. In an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the co-enrollment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among co-enrolled and non-co-enrolled patients. Among 3,746 patients enrolled in PROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial), 713 (19.0%) were co-enrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study and 9.4% in both). Six factors independently associated with co-enrollment (all P < 0.001) were illness severity (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.19 to 1.53 for each 10-point Acute Physiology and Chronic Health Evaluation (APACHE) II score increase), substitute decision-makers providing consent, rather than patients (OR 3.31, 2.03 to 5.41), experience of persons inviting consent (OR 2.67, 1.74 to 4.11 for persons with > 10 years' experience compared to persons with none), center size (all ORs > 10 for ICUs with > 15 beds), affiliation with trials groups (OR 5.59, 3.49 to 8.95), and main trial rather than pilot phase (all ORs > 8 for recruitment year beyond the pilot). Co-enrollment did not influence clinical or trial outcomes or risk of adverse events. Co-enrollment was strongly associated with features of the patients, research personnel, setting and study. Co-enrollment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis and further research are needed on the complex topic of co-enrollment during critical illness.

Long-Term Follow Up of Patients with Mild-to-Moderate Alzheimer's Disease Treated with Bapineuzumab in a Phase III, Open-Label, Extension Study.

PubMed

Salloway, Stephen P; Sperling, Reisa; Fox, Nick C; Sabbagh, Marwan N; Honig, Lawrence S; Porsteinsson, Anton P; Rofael, Hany; Ketter, Nzeera; Wang, Daniel; Liu, Enchi; Carr, Stephen; Black, Ronald S; Brashear, H Robert

2018-06-08

A 3-year extension of two Phase III parent studies of intravenous (IV) bapineuzumab in patients with mild-to-moderate Alzheimer's disease dementia (apolipoprotein (APOE) ɛ4 carriers and noncarriers) is summarized. The primary and secondary objectives were to evaluate the long-term safety, tolerability, and maintenance of efficacy of bapineuzumab. A multicenter study in patients who had participated in double-blind placebo-controlled parent studies. Patients enrolled in the extension study were assigned to receive IV infusions of bapineuzumab (0.5 or 1.0 mg/kg) every 13 weeks until termination but were blinded to whether they had received bapineuzumab or placebo in the parent studies. A total of 1,462 (688 were APOEɛ4 carriers and 774 were noncarriers) patients were enrolled. Extension-onset adverse events occurred in >81% of the patients in each dose group. Fall, urinary tract infection, agitation, and ARIA-E occurred in ≥10% of participants. The incidence proportion of ARIA-E was higher among carriers and noncarriers who received bapineuzumab for the first time in the extension study (11.8% and 5.4%, respectively) versus those who were previously exposed in the parent studies (5.1% and 1.3%, respectively). After 6 to 12 months exposure to bapineuzumab IV in the extension study, similar deterioration of cognition and function occurred with no significant differences between the dose groups. Infusion of bapineuzumab 0.5 or 1.0 mg/kg every 13 weeks for up to 3 years was generally well tolerated, with a safety and tolerability profile similar to that in previous studies.

Patient Protection and Affordable Care Act; program integrity: Exchange, SHOP, and eligibility appeals. Final rule.

PubMed

2013-08-30

This final rule implements provisions of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010 (collectively referred to as the Affordable Care Act). Specifically, this final rule outlines Exchange standards with respect to eligibility appeals, agents and brokers, privacy and security, issuer direct enrollment, and the handling of consumer cases. It also sets forth standards with respect to a State's operation of the Exchange and Small Business Health Options Program (SHOP). It generally is finalizing previously proposed policies without change.

Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative

PubMed Central

Johnsen, Jill M.; Fletcher, Shelley N.; Huston, Haley; Roberge, Sarah; Martin, Beth K.; Kircher, Martin; Josephson, Neil C.; Shendure, Jay; Ruuska, Sarah; Koerper, Marion A.; Morales, Jaime; Pierce, Glenn F.; Aschman, Diane J.

2017-01-01

Hemophilia A and B are rare, X-linked bleeding disorders. My Life, Our Future (MLOF) is a collaborative project established to genotype and study hemophilia. Patients were enrolled at US hemophilia treatment centers (HTCs). Genotyping was performed centrally using next-generation sequencing (NGS) with an approach that detected common F8 gene inversions simultaneously with F8 and F9 gene sequencing followed by confirmation using standard genotyping methods. Sixty-nine HTCs enrolled the first 3000 patients in under 3 years. Clinically reportable DNA variants were detected in 98.1% (2357/2401) of hemophilia A and 99.3% (595/599) of hemophilia B patients. Of the 924 unique variants found, 285 were novel. Predicted gene-disrupting variants were common in severe disease; missense variants predominated in mild–moderate disease. Novel DNA variants accounted for ∼30% of variants found and were detected continuously throughout the project, indicating that additional variation likely remains undiscovered. The NGS approach detected >1 reportable variants in 36 patients (10 females), a finding with potential clinical implications. NGS also detected incidental variants unlikely to cause disease, including 11 variants previously reported in hemophilia. Although these genes are thought to be conserved, our findings support caution in interpretation of new variants. In summary, MLOF has contributed significantly toward variant annotation in the F8 and F9 genes. In the near future, investigators will be able to access MLOF data and repository samples for research to advance our understanding of hemophilia. PMID:29296726

Predictors of 12-Months Relapse After Withdrawal Treatment in Hospitalized Patients With Chronic Migraine Associated With Medication Overuse: A Longitudinal Observational Study.

PubMed

Raggi, Alberto; Giovannetti, Ambra M; Leonardi, Matilde; Sansone, Emanuela; Schiavolin, Silvia; Curone, Marcella; Grazzi, Licia; Usai, Susanna; D'Amico, Domenico

2017-01-01

Studies addressing relapse rates conflate relapse into chronic migraine (CM) and medication overuse (MO), and the consequent need to repeat withdrawal. We aim to identify 12-months predictors of relapse into CM (based on headaches frequency) separately from occurrence of another structured withdrawal. Hospitalized patients with CM-MO under withdrawal were enrolled. Candidate predictors included demographic, disability, quality of life, depression scores, general self-efficacy, social support, headaches frequency and intensity, class of overused medications, history of withdrawal treatment in the three years prior to enrollment, attendance to emergency room (ER) between enrollment and follow-up, nonattendance to outpatient neurological examinations. Logistic regressions was used to address the significant predictors for the two outcomes. Complete data were available for 177 patients: 60 (33.9%) relapsed into CM, 38 (21.5%) underwent another withdrawal treatment. Recent history of withdrawal treatments, ER admission after discharge and high baseline BDI-II scores were significant predictors in both models. In addition to this, high baseline headache frequency predicted relapse into another withdrawal treatment. Predictors or relapse into CM and of occurrence of another withdrawal by 12-months are somehow similar. It is important to assess presence of recent previous withdrawal treatments and to plan regular follow-up afterwards, in particular for patients with high headache frequency and relevant mood disturbances: in this way, it will be more likely that situations requiring further structured withdrawal treatments can be identified before patients have to refer to ER. © 2016 American Headache Society.

Insurance Enrollment at a Student-Run Free Clinic After the Patient Protection and Affordable Care Act.

PubMed

McGeehan, Megan; DeMaria, Rebecca; Charney, Pamela; Batavia, Ashita S

2017-08-01

The Patient Protection and Affordable Care Act (ACA) aims to increase insurance coverage through government subsidies. Medical student-run free clinics (SRFC) are an important entry point into the healthcare system for the uninsured. SRFCs do not have a standardized approach for navigating the complexities of enrollment. The Weill Cornell Community Clinic (WCCC) developed a unique enrollment model that may inform other SRFCs. Our objective is to describe enrollment processes at SRFCs throughout New York City, and to evaluate enrollment outcomes and persistent barriers to coverage at WCCC. We surveyed SRFC leadership throughout NYC to understand enrollment processes. We evaluated enrollment outcomes at WCCC through chart review and structured phone interviews. Subjects included WCCC patients seen in clinic between October 1, 2013 and September 30, 2015 (N = 140). Demographic information, method of insurance enrollment, and qualitative description of enrollment barriers were collected. SRFCs in New York City have diverse enrollment processes. 48% (N = 42) of WCCC patients obtained health insurance. Immigration status was a barrier to coverage in 21% of patients. Failure to gain coverage was predicted by larger household size (p = 0.02). Gender and employment status were not associated with remaining uninsured. The main barriers to enrollment were inability to afford premiums and lack of interest. Insurance enrollment processes at SRFCs in New York City are mostly ad hoc and outcomes are rarely tracked. Following implementation of the ACA, WCCC stands out for its structured approach, with approximately half of eligible WCCC patients gaining coverage during the study period.

Why don't patients enroll in hospice? Can we do anything about it?

PubMed

Vig, Elizabeth K; Starks, Helene; Taylor, Janelle S; Hopley, Elizabeth K; Fryer-Edwards, Kelly

2010-10-01

United States hospice organizations aim to provide quality, patient-centered end-of-life care to patients in the last 6 months of life, yet some of these organizations observe that some hospice-eligible patients who are referred to hospice do not initially enroll. To identify reasons that eligible patients do not enroll in hospice (phase 1). To identify strategies used by hospice providers to address these reasons (phase 2). Semi-structured interviews analyzed using content analysis. In phase 1, we interviewed 30 patients and/or family members of patients who had a hospice admissions visit, but who did not enroll. In phase 2, we interviewed 19 hospice staff and national experts. In phase 1, we asked participants to describe the patient's illness, the hospice referral, and why they had not enrolled. We performed a content analysis to characterize their reasons for not enrolling in hospice. In phase 2, we enrolled hospice admissions staff and hospice experts. We asked them to describe how they would respond to each reason (from phase 1) during an admissions visit with a potential new hospice patient. We identified key phrases, and summarized their recommendations. Reasons that patients hadn't enrolled fell into three broad categories: patient/family perceptions (e.g., "not ready"), hospice specific issues (e.g., variable definitions of hospice-eligible patients), and systems issues (e.g., concerns about continuity of care). Hospice staff/experts had encountered each reason, and offered strategies at the individual and organizational level for responding. In hopes of increasing hospice enrollment among hospice-eligible patients, non-hospice and hospice clinicians may want to adopt some of the strategies used by hospice staff/experts for talking about hospice with patients/families and may want to familiarize themselves with the differences between hospice organizations in their area. Hospices may want to reconsider their admission policies and procedures in light of patients' and families' perceptions and concerns.

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial.

PubMed

Wang, Michael L; Lee, Hun; Chuang, Hubert; Wagner-Bartak, Nicolaus; Hagemeister, Frederick; Westin, Jason; Fayad, Luis; Samaniego, Felipe; Turturro, Francesco; Oki, Yasuhiro; Chen, Wendy; Badillo, Maria; Nomie, Krystle; DeLa Rosa, Maria; Zhao, Donglu; Lam, Laura; Addison, Alicia; Zhang, Hui; Young, Ken H; Li, Shaoying; Santos, David; Medeiros, L Jeffrey; Champlin, Richard; Romaguera, Jorge; Zhang, Leo

2016-01-01

Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progressive disease or unacceptable toxic effects. Rituximab 375 mg/m(2) was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing patients. Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45-86), and the median number of previous regimens was three (range 1-9). At a median follow-up of 16·5 months (IQR 12·09-19·28), 44 (88%, 95% CI 75·7-95·5) patients achieved an objective response, with 22 (44%, 30·0-58·7) patients achieving a complete response, and 22 (44%, 30·0-58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one patient each. Adverse events led to discontinuation of therapy in five (10%) patients (atrial fibrillation in three [6%] patients, liver infection in one [2%], and bleeding in one [2%]). Two patients died while on-study from cardiac arrest and septic shock; the latter was deemed possibly related to treatment. Ibrutinib combined with rituximab is active and well tolerated in patients with relapsed or refractory mantle cell lymphoma. Our results provide preliminary evidence for the activity of this combination in clinical practice. A phase 3 trial is warranted for more definitive data. Pharmacyclics LLC, an AbbVie Company. Copyright © 2016 Elsevier Ltd. All rights reserved.

PI3K inhibitors as new cancer therapeutics: implications for clinical trial design

PubMed Central

Massacesi, Cristian; Di Tomaso, Emmanuelle; Urban, Patrick; Germa, Caroline; Quadt, Cornelia; Trandafir, Lucia; Aimone, Paola; Fretault, Nathalie; Dharan, Bharani; Tavorath, Ranjana; Hirawat, Samit

2016-01-01

The PI3K–AKT–mTOR pathway is frequently activated in cancer. PI3K inhibitors, including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3Kα-selective inhibitor alpelisib (BYL719), currently in clinical development by Novartis Oncology, may therefore be effective as anticancer agents. Early clinical studies with PI3K inhibitors have demonstrated preliminary antitumor activity and acceptable safety profiles. However, a number of unanswered questions regarding PI3K inhibition in cancer remain, including: what is the best approach for different tumor types, and which biomarkers will accurately identify the patient populations most likely to benefit from specific PI3K inhibitors? This review summarizes the strategies being employed by Novartis Oncology to help maximize the benefits of clinical studies with buparlisib and alpelisib, including stratification according to PI3K pathway activation status, selective enrollment/target enrichment (where patients with PI3K pathway-activated tumors are specifically recruited), nonselective enrollment with mandatory tissue collection, and enrollment of patients who have progressed on previous targeted agents, such as mTOR inhibitors or endocrine therapy. An overview of Novartis-sponsored and Novartis-supported trials that are utilizing these approaches in a range of cancer types, including breast cancer, head and neck squamous cell carcinoma, non-small cell lung carcinoma, lymphoma, and glioblastoma multiforme, is also described. PMID:26793003

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study.

PubMed

Flisiak, R; Janczewska, E; Wawrzynowicz-Syczewska, M; Jaroszewicz, J; Zarębska-Michaluk, D; Nazzal, K; Bolewska, B; Bialkowska, J; Berak, H; Fleischer-Stępniewska, K; Tomasiewicz, K; Karwowska, K; Rostkowska, K; Piekarska, A; Tronina, O; Madej, G; Garlicki, A; Lucejko, M; Pisula, A; Karpińska, E; Kryczka, W; Wiercińska-Drapało, A; Mozer-Lisewska, I; Jabłkowski, M; Horban, A; Knysz, B; Tudrujek, M; Halota, W; Simon, K

2016-11-01

Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting. © 2016 John Wiley & Sons Ltd.

Do surgeons and patients discuss what they document on consent forms?

PubMed

Hall, Daniel E; Hanusa, Barbara H; Fine, Michael J; Arnold, Robert M

2015-07-01

Previous studies of surgeon behavior report that surgeons rarely meet basic standards of informed consent, raising concerns that current practice requires urgent remediation. We wondered if the Veterans Affairs Healthcare System's recent implementation of standardized, procedure-specific consent forms might produce a better practice of informed consent than has been reported previously. Our goal was to determine how the discussions shared between surgeons and patients correspond to the VA's standardized consent forms. We enrolled a prospective cohort of patients presenting for possible cholecystectomy or inguinal herniorrhaphy and the surgical providers for those patients. Audio recordings captured the clinical encounter(s) culminating in a decision to have surgery. Each patient's informed consent was documented using a standardized, computer-generated form. We abstracted and compared the information documented with the information discussed. Of 75 consecutively enrolled patients, 37 eventually decided to have surgery and signed the standardized consent form. Patients and providers discussed 37% (95% confidence interval, 0.07-0.67) and 33% (95% confidence interval, 0.21-0.43) of the information found on the cholecystectomy and herniorrhaphy consent forms, respectively. However, the patient-provider discussions frequently included relevant details nowhere documented on the standardized forms, culminating in discussions that included a median 27.5 information items for cholecystectomy and 20 items for herniorrhaphy. Fully, 80% of cholecystectomy discussions and 76% of herniorrhaphy discussions mentioned at least one risk, benefit or alternative, indication for, and description of the procedure. The patients and providers observed here collaborated in a detailed process of informed consent that challenges the initial reports suggesting the need to remediate surgeon's practice of informed consent. However, because the discrepancy between the information documented and discussed exposes legal and ethical liability, there is an opportunity to improve the iMed system so that it better reflects what surgeons discuss and more frequently includes all the information patients need. Published by Elsevier Inc.

J-School Enrollments Reach Record 71,594.

ERIC Educational Resources Information Center

Peterson, Paul V.

1980-01-01

Discusses trends in journalism program enrollments. Compares the 1979 figures from an annual survey of journalism schools with statistics from previous years. Lists journalism program enrollments at 188 campuses. (RL)

Dual Enrollment Participation from the Student Perspective

ERIC Educational Resources Information Center

Kanny, M. Allison

2015-01-01

This chapter examines the experiences of five high school students previously enrolled in dual enrollment courses, and discusses the perceived benefits and disadvantages of these experiences from the student perspective.

Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies

PubMed Central

Lebbé, C.; Weber, J. S.; Maio, M.; Neyns, B.; Harmankaya, K.; Hamid, O.; O'Day, S. J.; Konto, C.; Cykowski, L.; McHenry, M. B.; Wolchok, J. D.

2014-01-01

Background This report provides a survival update at a follow-up of >5 years (5.5–6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy data following ipilimumab retreatment are also reported. Patients and methods Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025. Results Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%–16.5%, and 15.5%–28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%–49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively. Conclusions At a follow-up of 5–6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS. ClinicalTrials.gov NCT00162123. PMID:25210016

Endoscopic submucosal dissection for locally recurrent colorectal lesions after previous endoscopic mucosal resection.

PubMed

Zhou, Pinghong; Yao, Liqing; Qin, Xinyu; Xu, Meidong; Zhong, Yunshi; Chen, Weifeng

2009-02-01

The objective of this study was to determine the efficacy and safety of endoscopic submucosal dissection for locally recurrent colorectal cancer after previous endoscopic mucosal resection. A total of 16 patients with locally recurrent colorectal lesions were enrolled. A needle knife, an insulated-tip knife and a hook knife were used to resect the lesion along the submucosa. The rate of the curative resection, procedure time, and incidence of complications were evaluated. Of 16 lesions, 15 were completely resected with endoscopic submucosal dissection, yielding an en bloc resection rate of 93.8 percent. Histologic examination confirmed that lateral and basal margins were cancer-free in 14 patients (87.5 percent). The average procedure time was 87.2 +/- 60.7 minutes. None of the patients had immediate or delayed bleeding during or after endoscopic submucosal dissection. Perforation in one patient (6.3 percent) was the only complication and was managed conservatively. The mean follow-up period was 15.5 +/- 6.8 months; none of the patients experienced lesion residue or recurrence. Endoscopic submucosal dissection appears to be effective for locally recurrent colorectal cancer after previous endoscopic mucosal resection, making it possible to resect whole lesions and provide precise histologic information.

Dyadic Recruitment in Complementary Therapy Studies: Experience from a Clinical Trial of Caregiver-Delivered Reflexology

PubMed Central

Holmstrom, Amanda J.; Wyatt, Gwen K.; Sikorskii, Alla; Musatics, Catherine; Stolz, Emily; Havener, Neala

2015-01-01

Purpose As home-based care continues to be a growing trend in health care, involvement of friend and family caregivers in the management of illness becomes essential. However, before nurses can prepare caregivers to engage in various types of care, an evidence base needs to be established via randomized controlled trials (RCTs). Research suggests that recruiting cancer patients and their friend or family caregivers into RCTs presents challenges. The purpose of this paper is to illustrate the barriers to recruitment of patient-caregiver dyads into a RCT of caregiver-delivered reflexology and to recommend strategies to address such barriers. Methods This paper reports on a nurse-directed RCT that involved recruitment efforts unique to a caregiver-delivered reflexology protocol for advanced-stage breast cancer patients. Ineligibility due to caregiver-related reasons, consent among eligible patients (out of 551 approached patients), and reasons for refusal were analyzed. Results Almost one-third of patients were found to be ineligible due to the lack of a caregiver to participate with them and provide this form of social support. Among eligible patients, the consent rate for this dyadic study is much lower than that of previous RCTs of reflexologist-delivered reflexology that enrolled just patients, not dyads. Conclusion Implications for nursing practice and research include addressing the need for greater social support for patients and strategies for problem-solving refusal reasons during study enrollment. PMID:26856504

Survey of tuberculosis drug resistance among Tibetan refugees in India.

PubMed

Salvo, F; Dorjee, K; Dierberg, K; Cronin, W; Sadutshang, T D; Migliori, G B; Rodrigues, C; Trentini, F; Di Serio, C; Chaisson, R; Cirillo, D M

2014-06-01

Tuberculosis (TB) is a major health problem among Tibetans living in exile in India. Although drug-resistant TB is considered common in clinical practice, precise data are lacking. To determine the proportion of drug-resistant cases among new and previously treated Tibetan TB patients. In a drug resistance survey in five Tibetan settlements in India, culture and drug susceptibility testing (DST) for first-line drugs were performed among all consecutive new and previously treated TB cases from April 2010 to September 2011. DST against kanamycin (KM), ethionamide, para-aminosalicylic acid and ofloxacin (OFX) was performed on multidrug-resistant TB (MDR-TB) isolates. Of 307 patients enrolled in the study, 264 (193 new and 71 previously treated) were culture-positive and had DST available. All patients tested for the human immunodeficiency virus (n = 250) were negative. Among new TB cases, 14.5% had MDR-TB and 5.7% were isoniazid (INH) monoresistant. Among previously treated cases, 31.4% had MDR-TB and 12.7% were INH-monoresistant. Of the MDR-TB isolates, 28.6% of new and 26.1% of previously treated cases were OFX-resistant, while 7.1% of new cases and 8.7% of previously treated cases were KM-resistant. Three patients had extensively drug-resistant TB. MDR-TB is common in new and previously treated Tibetans in India, who also show additional complex resistance patterns. Of particular concern is the high percentage of MDR-TB strains resistant to OFX, KM or both.

First national survey of anti-tuberculosis drug resistance in Azerbaijan and risk factors analysis

PubMed Central

Akhundova, I.; Seyfaddinova, M.; Mammadbayov, E.; Mirtskulava, V.; Rüsch-Gerdes, S.; Bayramov, R.; Suleymanova, J.; Kremer, K.; Dadu, A.; Acosta, C. D.; Harries, A. D.; Dara, M.

2014-01-01

Setting: Civilian population of the Republic of Azerbaijan. Objectives: To determine patterns of anti-tuberculosis drug resistance among new and previously treated pulmonary tuberculosis (TB) cases, and explore their association with socio-demographic and clinical characteristics. Design: National cross-sectional survey conducted in 2012–2013. Results: Of 789 patients (549 new and 240 previously treated) who met the enrolment criteria, 231 (42%) new and 146 (61%) previously treated patients were resistant to any anti-tuberculosis drug; 72 (13%) new and 66 (28%) previously treated patients had multidrug-resistant TB (MDR-TB). Among MDR-TB cases, 38% of new and 46% of previously treated cases had pre-extensively drug-resistant TB (pre-XDR-TB) or XDR-TB. In previously treated cases, 51% of those who had failed treatment had MDR-TB, which was 15 times higher than in relapse cases (OR 15.2, 95%CI 6–39). The only characteristic significantly associated with MDR-TB was a history of previous treatment (OR 3.1, 95%CI 2.1–4.7); for this group, history of incarceration was an additional risk factor for MDR-TB (OR 2.8, 95%CI 1.1–7.4). Conclusion: Azerbaijan remains a high MDR-TB burden country. There is a need to implement countrywide control and innovative measures to accelerate early diagnosis of drug resistance in individual patients, improve treatment adherence and strengthen routine surveillance of drug resistance. PMID:26393092

External validation of a six simple variable model of stroke outcome and verification in hyper-acute stroke.

PubMed

Reid, J M; Gubitz, G J; Dai, D; Reidy, Y; Christian, C; Counsell, C; Dennis, M; Phillips, S J

2007-12-01

We aimed to validate a previously described six simple variable (SSV) model that was developed from acute and sub-acute stroke patients in our population that included hyper-acute stroke patients. A Stroke Outcome Study enrolled patients from 2001 to 2002. Functional status was assessed at 6 months using the modified Rankin Scale (mRS). SSV model performance was tested in our cohort. 538 acute ischaemic (87%) and haemorrhagic stroke patients were enrolled, 51% of whom presented to hospital within 6 h of symptom recognition. At 6 months post-stroke, 42% of patients had a good outcome (mRS < or = 2). Stroke patients presenting within 6 h of symptom recognition were significantly older with higher stroke severity. In our Stroke Outcome Study dataset, the SSV model had an area under the curve of 0.792 for 6 month outcomes and performed well for hyper-acute or post-acute stroke, age < or > or = 75 years, haemorrhagic or ischaemic stroke, men or women, moderate and severe stroke, but poorly for mild stroke. This study confirms the external validity of the SSV model in our hospital stroke population. This model can therefore be utilised for stratification in acute and hyper-acute stroke trials.

Addison’s Disease Symptoms – A Cross Sectional Study in Urban South Africa

PubMed Central

Ross, Ian Louis; Levitt, Naomi S.

2013-01-01

Background Addison’s disease is a potentially life-threatening disorder, and prompt diagnosis, and introduction of steroid replacement has resulted in near normal life-expectancy. There are limited data describing the clinical presentation of Addison’s disease in South Africa. It is hypothesised that patients may present in advanced state of ill-health, compared to Western countries. Patients A national database of patients was compiled from primary care, referral centres and private practices. 148 patients were enrolled (97 white, 34 mixed ancestry, 5 Asian and 12 black). Methods Demographic and clinical data were elicited using questionnaires. Biochemical data were obtained from folder reviews and laboratory archived results. Results The majority of the cohort was women (62%). The median and inter-quartile age range (IQR) of patients at enrolment was 46.0 (32.0–61.0) years, with a wide range from 2.8–88.0 years. The median and IQR age at initial diagnosis was 34.0 (20.0–45.0) years (range 0.02–77.0) years, indicating that at the time of enrolment, the patients, on average, were diagnosed with Addison’s disease 12 years previously. Hyperpigmentation was observed in 76%, nausea and vomiting occurred in more than 40%, and weight loss was noted in 25%. Loss of consciousness as a presenting feature was recorded in 20%. with a 95% confidence interval [CI] of (14–28%) and shock occurred in 5% CI (1.5–8.5%). Case-finding was recorded at 3.1 per million. Conclusions The usual constellation of hyperpigmentation, nausea, vomiting and weight loss suggests Addison’s disease, but a significant proportion present with an advanced state of ill-health and Addisonian crises. A lower prevalence rate, compared to Western countries is suggested. PMID:23308244

Design, baseline characteristics, and early findings of the MPS VI (mucopolysaccharidosis VI) Clinical Surveillance Program (CSP).

PubMed

Hendriksz, Christian J; Giugliani, Roberto; Harmatz, Paul; Lampe, Christina; Martins, Ana Maria; Pastores, Gregory M; Steiner, Robert D; Leão Teles, Elisa; Valayannopoulos, Vassili

2013-03-01

To outline the design, baseline data, and 5-year follow-up data of patients with mucopolysaccharidosis (MPS) VI enrolled in the Clinical Surveillance Program (CSP), a voluntary, multinational, observational program. The MPS VI CSP was opened in 2005 to collect, for at least 15 years, observational data from standard clinical and laboratory assessments of patients with MPS VI. Baseline and follow-up data are documented by participating physicians in electronic case report forms. Between September 2005 and March 2010 the CSP enrolled 132 patients, including 123 who received enzyme replacement therapy (ERT) with galsulfase. Median age at enrolment was 13 years (range 1-59). Mean baseline data showed impaired growth, hepatosplenomegaly, and reduced endurance and pulmonary function. The most common findings were heart valve disease (90%), reduced visual acuity (79%), impaired hearing (59%), and hepatosplenomegaly (54%). Follow-up data up to 5 years in patients with pre- and post-ERT measurements showed a decrease in urinary glycosaminoglycans and increases in height and weight in patients <16 years and suggested reductions in liver and spleen size and improvements in endurance and pulmonary function after ERT was started. Vision, hearing, and cardiac function were unchanged. Safety data were in line with previous reports. The CSP represents the largest cross-sectional study of MPS VI to date. This first report provides information on the design and implementation of the program and population statistics for several clinical variables in patients with MPS VI. Data collected over 5 years suggest that ERT provides clinical benefit and is well-tolerated with no new safety concerns.

Comparison of Outcomes After Fluorouracil-Based Adjuvant Therapy for Stages II and III Colon Cancer Between 1978 to 1995 and 1996 to 2007: Evidence of Stage Migration From the ACCENT Database

PubMed Central

Shi, Qian; Andre, Thierry; Grothey, Axel; Yothers, Greg; Hamilton, Stanley R.; Bot, Brian M.; Haller, Daniel G.; Van Cutsem, Eric; Twelves, Chris; Benedetti, Jacqueline K.; O'Connell, Michael J.; Sargent, Daniel J.

2013-01-01

Purpose With improved patient care, better diagnosis, and more treatment options after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are expected to have improved over time in early-stage colon cancer. Data from 18,449 patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were evaluated for potential differences in time to recurrence (TTR), time from recurrence to death (TRD), and overall survival (OS) with regard to FU-based adjuvant regimens. Methods Trials were predefined as old versus newer era using initial accrual before or after 1995. Outcomes were compared between patients enrolled onto old- or newer-era trials, stratified by stage. Results Within the first 3 years, recurrence rates were lower in newer- versus old-era trials for patients with stage II disease, with no differences among those with stage III disease. Both TRD and OS were significantly longer in newer-era trials overall and within each stage. The lymph node (LN) ratio (ie, number of positive nodes divided by total nodes harvested) in those with stage III disease declined over time. TTR improved slightly, with larger number of LNs examined in both stages. Conclusion Improved TRD in newer trials supports the premise that more aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or surgery for recurrent disease) improves OS for patients previously treated in the adjuvant setting. Lower recurrence rates with identical treatments in those with stage II disease enrolled onto newer-era trials reflect stage migration over time, calling into question historical data related to the benefit of FU-based adjuvant therapy in such patients. PMID:23980089

Provider-Based Research Networks Demonstrate Greater Hospice Use for Minority Patients With Lung Cancer

PubMed Central

Penn, Dolly C.; Stitzenberg, Karyn B.; Cobran, Ewan K.; Godley, Paul A.

2014-01-01

Purpose: The Community Clinical Oncology Program (CCOP) and Minority-Based Community Clinical Oncology Program (MBCCOP) are provider-based research networks (PBRN) that improve minority enrollment in cancer-focused clinical trials. We hypothesized that affiliation with a PBRN may also mitigate racial differences in hospice enrollment for patients with lung cancer. Methods: We used the SEER-Medicare data, linked to the National Cancer Institute's CCOP program data, to identify all patients (≥ age 65 years) with lung cancer, diagnosed from 2001 to 2007. We defined clinical treatment settings as CCOP, MBCCOP, academic, or community-affiliated and used multivariable logistic regression analysis to determine factors associated with hospice enrollment. Results: Forty-one thousand eight hundred eighty-five (55.1%) patients with lung cancer enrolled in hospice before death. Approximately 55% of CCOP, 57% of MBCCOP, 57% of academic, and 52% of community patients enrolled. Patients who were more likely to enroll were female (odds ratio [OR], 1.36; 95% CI, 1.31 to 1.40); ≥ age 79 years (OR, 1.11; 95%CI, 1.06 to 1.16); white; lived in more educated areas; had minimal comorbidities; and had distant disease. Asian and black patients in academic (41.1% and 50.4%, respectively) and community practices (35.2% and 43.4%, respectively) were less likely to enroll in hospice compared with white patients (academic, 58.8%; community, 53.1%). However, hospice enrollment was equivalent for black and white patients in MBCCOP (59.5% v 57.2%) and CCOP (52.2% v 56.3%) practices. Conclusion: Minority patients with lung cancer receiving treatment in cancer-focused PBRN- affiliated practices have greater hospice enrollment than those treated in academic and community practices. PMID:24781367

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial

PubMed Central

O’Brien, Susan; Furman, Richard R; Coutre, Steven E; Sharman, Jeff P; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Richards, Donald A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Izumi, Raquel; Hamdy, Ahmed; Chang, Betty Y; Graef, Thorsten; Clow, Fong; Buggy, Joseph J; James, Danelle F; Byrd, John C

2014-01-01

Summary Background Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. Methods In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. Findings Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65–84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1–2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one developed grade 4 thrombocytopenia. After a median follow-up of 22·1 months (IQR 18·4–23·2), 22 (71%) of 31 patients achieved an objective response (95% CI 52·0–85·8); four patients (13%) had a complete response, one patient (3%) had a nodular partial response, and 17 (55%) patients had a partial response. Interpretation The safety and activity of ibrutinib in elderly, previously untreated patients with symptomatic chronic lymphocytic leukaemia, or small lymphocytic lymphoma is encouraging, and merits further investigation in phase 3 trials. Funding Pharmacyclics, Leukemia and Lymphoma Society, D Warren Brown Foundation, Mr and Mrs Michael Thomas, Harry Mangurian Foundation, P50 CA140158 to Prof J C Byrd MD. PMID:24332241

An Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective Randomized Control Trials

PubMed Central

Logan, Jennifer K; Tang, Chad; Liao, Zhongxing; Lee, J. Jack; Heymach, John V.; Swisher, Stephen G.; Welsh, James W.; Zhang, Jianjun; Lin, Steven H.; Gomez, Daniel R.

2018-01-01

Purpose Effective clinical trial enrollment can be difficult in a protocol designs that contain one treatment arm that is perceived as being more “aggressive” or “favorable.” There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to enrollment, particularly the influence of timing, in context of three prospective randomized oncology trials where one arm was considered more aggressive. Methods and materials From June 2011 to March 2015, patients who were enrolled on three prospective institutional protocols (an oligometastatic non-small cell lung cancer (NSCLC) trial, and two proton vs. intensity-modulated radiation therapy (IMRT) trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher’s exact test, Student’s t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results 309 eligible patients were approached about trial enrollment. The enrollment success rate (ESR) during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligomet protocol: 5 vs. 3 appointments (P<0.001), NSCLC protocol: 4 vs. 3 appointments (P = 0.0018), esophageal protocol: 3 vs. 2 appointments (P = 0.0086No other factors or patient characteristics significantly affected ESR. Conclusion Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success, and may help overcome accrual barriers without compromising trial design. PMID:28244413

The efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial.

PubMed

Tanaka, Nobumichi; Nishimura, Kazuo; Okajima, Eijiro; Ina, Kenji; Ogawa, Osamu; Nagata, Hirohiko; Akakura, Koichiro; Fujimoto, Kiyohide; Gotoh, Momokazu; Teramukai, Satoshi; Hirao, Yoshihiko

2017-03-01

Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients. This study was a single-arm multi-institutional phase II trial. Patients received 75 mg/m2 of docetaxel, and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. Treatment was planned for 10 cycles, and continued for at least four cycles depending on the observation of PSA flare. The primary endpoint was PSA response defined as a reduction from baseline of at least 50% that continued for at least 3 weeks. Secondary endpoints were safety, PSA flare, time to PSA failure and adherence rate to protocol treatment (10 cycles). Between January 2011 and February 2014, a total of 76 chemotherapy-naïve CRPC patients were enrolled. Seventy-five patients received docetaxel-based chemotherapy combined with dexamethasone. The median age and PSA level at enrollment were 71 years (53-85) and 23.2 ng/mL (2.9-852), respectively. PSA response rate was 76.8% (90% confidence interval (CI): 66.9-84.9). Of all patients, 30 patients completed 10 cycles of chemotherapy (40%). The incidence rate of PSA flare was 10.7% (eight patients). The median time to PSA failure was 369 days (95% CI: 245-369). The most frequently observed adverse event was hematotoxicity (neutropenia of G2 or greater: 100%). The present study showed a significantly high PSA response compared with previous reports. Most patients tolerated the protocol treatment well, whereas hematotoxicity was often observed. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Impact of a clinical trial initiative on clinical trial enrollment in a multidisciplinary prostate cancer clinic.

PubMed

Madsen, Lydia T; Kuban, Deborah A; Choi, Seungtaek; Davis, John W; Kim, Jeri; Lee, Andrew K; Domain, Delora; Levy, Larry; Pisters, Louis L; Pettaway, Curtis A; Ward, John F; Logothetis, Christopher; Hoffman, Karen E

2014-07-01

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative. Copyright © 2014 by the National Comprehensive Cancer Network.

Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial.

PubMed

Fuchs, Charles S; Doi, Toshihiko; Jang, Raymond W; Muro, Kei; Satoh, Taroh; Machado, Manuela; Sun, Weijing; Jalal, Shadia I; Shah, Manish A; Metges, Jean-Phillipe; Garrido, Marcelo; Golan, Talia; Mandala, Mario; Wainberg, Zev A; Catenacci, Daniel V; Ohtsu, Atsushi; Shitara, Kohei; Geva, Ravit; Bleeker, Jonathan; Ko, Andrew H; Ku, Geoffrey; Philip, Philip; Enzinger, Peter C; Bang, Yung-Jue; Levitan, Diane; Wang, Jiangdian; Rosales, Minori; Dalal, Rita P; Yoon, Harry H

2018-05-10

Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months. Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects. Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)-positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration. Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1-positive and PD-L1-negative tumors, respectively. Forty-six patients (17.8%) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8%) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment. Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1-positive and PD-L1-negative tumors. Further study of pembrolizumab for this group of patients is warranted. clinicaltrials.gov Identifier: NCT02335411.

Elevated plasma migration inhibitory factor in hypertension–hyperlipidemia patients correlates with impaired endothelial function

PubMed Central

Zhou, Boda; Ren, Chuan; Zu, Lingyun; Zheng, Lemin; Guo, Lijun; Gao, Wei

2016-01-01

Abstract Migration inhibitory factor (MIF) has been shown to be critical in the pathology of early artherosclerosis; this article aim to investigate the plasma levels of MIF in hypertension plus hyperlipidemia patients. A total of 39 hypertension plus hyperlipidemia patients without any previous treatment were enrolled (HTN-HLP). Twenty-five healthy subjects were enrolled as the healthy control group (HEALTHY). Plasma MIF was measured by ELISA; laboratory and clinical characteristics were analyzed. HUVECs were treated with pooled plasma from HTN-HLP and HEALTHY groups, and the protein levels of adhesion molecules VCAM-1 and ICAM-1 were determined by ELISA. We found that plasma MIF was significantly elevated in the HTN-HLP group. Serum NO and eNOS levels were significantly lower; serum ET-1 (endothelin) levels were significantly higher in the HTN-HLP group. Furthermore, blood pressure, baPWV (brachial–ankle pulse wave velocity), and serum ET-1 level were significantly positively; serum NO and eNOS levels were negatively correlated with plasma MIF levels. Plasma from HTN-HLP significantly stimulated VCAM-1 and ICAM-1 protein expression on the surface of HUVECs. Plasma MIF was elevated in HTN-HLP patients and correlates with impaired endothelial function. PMID:27787379

Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study.

PubMed

Burger, Jan A; Keating, Michael J; Wierda, William G; Hartmann, Elena; Hoellenriegel, Julia; Rosin, Nathalie Y; de Weerdt, Iris; Jeyakumar, Ghayathri; Ferrajoli, Alessandra; Cardenas-Turanzas, Marylou; Lerner, Susan; Jorgensen, Jeffrey L; Nogueras-González, Graciela M; Zacharian, Gracy; Huang, Xuelin; Kantarjian, Hagop; Garg, Naveen; Rosenwald, Andreas; O'Brien, Susan

2014-09-01

Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL. In this single-arm phase 2 study, we enrolled adult patients with high-risk CLL at the MD Anderson Cancer Center (Houston, TX, USA). All enrolled participants had high-risk cytogenetic abnormalities (deletion 17p, TP53 mutation, or deletion 11q) or a short progression-free survival (PFS <36 months) after previous first-line chemoimmunotherapy. Patients with symptomatic disease requiring therapy received 28-day cycles of once-daily ibrutinib 420 mg together with rituximab (375 mg/m(2), intravenously, every week during cycle 1, then once per cycle until cycle 6), followed by continuous daily single-agent ibrutinib 420 mg until disease progression or until toxicities or complications precluded further treatment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov number NCT01520519, and is no longer accruing patients. Between Feb 28, 2012, and Sept 11, 2012, we enrolled 40 patients with CLL with high-risk disease features, 20 of whom had deletion 17p (del[17p]) or TP53 mutations (16 previously treated, four untreated), 13 had relapsed CLL with deletion 11q (del[11q]), and seven a PFS less than 36 months after first-line chemoimmunotherapy. 18-month PFS in all patients was 78·0% (95% CI 60·6-88·5), whereas in those with a del(17p) or TP53 mutation it was 72·4% (45·6-87·6) Toxicity was mainly mild to moderate in severity (grade 1-2). Diarrhoea occurred in ten (25%) patients (grade 1 in nine patients and grade 2 in one), bleeding events in 14 (33%) patients (eight grade 1 and five grade 2), nausea or vomiting in 15 patients (38%) (ten grade 1 and five grade 2), and fatigue in seven (18%) patients (four grade 1 and three grade 2). Five patients (13%) had grade 3 infections (two lung infections, one upper respiratory tract infection, one sepsis, and one mucositis), and no grade 4 or 5 infections occurred. One patient had grade 4 neutropenia. The encouraging safety and activity of ibrutinib and rituximab in this population of patients with high-risk CLL merits further investigation of this combination. Pharmacyclics Inc, Cancer Prevention and Research Institute of Texas, Leukemia and Lymphoma Society, National Cancer Institute, MD Anderson Cancer Center. Copyright © 2014 Elsevier Ltd. All rights reserved.

[The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

PubMed

Chen, H; Wang, H P; Zhang, L; Si, X Y

2017-01-01

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points: Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

PubMed

Greene, Stephen J; Hernandez, Adrian F; Sun, Jie-Lena; Metra, Marco; Butler, Javed; Ambrosy, Andrew P; Ezekowitz, Justin A; Starling, Randall C; Teerlink, John R; Schulte, Phillip J; Voors, Adriaan A; Armstrong, Paul W; O'Connor, Christopher M; Mentz, Robert J

2016-09-01

Most international acute heart failure trials have failed to show benefit with respect to key end points. The impact of site enrollment and protocol execution on trial performance is unclear. We assessed the impact of varying site enrollment volume among all 7141 acute heart failure patients from the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure). Overall, 398 sites enrolled ≥1 patient, and median enrollment was 12 patients (interquartile range, 5-23). Patients from high enrolling sites (>60 patients/site) tended to have lower ejection fraction, worse New York Heart Association functional class, and lower utilization of guideline-directed medical therapy but fewer comorbidities and lower B-type natriuretic peptide level. Every 10 patient increase (up to 100 patients) in site enrollment correlated with lower likelihood of protocol noncompletion (odds ratio, 0.93; 95% confidence interval [CI], 0.89-0.98). After adjustment, increasing site enrollment predicted higher risk of persistent dyspnea at 6 hours (per 10 patient increase: odds ratio 1.02; 95% CI, 1.01-1.03) but not at 24 hours (odds ratio, 0.99; 95% CI, 0.98-1.00). Higher site enrollment was independently associated with lower risk of 30-day death or rehospitalization (per 10 patient increase: odds ratio, 0.98, 95% CI, 0.96-0.99) but not 180-day mortality (hazard ratio, 0.99; 95% CI, 0.98-1.01). The influence of increasing site enrollment on clinical end points varied across geographic regions with strongest associations in Latin America and Asia-Pacific (all interaction P<0.01). In this large, acute heart failure trial, site enrollment correlated with protocol completion and was independently associated with trial end points. Individual and regional site performance present challenges to be considered in design of future acute heart failure trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. © 2016 American Heart Association, Inc.

Safety, tolerability and efficacy of lixisenatide as monotherapy in Japanese patients with type 2 diabetes mellitus: An open-label, multicenter study.

PubMed

Seino, Yutaka; Terauchi, Yasuo; Wang, Xiangling; Watanabe, Daisuke; Niemoeller, Elisabeth

2018-01-01

To assess the overall safety of lixisenatide monotherapy in Japanese patients with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus, previously treated with ≤1 oral antidiabetic drug, were enrolled in an uncontrolled, open-label, single-arm study over 24 and 52 weeks. Any oral antidiabetic drug treatment was stopped at the start of the 6-week run-in period. From baseline, patients received once-daily lixisenatide monotherapy (10 μg for 1 week, 15 μg for 1 week, 20 μg thereafter) for 52 weeks (first 140 patients enrolled) or 24 weeks (subsequently enrolled patients). The primary end-point was safety over 24 and 52 weeks. Secondary efficacy end-points included absolute change in glycated hemoglobin, fasting plasma glucose and bodyweight from baseline. Of 428 patients screened, 361 and 140 were treated for 24 and 52 weeks, respectively; 88.4 and 90.0% completed treatment. During the 24- and 52-week treatment periods, 268/361 (74.2%) and 117/140 (83.6%) patients, respectively, had treatment-emergent adverse events; the most frequently reported was nausea (33.2 and 31.4%, respectively). The risk of severe hypoglycemia was low; only one case was reported. Lixisenatide treatment resulted in a decrease in mean glycated hemoglobin A1c (-0.98 and -0.86%), fasting plasma glucose (-1.05 and -0.85 mmol/L), and bodyweight (-1.33 and -1.48 kg) for the 24- and 52-week treatment periods, respectively. Once-daily lixisenatide monotherapy was associated with a safety profile in line with the glucagon-like peptide-1 receptor agonist class, and improved glycemic control in Japanese patients with type 2 diabetes mellitus. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Performance of the 2-hour Accelerated Diagnostic Protocol Within the American College of Radiology Imaging Network PA 4005 Cohort

PubMed Central

Mahler, Simon A.; Miller, Chadwick D.; Litt, Harold I.; Gatsonis, Constantine A.; Snyder, Bradley S.; Hollander, Judd E.

2015-01-01

Objectives The 2-hour accelerated diagnostic protocol (ADAPT) is a decision rule designed to identify emergency department (ED) patients with chest pain for early discharge. Previous studies in the Asia-Pacific region demonstrated high sensitivity (97.9% to 99.7%) for major adverse cardiac events (MACE) at 30 days. The objective of this study was to determine the validity of ADAPT for risk stratification in a cohort of U.S. ED patients with suspected acute coronary syndrome (ACS). Methods A secondary analysis of participants enrolled in the American College of Radiology Imaging Network (ACRIN) PA 4005 trial was conducted. This trial enrolled 1,369 patients at least 30 years old with symptoms suggestive of ACS. All data elements were collected prospectively at the time of enrollment. Each patient was classified as low risk or at risk by ADAPT. Early discharge rate and sensitivity for MACE, defined as cardiac death, myocardial infarction (MI), or coronary revascularization at 30 days, were calculated. Results Of 1,140 patients with complete biomarker data, MACE occurred in 31 patients (2.7%). Among 551 of the 1,140 (48.3%, 95% confidence interval [CI] = 45.4% to 51.3%), ADAPT identified for early discharge; five of the 551 (0.9%, 95% CI = 0.3% to 2.1%) had MACE at 30 days. ADAPT was 83.9% (95% CI = 66.3% to 94.5%) sensitive, identifying 26 of 31 patients with MACE. Of the five patients identified for early discharge by ADAPT with MACE, there were no deaths, one patient with MI, and five with revascularizations. Conclusions In this first North American application of the ADAPT strategy, sensitivity for MACE within 30 days was 83.9%. One missed adverse event was a MI, with the remainder representing coronary revascularizations. The effect of missing revascularization events needs further investigation. PMID:25810343

Results of a prospective randomized control trial comparing hydrophilic to uncoated catheters in children with neurogenic bladder.

PubMed

DeFoor, William; Reddy, Pramod; Reed, Melissa; VanderBrink, Brian; Jackson, Elizabeth; Zhang, Bin; Denlinger, Julie; Noh, Paul; Minevich, Eugene; Sheldon, Curtis

2017-08-01

Children with neurogenic bladder (NGB) often require a lifetime of clean intermittent catheterization (CIC), typically using uncoated catheters (UCs). Hydrophilic catheters (HCs) have lower friction than UCs with reported less damage to the urethra. The purpose of this study is to compare outcomes between these catheters. An investigator-initiated, prospective, randomized clinical trial was conducted to compare HCs versus UCs. Children aged 2-17 years with NGB on CIC were enrolled for 1 year. Block randomization was used. Dexterity scores were obtained in those who perform self-catheterization. Outcomes were UTI, difficulty passing the catheter, urethral injury, and patient satisfaction. Demographic data is presented in the Table. Seventy-eight patients were enrolled. Age and gender were similar between the groups. Fifteen patients in each group performed CIC via an abdominal wall stoma. Eight and 15 patients withdrew from the UC and HC groups, respectively. The HC group overall had more problems with the catheter, mainly difficulty with handling. There were no differences for passing the catheter, pain, hematuria, or urethral injuries. There were two urinary tract infections (UTIs) in two HC patients and 17 UTIs in seven UC patients (p = 0.003). Patients with UTIs in the HC group went from 16% in the previous year to 5% during the study. Three children in the HC group had three or more UTIs in the year before enrollment and none during the study. The patients that completed the study with HC were overall satisfied and many requested to continue with the HC. HCs may decrease the risk of UTI in children with NGB. Urethral complications were low in both groups. Most HC patients were pleased but some found the slippery coating difficult to handle. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Retreatment using a dual mode of low-fluence Q-switched and long-pulse Nd:YAG laser in patients with melasma aggravation after previous therapy.

PubMed

Choi, Chun Pil; Yim, Seon Mi; Seo, Soo Hong; Ahn, Hyo Hyun; Kye, Young Chul; Choi, Jae Eun

2015-06-01

Aggravated melasma after treatment is vulnerable to stimulation, can easily deteriorate, and may be distressing without proper management. To retrospectively assess the effectiveness and safety of combination therapy using low-fluence Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (QSNY) and long-pulse Nd:YAG laser (LPNY) (dual toning) in patients with rebound melasma. A total of 30 patients with aggravated melasma after previous therapy who were treated with dual toning were enrolled. A total of 10 sessions were conducted at 1-week intervals, followed by maintenance treatment. The results were evaluated using the modified Melasma Area and Severity Index (mMASI) and the physician's global assessment (PGA) before and 2 months after completing the 10 treatment sessions. The baseline mMASI was 10.48 ± 3.64, which significantly decreased to 3.22 ± 1.45 2 months after completing the 10 treatment sessions (p < 0.001). Twenty-four patients (80%) had PGA grade 4 (76-100% improvement) and 6 patients (20%) had PGA grade 3 (51-75% improvement). Dual toning may be a safe and effective salvage treatment for patients with aggravated melasma after previous treatment. LPNY may stabilize melasma activity to prevent rebound hyperpigmentation via dermal remodeling.

Demographic, Insurance, and Health Characteristics of Newly Enrolled HIV-Positive Patients After Implementation of the Affordable Care Act in California

PubMed Central

Parthasarathy, Sujaya; Altschuler, Andrea; Silverberg, Michael J.; Storholm, Erik; Campbell, Cynthia I.

2016-01-01

Objectives. To examine changes in HIV-positive patient enrollment in a large health care delivery system before and after key Affordable Care Act (ACA) provisions went into effect in 2014. Methods. Analyses compared HIV-positive patients newly enrolled in Kaiser Permanente Northern California between January and June 2012 (n = 339) to those newly enrolled between January and June 2014 through the California insurance exchange or via other mechanisms (n = 549). Results. After the ACA, the HIV-positive patient enrollment increased. These new enrollees were more likely to be male (93.6% vs 89.1%; P = .01), to be enrolled in high-deductible benefit plans (≥ $1000; 18.8% vs 5.5%; P = .01), and to have better HIV viral control (HIV RNA levels below limits of quantification 79.5% vs 73.6%; P = .05) compared with pre-ACA new enrollees. Among post-ACA new enrollees, there were more patients in the lowest and highest age groups. Post-ACA exchange enrollees (22%) were more likely to be male and to have high-deductible plans than those enrolled through other mechanisms. Conclusions. More men, higher deductibles, and better HIV viral control characterize newly enrolled HIV-positive patients after the ACA in California. Public health implications. Evolving characteristics of HIV-positive enrollees may affect HIV policy, patient care needs, and service utilization. PMID:27077361

Prognostic value of severity indicators of nursing-home-acquired pneumonia versus community-acquired pneumonia in elderly patients.

PubMed

Ugajin, Motoi; Yamaki, Kenichi; Hirasawa, Natsuko; Kobayashi, Takanori; Yagi, Takeo

2014-01-01

The credibility of prognostic indicators in nursing-home-acquired pneumonia (NHAP) is not clear. We previously reported a simple prognostic indicator in community-acquired pneumonia (CAP): blood urea nitrogen to serum albumin (B/A) ratio. This retrospective study investigated the prognostic value of severity indicators in NHAP versus CAP in elderly patients. Patients aged ≥65 years and hospitalized because of NHAP or CAP within the previous 3 years were enrolled. Demographics, coexisting illnesses, laboratory and microbiological findings, and severity scores (confusion, urea, respiratory rate, blood pressure, and age ≥65 [CURB-65] scale; age, dehydration, respiratory failure, orientation disturbance, and pressure [A-DROP] scale; and pneumonia severity index [PSI]) were retrieved from medical records. The primary outcome was mortality within 28 days of admission. In total, 138 NHAP and 307 CAP patients were enrolled. Mortality was higher in NHAP (18.1%) than in CAP (4.6%) (P<0.001). Patients with NHAP were older and had lower functional status and a higher rate of do-not-resuscitate orders, heart failure, and cerebrovascular diseases. The NHAP patients more frequently had typical bacterial pathogens. Using the receiver-operating characteristics curve for predicting mortality, the area under the curve in NHAP was 0.70 for the A-DROP scale, 0.69 for the CURB-65 scale, 0.67 for the PSI class, and 0.65 for the B/A ratio. The area under the curve in CAP was 0.73 for the A-DROP scale, 0.76 for the CURB-65 scale, 0.81 for the PSI class, and 0.83 for the B/A ratio. Patient mortality was greater in NHAP than in CAP. Patient characteristics, coexisting illnesses, and detected pathogens differed greatly between NHAP and CAP. The existing severity indicators had less prognostic value for NHAP than for CAP.

Comparison of the Performance Between Sepsis-1 and Sepsis-3 in ICUs in China: A Retrospective Multicenter Study.

PubMed

Cheng, Baoli; Li, Zhongwang; Wang, Jingya; Xie, Guohao; Liu, Xu; Xu, Zhipeng; Chu, Lihua; Zhao, Jialian; Yao, Yongming; Fang, Xiangming

2017-09-01

The definition of sepsis was updated to sepsis-3 in February 2016. However, the performance of the previous and new definition of sepsis remains unclear in China. This was a retrospective multicenter study in six intensive care unit (ICUs) from five university-affiliated hospitals to compare the performance between sepsis-1 and sepsis-3 in China. From May 1, 2016 to June 1, 2016, 496 patients were enrolled consecutively. Data were extracted from the electronic clinical records. We evaluated the performance of sepsis-1 and sepsis-3 by measuring the area under the receiver operating characteristic curves (AUROC) to predict 28-day mortality rates. Of 496 enrolled patients, 186 (37.5%) were diagnosed with sepsis according to sepsis-1, while 175 (35.3%) fulfilled the criteria of sepsis-3. The AUROC of systemic inflammatory response syndrome (SIRS) is significantly smaller than that of sequential organ failure assessment (SOFA) (0.55 [95% confidence interval, 0.46-0.64] vs. 0.69 (95% confidence interval, 0.61-0.77], P = 0.008) to predict 28-day mortality rates of infected patients. Moreover, 5.9% infected patients (11 patients) were diagnosed as sepsis according to sepsis-1 but not to sepsis-3. The APACHE II, SOFA scores, and mortality rate of the 11 patients were significantly lower than of patients whose sepsis was defined by both the previous and new criteria (8.6±3.5 vs. 16.3±6.2, P =  < 0.001; 1 (0-1) vs. 6 (4-8), P = <0.001; 0.0 vs. 33.1%, P = 0.019). In addition, the APACHE II, length of stay in ICU, and 28-day mortality rate of septic patients rose gradually corresponding with the raise in SOFA score (but not the SIRS score). Sepsis-3 performed better than sepsis-1 in the study samples in ICUs in China.

Involving American Indians and medically underserved rural populations in cancer clinical trials.

PubMed

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Fox Dunn, Emily; Patnaik, Asha

2009-12-01

To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7-11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69-75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4-7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3-16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5-17%). Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group.

Involving American Indians and medically underserved rural populations in cancer clinical trials

PubMed Central

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Dunn, Emily Fox; Patnaik, Asha

2010-01-01

Purpose To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. Methods We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Results Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7–11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69–75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4–7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3–16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5–17%). Limitations Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Conclusion Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group. PMID:19933720

Relationship Between Physicians' Active Participation in Maintenance of Certification and Patients' Perspective of Care Surveys.

PubMed

Morrell, Jessica; Stratman, Erik J

2016-06-01

Medical specialty boards have a Maintenance of Certification (MOC) paradigm whose intention is to ensure high-quality patient care. How the patient experience is affected by physician MOC enrollment/participation is unknown. Our goal was to determine if patient experience is associated with physician board certification and MOC status. We analyzed physician experience and MOC databases to determine the relationships among physicians' patient experience national percentile rankings and board certification status and MOC enrollment and activity status. Board-certified physicians enrolled in MOC did not have statistically significant different patient experience scores compared to board-certified physicians not enrolled in MOC. Mid-career physicians enrolled in MOC had patients more likely to recommend them and reported higher confidence in them. Patients did not perceive physicians participating in MOC patient safety modules as more cautious in providing patient care. Although most analyses did not demonstrate significant differences in patient experience scores for physicians actively participating in MOC compared to those not, some differences were noted. Higher provider-specific patient experience scores were noted, particularly for mid-career physicians.

A Patient Focused Solution for Enrolling Clinical Trials in Rare and Selective Cancer Indications: A Landscape of Haystacks and Needles

PubMed Central

Lynam, Eric B.; Leaw, Jiin; Wiener, Matthew B.

2013-01-01

Participation of adult cancer patients in US based clinical trials has remained near 3% for decades. Traditional research methodology reaches a small fraction of the target population with a fixed number of predetermined sites. Solutions are needed to ethically increase patient participation and accelerate cancer trial completion. We compared enrollment outcomes of traditional and patient focused research methodologies. A patient prioritized method (Just-In-Time, JIT) was implemented in parallel with traditionally managed sites in three cancer trials. JIT research sites were initiated after candidate patients presented, while traditional sites were initiated in advance. JIT sites enrolled with mean rates no less than, and up to 2.75 fold greater than, traditional sites. Mean patients enrolled per site was comparable (JIT-1.82, traditional-1.78). There were fewer non-enrolling JIT sites (2/28, 7%) compared to traditional sites 19/52, 37%). This retrospective analysis supports JIT as a prospective solution to increase cancer clinical trial enrollment and the efficiency of clinical trial administrative activities. PMID:23990689

Advanced Disease at Enrollment in HIV Care in Four Sub-Saharan African Countries: Change from 2006-2011 and Multi-Level Predictors in 2011

PubMed Central

Hoffman, Susie; Wu, Yingfeng; Lahuerta, Maria; Kulkarni, Sarah Gorrell; Nuwagaba-Biribonwoha, Harriet; Sadr, Wafaa El; Remien, Robert H.; Mugisha, Veronicah; Hawken, Mark; Chuva, Ema; Nash, Denis; Elul, Batya

2015-01-01

Objectives To examine changes between 2006 and 2011 in the proportion of HIV-positive patients newly-enrolled in HIV care with advanced disease and the median CD4+ cell count at enrollment; and identify patient-, facility-, and contextual-level factors associated with late enrollment in care in 2011. Design Cross sectional over time. Methods For time trends analyses, routinely-collected patient-level data (307,110 adults newly-enrolled in 138 HIV clinical care facilities) in Kenya, Mozambique, Rwanda and Tanzania; and for analyses of correlates, patient-level data (46,201 in 195 facilities), and facility- and population-level survey data were used. Late enrollment was defined as CD4+ count ≤350 cells/μl and/or WHO clinical stage 3/4. Results Late enrollment declined from 69.9% to 57.2%, (p<0.0001); median CD4+ count increased from 242 to 292 cells/μL (ptrend<0.0001). In 2011, risk of late enrollment was significantly higher for men and non-pregnant women vs. pregnant women; patients aged >25 vs. 15-25 years; non-married vs. married; and those entering from sites other than prevention of mother to child transmission (PMTCT). More extensive HIV testing coverage in the region of a facility was significantly associated with lower risk of late enrollment. Conclusions Despite improvement, in 2011, 57% of patients entered HIV care already ART-eligible. The lower risk of late enrollment among those referred from PMTCT and in regions where HIV testing coverage was higher suggests that innovative approaches to rapidly increase testing uptake among people living with HIV prior to the development of symptoms have the potential to reduce late enrollment in care. PMID:25136842

Multidrug-resistant Pulmonary Tuberculosis Among Young Korean Soldiers in a Communal Setting

PubMed Central

Lee, Sei Won; Kim, Kwang Hyun; Min, Kyung Hoon

2009-01-01

The goal of this study was to evaluate the prevalence of first-line anti-tuberculosis drug resistance and risk factors associated with multidrug-resistant tuberculosis (MDR TB) among young soldiers in the Korean military, which has a strict tuberculosis control program. All patients with culture-confirmed pulmonary tuberculosis during their service at the Armed Forces Capital Hospital from January 2001 to December 2006 were enrolled in the study. Drug resistant Mycobacterium tuberculosis was isolated from 18 patients (12.2%) and multidrug-resistant M. tuberculosis was isolated from 12 patients (8.1%). Previous treatment of tuberculosis and the presence of a cavity on the patient's chest computed tomography scan were associated with MDR TB; military rank, smoking habits, and positive acid-fast bacilli smears were not associated with MDR TB. In a multiple logistic regression analysis, previous treatment of tuberculosis was a significant independent risk factor for MDR TB (odds ratio 6.12, 95% confidence interval 1.53-24.46). The prevalence of drug resistant tuberculosis among young soldiers in the Korean military was moderately high and the majority of resistant cases were found in patients who had undergone previous treatment of tuberculosis. Based on our results, we suggest that relapsed tuberculosis cases within communal settings should be cautiously managed until the drug susceptibility tests report is completed, even if previous treatment results were satisfactory. PMID:19654938

Roster of Astronomy Departments with Enrollment and Degree Data, 2014: Results from the 2014 Survey of Enrollments and Degrees. Focus On

ERIC Educational Resources Information Center

Nicholson, Starr; Mulvey, Patrick J.

2015-01-01

Undergraduate astronomy enrollments in the US continue to rise with junior and senior level enrollments exceeding the previous year's all-time high. The increasing undergraduate enrollments have produced 428 bachelor's in the 2013-14 academic year, also an all-time high. Undergraduate astronomy degree production will continue to rise given the…

Higher Education Enrollment: Fall 1987 to Fall 1993. Targeted Forecast.

ERIC Educational Resources Information Center

National Center for Education Statistics (ED), Washington, DC.

Total higher education enrollment in fall 1989 is projected at 13.1 million, nearly 2% over the previous year. Full-time enrollment is expected to remain around 7.4 million, with part-time enrollment increasing from 5.5 million in 1988 to 5.7 million in 1989. Enrollment at public institutions will rise from 10.0 million in 1988 to 10.2 million in…

2015 Survey of Journalism and Mass Communication Enrollments: Challenges and Opportunities for a Changing and Diversifying Field

ERIC Educational Resources Information Center

Gotlieb, Melissa R.; McLaughlin, Bryan; Cummins, R. Glenn

2017-01-01

As with previous years, enrollments in journalism and mass communication programs in the United States have continued to decline. In 2015, such decline among undergraduate student enrollments was particularly prevalent in journalism sequences; in contrast, undergraduate enrollments in strategic communication sequences have seen some growth since…

HIV Model Parameter Estimates from Interruption Trial Data including Drug Efficacy and Reservoir Dynamics

PubMed Central

Luo, Rutao; Piovoso, Michael J.; Martinez-Picado, Javier; Zurakowski, Ryan

2012-01-01

Mathematical models based on ordinary differential equations (ODE) have had significant impact on understanding HIV disease dynamics and optimizing patient treatment. A model that characterizes the essential disease dynamics can be used for prediction only if the model parameters are identifiable from clinical data. Most previous parameter identification studies for HIV have used sparsely sampled data from the decay phase following the introduction of therapy. In this paper, model parameters are identified from frequently sampled viral-load data taken from ten patients enrolled in the previously published AutoVac HAART interruption study, providing between 69 and 114 viral load measurements from 3–5 phases of viral decay and rebound for each patient. This dataset is considerably larger than those used in previously published parameter estimation studies. Furthermore, the measurements come from two separate experimental conditions, which allows for the direct estimation of drug efficacy and reservoir contribution rates, two parameters that cannot be identified from decay-phase data alone. A Markov-Chain Monte-Carlo method is used to estimate the model parameter values, with initial estimates obtained using nonlinear least-squares methods. The posterior distributions of the parameter estimates are reported and compared for all patients. PMID:22815727

Addison's disease symptoms--a cross sectional study in urban South Africa.

PubMed

Ross, Ian Louis; Levitt, Naomi S

2013-01-01

Addison's disease is a potentially life-threatening disorder, and prompt diagnosis, and introduction of steroid replacement has resulted in near normal life-expectancy. There are limited data describing the clinical presentation of Addison's disease in South Africa. It is hypothesised that patients may present in advanced state of ill-health, compared to Western countries. A national database of patients was compiled from primary care, referral centres and private practices. 148 patients were enrolled (97 white, 34 mixed ancestry, 5 Asian and 12 black). Demographic and clinical data were elicited using questionnaires. Biochemical data were obtained from folder reviews and laboratory archived results. The majority of the cohort was women (62%). The median and inter-quartile age range (IQR) of patients at enrolment was 46.0 (32.0-61.0) years, with a wide range from 2.8-88.0 years. The median and IQR age at initial diagnosis was 34.0 (20.0-45.0) years (range 0.02-77.0) years, indicating that at the time of enrolment, the patients, on average, were diagnosed with Addison's disease 12 years previously. Hyperpigmentation was observed in 76%, nausea and vomiting occurred in more than 40%, and weight loss was noted in 25%. Loss of consciousness as a presenting feature was recorded in 20%. with a 95% confidence interval [CI] of (14-28%) and shock occurred in 5% CI (1.5-8.5%). Case-finding was recorded at 3.1 per million. The usual constellation of hyperpigmentation, nausea, vomiting and weight loss suggests Addison's disease, but a significant proportion present with an advanced state of ill-health and Addisonian crises. A lower prevalence rate, compared to Western countries is suggested.

Treatment compliance in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection treated with tobramycin inhalation powder: The FREE study.

PubMed

Blasi, Francesco; Carnovale, Vincenzo; Cimino, Giuseppe; Lucidi, Vincenzina; Salvatore, Donatello; Messore, Barbara; Bartezaghi, Marta; Muscianisi, Elisa; Porpiglia, Pasquale Alberto

2018-05-01

A high treatment burden with nebulised therapies in cystic fibrosis (CF) patients is the major limitation for treatment compliance; moreover, studies on treatment compliance with inhaled antibiotics are limited. This study assessed compliance to TOBI ® Podhaler™ (TIP) treatment in CF patients with chronic Pseudomonas aeruginosa (Pa) infections in a real-world setting using the Italian Treatment Adherence CF Questionnaire (ITA-CFq). This longitudinal, multicentre, cohort study included 2 follow-up (FU) visits: FU-1 at 3-months±15-days from the baseline visit and FU-2 at the end of third TIP cycle (or 6-months after enrolment, whichever occurred first). The effect of TIP on quality-of-life (QoL) and treatment satisfaction were evaluated using Cystic Fibrosis Questionnaire-Revised (CFQ-R) and Treatment Satisfaction Questionnaire for Medication (TSQM), respectively. Overall compliance to treatments was assessed using ITA-CFq. Eighty-two patients (mean age, 24.8 ± 7.9 years), including 22 paediatric patients (age, <18 years), were enrolled in the study; 56 (68.3%) patients, including 17 paediatric patients, completed the study. At baseline, the mean compliance score to aerosol antibiotic treatment was 7.8 ± 3.2; upon introducing TIP, the compliance score improved to 9.4 ± 1.2 at the FU-1 and thereafter remained stable at 9.5 ± 1.2. TSQM was higher for the convenience domain (74.2 ± 17.1 at enrolment and slightly improved to 77.8 ± 15.9 at FU-2) following TIP initiation. No substantial effect of TIP was observed on the QoL when measured using the revised CFQ-R. The safety profile was in line with previous findings. TIP was convenient to use and led to improved treatment adherence in CF patients with chronic Pa-infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Differences in melanoma outcomes among Hispanic Medicare enrollees.

PubMed

Rouhani, Panta; Arheart, Kristopher L; Kirsner, Robert S

2010-05-01

Hispanics are given the diagnosis of melanoma at later stages and have reduced survival. We sought to evaluate the effect of Hispanic ethnicity and different health care delivery systems (fee-for-service [FFS] and health maintenance organizations) on melanoma stage at diagnosis and survival. We studied a retrospective cohort of 40,633 patients, with at least 3 years of follow-up, who were given the diagnosis of incident melanoma from 1991 to 2002 and were 65 years or older using data from the Surveillance, Epidemiology, and End Results-Medicare linked database. The analytic sample consisted of 39,962 non-Hispanic whites (NHW) and 671 Hispanics. Logistic regression models examined the roles of the health care delivery system and race/ethnicity in stage at diagnosis and survival. For FFS patients, Hispanics were more likely to be given a diagnosis at an advanced stage (distant vs earlier stages [odds ratio {OR} = 2.07; 95% confidence interval CI = 1.36-3.16]; regional vs earlier stages [OR = 2.31; 95% CI = 1.75-3.03]) compared with NHW. Among Hispanic patients, those enrolled in health maintenance organizations were less likely to be given a diagnosis at later stage (regional vs earlier stages [OR = 0.50; 95% CI = 0.31-0.81]) than FFS patients; however, the earlier stage at diagnosis did not improve survival. For patients with a previous cancer before their melanoma diagnoses, NHW enrolled in health maintenance organizations from 1991 to 2002 were given a diagnosis at earlier stages compared with NHW FFS patients (OR = 0.72; 95% CI = 0.52-0.99); this was not found among Hispanics. These results reflect findings in a Medicare-aged population and it is not clear if they are generalizable to younger patients. Differences in melanoma outcomes among different ethnic groups are, in part, dependent on the health care setting in which patients are enrolled. Copyright 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Co-enrolment of Participants into Multiple Cancer Trials: Benefits and Challenges.

PubMed

Cafferty, F H; Coyle, C; Rowley, S; Berkman, L; MacKensie, M; Langley, R E

2017-07-01

Opportunities to enter patients into more than one clinical trial are not routinely considered in cancer research and experiences with co-enrolment are rarely reported. Potential benefits of allowing appropriate co-enrolment have been identified in other settings but there is a lack of evidence base or guidance to inform these decisions in oncology. Here, we discuss the benefits and challenges associated with co-enrolment based on experiences in the Add-Aspirin trial - a large, multicentre trial recruiting across a number of tumour types, where opportunities to co-enrol patients have been proactively explored and managed. The potential benefits of co-enrolment include: improving recruitment feasibility; increased opportunities for patients to participate in trials; and collection of robust data on combinations of interventions, which will ensure the ongoing relevance of individual trials and provide more cohesive evidence to guide the management of future patients. There are a number of perceived barriers to co-enrolment in terms of scientific, safety and ethical issues, which warrant consideration on a trial-by-trial basis. In many cases, any potential effect on the results of the trials will be negligible - limited by a number of factors, including the overlap in trial cohorts. Participant representatives stress the importance of autonomy to decide about trial enrolment, providing a compelling argument for offering co-enrolment where there are multiple trials that are relevant to a patient and no concerns regarding safety or the integrity of the trials. A number of measures are proposed for managing and monitoring co-enrolment. Ensuring acceptability to (potential) participants is paramount. Opportunities to enter patients into more than one cancer trial should be considered more routinely. Where planned and managed appropriately, co-enrolment can offer a number of benefits in terms of both scientific value and efficiency of study conduct, and will increase the opportunities for patients to participate in, and benefit from, clinical research. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Previous cerebrovascular disease is an important predictor of clinical outcomes in elderly patients with percutaneous coronary interventions: The Nobori-Biolimus eluting stent prospective multicenter 1-year observational registry in South Korea

PubMed Central

Kim, Yong Hoon; Her, Ae-Young; Kim, Byeong-Keuk; Shin, Dong-Ho; Kim, Jung-Sun; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo

2017-01-01

Objective: The appropriate selection of elderly patients for revascularization has become increasingly important because these subsets of patients are more likely to experience a major cardiac or cerebrovascular event—percutaneous coronary intervention (PCI). The objective of this study was to determine important independent risk factor for predicting clinical outcomes in the elderly patients after successful PCI, particularly in a series of South Korean population. Methods: This study is prospective, multicenter, observational cross-sectional study. A total of 1,884 consecutive patients who underwent successful PCI with Nobori® Biolimus A9-eluting stents were enrolled between April 2010 and December 2012. They were divided into two groups according to the age: patients <75 years old (younger patient group) and ≥75 years old (elderly patient group). The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE) at 1-year after index PCI. Results: The 1-year cumulative incidence of MACCE (12.9% vs. 4.3%, p<0.001) and total death (7.1% vs. 1.5%, p<0.001) was significantly higher in the elderly group than in younger group. Previous cerebrovascular disease was significantly correlated with MACCE in elderly patients 1-year after PCI (hazard ratio, 2.804; 95% confidence interval, 1.290–6.093 p=0.009). Conclusion: Previous cerebrovascular disease is important independent predictor of the MACCE in elderly patients at 1-year after PCI with Nobori® Biolimus A9-eluting stents especially in a series of South Korean population. Therefore, careful PCI with intensive monitoring and management can improve major clinical outcomes after successful PCI in elderly patients with previous cerebrovascular disease compared with younger patients. PMID:28554989

Parkinson's Patients with Dyskinesia Switched from Immediate Release Amantadine to Open‐label ADS‐5102

PubMed Central

Fahn, Stanley; Pahwa, Rajesh; Tanner, Caroline M.; Espay, Alberto J.; Trenkwalder, Claudia; Adler, Charles H.; Patni, Rajiv; Johnson, Reed

2018-01-01

Abstract Background ADS‐5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS‐5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility. Methods In an ongoing, open‐label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS‐5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years. Study outcomes included safety and assessment of motor complications, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part IV. This manuscript focuses on those patients switched to ADS‐5102 from amantadine IR. Results in two groups of patients who previously completed a randomized controlled trial (EASE LID or EASE LID 3) are also presented according to use of ADS‐5102 or placebo in that study before enrollment in the open‐label study. Results Change in MDS‐UPDRS Part IV at week 8 was –0.3 in the previous ADS‐5102 subgroup (n = 61), –3.4 in the previous placebo subgroup (n = 79), and –3.4 in the previous amantadine IR subgroup (n = 32). Effects were maintained to week 64. In the previous amantadine IR subgroup (mean treatment duration, 2.5 years), mean amantadine IR dose was 221 mg. Safety data were consistent with previous randomized controlled trials of ADS‐5102. Conclusion These open‐label data suggest ADS‐5102 provides incremental reduction from baseline in MDS‐UDPRS Part IV score in patients switched directly from amantadine IR, without exacerbating adverse events.

Engineering Enrollments, Fall 1986.

ERIC Educational Resources Information Center

Ellis, Richard A.

1987-01-01

Reports on the results of the Engineering Manpower Commission's 1986 survey of engineering enrollments, comparing them to the previous ten years of surveys. Provides tables of fall 1986 engineering enrollments categorized by curriculum, women, minorities, foreign nationals, schools, and by all students. (TW)

Time to Initiation of Antiretroviral Therapy Among Patients Who Are ART Eligible in Rwanda: Improvement Over Time

PubMed Central

Teasdale, Chloe A.; Wang, Chunhui; Francois, Uwinkindi; d’Amour Ndahimana, Jean; Vincent, Mutabazi; Sahabo, Ruben; El-Sadr, Wafaa M.; Abrams, Elaine J.

2016-01-01

Background Delayed initiation of antiretroviral therapy (ART) in eligible patients is a concern in resource-limited countries. Methods We analyzed data on HIV-positive patients ≥15 years enrolled at 41 ICAP-supported health care facilities in Rwanda, 2005–2010, to determine time to ART initiation among patients eligible at enrollment compared with those ineligible or of indeterminate eligibility who become eligible during follow-up. ART eligibility was based on CD4+ cell count (CD4+) and WHO staging; patients lacking CD4+ and WHO stage were considered indeterminate. Cumulative incidence of reaching ART eligibility and to ART initiation after eligibility was generated using competing risk estimators. Results A total of 31,033 ART-naive adults were enrolled; 64.2% were female. At enrollment, 10,158 (32.7%) patients were ART eligible, 13,372 (43.1%) were ineligible for ART, and 7503 (24.2%) patients were indeterminate. Among patients retained in care pre-ART eligibility, 17.9% [95% confidence interval (CI): 17.2 to 18.6] of ineligible and 22.8% (95% CI: 21.7 to 23.8) of indeterminate patients at enrollment reached ART eligibility within 12 months. Cumulative incidence of ART initiation within 3 months for patients eligible at enrollment was 77.2% (95% CI: 76.4 to 78.0) compared with 67.9% (95% CI: 66.4 to 69.3) for ineligible and 63.8% (95% CI: 61.9 to 65.8) for patients with indeterminate eligibility at enrollment (P < 0.05). Over the study period, there was more rapid ART initiation for patients who became ART eligible. Conclusions We found higher rates of ART initiation within 3 months among patients who were ART eligible at enrollment compared with those who reached eligibility during follow-up. From 2006 to 2011, earlier initiation of ART after eligibility was observed likely reflecting improved program quality. PMID:25415291

Visual outcomes in treated bacterial keratitis: four years of prospective follow-up.

PubMed

McClintic, Scott M; Prajna, Namperumalsamy V; Srinivasan, Muthiah; Mascarenhas, Jeena; Lalitha, Prajna; Rajaraman, Revathi; Oldenburg, Catherine E; O'Brien, Kieran S; Ray, Kathryn J; Acharya, Nisha R; Lietman, Thomas M; Keenan, Jeremy D

2014-05-02

We described the change in visual acuity experienced by eyes successfully treated for bacterial keratitis. This was a prospective cohort study of a subset of study participants who had previously enrolled in the Steroids for Corneal Ulcers Trial (SCUT). All study participants had been diagnosed with culture-proven bacterial keratitis before enrollment in SCUT and subsequently were randomized to adjunctive topical corticosteroids or placebo. During SCUT, we monitored study participants at enrollment, 3 weeks, 3 months, and 12 months. We invited a subset to complete a comprehensive eye examination approximately 4 years after enrollment in SCUT. Certified refractionists assessed best spectacle-corrected visual acuity (BSCVA) using the same protocol at each study visit. We examined 50 SCUT participants at 4 years after enrollment. Among those in this cohort, mean logMAR BSCVA at enrollment was 0.85 (Snellen equivalent, 20/160; 95% confidence interval [CI], 0.71-0.99). On average, visual acuity improved by 2.9 logMAR lines from enrollment to 3 weeks (P < 0.001), 1.2 lines from 3 weeks to 3 months (P = 0.002), and 0.8 lines from 3 to 12 months (P = 0.01). The BSCVA did not change significantly between 12 months and 4 years (0.04-line improvement, P = 0.88). After controlling for visual acuity at enrollment, BSCVA was not significantly different between the corticosteroid and placebo groups at 4 years (P = 0.53). Cases of bacterial keratitis may continue to demonstrate improvements in visual acuity up to 12 months following diagnosis, but further improvements are unlikely. These findings may guide the appropriate timing of surgical intervention in these patients. (ClinicalTrials.gov number, NCT00324168.).

Visual Outcomes in Treated Bacterial Keratitis: Four Years of Prospective Follow-up

PubMed Central

McClintic, Scott M.; Prajna, Namperumalsamy V.; Srinivasan, Muthiah; Mascarenhas, Jeena; Lalitha, Prajna; Rajaraman, Revathi; Oldenburg, Catherine E.; O'Brien, Kieran S.; Ray, Kathryn J.; Acharya, Nisha R.; Lietman, Thomas M.; Keenan, Jeremy D.

2014-01-01

Purpose. We described the change in visual acuity experienced by eyes successfully treated for bacterial keratitis. Methods. This was a prospective cohort study of a subset of study participants who had previously enrolled in the Steroids for Corneal Ulcers Trial (SCUT). All study participants had been diagnosed with culture-proven bacterial keratitis before enrollment in SCUT and subsequently were randomized to adjunctive topical corticosteroids or placebo. During SCUT, we monitored study participants at enrollment, 3 weeks, 3 months, and 12 months. We invited a subset to complete a comprehensive eye examination approximately 4 years after enrollment in SCUT. Certified refractionists assessed best spectacle-corrected visual acuity (BSCVA) using the same protocol at each study visit. Results. We examined 50 SCUT participants at 4 years after enrollment. Among those in this cohort, mean logMAR BSCVA at enrollment was 0.85 (Snellen equivalent, 20/160; 95% confidence interval [CI], 0.71–0.99). On average, visual acuity improved by 2.9 logMAR lines from enrollment to 3 weeks (P < 0.001), 1.2 lines from 3 weeks to 3 months (P = 0.002), and 0.8 lines from 3 to 12 months (P = 0.01). The BSCVA did not change significantly between 12 months and 4 years (0.04-line improvement, P = 0.88). After controlling for visual acuity at enrollment, BSCVA was not significantly different between the corticosteroid and placebo groups at 4 years (P = 0.53). Conclusions. Cases of bacterial keratitis may continue to demonstrate improvements in visual acuity up to 12 months following diagnosis, but further improvements are unlikely. These findings may guide the appropriate timing of surgical intervention in these patients. (ClinicalTrials.gov number, NCT00324168.) PMID:24618327

QualiCOP: real-world effectiveness, tolerability, and quality of life in patients with relapsing-remitting multiple sclerosis treated with glatiramer acetate, treatment-naïve patients, and previously treated patients.

PubMed

Ziemssen, Tjalf; Calabrese, Pasquale; Penner, Iris-Katharina; Apfel, Rainer

2016-04-01

Treatment of symptoms and signs beyond the expanded disability status scale remains a major target in multiple sclerosis. QualiCOP was an observational, non-interventional, open-label study conducted at 170 sites in Germany. Of the 754 enrolled patients, 96 % had relapsing-remitting multiple sclerosis (MS) and were either disease-modifying therapy naïve (de novo, n = 481) or previously treated (n = 237) with once-daily, subcutaneous 20-mg/mL glatiramer acetate (GA). Assessments of relapse rate, disease progression, overall functioning, quality of life (QoL), cognition, fatigue, and depression were performed over 24 months. GA treatment over 24 months was associated with reduced annual relapse rate for previously treated (from 0.98 to 0.54 relapses) and de novo (from 0.81 to 0.48 relapses) patients. Multiple Sclerosis Functional Composite scores showed slight improvement in both cohorts (all p < 0.01). Paced Auditory Serial Addition Test and Multiple Sclerosis Inventory Cognition scale scores showed robust improvement in cognition among previously treated and de novo cohorts (all p < 0.001). General Depression Scale scores showed significantly reduced depressive symptoms (p < 0.001). Disease severity, fatigue, and QoL were stable over the observational period. These real-world findings suggest that patients with MS show benefit from GA treatment in important QoL parameters beyond standard measures of relapse and disease severity.

Long-term healthcare costs and functional outcomes associated with lack of remission in schizophrenia: a post-hoc analysis of a prospective observational study

PubMed Central

2012-01-01

Background Little is known about the long-term outcomes for patients with schizophrenia who fail to achieve symptomatic remission. This post-hoc analysis of a 3-year study compared the costs of mental health services and functional outcomes between individuals with schizophrenia who met or did not meet cross-sectional symptom remission at study enrollment. Methods This post-hoc analysis used data from a large, 3-year prospective, non-interventional observational study of individuals treated for schizophrenia in the United States conducted between July 1997 and September 2003. At study enrollment, individuals were classified as non-remitted or remitted using the Schizophrenia Working Group Definition of symptom remission (8 core symptoms rated as mild or less). Mental health service use was measured using medical records. Costs were based on the sites’ medical information systems. Functional outcomes were measured with multiple patient-reported measures and the clinician-rated Quality of Life Scale (QLS). Symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Outcomes for non-remitted and remitted patients were compared over time using mixed effects models for repeated measures or generalized estimating equations after adjusting for multiple baseline characteristics. Results At enrollment, most of the 2,284 study participants (76.1%) did not meet remission criteria. Non-remitted patients had significantly higher PANSS total scores at baseline, a lower likelihood of being Caucasian, a higher likelihood of hospitalization in the previous year, and a greater likelihood of a substance use diagnosis (all p < 0.05). Total mental health costs were significantly higher for non-remitted patients over the 3-year study (p = 0.008). Non-remitted patients were significantly more likely to be victims of crime, exhibit violent behavior, require emergency services, and lack paid employment during the 3-year study (all p < 0.05). Non-remitted patients also had significantly lower scores on the QLS, SF-12 Mental Component Summary Score, and Global Assessment of Functioning during the 3-year study. Conclusions In this post-hoc analysis of a 3-year prospective observational study, the failure to achieve symptomatic remission at enrollment was associated with higher subsequent healthcare costs and worse functional outcomes. Further examination of outcomes for schizophrenia patients who fail to achieve remission at initial assessment by their subsequent clinical status is warranted. PMID:23216976

Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma.

PubMed

Lowery, Maeve A; Kelsen, David P; Capanu, Marinela; Smith, Sloane C; Lee, Jonathan W; Stadler, Zsofia K; Moore, Malcolm J; Kindler, Hedy L; Golan, Talia; Segal, Amiel; Maynard, Hannah; Hollywood, Ellen; Moynahan, MaryEllen; Salo-Mullen, Erin E; Do, Richard Kinh Gian; Chen, Alice P; Yu, Kenneth H; Tang, Laura H; O'Reilly, Eileen M

2018-01-01

BRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC). Patients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1-2 lines of treatment, Eastern Cooperative Oncology Group 0-2, were enrolled. Veliparib was dosed at a volume of 300 mg twice-daily (N = 3), then 400 mg twice-daily (N = 15) days 1-28. The primary end-point was to determine the response rate of veliparib; secondary end-points included progression-free survival (PFS), duration of response, overall survival (OS) and safety. Sixteen patients were enrolled; male N = 8 (50%). Median age was 52 years (range 43-77). Five (31%) had a BRCA1 and 11 (69%) had a BRCA2 mutation. Fourteen (88%) patients had received prior platinum-based therapy. No confirmed partial responses (PRs) were seen: one (6%) unconfirmed PR was observed at 4 months with disease progression (PD) at 6 months; four (25%) had stable disease (SD), whereas 11 (69%) had PD as best response including one with clinical PD. Median PFS was 1.7 months (95% confidence interval [CI] 1.57-1.83) and median OS was 3.1 months (95% CI 1.9-4.1). Six (38%) patients had grade III toxicity, including fatigue (N = 3), haematology (N = 2) and nausea (N = 1). Veliparib was well tolerated, but no confirmed response was observed although four (25%) patients remained on study with SD for ≥ 4 months. Additional strategies in this population are needed, and ongoing trials are evaluating PARPis combined with chemotherapy (NCT01585805) and as a maintenance strategy (NCT02184195). Copyright © 2017 Elsevier Ltd. All rights reserved.

Baseline Characteristics and Prescription Patterns of Standard Drugs in Patients with Angiographically Determined Coronary Artery Disease and Renal Failure (CAD-REF Registry)

PubMed Central

Reinecke, Holger; Breithardt, Günter; Engelbertz, Christiane; Schmieder, Roland E.; Fobker, Manfred; Pinnschmidt, Hans O.; Schmitz, Boris; Bruland, Philipp; Wegscheider, Karl; Pavenstädt, Hermann; Brand, Eva

2016-01-01

Background Chronic kidney disease (CKD) is strongly associated with coronary artery disease (CAD). We established a prospective observational nationwide multicenter registry to evaluate current treatment and outcomes in patients with both CKD and angiographically documented CAD. Methods In 32 cardiological centers 3,352 CAD patients with ≥50% stenosis in at least one coronary artery were enrolled and classified according to their estimated glomerular filtration rate and proteinuria into one of five stages of CKD or as a control group. Results 2,723 (81.2%) consecutively enrolled patients suffered from CKD. Compared to controls, CKD patients had a higher prevalence of diabetes, hypertension, peripheral artery diseases, heart failure, and valvular heart disease (each p<0.001). Myocardial infarctions (p = 0.02), coronary bypass grafting, valve replacements and pacemaker implantations had been recorded more frequently (each p<0.001). With advanced CKD, the number of diseased coronary vessels and the proportion of patients with reduced left ventricular ejection fraction (LVEF) increased significantly (both p<0.001). Percutaneous coronary interventions were performed less frequently (p<0.001) while coronary bypass grafting was recommended more often (p = 0.04) with advanced CKD. With regard to standard drugs in CAD treatment, prescriptions were higher in our registry than in previous reports, but beta-blockers (p = 0.008), and angiotensin-converting-enzyme inhibitors and/or angiotensin-receptor blockers (p<0.001) were given less often in higher CKD stages. In contrast, in the subgroup of patients with moderately to severely reduced LVEF the prescription rates did not differ between CKD stages. In-hospital mortality increased stepwise with each CKD stage (p = 0.02). Conclusions In line with other studies comprising CKD cohorts, patients’ morbidity and in-hospital mortality increased with the degree of renal impairment. Although cardiologists’ drug prescription rates in CAD-REF were higher than in previous studies, they were still lower especially in advanced CKD stages compared to cohorts treated by nephrologists. PMID:26859890

Management of patients with placenta accreta in association with fever following vaginal delivery

PubMed Central

Zhong, Liuying; Chen, Dunjin; Zhong, Mei; He, Yutian; Su, Chunhong

2017-01-01

Abstract This study aims to analyze the clinical characteristics and to manage patients with retained placenta left in situ accompanied by fever following vaginal delivery. Twenty-one patients with retained placenta in association with fever following vaginal delivery were enrolled and managed at the maternity department of our university hospital between 2012 and 2014. All patients had risk factors for development of placenta accreta: previous cesarean sections (4/21), previous curettage (15/21), or uterine malformations (7/21). Placenta accreta was diagnosed following vaginal delivery in all patients, and manual removal of the placenta was attempted in 20 of 21 patients. The placenta left in situ was partial in 19 patients and was complete in 2 patients. All patients were managed with a multidisciplinary approach. Mifepristone was administrated to 16 patients. Fourteen patients received uterine artery embolization. Eleven patients were treated with ultrasound-guided curettage within 24 hours following delivery. Seven patients needed delayed-hysterectomy due to development of complications. Intrauterine operations during labor are not recommended if placenta accreta occurs in the fundus and/or in the cornual region of the uterus. Antibiotic treatment, interventional therapy, and ultrasound-guided curettage within 24 hours following vaginal delivery are the recommended conservative management strategies. PMID:28272244

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy

PubMed Central

Choi, Michael; Furman, Richard R.; Eradat, Herbert; Heffner, Leonard; Jones, Jeffrey A.; Chyla, Brenda; Zhou, Lang; Agarwal, Suresh; Waskiewicz, Tina; Verdugo, Maria; Humerickhouse, Rod A.; Potluri, Jalaja; Wierda, William G.; Davids, Matthew S.

2018-01-01

B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282. PMID:29305552

Dyadic recruitment in complementary therapy studies: experience from a clinical trial of caregiver-delivered reflexology.

PubMed

Holmstrom, Amanda J; Wyatt, Gwen K; Sikorskii, Alla; Musatics, Catherine; Stolz, Emily; Havener, Neala

2016-02-01

As home-based care continues to be a growing trend in health care, involvement of friend and family caregivers in the management of illness becomes essential. However, before nurses can prepare caregivers to engage in various types of care, an evidence base needs to be established via randomized controlled trials (RCTs). Research suggests that recruiting cancer patients and their friend or family caregivers into RCTs presents challenges. The purpose of this paper is to illustrate the barriers to recruitment of patient-caregiver dyads into a RCT of caregiver-delivered reflexology and to recommend strategies to address such barriers. This paper reports on a nurse-directed RCT that involved recruitment efforts unique to a caregiver-delivered reflexology protocol for advanced-stage breast cancer patients. Ineligibility due to caregiver-related reasons, consent among eligible patients (out of 551 approached patients), and reasons for refusal were analyzed. Almost one-third of patients were found to be ineligible due to the lack of a caregiver to participate with them and provide this form of social support. Among eligible patients, the consent rate for this dyadic study is much lower than that of previous RCTs of reflexologist-delivered reflexology that enrolled just patients, not dyads. Implications for nursing practice and research include addressing the need for greater social support for patients and strategies for problem-solving refusal reasons during study enrollment. Copyright © 2015 Elsevier Inc. All rights reserved.

The potential for integrated care programmes to improve quality of care as assessed by patients with COPD: early results from a real-world implementation study in The Netherlands

PubMed Central

Cramm, Jane Murray; Rutten-Van Mölken, Maureen PMH; Nieboer, Anna Petra

2012-01-01

Objective We investigated whether patients with chronic obstructive pulmonary disease (COPD) who were enrolled in disease-management programmes (DMPs) felt that they received a better quality of care than non-enrolled COPD patients. Methods Our cross-sectional study was performed among patients (n=665) enrolled in four DMPs in the Netherlands. We also evaluated COPD patients (n=227) not enrolled in such programmes. Patients’ assessment of chronic-illness care (PACIC) was measured with a 20-item questionnaire. The instrument had five pre-defined domains: patient activation (three items), delivery-system/practice design (three items), goal setting/tailoring (five items), problem solving/contextual (four items), and follow-up/coordination (five items). Results The mean overall PACIC score (scale: 1–5) of enrolled DMP patients was 2.94, and that of non-enrolled DMP patients was 2.73 (p≤0.01). Differences in the same direction were found in the subscales of patient activation (p≤0.01), delivery-system/practice design (p≤0.001), and problem solving/contextual (p≤0.001). Conclusions Our results suggest that even in the early stages of implementation, DMPs for COPD may significantly improve care. PMID:23593052

Washington Community Colleges Factbook. Addendum A: Student Enrollments, Academic Year 1977-78.

ERIC Educational Resources Information Center

Meier, Terre; Story, Sherie

In order to reveal trends in community college enrollments in Washington, student demographic and enrollment data for academic year 1977-78 were compiled and compared with figures for previous years. The report provides annualized averages for full-time equivalent (FTE) enrollments for the system for the years 1967 to 1977, and for FTE students by…

Washington Community College Factbook Addendum A: Student Enrollments, Academic Year 1978-79.

ERIC Educational Resources Information Center

Meier, Terre

In order to reveal trends in community college enrollments in Washington, student demographic and enrollment data for academic year 1978-79 were compiled and compared with figures for previous years. The study report provides annualized averages for full-time equivalent (FTE) enrollments for the years 1968-69 to 1978-79 and quarterly and…

Management of Radiation-induced Severe Anophthalmic Socket Contracture in Patients with Uveal Melanoma

PubMed Central

Nasser, Qasiem J.; Gombos, Dan S.; Williams, Michelle D.; Guadagnolo, B. Ashleigh; Morrison, William H.; Garden, Adam S.; Beadle, Beth M.; Canseco, Elvia; Esmaeli, Bita

2012-01-01

Purpose High-dose radiotherapy can cause contracture of the anophthalmic socket, but the incidence of this complication in patients with enucleation for uveal melanoma has not previously been reported. We reviewed the surgical management and outcomes in terms of successful prosthesis wear in patients with severe contracture of the anophthalmic socket treated with high-dose radiotherapy for high-risk uveal melanoma and estimated the relative risk of this complication. Methods The medical records of all consecutive patients enrolled in a prospective uveal-melanoma tissue-banking protocol at our institution who underwent enucleation between January 2003 and December 2010 were reviewed. Patients who underwent adjuvant radiotherapy of the enucleated socket were further studied. Results Of the 68 patients enrolled in the prospective tissue banking protocol, 12 had high-risk histologic features (e.g., extrascleral spread or vortex vein invasion) and were treated with 60 Gy of external-beam radiotherapy after enucleation. Five of these patients (41.7%) experienced severe socket contracture precluding prosthesis wear. The median time to onset of contracture following completion of radiotherapy was 20 months. Three patients underwent surgery, which entailed scar tissue release, oral mucous membrane grafting, and socket reconstruction; 2 patients declined surgery. All 3 patients who had surgery experienced significant improvement of socket contracture that enabled patients to wear a prosthesis again. Conclusion High-dose radiotherapy after enucleation in patients with uveal melanoma caused severe socket contracture and inability to wear a prosthesis in approximately 40% of patients. Surgical repair of the contracted socket using oral mucous membrane grafting can allow resumption of prosthesis wear. PMID:22581085

Comparison of salt taste thresholds and salt usage behaviours between adults in Myanmar and Korea.

PubMed

Cho, Hyungjin; Kim, So Mi; Jeong, Seong Su; Kim, Soon Bae

2016-12-01

Excessive oral salt intake can induce hypertension. According to previous studies, the prevalence of hypertension is higher in Myanmar than in Korea. We postulated that Myanmar adults had higher salt taste thresholds and eat much saltier food. This study aimed to compare salt taste thresholds and salt usage behaviour scores between adults in Myanmar and Korea. This cross-sectional study enrolled patients who visited volunteer medical service clinics at Ansung in Korea and Hlegu and Bago in Myanmar in August 2014. We measured the vital signs, heights, and weights of each patient and evaluated detection thresholds, recognition thresholds, and salt preferences. All patients underwent urinalysis and spot urine Na tests. Additionally, they each completed a salt usage behaviour questionnaire. A total of 131 patients were enrolled, including 64 Myanmarese patients and 67 Korean patients. Blood pressure was significantly higher in the Myanmarese than in the Koreans. Detection and recognition thresholds, salt preferences, and spot urine sodium and salt usage behaviour scores were also higher in the Myanmarese than in the Korean subjects. We calculated correlation coefficients between systolic blood pressure and parameters that were related to salt intake. The detection and recognition thresholds were significantly correlated with systolic blood pressure. All parameters related to salt intake, including detection and recognition thresholds, salt preference, salt usage behaviour scores and spot urine sodium concentrations, are significantly higher in Myanmarese than in Korean individuals.

Real-life safety and efficacy of vildagliptin as add-on to metformin in patients with type 2 diabetes in Turkey--GALATA study.

PubMed

Ayvaz, Goksun; Keskin, Lezzan; Akin, Fulya; Dokmetas, Hatice Sebile; Tasan, Ertugrul; Ar, Idilhan Baloglu; Uren, Emel

2015-04-01

To evaluate tolerability/safety and the efficacy of the combination of vildagliptin plus metformin in a real-life population of patients with type 2 diabetes mellitus (T2DM). This multicenter, single-arm, 6 month, observational, prospective cohort study was conducted at 39 centers across Turkey. T2DM patients on vildagliptin and metformin for ≤4 weeks were enrolled regardless of their previous antidiabetic therapy. Efficacy was evaluated by measuring hemoglobin A1c (HbA1c) levels. Tolerability/safety parameters evaluated included hypoglycemic events, gastrointestinal events, peripheral edema and weight gain. This study enrolled 665 patients with a mean ± standard deviation (SD) age of 55.1 ± 10.2 years and female predominance (n = 394, 59.2%). Safety was assessed in all enrolled patients. Hypoglycemia was reported in 10 (1.5%) patients (95% confidence interval = 0.8-2.7%). Efficacy was assessed in 289 (43.5%) patients treated for 6 ± 1 months; these patients showed a mean decrease in HbA1c of 0.8% from baseline value of 7.8% (p < 0.001). The percentages of patients who achieved HbA1c targets of ≤6.5% and ≤7.0% were significantly increased, from 10.7% to 33.6% and from 22.1% to 52.6%, respectively (p < 0.001 each). The decrease in HbA1c was independent of baseline HbA1c (≤8% vs. 8-10% vs. ≥10%), age (≤65 vs. >65 years) and body mass index (<30 vs. ≥30 kg/m(2)) (p < 0.001 each). In total, 136 adverse events (AEs) were observed in 71 (10.7%) patients; 10 (1.5%) patients experienced hypoglycemia and gastrointestinal AEs were most commonly reported (n = 29, 4.4%). In a 'real-life' setting, the vildagliptin and metformin combination was associated with significant improvements in reaching target HbA1c levels, even in elderly and obese patients with T2DM. Moreover, vildagliptin and metformin demonstrated a good overall tolerability/safety profile.

Incidence of syphilis seroconversion among HIV-infected persons in Asia: results from the TREAT Asia HIV Observational Database

PubMed Central

Ahn, Jin Young; Boettiger, David; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Huy, Bui Vu; Wong, Wing Wai; Ditangco, Rossana; Lee, Man Po; Oka, Shinichi; Durier, Nicolas; Choi, Jun Yong

2016-01-01

Introduction Outbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries. Methods Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non-treponemal test after previously testing negative, was evaluated among patients at sites performing non-treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non-treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis. Results We included 1010 patients from five sites that performed non-treponemal tests in all new patients; those included had negative non-treponemal test results during enrolment and subsequent follow-ups. Among them, 657 patients were from three sites conducting regular non-treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person-years (PY). Incidence was higher in MSM than non-MSM (7.64/100 PY vs. 2.44/100 PY, p<0.001). Among MSM, the incidence rate ratio (IRR) for every additional year from 2009 was 1.19 (p=0.051). MSM status (IRR 3.48, 95% confidence interval (CI) 1.88–6.47), past syphilis diagnosis (IRR 5.15, 95% CI 3.69–7.17) and younger age (IRR 0.84 for every additional 10 years, 95% CI 0.706–0.997) were significantly associated with syphilis seroconversion. Conclusions We observed a higher incidence of syphilis seroconversion among HIV-infected MSM and a trend to increasing annual incidence. Regular screening for syphilis and targeted interventions to limit transmission are needed in this population. PMID:27774955

Incidence of syphilis seroconversion among HIV-infected persons in Asia: results from the TREAT Asia HIV Observational Database.

PubMed

Ahn, Jin Young; Boettiger, David; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Huy, Bui Vu; Wong, Wing Wai; Ditangco, Rossana; Lee, Man Po; Oka, Shinichi; Durier, Nicolas; Choi, Jun Yong

2016-01-01

Outbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries. Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non-treponemal test after previously testing negative, was evaluated among patients at sites performing non-treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non-treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis. We included 1010 patients from five sites that performed non-treponemal tests in all new patients; those included had negative non-treponemal test results during enrolment and subsequent follow-ups. Among them, 657 patients were from three sites conducting regular non-treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person-years (PY). Incidence was higher in MSM than non-MSM (7.64/100 PY vs. 2.44/100 PY, p< 0.001). Among MSM, the incidence rate ratio (IRR) for every additional year from 2009 was 1.19 ( p= 0.051). MSM status (IRR 3.48, 95% confidence interval (CI) 1.88-6.47), past syphilis diagnosis (IRR 5.15, 95% CI 3.69-7.17) and younger age (IRR 0.84 for every additional 10 years, 95% CI 0.706-0.997) were significantly associated with syphilis seroconversion. We observed a higher incidence of syphilis seroconversion among HIV-infected MSM and a trend to increasing annual incidence. Regular screening for syphilis and targeted interventions to limit transmission are needed in this population.

Enrollments in Schools and Colleges of Pharmacy, 1986-1987.

ERIC Educational Resources Information Center

Penna, Richard P.; Sherman, Michael S.

1987-01-01

National survey data on pharmaceutical education enrollment rates and trends at all degree levels include information on full- and part-time enrollments, student gender and ethnic characteristics, patterns of specialization, sources of previous degrees, student country of origin, and fellowships. (MSE)

Post-relapse survival in patients with Ewing sarcoma.

PubMed

Ferrari, Stefano; Luksch, Roberto; Hall, Kirsten Sundby; Fagioli, Franca; Prete, Arcangelo; Tamburini, Angela; Tienghi, Amelia; DiGirolamo, Stefania; Paioli, Anna; Abate, Massimo Eraldo; Podda, Marta; Cammelli, Silvia; Eriksson, Mikael; Brach del Prever, Adalberto

2015-06-01

Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients. EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT. Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS. Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT. © 2015 Wiley Periodicals, Inc.

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

PubMed

Besser, Michal J; Shapira-Frommer, Ronnie; Treves, Avraham J; Zippel, Dov; Itzhaki, Orit; Schallmach, Ester; Kubi, Adva; Shalmon, Bruria; Hardan, Izhar; Catane, Raphael; Segal, Eran; Markel, Gal; Apter, Sara; Nun, Alon Ben; Kuchuk, Iryna; Shimoni, Avichai; Nagler, Arnon; Schachter, Jacob

2009-05-01

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges.

PubMed

Spiegel, Marshall L; Goldman, Jonathan W; Wolf, Brian R; Nameth, Danielle J; Grogan, Tristan R; Lisberg, Aaron E; Wong, Deborah J L; Ledezma, Blanca A; Mendenhall, Melody A; Genshaft, Scott J; Gutierrez, Antonio J; Abtin, Fereidoun; Wallace, W Dean; Adame, Carlos R; McKenzie, Jordan R; Abarca, Phillip A; Li, Alice J; Strunck, Jennifer L; Famenini, Sina; Carroll, James M; Tucker, D Andrew; Sauer, Lauren M; Moghadam, Nima M; Elashoff, David A; Abaya, Christina D; Brennan, Meghan B; Garon, Edward B

2017-12-15

Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated. The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800-7. © 2017 American Cancer Society. © 2017 American Cancer Society.

Cross-cultural comparisons of attitudes toward schizophrenia amongst the general population and physicians: a series of web-based surveys in Japan and the United States.

PubMed

Richards, Misty; Hori, Hiroaki; Sartorius, Norman; Kunugi, Hiroshi

2014-02-28

Cross-cultural differences in attitudes toward schizophrenia are suggested, while no studies have compared such attitudes between the United States and Japan. In our previous study in Japan (Hori et al., 2011), 197 subjects in the general population and 112 physicians (excluding psychiatrists) enrolled in a web-based survey using an Internet-based questionnaire format. Utilizing the identical web-based survey method in the United States, the present study enrolled 172 subjects in the general population and 45 physicians. Participants' attitudes toward schizophrenia were assessed with the English version of the 18-item questionnaire used in our previous Japanese survey. Using exploratory factor analysis, we identified four factors labeled "social distance," "belief of dangerousness," "underestimation of patients' abilities," and "skepticism regarding treatment." The two-way multivariate analysis of covariance on the four factors, with country and occupation as the between-subject factors and with potentially confounding demographic variables as the covariates, revealed that the general population in the US scored significantly lower than the Japanese counterparts on the factors "social distance" and "skepticism regarding treatment" and higher on "underestimation of patients' abilities." Our results suggest that culture may have an important role in shaping attitudes toward mental illness. Anti-stigma campaigns that target culture-specific biases are considered important. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Implementation and Operational Research: Affordable Care Act Implementation in a California Health Care System Leads to Growth in HIV-Positive Patient Enrollment and Changes in Patient Characteristics.

PubMed

Satre, Derek D; Altschuler, Andrea; Parthasarathy, Sujaya; Silverberg, Michael J; Volberding, Paul; Campbell, Cynthia I

2016-12-15

This study examined implementation of the Affordable Care Act (ACA) in relation to HIV-positive patient enrollment in an integrated health care system; as well as changes in new enrollee characteristics, benefit structure, and health care utilization after key ACA provisions went into effect in 2014. This mixed-methods study was set in Kaiser Permanente Northern California (KPNC). Qualitative interviews with 29 KPNC leaders explored planning for ACA implementation. Quantitative analyses compared newly enrolled HIV-positive patients in KPNC between January and December 2012 ("pre-ACA," N = 661) with newly enrolled HIV-positive patients between January and December 2014 ("post-ACA," N = 880) on demographics; medical, psychiatric, and substance use disorder diagnoses; HIV clinical indicators; and type of health care utilization. Interviews found that ACA preparation focused on enrollment growth, staffing, competition among health plans, concern about cost sharing, and HIV pre-exposure prophylaxis (PrEP) services. Quantitative analyses found that post-ACA HIV-positive patient enrollment grew. New enrollees in 2014 were more likely than 2012 enrollees to be enrolled in high-deductible plans (P < 0.01) or through Medicaid (P < 0.01), and marginally more likely to have better HIV viral control (P < 0.10). They also were more likely to be diagnosed with asthma (P < 0.01) or substance use disorders (P < 0.05) and to have used primary care health services in the 6 months postenrollment (P < 0.05) than the pre-ACA cohort. As anticipated by KPNC interviewees, ACA implementation was followed by HIV-positive patient enrollment growth and changing benefit structures and patient characteristics. Although HIV viral control improved, comorbid diagnosis findings reinforced the importance of coordinated health care.

Do Affirmative Action Bans Lower Minority College Enrollment and Attainment?: Evidence from Statewide Bans

ERIC Educational Resources Information Center

Backes, Ben

2012-01-01

Using institutional data on race-specific college enrollment and completion, I examine whether minority students were less likely to enroll in a four-year public college or receive a degree following a statewide affirmative action ban. As in previous studies, I find that black and Hispanic enrollment dropped at the top institutions; however, there…

5 CFR 894.511 - What are the QLEs that are consistent with decreasing my type of enrollment?

Code of Federal Regulations, 2012 CFR

2012-01-01

... decreasing my type of enrollment? (a) Loss of an eligible family member due to: (1) Divorce; (2) Death; or (3) Loss of eligibility of a previously enrolled child. (b) Your spouse deploys to active military service. ...

5 CFR 894.511 - What are the QLEs that are consistent with decreasing my type of enrollment?

Code of Federal Regulations, 2014 CFR

2014-01-01

... decreasing my type of enrollment? (a) Loss of an eligible family member due to: (1) Divorce; (2) Death; or (3) Loss of eligibility of a previously enrolled child. (b) Your spouse deploys to active military service. ...

5 CFR 894.511 - What are the QLEs that are consistent with decreasing my type of enrollment?

Code of Federal Regulations, 2013 CFR

2013-01-01

... decreasing my type of enrollment? (a) Loss of an eligible family member due to: (1) Divorce; (2) Death; or (3) Loss of eligibility of a previously enrolled child. (b) Your spouse deploys to active military service. ...

Comparison between Bactec Peds Plus F Broth and Conventional Medium for Vitreous Culture.

PubMed

Tabatabaei, Seyed Ali; Tabatabaei, Seyed Mehdi; Soleimani, Mohammad; Hejrati, Bahman; Mirshahi, Ahmad; Khadabandeh, Alireza; Ahmadraji, Aliasghar; Valipour, Niloofar

2018-05-10

To evaluate the yield of Bactec Peds Plus F broth for vitreous sample culture in cases with infectious endophthalmitis in comparison to conventional medium. Consecutive cases of clinically suspected endophthalmitis were prospectively enrolled in this study. Cultures of the vitreous sample were performed in both Bactec Peds Plus F broth and conventional mediums. Forty eyes of 40 patients who were clinically suspected of infectious endophthalmitis with different etiologies were enrolled in this study. The positive culture yield was 50% and 35% in Bactec Peds Plus F broth and conventional mediums, respectively (p = 0.07). The result of Bactec group was not significantly different among patients who had a history of intravitreal antibiotic injection (p > 0.05) (Table 2). However, results of the conventional method were significantly negative in the previous intravitreal antibiotic injection group (p = 0.02). There was no correlation between the methods of vitreous sampling in both culture methods. Although the difference between two culture methods was not statistically significant in this study, Bactec Peds Plus F broth showed higher positive culture yield in patients with a history of intravitreal antibiotic injection.

Acromion Index in Korean Population and Its Relationship with Rotator Cuff Tears.

PubMed

Kum, Dong Ho; Kim, Jun Ho; Park, Keun Min; Lee, Eun Su; Park, Yong Bok; Yoo, Jae Chul

2017-06-01

Among the many causes of rotator cuff tears, scapular morphology is associated with the accelerating degenerative process of the rotator cuff. Acromion index (AI) was previously introduced and compared in two populations. We enrolled 100 Korean patients diagnosed with full-thickness rotator cuff tears by magnetic resonance imaging and intraoperative arthroscopic findings between January and December 2013. Another 100 Korean patients with an intact rotator cuff tendon identified on magnetic resonance imaging and other shoulder diseases, such as frozen shoulder and instability, were enrolled as controls. We retrospectively compared these 100 rotator cuff tear patients (mean age, 63 years) and 100 controls (mean age, 51 years) in this study. Two independent orthopedic surgeons assessed the AI on radiographs. We performed an interobserver reliability test of the AI assessment, and then compared the AI between two groups. The measurement of the AI showed excellent reliability (intraclass correlation coefficient, 0.82). The mean AI in the rotator cuff tear group was 0.68 and it was significantly different between groups ( p <0.001, 95% confidence interval). The AI was not related to tear size. Our study showed that the AI was an effective predictive factor for rotator cuff tears in a Korean population.

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

PubMed

Salah, Samer; Ardissone, Francesco; Gonzalez, Michel; Gervaz, Pascal; Riquet, Marc; Watanabe, Kazuhiro; Zabaleta, Jon; Al-Rimawi, Dalia; Toubasi, Samar; Massad, Ehab; Lisi, Elena; Hamed, Osama H

2015-01-01

Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France.

PubMed

Mailles, Alexandra; De Broucker, Thomas; Costanzo, Pascale; Martinez-Almoyna, Laurent; Vaillant, Véronique; Stahl, Jean-Paul

2012-05-01

A prospective study of infectious encephalitis was conducted in France in 2007. In total, 253 patients were enrolled with a proven etiological diagnosis for 52%. The cohort of surviving patients with encephalitis was assessed for sequelae and impairment 3 years after enrollment. Patients, their family, and general practitioners (GPs) were interviewed by phone to document persisting symptoms, return to work, and past and current leisure activities, with standardized questionnaires. The IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) was completed with relatives. The global outcome was determined in all patients with the Glasgow outcome scale. In 2010, 20 patients (10%) were unavailable for follow-up, 2 (1%) were excluded, and 18 (9%) had died since hospital discharge. Data were available for 167 survivors and 9 patients whose death was related to the encephalitis. The outcome was favorable in 108 of 176 patients (61%) (71 with complete resolution), 31 (18%) were mildly impaired, 25 (14%) were severely impaired, and 3 (1%) were in a vegetative state. The most frequent symptoms were difficulty concentrating (42%), behavioral disorders (27%), speech disorders (20%), and memory loss (19%). Fifteen of 63 patients (24%) previously employed were still unable to resume work. Long-term outcome was significantly associated with comorbid conditions, age, level of education, and the causative agent of encephalitis. Most patients with encephalitis experienced a favorable outcome 3 years after hospital discharge. However, minor to severe disability persists in a high number of cases with consequences for everyday life. Physical and mental impairment should be evaluated in all patients with encephalitis, and neuropsychological rehabilitation implemented whenever needed.

Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study.

PubMed

Jabaudon, Matthieu; Berthelin, Pauline; Pranal, Thibaut; Roszyk, Laurence; Godet, Thomas; Faure, Jean-Sébastien; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Cayot, Sophie; Gillart, Thierry; Pascal, Julien; Skrzypczak, Yvan; Souweine, Bertrand; Blanchon, Loic; Sapin, Vincent; Pereira, Bruno; Constantin, Jean-Michel

2018-02-08

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS.

Previous Dosage of Allopurinol Is a Strong Determinant of Febuxostat Efficacy.

PubMed

Koide, Hiroyoshi; Hira, Daiki; Tsujimoto, Masayuki; Katsube, Yurie; Minegaki, Tetsuya; Uzu, Takashi; Ikeda, Yoshito; Morita, Shin-Ya; Nishiguchi, Kohshi; Terada, Tomohiro

2017-01-01

Febuxostat has currently played pivotal role in the treatment of hyperuricemia, but there is little comprehensive information for the determinants of individual difference in efficacy of febuxostat. Therefore, the present study, a retrospective investigation, was carried out to analyze the effects of patient characteristics on the efficacy of febuxostat. A total of 225 patients who were continuously prescribed the same dose of febuxostat for 8-12 weeks from the initial therapy were enrolled in the present study. The data, including patient information and laboratory data, were collected from electronic medical records. Serum urate lowering effects of febuxostat were evaluated by calculating the change in serum urate level at baseline and at 8-12 weeks after starting febuxostat. The multiple regression analysis showed the change in serum urate level was significantly lower in male patients and in those with a lower baseline serum urate level, higher previous dose of allopurinol, lower dose of febuxostat and lower body surface area-unadjusted estimated glomerular filtration rate. Concomitantly administered drugs did not show a significantly influence on the efficacy of febuxostat. In conclusion, it should be noted that the serum urate lowering efficacy of febuxostat may decrease in patients with a higher previous dose of allopurinol, renal impairment or male patients. The basic findings of the present study are believed to contribute to the proper use of febuxostat.

Emotion, working memory, and cognitive control in patients with first-onset and previously untreated minor depressive disorders.

PubMed

Li, Mi; Lu, Shengfu; Wang, Gang; Feng, Lei; Fu, Bingbing; Zhong, Ning

2016-06-01

To explore working memory and the ability to process different emotional stimuli in patients with first-onset and untreated minor (mild or moderate) depression. Patients with first-onset and previously untreated minor depression, and healthy controls, were enrolled. Using a modified Sternberg working memory paradigm to investigate the combined effects of emotional stimuli with working memory, participants were exposed to experimental stimuli comprising pictures that represented positive, neutral and negative emotions. Working memory ability was measured using reaction time and accuracy, and emotion-processing ability was measured using pupil diameter. Out of 36 participants (18 patients with minor depression and 18 controls), there were no statistically significant between-group differences in response time and accuracy. Positive stimuli evoked changes in pupil diameter that were significantly smaller in patients with minor depression versus controls, but changes in pupil diameter evoked by negative stimuli were not significantly different between the two groups. Healthy subjects showed a stronger emotional response to positive emotional stimuli than patients with first onset and previously untreated minor depression, but there were no differences in response to negative emotions. There were no statistically significant between-group differences in terms of speed of cognitive response, but this may have been due to the relatively small samples sizes assessed. Studies with larger sample populations are required to further investigate these results. © The Author(s) 2016.

Waiver of consent in noninterventional, observational emergency research: the PROMMTT experience.

PubMed

Fox, Erin E; Bulger, Eileen M; Dickerson, Aisha S; del Junco, Deborah J; Klotz, Patricia; Podbielski, Jeanette; Matijevic, Nena; Brasel, Karen J; Holcomb, John B; Schreiber, Martin A; Cotton, Bryan A; Phelan, Herb A; Cohen, Mitchell J; Myers, John G; Alarcon, Louis H; Muskat, Peter; Wade, Charles E; Rahbar, Mohammad H

2013-07-01

In the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, waiver of consent was used because previous literature reported low response rates and subsequent bias. The goal of this article was to examine the rationale and tradeoffs of using waiver of consent in PROMMTT. PROMMTT enrolled trauma patients receiving at least 1 U of red blood cells within 6 hours after admission at 10 US Level 1 trauma centers. Local institutional review boards (IRBs) from all sites approved the study. Site 8 was required by their IRB to attempt consent but was allowed to retain data on patients unable to be consented. Of 121 subjects enrolled at Site 8, 55 consents were obtained (46%), and no patient or legally authorized representative refused to give consent. Of the patients, 36 (30%) died, and 6 (5%) were discharged before consent could be attempted. Consent was attempted but not possible among 24 patients (20%). Of the 10 clinical sites, 6 of the local IRBs approved collection of residual blood samples, 1 had previous approval to collect timed blood samples under a separate protocol, and 3 reported that their local IRBs would not approve collection of residual blood under a waiver of consent. Waiver of consent was used in PROMMTT because of the potential adverse impact of consent refusals; however, there were no refusals. If the IRB for Site 8 had required withdrawal of patients unable to consent and destruction of their data, a serious bias would likely have been introduced. Other tradeoffs included a reduction in sites participating in residual blood collection and a smaller than expected amount of residual blood collected among sites operating under a waiver of consent. Noninterventional emergency research studies should consider these potential tradeoffs carefully before deciding whether waiver of consent would best achieve the goals of a study.

An Assessment of the Importance of Admission Test for Enrollments in Public Universities of Bangladesh

ERIC Educational Resources Information Center

Bhuia, Mohammad Romel; Das, Sumonkanti; Rahman, Khalidur; Alam, Khurshid,; Kawsar, Luthful Alahi; Hossain, Md. Kabir

2016-01-01

Public universities in Bangladesh arrange admission test to judge the students' merit before the enrollment. Academic results of previous examinations (SSC and HSC) are also considered in the admission procedure. There are some disputes regarding the importance of admission test besides the previous academic records. The universities emphasize on…

Results of Percutaneous Balloon Compression in Trigeminal Pain Syndromes.

PubMed

Grewal, Sanjeet S; Kerezoudis, Panagiotis; Garcia, Oscar; Quinones-Hinojosa, Alfredo; Reimer, Ronald; Wharen, Robert E

2018-06-01

To investigate initial pain relief and subsequent recurrence after percutaneous balloon compression (PBC) and describe its association with the nature of trigeminal pain, previous procedures, or other clinical factors. A total of 222 patients with medically refractory trigeminal pain treated with PBC at Mayo Clinic Florida between 1998 and 2017 were enrolled into this study. Patients were divided into those with typical trigeminal neuralgia (TN) and those with atypical trigeminal pain. The postprocedural rate of pain recurrence and associations between patient characteristics and recurrence were studied. One hundred fifty-two patients had TN and 70 patients had atypical pain. At the last follow-up, 158 patients had excellent pain relief, 37 had good pain relief, 11 had fair pain relief, and 16 had poor pain relief. The median duration of follow-up was 31.1 months. Patients with atypical pain were less likely to have an excellent result compared with patients with typical pain (61.4% vs. 82.9%; P < 0.001). Recurrence was observed in 103 patients (46.4%) and was associated with previous procedures (hazard ratio, 1.658; 95% confidence interval, 1.09-2.49; P = 0.017). Other clinical factors were not significant. Our study demonstrates the safety and efficacy of PBC, with 88% of patients pain-free at last follow-up. Patients with atypical pain have worse outcomes, and patients with previous procedures have a higher risk of recurrence. Repeat surgery does not decrease efficacy. We recommend conservative parameter selection at the initial procedure. Copyright © 2018 Elsevier Inc. All rights reserved.

Encouraging Patient Portal Use in the Patient-Centered Medical Home: Three Stakeholder Perspectives

PubMed Central

2016-01-01

Background Health care organizations are increasingly offering patients access to their electronic medical record and the ability to communicate with their providers through Web-based patient portals, thus playing a prominent role within the patient-centered medical home (PCMH). However, despite enthusiasm, adoption remains low. Objective We examined factors in the PCMH context that may affect efforts to improve enrollment in a patient portal. Methods Using a sociotechnical approach, we conducted qualitative, semistructured interviews with patients and providers from 3 primary care clinics and with national leaders from across a large integrated health care system. Results We gathered perspectives and analyzed data from 4 patient focus groups and one-on-one interviews with 1 provider from each of 3 primary care clinics and 10 program leaders. We found that leaders were focused on marketing in primary care, whereas patients and providers were often already aware of the portal. In contrast, both patients and providers cited administrative and logistical barriers impeding enrollment. Further, although leadership saw the PCMH as the logical place to focus enrollment efforts, providers and patients were more circumspect and expressed concern about how the patient portal would affect their practice and experience of care. Further, some providers expressed ambivalence about patients using the portal. Despite absence of consensus on how and where to encourage portal adoption, there was wide agreement that promoting enrollment was a worthwhile goal. Conclusions Patients, clinicians, and national leaders agreed that efforts were needed to increase enrollment in the patient portal. Opinions diverged regarding the suitability of the PCMH and, specifically, the primary care clinic for promoting patient portal enrollment. Policymakers should consider diverse stakeholder perspectives in advance of interventions to increase technology adoption. PMID:27876686

Pre-treatment drug resistance among patients initiating antiretroviral therapy (ART) in Zimbabwe: 2008-2010.

PubMed

Mungati, More; Mhangara, Mutsa; Gonese, Elizabeth; Mugurungi, Owen; Dzangare, Janet; Ngwende, Stella; Musasa, Patience; Wellington, Maureen; Shambira, Gerald; Apollo, Tsitsilina; Yang, Chunfu; DeVos, Joshua; Sabatier, Jennifer; Kilmarx, Peter; Chakanyuka-Musanhu, Christine; Tshimanga, Mufuta

2016-06-10

Zimbabwe set up 12 sentinel sites to monitor HIV drug resistance (HIVDR) following the international standards for prevention of HIVDR from 2008 to 2010. Participants were consecutively enrolled. Blood was collected and used for CD4 count, viral load (VL) and pre-treatment DR (PDR) tests besides routine baseline tests. We analyzed the characteristics of participants enrolled into the survey and estimated the point prevalence of PDR and its associated factors among ART initiators in a cross-sectional analysis using the baseline data collected from a prospective cohort in 12 purposefully selected sentinel sites. A total of 1728 participants (96 % response rate) were enrolled and 1610 had complete data. Of the 1610 there were more females (68.7 %) than males (31.3 %). The median CD4 count was 168 cells/mm(3) with males having lower values (P = 0.003). Ninety-six percent of participants had a VL ≥ 1000 copies/ml and the median VL was 128,000. Previous exposure to antiretroviral drugs (ARVs) was mainly through PMTCT (5 % of the participants). Overall, PDR mutations were detected in 6.3 % (95 % CI 5.2-7.7) of the 1480 successfully genotyped participants. However, the prevalence of PDR mutations was double for those with previous exposure (12.1 %) to ARVs compared with those without previous exposure (5.7 %, P = 0.002). The results show a moderate level of PDR prevalence among ART initiators. To maintain the efficacy of the current first-line regimens, there is need to strengthen all HIVDR prevention efforts and to conduct further studies to investigate optimal strategies that can prolong the efficacy of first-line ARV regimens in the country.

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial.

PubMed

Tawbi, Hussein A; Burgess, Melissa; Bolejack, Vanessa; Van Tine, Brian A; Schuetze, Scott M; Hu, James; D'Angelo, Sandra; Attia, Steven; Riedel, Richard F; Priebat, Dennis A; Movva, Sujana; Davis, Lara E; Okuno, Scott H; Reed, Damon R; Crowley, John; Butterfield, Lisa H; Salazar, Ruth; Rodriguez-Canales, Jaime; Lazar, Alexander J; Wistuba, Ignacio I; Baker, Laurence H; Maki, Robert G; Reinke, Denise; Patel, Shreyaskumar

2017-11-01

Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma. In this two-cohort, single-arm, open-label, phase 2 study, we enrolled patients with soft-tissue sarcoma or bone sarcoma from 12 academic centres in the USA that were members of the Sarcoma Alliance for Research through Collaboration (SARC). Patients with soft-tissue sarcoma had to be aged 18 years or older to enrol; patients with bone sarcoma could enrol if they were aged 12 years or older. Patients had histological evidence of metastatic or surgically unresectable locally advanced sarcoma, had received up to three previous lines of systemic anticancer therapy, had at least one measurable lesion according to the Response Evaluation Criteria In Solid Tumors version 1.1, and had at least one lesion accessible for biopsy. All patients were treated with 200 mg intravenous pembrolizumab every 3 weeks. The primary endpoint was investigator-assessed objective response. Patients who received at least one dose of pembrolizumab were included in the safety analysis and patients who progressed or reached at least one scan assessment were included in the activity analysis. Accrual is ongoing in some disease cohorts. This trial is registered with ClinicalTrials.gov, number NCT02301039. Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort). Median follow-up was 17·8 months (IQR 12·3-19·3). Seven (18%) of 40 patients with soft-tissue sarcoma had an objective response, including four (40%) of ten patients with undifferentiated pleomorphic sarcoma, two (20%) of ten patients with liposarcoma, and one (10%) of ten patients with synovial sarcoma. No patients with leiomyosarcoma (n=10) had an objective response. Two (5%) of 40 patients with bone sarcoma had an objective response, including one (5%) of 22 patients with osteosarcoma and one (20%) of five patients with chondrosarcoma. None of the 13 patients with Ewing's sarcoma had an objective response. The most frequent grade 3 or worse adverse events were anaemia (six [14%]), decreased lymphocyte count (five [12%]), prolonged activated partial thromboplastin time (four [10%]), and decreased platelet count (three [7%]) in the bone sarcoma group, and anaemia, decreased lymphocyte count, and prolonged activated partial thromboplastin time in the soft-tissue sarcoma group (three [7%] each). Nine (11%) patients (five [12%] in the bone sarcoma group and four [10%] in the soft-tissue sarcoma group) had treatment-emergent serious adverse events (SAEs), five of whom had immune-related SAEs, including two with adrenal insufficiency, two with pneumonitis, and one with nephritis. The primary endpoint of overall response was not met for either cohort. However, pembrolizumab showed encouraging activity in patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma. Enrolment to expanded cohorts of those subtypes is ongoing to confirm and characterise the activity of pembrolizumab. Merck, SARC, Sarcoma Foundation of America, QuadW Foundation, Pittsburgh Cure Sarcoma, and Ewan McGregor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sentinel node localization in oral cavity and oropharynx squamous cell cancer.

PubMed

Taylor, R J; Wahl, R L; Sharma, P K; Bradford, C R; Terrell, J E; Teknos, T N; Heard, E M; Wolf, G T; Chepeha, D B

2001-08-01

To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. Tertiary referral center. Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.

Patient and physician satisfaction with rofecoxib in osteoarthritis: results of a post-marketing surveillance study in primary care in Germany.

PubMed

Zacher, Josef; Schattenkirchner, Manfred

2002-01-01

A post-marketing surveillance study was conducted in Germany to assess the efficacy and tolerability of rofecoxib in the treatment of osteoarthritis (OA). Patients were eligible for inclusion in this study if they were being treated for the first time or being switched from other medications. More than three-quarters of the 80,371 patients enrolled in the study reported improved pain relief and function during treatment with rofecoxib (12.5 or 25 mg/day), including a reduction in pain experienced when walking on a flat surface or climbing or descending stairs. A majority of patients also considered that the duration of analgesia provided by rofecoxib was longer than with previous medications (predominantly non-steroidal anti-inflammatory drugs). Some 85% of patients reported an improvement in quality of life during rofecoxib therapy and a similar proportion considered once-daily rofecoxib to be a simpler regimen than their previous medications. Tolerability of rofecoxib was consistent with previous experience in controlled trials, with adverse events recorded in less than 1.5% of patients (n = 1090). No new or unexpected types of adverse events were recorded. A total of 81 serious adverse events were reported, corresponding to an event rate of approximately one per 1000 patient-years of treatment. Most of these serious events were not considered attributable to rofecoxib use. Physicians considered that rofecoxib provided better and more prolonged analgesia than previous medications and improved quality of life for more than 80% of patients, and regarded once-daily rofecoxib as a simpler treatment regimen than previous therapies in more than 90% of patients. Patient and physician satisfaction with rofecoxib was high in this survey. Most respondents regarded the drug as effective, easy to use, and a well-tolerated medication for the treatment of OA.

Bacterial pneumonia in patients with liver cirrhosis, with or without HIV co-infection: a possible definition of antibiotic prophylaxis associated pneumonia (APAP).

PubMed

Cuomo, Gianluca; Brancaccio, Giuseppina; Stornaiuolo, Gianfranca; Manno, Daniela; Gaeta, Giuseppe L; Mussini, Cristina; Puoti, Massimo; Gaeta, Giovanni B

2018-02-01

Introducion: Bacterial infections frequently complicate liver cirrhosis. The aim of this study was to identify risk factors and clinical impact of bacterial pneumonia in patients with cirrhosis. Bacterial infection prevalence study: consecutive patients with cirrhosis were enroled over a six-month period in 13 Italian centres. Pneumonia and other infections were diagnosed by standard methods. Pneumonia study: cirrhotic patients with pneumonia were enroled for an additional six-month period and HIV-positive patients were included. Pneumonia was the fourth most frequent infection. In the two parts of the study, 79 cases of pneumonia were recorded and 441 patients with cirrhosis without infections served as controls. Seventy-eight patients had extra-pulmonary infections. There were no clinical differences between HIV-negative and -positive cases with pneumonia. Previous gastro-intestinal bleeding (p = .02) and long-term prophylactic antibiotic use (p < .0001) were associated with pneumonia. Hospital stay was longer and renal failure more frequent than in patients without infections. Pneumonia was hospital acquired (HAP) in 6 cases, healthcare associated (HCAP) in 24 and community acquired (CAP) in 28. A new category of antibiotic prophylaxis associated pneumonia (APAP) was proposed for 21 cases. Cultures were positive in 21/79 patients (26.6%) with Gram-positive isolates in 57%. Unfavourable outcomes were recorded in 11.4% of the cases (3.6% of CAP, 33% of HAP, 12.5% of HCAP and 14.3% of APAP). Receiving antibiotic prophylaxis was associated with pneumonia and the study identified a new sub-group of patients, who require broad spectrum initial antibiotic therapy.

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study.

PubMed

Han, Hye Sook; Park, Ji Chan; Park, Suk Young; Lee, Kyu Taek; Bae, Sang Byung; Kim, Han Jo; Kim, Samyoung; Yun, Hwan Jung; Bae, Woo Kyun; Shim, Hyun-Jeong; Hwang, Jun-Eul; Cho, Sang-Hee; Park, Moo-Rim; Shim, Hyeok; Kwon, Jihyun; Choi, Moon Ki; Kim, Seung Taik; Lee, Ki Hyeong

2015-12-01

In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate. ©AlphaMed Press.

Patient-centered disease management (PCDM) for heart failure: study protocol for a randomised controlled trial.

PubMed

Bekelman, David B; Plomondon, Mary E; Sullivan, Mark D; Nelson, Karin; Hattler, Brack; McBryde, Connor; Lehmann, Kenneth G; Potfay, Jonathan; Heidenreich, Paul; Rumsfeld, John S

2013-07-09

Chronic heart failure (HF) disease management programs have reported inconsistent results and have not included comorbid depression management or specifically focused on improving patient-reported outcomes. The Patient Centered Disease Management (PCDM) trial was designed to test the effectiveness of collaborative care disease management in improving health status (symptoms, functioning, and quality of life) in patients with HF who reported poor HF-specific health status. Patients with a HF diagnosis at four VA Medical Centers were identified through population-based sampling. Patients with a Kansas City Cardiomyopathy Questionnaire (KCCQ, a measure of HF-specific health status) score of < 60 (heavy symptom burden and impaired quality of life) were invited to enroll in the PCDM trial. Enrolled patients were randomized to receive usual care or the PCDM intervention, which included: (1) collaborative care management by VA clinicians including a nurse, cardiologist, internist, and psychiatrist, who worked with patients and their primary care providers to provide guideline-concordant care management, (2) home telemonitoring and guided patient self-management support, and (3) screening and treatment for comorbid depression. The primary study outcome is change in overall KCCQ score. Secondary outcomes include depression, medication adherence, guideline-based care, hospitalizations, and mortality. The PCDM trial builds on previous studies of HF disease management by prioritizing patient health status, implementing a collaborative care model of health care delivery, and addressing depression, a key barrier to optimal disease management. The study has been designed as an 'effectiveness trial' to support broader implementation in the healthcare system if it is successful. Unique identifier: NCT00461513.

Racial differences in enrolment in a cancer genetics registry.

PubMed

Moorman, Patricia G; Skinner, Celette Sugg; Evans, James P; Newman, Beth; Sorenson, James R; Calingaert, Brian; Susswein, Lisa; Crankshaw, T Sydnee; Hoyo, Cathrine; Schildkraut, Joellen M

2004-08-01

Lower enrolment of minorities into research studies has been reported frequently. Most studies have little information about nonparticipants, making it difficult to identify characteristics associated with enrolment and how they might vary by race. Women who had previously participated in a population-based, case-control study of breast cancer in North Carolina were invited to enroll in a cancer genetics registry. Detailed questionnaire data on sociodemographic characteristics and cancer risk factors were available for all women. We compared characteristics of women who agreed to be in the registry with those who were deceased, were unlocatable, or declined enrolment. Unconditional logistic regression analyses were done to identify predictors of enrolment. Enrolment rates were markedly lower among African Americans than Whites (15% and 36%, respectively) due to both lower contact rates (41% versus 63%) and lower enrolment rates among those contacted (37% versus 58%). Logistic regression models suggested that racial differences in enrolment were not due to socioeconomic characteristics or other cancer risk factors; race was the only significant predictor of enrolment in multivariable models (odds ratio 0.41, 95% confidence interval 0.23-0.72). Although all women had previously taken part in a research study, African American women were less likely to enroll in the cancer genetics registry than White women. A possible explanation of these findings is that studies of genetics may present particular concerns for African Americans. Further research is needed to identify attitudes and issues that present barriers to participation among minorities.

Apatinib for metastatic breast cancer in non-clinical trial setting: Satisfying efficacy regardless of previous anti-angiogenic treatment.

PubMed

Lin, Ying; Wu, Zheng; Zhang, Jian; Hu, Xichun; Wang, Zhonghua; Wang, Biyun; Cao, Jun; Wang, Leiping

2017-06-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. This study aimed to evaluate the efficacy and safety of apatinib in metastatic breast cancer (MBC) under non-clinical trial setting, and to study the impact of previous antiangiogenic treatment to the efficacy of apatinib. 52 MBC patients treated with apatinib under non-clinical trial setting in Fudan University Shanghai Cancer Center between January 1st 2015 and October 1st 2016 were included. All patients were included in time-to-treatment failure (TTF) analysis, while 45 patients were enrolled for progression-free survival (PFS) and overall survival (OS) analysis because 7 of the patients with treatment discontinuation due to intolerable toxicities had too short time for efficacy assessment. Impact of previous exposure to antiangiogenic treatment and other factors to patients' survival were analyzed by Log-rank analysis and Cox multivariate analysis. The median PFS, median OS, and median TTF were 4.90 (95% confidence interval [CI] 3.44 - 6.36), 10.3 (unable to calculate 95% CI), and 3.93 (95% CI 1.96 - 5.90) months, respectively. Previous treatment of bevacizumab did not affect the efficacy of apatinib. Previous exposure to anthracycline, age of 60 years or older and palmar-plantar erythrodysesthesia syndrome were independent predictors for prolonged PFS. Discontinuation of treatment was more common in age group of 60 years or older than that in younger group, although the difference was not significant. Although toxicities were generally managable, a previously unrecorded grade 3~4 adverse event of dyspnea has been observed. This study confirmed the encouraging efficacy and manageable safety of apatinib on pretreated MBC patients in non-clinical trial setting. For the first time to our knowledge, this study found that previous treatment of bevacizumab did not affect the efficacy of apatinib, and reported an undocumented severe adverse effect of dyspnea.

A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer.

PubMed

Sakai, Daisuke; Chung, Hyun Cheol; Oh, Do-Youn; Park, Se Hoon; Kadowaki, Shigenori; Kim, Yeul Hong; Tsuji, Akihito; Komatsu, Yoshito; Kang, Yoon-Koo; Uenaka, Kazunori; Wijayawardana, Sameera R; Wacheck, Volker; Wang, Xuejing; Yamamura, Ayuko; Doi, Toshihiko

2017-12-01

Mesenchymal-epithelial transition factor (MET) is expressed in gastric cancer and associated with poor clinical outcomes. We assessed activity, safety, and pharmacokinetics of emibetuzumab, a bivalent monoclonal anti-MET antibody that blocks ligand-dependent and ligand-independent MET signaling. This non-randomized, single-arm, Phase 2 study enrolled Asian patients with MET diagnostic positive advanced gastric adenocarcinoma. Emibetuzumab (2000 mg, intravenous) was given on days 1 and 15 (28-day cycle). The primary endpoint was 8-week progression-free survival rate. Secondary objectives included safety, pharmacokinetics, overall survival, and change in tumor size. Tumors from 65 patients were immunohistochemically screened to enroll 15 MET diagnostic positive patients (23% positivity; 8 Japanese, 7 Korean; 10 male). Eight-week progression-free survival rate was 0.47 (70% CI, 0.33-0.59). Disease control rate was 40% (target lesion decreases, three patients; no complete/partial responses according to RECIST). Median overall survival was 17.1 weeks (95% CI, 6.3-not achievable). No serious emibetuzumab-related adverse events or new safety signals emerged. Grade ≥ 3 possibly drug-related adverse events were hyperkalemia, hyponatremia, and hyperuricemia (one each). Emibetuzumab's pharmacokinetics profile was similar to that observed previously. MET expression and clinical outcomes were not obviously associated. Emibetuzumab was well tolerated with limited single-agent activity in advanced gastric adenocarcinoma.

The relationship of plasma decoy receptor 3 and coronary collateral circulation in patients with coronary artery disease.

PubMed

Yan, Youyou; Song, Dandan; Liu, Lulu; Meng, Xiuping; Qi, Chao; Wang, Junnan

2017-11-15

Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. Plasma DcR3 level was significantly higher in good CCC group (328.00±230.82 vs 194.84±130.63ng/l, p<0.01) and positively correlated with Rentrope grade (p<0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. Copyright © 2017. Published by Elsevier Inc.

The impact of rifaximin in the prevention of bacterial infections in cirrhosis.

PubMed

Mariani, M; Zuccaro, V; Patruno, S F A; Scudeller, L; Sacchi, P; Lombardi, A; Vecchia, M; Columpsi, P; Marone, P; Filice, G; Bruno, R

2017-03-01

Bacterial infections are a leading factor in the progression from compensated to decompensated cirrhosis, with consequent worsening of the prognosis, and concerted efforts have been made to reduce infections and improve the survival rate of these patients. We retrospectively investigated the rate of infections in hospitalized cirrhotic patients under treatment with rifaximin. We enrolled 649 patients whose clinical and personal data, prescribed therapy, microbiological findings and laboratory tests were collected from previous discharge letters and our institution database. The efficacy of rifaximin in preventing several types infection was evaluated by comparing outcomes for rifaximin-treated patients vs patients receiving no antibiotic treatment. The risk of developing selected bacterial infections was significantly lower in patients treated with rifaximin (OR 0.29; 95% CI 0.20-0.40, p < 0.001). Continuous treatment with rifaximin may prevent bacterial infections in cirrhotic patients.

Determinants of facilitated health insurance enrollment for patients with HIV disease, and impact of insurance enrollment on targeted health outcomes.

PubMed

Furl, Renae; Watanabe-Galloway, Shinobu; Lyden, Elizabeth; Swindells, Susan

2018-03-16

The introduction of the Affordable Care Act (ACA) has provided unprecedented opportunities for uninsured people with HIV infection to access health insurance, and to examine the impact of this change in access. AIDS Drug Assistance Programs (ADAPs) have been directed to pursue uninsured individuals to enroll in the ACA as both a cost-saving strategy and to increase patient access to care. We evaluated the impact of ADAP-facilitated health insurance enrollment on health outcomes, and demographic and clinical factors that influenced whether or not eligible patients enrolled. During the inaugural open enrollment period for the ACA, 284 Nebraska ADAP recipients were offered insurance enrollment; 139 enrolled and 145 did not. Comparisons were conducted and multivariate models were developed considering factors associated with enrollment and differences between the insured and uninsured groups. Insurance enrollment was associated with improved health outcomes after controlling for other variables, and included a significant association with undetectable viremia, a key indicator of treatment success (p < .0001). We found that minority populations and unstably housed individuals were at increased risk to not enroll in insurance. The National HIV/AIDS Strategy calls for new interventions to improve HIV health outcomes for disproportionately impacted populations. This study provides evidence to prioritize future ADAP-facilitated insurance enrollment strategies to reach minority populations and unstably housed individuals.

Prevalence of incidental pancreatic cyst on upper endoscopic ultrasound

PubMed Central

Martínez, Belén; Martínez, Juan F.; Aparicio, José R.

2018-01-01

Background: This study aimed to determine the prevalence of incidental pancreatic cysts in patients undergoing upper endoscopic ultrasound without a known pancreatic abnormality. Methods: This prospective study was conducted in two hospitals in Spain and enrolled consecutive patients referred for upper endoscopic ultrasound for a condition unrelated to the pancreas. Patients with a previous pancreatic anomaly, history of acute or chronic pancreatitis, evidence of acute pancreatitis, previous upper gastrointestinal surgery, or chronic abdominal pain suggestive of pancreatic origin were excluded. Univariate logistic regression was performed to evaluate individual covariates and the incidental pancreatic cyst risk. Results: A total of 298 patients were included, of whom 64 had pancreatic cysts (21.5%; 16.9-26.6%). The mean size of the cysts was 6.3±3.7 (range 3-25) mm. Six cysts (2%) were >10 mm and 16 (5.4%) were compatible with branch duct intraductal papillary mucinous neoplasm. The pancreatic cyst prevalence was similar in the two hospitals and increased significantly with age. Conclusion: The prevalence of incidental pancreatic cysts during endoscopic ultrasound was very high in our study population. PMID:29333072

A Cost-Sharing Exemption Program for Patients With Mental Illness in Taiwan: Who Enrolls?

PubMed

Huang, Hsin-Hui; Chen, Chuan-Yu; Chou, Yiing-Jenq; Huang, Nicole

2015-11-01

The purpose of this study was to identify patient and provider characteristics associated with enrollment in a cost-sharing exemption program among people newly diagnosed as having schizophrenia. The study used a nationally representative sample from Taiwan's National Health Insurance (NHI) program. Enrollment in a cost-sharing exemption program among 1,824 individuals with schizophrenia was observed for one year and three years after the individuals received a diagnosis of schizophrenia for the first time. Generalized estimating equations were applied to estimate the effect of various patient and physician characteristics on the odds of enrollment. The one-year and three-year program enrollment rates were 52% and 58%, respectively. People ages 35 or older were significantly more likely to enroll compared with younger people. People with low incomes and people who were hospitalized for schizophrenia were significantly more likely to enroll. Regarding provider characteristics, patients cared for by psychiatrists (adjusted odds ratio [AOR]=1.10) or by psychiatric institutions (AOR=1.10) were significantly more likely to enroll in the cost-sharing exemption program within the first year of diagnosis. The results suggest that enrollment in the NHI's cost-sharing exemption program by people newly diagnosed as having schizophrenia was relatively low. The role of providers must not be overlooked. Effective strategies targeting high-risk subgroups for nonparticipation are necessary in addressing mental health parity.

Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer

PubMed Central

Blackhall, Fiona; Ross Camidge, D; Shaw, Alice T; Soria, Jean-Charles; Solomon, Benjamin J; Mok, Tony; Hirsh, Vera; Jänne, Pasi A; Shi, Yuankai; Yang, Pan-Chyr; Pas, Tommaso De; Hida, Toyoaki; Carpeño, Javier De Castro; Lanzalone, Silvana; Polli, Anna; Iyer, Shrividya; Reisman, Arlene; Wilner, Keith D; Kim, Dong-Wan

2017-01-01

Purpose Crizotinib is a potent, orally administered tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). We report final results from PROFILE 1005, the largest clinical trial to date for an ALK inhibitor in ALK-positive NSCLC. Patients and methods PROFILE 1005 (NCT00932451) was a multicenter, single-arm phase 2 trial of the efficacy, safety and tolerability of crizotinib (250 mg twice daily; 3 week continuous treatment cycles) in patients with ALK-positive NSCLC after failure of ≥1 lines of systemic treatment for locally advanced/metastatic disease. Patients’ tumour ALK status was initially determined by a central laboratory until a protocol amendment permitted enrolment of patients based on locally determined ALK status. Co-primary endpoints were objective response rate (ORR), evaluated using Response Evaluation Criteria in Solid Tumours V.1.1 and adverse events (AEs). Cancer-specific patient-reported outcomes (PROs) were also assessed using the European Organisation for the Research and Treatment of Cancer QLQ-C30 and its lung cancer module QLQ-LC13. Results 1069 patients were enrolled; 1066 received crizotinib. The as-treated population comprised 908 and 158 patients, in whom tumour positive ALK-status was determined centrally (± locally) or locally only, respectively. At baseline, a majority of patients were <65 years (84%), 66% were never smokers and 46% were Asian. Derived investigator-assessed ORR was 54% (95% CI 51 to 57) and 41% (95% CI 33 to 49) in the central-testing and local-testing subgroups, respectively. The most common treatment-related AEs in the overall population (any grade) were vision disorder (58%), nausea (51%), diarrhoea (47%) and vomiting (47%). PRO scores demonstrated clinically meaningful improvement in lung cancer symptoms and global quality of life. Conclusion The efficacy, safety and PRO profiles of crizotinib in this cohort of 1066 patients with ALK-positive NSCLC are consistent with previous reports. Trial registration number Phase 2 trial (NCT00932451); Results. PMID:29209525

Evaluation of atrial electromechanical conduction delay in case of hemodynamically insignificant rheumatic heart disease: A tissue Doppler study.

PubMed

Cagdas, Metin; Velibey, Yalcin; Guvenc, Tolga Sinan; Gungor, Baris; Guzelburc, Ozge; Calik, Nazmi; Ugur, Murat; Tekkesin, Ahmet Ilker; Gurkan, Kadir; Eren, Mehmet

2015-01-01

Atrial electromechanical delay (AEMD) that reflects delayed conduction may show us the clinical reflection of pathological changes in the atria. The main objective of the present study is to investigate AEMD in patients who had previous rheumatic carditis but without hemodynamically significant valvular disease. A total of 40 patients, previously diagnosed as rheumatic carditis but without significant valvular stenosis/regurgitation and atrial enlargement; and 39 age- and-sex matched controls were enrolled for the present study. Parameters of AEMD (lateral mitral annulus electromechanical delay, septal mitral annulus electromechanical delay and lateral tricuspid annulus electromechanical delay) were measured with tissue Doppler echocardiography and left intra-atrial and inter-atrial conduction times were calculated accordingly. A 24h ambulatory Holter monitoring was used in both groups to detect atrial fibrillation episodes and quantify atrial extrasystoles. Parameters of AEMD, including left intra-atrial and inter-atrial conduction times of subjects in the study group were longer compared to the control group (23.7 ± 7.0 vs. 18.3 ± 6.2). Increased AEMD is observed in patients with previous rheumatic carditis and no significant valvular stenosis/regurgitation and atrial enlargement, which may partly explain the increased incidence of atrial fibrillation observed in these patients.

Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.

PubMed

Prince, H Miles; Kim, Youn H; Horwitz, Steven M; Dummer, Reinhard; Scarisbrick, Julia; Quaglino, Pietro; Zinzani, Pier Luigi; Wolter, Pascal; Sanches, Jose A; Ortiz-Romero, Pablo L; Akilov, Oleg E; Geskin, Larisa; Trotman, Judith; Taylor, Kerry; Dalle, Stephane; Weichenthal, Michael; Walewski, Jan; Fisher, David; Dréno, Brigitte; Stadler, Rudolf; Feldman, Tatyana; Kuzel, Timothy M; Wang, Yinghui; Palanca-Wessels, Maria Corinna; Zagadailov, Erin; Trepicchio, William L; Zhang, Wenwen; Lin, Hui-Min; Liu, Yi; Huebner, Dirk; Little, Meredith; Whittaker, Sean; Duvic, Madeleine

2017-08-05

Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m 2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy.

PubMed

Coutre, Steven; Choi, Michael; Furman, Richard R; Eradat, Herbert; Heffner, Leonard; Jones, Jeffrey A; Chyla, Brenda; Zhou, Lang; Agarwal, Suresh; Waskiewicz, Tina; Verdugo, Maria; Humerickhouse, Rod A; Potluri, Jalaja; Wierda, William G; Davids, Matthew S

2018-04-12

B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282. © 2018 by The American Society of Hematology.

Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study.

PubMed

DiNardo, Courtney D; Pratz, Keith W; Letai, Anthony; Jonas, Brian A; Wei, Andrew H; Thirman, Michael; Arellano, Martha; Frattini, Mark G; Kantarjian, Hagop; Popovic, Relja; Chyla, Brenda; Xu, Tu; Dunbar, Martin; Agarwal, Suresh K; Humerickhouse, Rod; Mabry, Mack; Potluri, Jalaja; Konopleva, Marina; Pollyea, Daniel A

2018-02-01

Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study. Previously untreated patients aged 65 years and over with acute myeloid leukaemia who were ineligible for standard induction therapy were enrolled into this non-randomised, open-label, phase 1b study. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0-2 and either intermediate-risk or poor-risk cytogenetics. Patients were enrolled into one of three groups for the dose-escalation phase of this study: group A (venetoclax and intravenous decitabine 20 mg/m 2 [days 1-5 of each 28-day cycle]), group B (venetoclax and subcutaneous or intravenous azacitidine 75 mg/m 2 [days 1-7 of each 28-day cycle]), and group C (a venetoclax and decitabine substudy with the oral CYP3A inhibitor posaconazole, 300 mg twice on cycle 1, day 21, and 300 mg once daily from cycle 1, days 22-28, to assess its effect on venetoclax pharmacokinetics). Dose escalation followed a standard 3 + 3 design with at least three evaluable patients enrolled per cohort; daily target doses of venetoclax for groups A and B were 400 mg (cohort 1), 800 mg (cohorts 2 and 3), and 1200 mg (cohort 4), and 400 mg for group C. The primary endpoints were the safety and pharmacokinetics of venetoclax plus decitabine or azacitidine, and to determine the maximum tolerated dose and recommended phase 2 dose. Secondary endpoints included the preliminary anti-leukaemic activity of venetoclax with decitabine or azacitidine through the analysis of overall response, duration of response, and overall survival. We analysed safety, pharmacokinetics, and anti-leukaemic activity in all patients who received one or more venetoclax doses. The expansion phase of the study is ongoing but is closed to accrual. This trial is registered with ClinicalTrials.gov, number NCT02203773. 57 patients were enrolled in the study. 23 patients in group A and 22 patients in group B were enrolled between Nov 19, 2014, and Dec 15, 2015, and 12 patients in group C were enrolled between June 14, 2015, and Jan 16, 2016. As of data cutoff on June 15, 2016, the most common grade 3-4 treatment-emergent adverse events were thrombocytopenia (27 [47%] of 57 patients; nine in group A, 13 in group B, and five in group C), febrile neutropenia (24 [42%] of 57; 11 in group A, ten in group B, and three in group C), and neutropenia (23 [40%] of 57; 12 in group A, eight in group B, and three in group C). The most common serious treatment-emergent adverse event in groups A and B was febrile neutropenia (seven [30%] of 23 patients vs seven [32%] of 22), whereas in group C it was lung infection (four [33%] of 12 patients). 49 (86%) of 57 patients had treatment-related adverse events; the most common in groups A and B included nausea (12 [52%] patients vs seven [32%] patients), fatigue (six [26%] patients vs seven [32%]), and decreased neutrophil count (six [26%] patients vs six [27%]), whereas in group C the most common were nausea (seven [58%] of 12 patients), leucopenia (six [50%]), vomiting (five [42%]), and decreased platelet count (five [42%]). The maximum tolerated dose was not reached. The recommended phase 2 dose was 400 mg once a day or 800 mg with an interrupted dosing schedule (safety expansion). In total, four (7%) of 57 patients had died within 30 days of the first venetoclax dose caused by sepsis (group B), bacteraemia (group A), lung infection (group C), and respiratory failure (group A). Tumour lysis syndrome was not observed. Decitabine and azacitidine did not substantially affect venetoclax exposures. Overall, 35 (61%; 95% CI 47·6-74·0) of 57 patients achieved complete remission or complete remission with incomplete marrow recovery. In groups A and B, 27 (60%; 95% CI 44·3-74·3) of 45 patients had complete remission or complete remission with incomplete marrow recovery. Venetoclax plus hypomethylating agent therapy seems to be a novel, well-tolerated regimen with promising activity in this underserved patient population. Evaluation of expansion cohorts is ongoing at 400 mg and 800 mg doses using both hypomethylating agent combinations. AbbVie and Genentech. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preoperative cetuximab, irinotecan, cisplatin, and radiation therapy for patients with locally advanced esophageal cancer.

PubMed

Lee, Michael S; Mamon, Harvey J; Hong, Theodore S; Choi, Noah C; Fidias, Panagiotis M; Kwak, Eunice L; Meyerhardt, Jeffrey A; Ryan, David P; Bueno, Raphael; Donahue, Dean M; Jaklitsch, Michael T; Lanuti, Michael; Rattner, David W; Fuchs, Charles S; Enzinger, Peter C

2013-01-01

To determine the efficacy and toxicity of weekly neoadjuvant cetuximab combined with irinotecan, cisplatin, and radiation therapy in patients with locally advanced esophageal or gastroesophageal junction cancer. Patients with stage IIA-IVA esophageal or gastroesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received weekly cetuximab on weeks 0-8 and irinotecan and cisplatin on weeks 1, 2, 4, and 5, with concurrent radiotherapy (50.4 Gy on weeks 1-6), followed by surgical resection. In the first stage, 17 patients were enrolled, 16 of whom had adenocarcinoma. Because of a low pathologic complete response (pCR) rate in this cohort, the trial was discontinued for patients with adenocarcinoma but squamous cell carcinoma patients continued to be enrolled; two additional patients were enrolled before the study was closed as a result of poor accrual. Of the 19 patients enrolled, 18 patients proceeded to surgery, and 16 patients underwent an R0 resection. Three patients (16%) had a pCR. The median progression-free survival interval was 10 months, and the median overall survival duration was 31 months. Severe neutropenia occurred in 47% of patients, and severe diarrhea occurred in 47% of patients. One patient died preoperatively from sepsis, and one patient died prior to hospital discharge following surgical resection. This schedule of cetuximab in combination with irinotecan, cisplatin, and radiation therapy was toxic and did not achieve a sufficient pCR rate in patients with localized esophageal adenocarcinoma to undergo further evaluation.

Recurrence of ICH after resumption of anticoagulation with VK antagonists: CHIRONE study.

PubMed

Poli, Daniela; Antonucci, Emilia; Dentali, Francesco; Erba, Nicoletta; Testa, Sophie; Tiraferri, Eros; Palareti, Gualtiero

2014-03-25

To evaluate the risk of recurrent intracranial hemorrhage (ICH) in patients on vitamin K antagonists (VKAs) after a first episode of ICH. The Cerebral Haemorrhage in patients Restarting Oral Anticoagulant Therapy (CHIRONE) Study collected data of patients eligible for the study from the database of 27 centers affiliated with the Italian Federation of Anticoagulation Clinics. We enrolled 267 patients (163 male, median age 73.9 years) who had received VKA anticoagulation after an ICH event. During the total period of follow-up (778 patient-years), ICH recurred in 20 patients (7.5%; rate 2.56 × 100 patient-years) at a median time of 16.5 months, and was fatal in 5 patients (25%; rate 0.4 × 100 patient-years). Male sex, hypertension, prosthetic valves, previous ischemic stroke, renal failure, cancer, and spontaneous events were associated with the risk of recurrence, though none of them in isolation reached statistical significance. More than one-third of spontaneous recurrences occurred in patients with a posttraumatic index event. Our results show that patients with a history of ICH carry a significant risk of recurrent ICH when treated with VKA anticoagulation. The risk is also present, though to a lower degree, in patients with previous posttraumatic events. All patients with a history of ICH require a careful evaluation of their thromboembolic risk to estimate the net clinical benefit of (re)starting anticoagulation with VKAs.

Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme.

PubMed

Bodensteiner, David; Scott, C Ronald; Sims, Katherine B; Shepherd, Gillian M; Cintron, Rebecca D; Germain, Dominique P

2008-05-01

To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta. The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled. During rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug. Agalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme.

Causes and Severity of Ischemic Stroke in Patients with Symptomatic Intracranial Arterial Stenosis

PubMed Central

Famakin, Bolanle M; Chimowitz, Marc I; Lynn, Michael J; Stern, Barney J; George, Mary G.

2009-01-01

Background and purpose There are limited data on the causes and severity of subsequent stroke in patients presenting initially with TIA or stroke attributed to intracranial arterial stenosis. Methods We evaluated the location, type (lacunar vs. non-lacunar), cause, and severity of stroke in patients who had an ischemic stroke endpoint in the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. Results Of the 569 patients enrolled in the WASID trial, 106 patients (18.6%) had an ischemic stroke during a mean follow-up of 1.8 years. Stroke occurred in the territory of the symptomatic artery in 77 (73%) of 106 patients. Among the 77 strokes in the territory, 70 (91%) were non-lacunar and 34 (44%) were disabling. Stroke out of the territory of the symptomatic artery occurred in 29 (27%) of 106 patients. Among these 29 strokes, 24 (83%) were non-lacunar, 14 (48%) were due to previously asymptomatic intracranial stenosis, and 9 (31%) were disabling. Conclusions Most subsequent strokes in patients with symptomatic intracranial artery stenosis are in the same territory and non-lacunar, and nearly half of the strokes in the territory are disabling. The most commonly identified cause of stroke out of the territory was a previously asymptomatic intracranial stenosis. Penetrating artery disease was responsible for a low number of strokes. PMID:19407228

Long-term safety and tolerability of once-daily mesalamine granules in the maintenance of remission of ulcerative colitis.

PubMed

Lichtenstein, Gary R; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2014-08-01

Ulcerative colitis (UC), a chronic, relapsing, and remitting inflammatory bowel disease, requires long-term treatment to maintain remission. In this study, the long-term safety and tolerability of mesalamine granules (MG) therapy was evaluated in the maintenance of UC remission. Previous prospective studies evaluating different oral mesalamine formulations have not exceeded a duration of 14 months. A phase 3, multicenter, 24-month, open-label extension study evaluating MG 1.5 g once daily in patients who achieved previous remission from mild to moderate UC was performed. Eligible patients had successfully participated in 1 of 2 previous 6-month double-blind, placebo-controlled trials or were new patients in remission. Safety assessments included monitoring of adverse events (AEs) and clinical laboratory tests. Risk of UC recurrence was assessed by the occurrence of UC-related AEs. Of the 393 patients enrolled (280 from the double-blind studies; 113 new patients), 388 were included in the safety population. The most common AEs included nasopharyngitis (13.9%), headache (11.6%), and diarrhea (10.8%), and the incidence of these events was generally lower in the MG group versus historical placebo group from the double-blind studies. Pancreatic, renal, and hepatic AEs occurred in 23 patients (5.9%). The risk of UC-related AEs was low and was maintained for 24 months during the open-label study. Once-daily MG has a favorable safety profile for the maintenance of remission for up to 2 years in patients with UC.

Nonimpacted Third Molars Affect the Periodontal Status of Adjacent Teeth: A Cross-Sectional Study.

PubMed

Li, Zhi-Bang; Qu, Hong-Lei; Zhou, Li-Na; Tian, Bei-Min; Gao, Li-Na; Chen, Fa-Ming

2017-07-01

Most previous studies of the effect of third molars (M3s) on the health of adjacent second molars (A-M2s) have focused on impacted M3s (I-M3s). The purpose of this study was to investigate whether nonimpacted M3 (N-M3s) could affect the periodontal status of A-M2s. In this cross-sectional study, patients (≥18 years) who had at least 1 quadrant with intact first and second molars and a nonimpacted or absent M3 were enrolled in this study. The periodontal measurements of M2 (6 sites) in the examined quadrants included the gingival index (GI), plaque index (PLI), probing pocket depth (PPD), clinical attachment level (CAL), gingival recession, and bleeding on probing (BOP). The mean GI, PLI, PPD, CAL, and BOP proportion and the proportion with at least 1 site with a PPD of at least 5 mm (PPD5 + ) were compared using the t test or χ 2 test. The association of PPD5 + (percentage) or BOP (percentage) with the presence of N-M3s was assessed using a 2-level logistic regression model (quadrant-based analysis). One hundred thirty-five patients (43.7% men; 40.6 ± 11.5 yr old) were enrolled in this study. Patients who had at least 1 quadrant with 3 intact molars and an N-M3 were enrolled in group A (105 patients), and patients who had at least 1 quadrant with intact first and second molars without an M3 were enrolled in group B (30 patients). The periodontal parameters (ie, GI, PLI, PPD, CAL, BOP, and PPD5 + ) were markedly greater in group A. When other factors associated with periodontal disease were controlled, N-M3s were associated with the PPD5 + (odds ratio = 6.7) and BOP (odds ratio = 4.0) of the A-M2s. Other factors positively associated with A-M2 PPD5 + were location on the mandible, age older than 35 years, and smoking. The presence of N-M3s is a potential risk factor for the development of periodontitis in A-M2s. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Risk selection and cost shifting in a prospective physician payment system: evidence from Ontario.

PubMed

Kantarevic, Jasmin; Kralj, Boris

2014-04-01

We study the risk-selection and cost-shifting behavior of physicians in a unique capitation payment model in Ontario, using the incentive to enroll and care for complex and vulnerable patients as a case study. This incentive, which is incremental to the regular capitation payment, ceases after the first year of patient enrollment and may therefore impact on the physician's decision to continue to enroll the patient. Furthermore, because the enrolled patients in Ontario can seek care from any provider, the enrolling physician may shift some treatment costs to other providers. Using longitudinal administrative data and a control group of physicians in the fee-for-service model who were eligible for the same incentive, we find no evidence of either patient 'dumping' or cost shifting. These results highlight the need to re-examine the conventional wisdom about risk selection for physician payment models that significantly deviate from the stylized capitation model. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prediction of early death among patients enrolled in phase I trials: development and validation of a new model based on platelet count and albumin.

PubMed

Ploquin, A; Olmos, D; Lacombe, D; A'Hern, R; Duhamel, A; Twelves, C; Marsoni, S; Morales-Barrera, R; Soria, J-C; Verweij, J; Voest, E E; Schöffski, P; Schellens, J H; Kramar, A; Kristeleit, R S; Arkenau, H-T; Kaye, S B; Penel, N

2012-09-25

Selecting patients with 'sufficient life expectancy' for Phase I oncology trials remains challenging. The Royal Marsden Hospital Score (RMS) previously identified high-risk patients as those with ≥ 2 of the following: albumin <35 g l(-1); LDH > upper limit of normal; >2 metastatic sites. This study developed an alternative prognostic model, and compared its performance with that of the RMS. The primary end point was the 90-day mortality rate. The new model was developed from the same database as RMS, but it used Chi-squared Automatic Interaction Detection (CHAID). The ROC characteristics of both methods were then validated in an independent database of 324 patients enrolled in European Organization on Research and Treatment of Cancer Phase I trials of cytotoxic agents between 2000 and 2009. The CHAID method identified high-risk patients as those with albumin <33 g l(-1) or ≥ 33 g l(-1), but platelet counts ≥ 400.000 mm(-3). In the validation data set, the rates of correctly classified patients were 0.79 vs 0.67 for the CHAID model and RMS, respectively. The negative predictive values (NPV) were similar for the CHAID model and RMS. The CHAID model and RMS provided a similarly high level of NPV, but the CHAID model gave a better accuracy in the validation set. Both CHAID model and RMS may improve the screening process in phase I trials.

Analysis of lipid-lowering therapy and factors affecting regularity of statin intake in patients with cardiovascular disease enrolled in the PROFILE registry.

PubMed

Gaisenok, Oleg; Martsevich, Sergey; Tripkosh, Svetlana; Lukina, Yulia

2015-02-01

The aim of this study was to analyze the quality of lipid-lowering therapy in a cohort of patients with cardiovascular disease enrolled in a Moscow-based registry, and to analyze the factors affecting the regularity of statin administration in this patient category. The present study included all patients who successively sought medical advice in the Preventive Pharmacotherapy Department of the Ministry of Healthcare of the Russian Federation between May 1 and December 31, 2011 (n=274). Each patient was given a specially designed questionnaire in order to assess compliance with the prescribed treatment that included the following questions: (1) if they knew, according to the results of previous exams, that they had elevated cholesterol levels (yes, no, don't know); (2) what method of hypercholesterolemia correction they used (diet, medication, physical exercise, or other); (3) if they were taking any statins (regularly, no, irregularly); and (4) if yes, what statin preparation and what dose they were taking. Patients' compliance with statin therapy was assessed on the basis of the responses received and the regularity of statin intake. The influence of various factors on regularity of statin intake in patients with cardiovascular disease was assessed by calculating odds ratios (OR) and 95% confidence intervals (CI) for advanced age (>70 years) (OR 0.49); higher statin dose than standard (OR 0.49); hypertension (OR 1.659); history of acute cerebrovascular event (OR 2.019); diabetes (OR 1.023); coronary heart disease (CHD) (OR 4.357); history of myocardial infarction (MI) (OR 4.838); history of coronary angiography/percutaneous coronary intervention (PCI) (OR 5.167). Analysis of factors with impact on regular compliance with statin therapy showed that the following were most significant: CHD, history of MI, and history of PCI. Previous cerebrovascular events and presence of diabetes did not motivate these patients to take statins on a regular basis. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Protocol update and preliminary results of EACVI/HFA Cardiac Oncology Toxicity (COT) Registry of the European Society of Cardiology.

PubMed

Lancellotti, Patrizio; Galderisi, Maurizio; Donal, Erwan; Edvardsen, Thor; Popescu, Bogdan A; Farmakis, Dimitrios; Filippatos, Gerasimos; Habib, Gilbert; Lestuzzi, Chiara; Santoro, Ciro; Moonen, Marie; Jerusalem, Guy; Andarala, Maryna; Anker, Stefan D

2017-08-01

European Association of Cardiovascular Imaging/Heart Failure Association Cardiac Oncology Toxicity Registry was launched in October 2014 as a European Society of Cardiology multicentre registry of breast cancer patients referred to imaging laboratories for routine surveillance, suspected, or confirmed anticancer drug-related cardiotoxicity (ADRC). After a pilot phase (1 year recruitment and 1 year follow-up), some changes have been made to the protocol (version 1.0) and electronic case report form. Main changes of the version 2.0 concerned exclusion criteria, registry duration, and clarification of the population characteristics. Breast cancer radiotherapy has been removed as an exclusion criterion, which involves now only history of a pre-chemotherapy left ventricular dysfunction. The period for long-term registry recruitment has been reduced (December 2017), but the target study population was extended to 3000 patients. The characteristics of the population are now better defined: patients seen in an imaging lab, which will include patients undergoing chemotherapy with associated targeted therapy or no targeted therapy, at increased risk of ADRC. In total, 1294 breast cancer patients have been enrolled, and 783 case report forms locked from October 2014 to November 2016. Of these, 481 (61.4%) were seen at first evaluation and 302 (38.6%) while on oncologic treatment with anticancer drugs. Fifty-two patients (17.2%) were not in targeted therapies, 191 (63.3%) were ongoing targeted therapy, and 59 (19.5%) had completed it. Twenty-three (2.9%) patients had a suspected diagnosis and 35 (4.5%) a confirmed diagnosis of ADRC. Arterial hypertension was the most prevalent cardiovascular risk factor (29.2%) followed by diabetes (6.1%). Previous history of heart failure accounted for 0.5%, whereas previous cardiac disease was identified in 6.3% of population. The changes of the original protocol of the COT Registry and first update allow a first glance to the panorama of cardiovascular characteristics of breast cancer patients enrolled. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Protocol update and preliminary results of EACVI/HFA Cardiac Oncology Toxicity (COT) Registry of the European Society of Cardiology

PubMed Central

Galderisi, Maurizio; Donal, Erwan; Edvardsen, Thor; Popescu, Bogdan A.; Farmakis, Dimitrios; Filippatos, Gerasimos; Habib, Gilbert; Lestuzzi, Chiara; Santoro, Ciro; Moonen, Marie; Jerusalem, Guy; Andarala, Maryna; Anker, Stefan D.

2017-01-01

Abstract Aims European Association of Cardiovascular Imaging/Heart Failure Association Cardiac Oncology Toxicity Registry was launched in October 2014 as a European Society of Cardiology multicentre registry of breast cancer patients referred to imaging laboratories for routine surveillance, suspected, or confirmed anticancer drug‐related cardiotoxicity (ADRC). After a pilot phase (1 year recruitment and 1 year follow‐up), some changes have been made to the protocol (version 1.0) and electronic case report form. Methods and results Main changes of the version 2.0 concerned exclusion criteria, registry duration, and clarification of the population characteristics. Breast cancer radiotherapy has been removed as an exclusion criterion, which involves now only history of a pre‐chemotherapy left ventricular dysfunction. The period for long‐term registry recruitment has been reduced (December 2017), but the target study population was extended to 3000 patients. The characteristics of the population are now better defined: patients seen in an imaging lab, which will include patients undergoing chemotherapy with associated targeted therapy or no targeted therapy, at increased risk of ADRC. In total, 1294 breast cancer patients have been enrolled, and 783 case report forms locked from October 2014 to November 2016. Of these, 481 (61.4%) were seen at first evaluation and 302 (38.6%) while on oncologic treatment with anticancer drugs. Fifty‐two patients (17.2%) were not in targeted therapies, 191 (63.3%) were ongoing targeted therapy, and 59 (19.5%) had completed it. Twenty‐three (2.9%) patients had a suspected diagnosis and 35 (4.5%) a confirmed diagnosis of ADRC. Arterial hypertension was the most prevalent cardiovascular risk factor (29.2%) followed by diabetes (6.1%). Previous history of heart failure accounted for 0.5%, whereas previous cardiac disease was identified in 6.3% of population. Conclusion The changes of the original protocol of the COT Registry and first update allow a first glance to the panorama of cardiovascular characteristics of breast cancer patients enrolled. PMID:28772051

Examining the Marketing Strategies for Three Private Universities in Cyprus

ERIC Educational Resources Information Center

Hadjiphanis, Lycourgos

2010-01-01

Previous studies have found a relationship between the implementation of marketing segmentation and promotion strategies in enrollment. However, these two factors had not yet been examined and applied to a university setting as a possible solution to decreased enrollment. The problem addressed in this study was that enrollment diminished when…

The Study of Attrition at Hudson County Community College. Status Report. Special Report 92.02.

ERIC Educational Resources Information Center

Fujita, Eleanor; Oromaner, Mark

At Hudson County Community College (HCCC), in New Jersey, research on student attrition has included cohort specific studies of enrollment and completion patterns, enrollment pattern studies of instructional programs, and periodic surveys of enrolled students, former students, and graduates. A comparative analysis conducted of previous attrition…

Falling Enrolments and Rising Expenditures: The School Board's Dilemma.

ERIC Educational Resources Information Center

Sharples, Brian

Previous increases in the costs of Canadian education were easily explained by rising enrollments. In an era of declining enrollments, increased costs are much more difficult to explain. One reason for increased costs is the large proportion of Canadian student population concentrated in high schools where programs are more expensive than at other…

The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences

PubMed Central

2010-01-01

Background In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year. Methods Cohort study with a baseline interview and a follow-up after 10.4 ± 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses. Results DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have ≥ 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up. Conclusions In the light of patient's experiences the DMP enhances the process quality of medical care for type 2 diabetes in Germany. The lack of significant differences in outcome quality between enrolled and not enrolled patients might be due to the short program duration. Our data suggest that the DMP for type 2 diabetes should not be withdrawn unless an evidently more promising approach is found. PMID:20199685

The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences.

PubMed

Schäfer, Ingmar; Küver, Claudia; Gedrose, Benjamin; Hoffmann, Falk; Russ-Thiel, Barbara; Brose, Hans-Peter; van den Bussche, Hendrik; Kaduszkiewicz, Hanna

2010-03-03

In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year. Cohort study with a baseline interview and a follow-up after 10.4 +/- 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses. DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have > or = 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up. In the light of patient's experiences the DMP enhances the process quality of medical care for type 2 diabetes in Germany. The lack of significant differences in outcome quality between enrolled and not enrolled patients might be due to the short program duration. Our data suggest that the DMP for type 2 diabetes should not be withdrawn unless an evidently more promising approach is found.

Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among Veterans dually enrolled in VA and Medicare Part D

PubMed Central

Gellad, Walid F.; Zhao, Xinhua; Thorpe, Carolyn T.; Thorpe, Joshua M.; Sileanu, Florentina E.; Cashy, John P.; Mor, Maria; Hale, Jennifer A.; Radomski, Thomas; Hausmann, Leslie R. M.; Fine, Michael J.; Good, Chester B.

2016-01-01

Background Buprenorphine is a key tool in the management of opioid use disorder, but there are growing concerns about abuse, diversion and safety. These concerns are amplified for the Department of Veterans Affairs (VA), whose patients may receive care concurrently from multiple prescribers within and outside VA. To illustrate the extent of this challenge, we examined overlapping prescriptions for buprenorphine, opioids, and benzodiazepines among Veterans dually enrolled in VA and Medicare Part D. Methods We constructed a cohort of all Veterans dually enrolled in VA and Part D who filled an opioid prescription in 2012. We identified patients who received tablet or film buprenorphine products from either source. We calculated the proportion of buprenorphine recipients with any overlapping prescription (based on days supply) for a non-buprenorphine opioid or benzodiazepine, focusing on Veterans who received overlapping prescriptions from a different system than their buprenorphine prescription (Part D buprenorphine recipients receiving overlapping opioids or benzodiazepines from VA and vice versa). Results We identified 1,790 dually enrolled Veterans with buprenorphine prescriptions, including 760 (43%) from VA and 1,091 (61%) from Part D (61 Veterans with buprenorphine from both systems were included in each group). Among VA buprenorphine recipients, 199 (26%) received an overlapping opioid prescription and 11 (1%) received an overlapping benzodiazepine prescription from Part D. Among Part D buprenorphine recipients, 208 (19%) received an overlapping opioid prescription and 178 (16%) received an overlapping benzodiazepine prescription from VA. Among VA and Part D buprenorphine recipients with cross-system opioid overlap, 25% (49/199) and 35% (72/208), respectively, had >90 days of overlap. Conclusions Many buprenorphine recipients receive overlapping prescriptions for opioids and benzodiazepines from a different health care system than the one in which their buprenorphine was filled. These findings highlight a previously undocumented safety risk for Veterans dually enrolled in VA and Medicare. PMID:27925868

Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among veterans dually enrolled in Department of Veterans Affairs and Medicare Part D.

PubMed

Gellad, Walid F; Zhao, Xinhua; Thorpe, Carolyn T; Thorpe, Joshua M; Sileanu, Florentina E; Cashy, John P; Mor, Maria; Hale, Jennifer A; Radomski, Thomas; Hausmann, Leslie R M; Fine, Michael J; Good, Chester B

2017-01-01

Buprenorphine is a key tool in the management of opioid use disorder, but there are growing concerns about abuse, diversion, and safety. These concerns are amplified for the Department of Veterans Affairs (VA), whose patients may receive care concurrently from multiple prescribers within and outside VA. To illustrate the extent of this challenge, we examined overlapping prescriptions for buprenorphine, opioids, and benzodiazepines among veterans dually enrolled in VA and Medicare Part D. We constructed a cohort of all veterans dually enrolled in VA and Part D who filled an opioid prescription in 2012. We identified patients who received tablet or film buprenorphine products from either source. We calculated the proportion of buprenorphine recipients with any overlapping prescription (based on days supply) for a nonbuprenorphine opioid or benzodiazepine, focusing on veterans who received overlapping prescriptions from a different system than their buprenorphine prescription (Part D buprenorphine recipients receiving overlapping opioids or benzodiazepines from VA and vice versa). There were 1790 dually enrolled veterans with buprenorphine prescriptions, including 760 (43%) from VA and 1091 (61%) from Part D (61 veterans with buprenorphine from both systems were included in each group). Among VA buprenorphine recipients, 199 (26%) received an overlapping opioid prescription and 11 (1%) received an overlapping benzodiazepine prescription from Part D. Among Part D buprenorphine recipients, 208 (19%) received an overlapping opioid prescription and 178 (16%) received an overlapping benzodiazepine prescription from VA. Among VA and Part D buprenorphine recipients with cross-system opioid overlap, 25% (49/199) and 35% (72/208), respectively, had >90 days of overlap. Many buprenorphine recipients receive overlapping prescriptions for opioids and benzodiazepines from a different health care system than the one in which their buprenorphine was filled. These findings highlight a previously undocumented safety risk for veterans dually enrolled in VA and Medicare.

Nuclear factor kappa B in patients with a history of unstable angina: case re-opened.

PubMed

Mozzini, Chiara; Garbin, Ulisse; Stranieri, Chiara; Salandini, Giulia; Pesce, Giancarlo; Fratta Pasini, Anna Maria; Cominacini, Luciano

2018-06-01

This study aims at assessing NF-kB activity in unstable angina (UA) patients free of symptoms after a 1 year follow-up (1YFU). Plasma oxidized low-density lipoproteins (oxLDL), circulating NF-kB, Interleukin 6 (IL-6) and Interleukin 1β (IL-1β), high-sensitivity C-reactive protein (hs-CRP), as markers of oxidative stress and inflammation and plasma double-stranded DNA (ds-DNA), as marker of Neutrophil Extracellular Traps (NETs), were measured in 23 of the previously enrolled 27 UA patients. These measurements were compared to the UA data at baseline, and then compared to the data derived from the stable angina (SA) and controls (C) enrolled in our previous study (we demonstrated that UA had higher levels of NF-kB compared to SA and C). After a 1YFU, UA patients show a significant decrease in NF-kB, IL-6, hs-CRP, oxLDL, and ds-DNA plasma levels (p < 0.001) and in IL-1β and White Blood Cells (WBC) (p < 0.005), without differences in lipid and glucose assessment. If compared to SA and C, UA after a 1YFU have higher levels of NF-kB, IL-6, ds-DNA, WBC, and oxLDL compared to C (p < 0.001), but only IL-6 is higher than SA (p < 0.001). No differences are found in lipid and glucose assessment. After a 1YFU, patients with a history of UA improve their oxidative and inflammatory status, such as the levels of circulating ds-DNA, without achieving the status of C. They become comparable to SA subjects. This study provides new insight on the multiple and apparently contradictory facets of NF-kB in UA and on its possible role as mediator in NETs' formation.

AN OPEN-LABEL EXTENSION STUDY OF PARATHYROID HORMONE RHPTH(1-84) IN ADULTS WITH HYPOPARATHYROIDISM.

PubMed

Lakatos, Peter; Bajnok, Laszlo; Lagast, Hjalmar; Valkusz, Zsuzsanna

2016-05-01

Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism. This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia. Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred. This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.

Zilver PTX Post-Market Surveillance Study of Paclitaxel-Eluting Stents for Treating Femoropopliteal Artery Disease in Japan: 12-Month Results.

PubMed

Yokoi, Hiroyoshi; Ohki, Takao; Kichikawa, Kimihiko; Nakamura, Masato; Komori, Kimihiro; Nanto, Shinsuke; O'Leary, Erin E; Lottes, Aaron E; Snyder, Scott A; Dake, Michael D

2016-02-08

This multicenter, prospective, post-market surveillance study in Japan evaluates the paclitaxel-coated Zilver PTX stent in real-world patients with complex lesions. The Zilver PTX stent is the first drug-eluting stent (DES) approved for the superficial femoral artery. Previously, results from a large randomized study and a complementary, large single-arm study supported the safety and effectiveness of the DES. There were no exclusion criteria, and consecutive patients with symptomatic peripheral artery disease (PAD) treated with the DES were enrolled in the study. Clinically driven target lesion revascularization (TLR) was defined as reintervention performed for ≥50% diameter stenosis after recurrent clinical symptoms of PAD. Clinical benefit was defined as freedom from persistent or worsening symptoms of ischemia. Patency was evaluated by duplex ultrasound where physicians considered this standard of care. In this study, 907 patients were enrolled at 95 institutions in Japan. There were numerous comorbidities including high incidences of diabetes (58.8%), chronic kidney disease (43.8%), and critical limb ischemia (21.5%). Lesions were also complex, with an average length of 14.7 cm, 41.6% total occlusions, and 18.6% in-stent restenosis. In total, 1,861 DES were placed in 1,075 lesions. Twelve-month follow-up was obtained for >95% of eligible patients. Freedom from TLR was 91.0%, and clinical benefit was 87.7% through 12 months. The 12-month primary patency rate was 86.4%. Despite more challenging lesions, results from the current study are similar to outcomes from the previous Zilver PTX studies, confirming the benefit of the Zilver PTX DES in a real-world patient population. (Zilver PTX Post-Market Study in Japan; NCT02254837). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Whole-Exome Sequencing to Identify Rare Variants and Gene Networks that Increase Susceptibility to Scleroderma in African Americans.

PubMed

Gourh, Pravitt; Remmers, Elaine F; Boyden, Steven E; Alexander, Theresa; Morgan, Nadia D; Shah, Ami A; Mayes, Maureen D; Doumatey, Ayo; Bentley, Amy R; Shriner, Daniel; Domsic, Robyn T; Medsger, Thomas A; Steen, Virginia D; Ramos, Paula S; Silver, Richard M; Korman, Benjamin; Varga, John; Schiopu, Elena; Khanna, Dinesh; Hsu, Vivien; Gordon, Jessica K; Saketkoo, Lesley Ann; Gladue, Heather; Kron, Brynn; Criswell, Lindsey A; Derk, Chris T; Bridges, S Louis; Shanmugam, Victoria K; Kolstad, Kathleen D; Chung, Lorinda; Jan, Reem; Bernstein, Elana J; Goldberg, Avram; Trojanowski, Marcin; Kafaja, Suzanne; Maksimowicz-McKinnon, Kathleen M; Mullikin, James C; Adeyemo, Adebowale; Rotimi, Charles; Boin, Francesco; Kastner, Daniel L; Wigley, Fredrick M

2018-05-06

Whole-exome sequencing (WES) studies in systemic sclerosis (SSc) patients of European American (EA) ancestry have identified variants in the ATP8B4 gene and enrichment of variants in genes in the extracellular matrix (ECM)-related pathway increasing SSc susceptibility. Our goal was to evaluate the association of the ATP8B4 gene and the ECM-related pathway with SSc in a cohort of African Americans (AA). SSc patients of AA ancestry were enrolled from 23 academic centers across the United States under the Genome Research in African American Scleroderma Patients (GRASP) consortium. Unrelated AA individuals without serological evidence of autoimmunity enrolled in the Howard University Family Study were used as unaffected controls. Functional variants in genes reported in the two WES studies in EA SSc were selected for gene association testing using the optimized sequence kernel association test (SKAT-O) and pathway analysis by Ingenuity pathway analysis in 379 patients and 411 controls. Principal components analysis demonstrated that the patients and controls had similar ancestral backgrounds with about equal proportions of mean European admixture. Using SKAT-O, we examined the association of individual genes that were previously reported in EAs, and none remained significant including ATP8B4 (P U nCorr =0.98). However, we confirm the previously reported association of the ECM-related pathway with enrichment of variants within the COL13A1, COL18A1, COL22A1, COL4A3, COL4A4, COL5A2, PROK1, and SERPINE1 genes (P C orr =1.95×10 -4 ). This is the largest genetic study in AAs with SSc to date, corroborating the role of functional variants aggregating in a fibrotic pathway and increasing SSc susceptibility. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[The safety of long-term administration of losartan in current clinical practice: a non-intervention NCT-CZ 14/04/LOZ study].

PubMed

Krupicka, J; Ceypová, K; Kristenová, P; Hauser, T

2008-11-01

Losartan is the longest used angiotensin II receptor blocker in clinical practice. It is one of the first-line drugs for the treatment of hypertensive disease and there is enough data available today about its use in the treatment of the disease, including some specific situations (left ventricular hypertrophy, cerebrovascular accidents) and cases when the hypertension disease combines with another disease (e.g. diabetic nephropathy). The primary objective of the non-intervention multicentre prospective observational open clinical assessment NCT-CZ 14/04/LOZ was to verify on a large sample of patients the safety of Lozap and Lozap H in current clinical practice. The six-month clinical study enrolled patients with recently diagnosed hypertension and/or poorly controlled hypertension [blood pressure > or = 140/90 mm Hg: 4432 patients (96%); blood pressure: < or = 139/89 mm Hg 84 patients (2%); value unspecified: 83 patients (2%)]. A standard form was used for data acquisition. A total of 4,599 patients was enrolled (of which 2,386 women, i.e. 51.9%) with mean age 61 +/- 12 years (18-95 years; median 60 years) with additional risk factors (cardiovascular diseases in 48%, diabetes mellitus in 33%, lipid metabolism disorder in 42%, obesity in 45% and smoking in 26% of cases, respectively). 2,631 patients (57%) had previously diagnosed hypertension. The average blood pressure (BP) at enrolment in the study was 159/95mm Hg (median 160/95 mm Hg), and the average heart rate was 76 strokes/min (median 76). The most frequently used dose was 50 mg of losartan (Lozap or Lozap H)--in 4,006 patients (87%) at enrolment in the study and in 3,982 patients (87%) at the end of the study. Adverse effects related to the treatment during the study were reported in a total of 9 patients (0.2%). The therapy was assessed as well tolerated in 96% of patients (4,409), as fairly tolerated in 3% of patients (131) and as poorly tolerated in 0.1% of patients (4). Systolic and diastolic blood pressure decreased by 23mm Hg and 14mm Hg respectively to a mean value of 136/81 mm Hg (median 135/80mm Hg) (P < 0.001 for both systolic and diastolic BP). Improvement in patient status was recorded in 93% of cases (4,254 patients) and no change was recorded in 6% of cases (294 patients). Losartan in the form of Lozap or Lozap is a safe and effective treatment of patients with hypertensive disease. It is effective and safe beginning with the dose of 50 mg and its combination with a diuretic represents a good and safe therapy in patients with insufficient BP response to a 50 mg dose of losartan alone. In case of poor blood pressure response the dose has to be titrated to 100 mg.

[Tele-medicine system for high-risk asthmatic patients].

PubMed

Kokubu, F; Suzuki, H; Sano, Y; Kihara, N; Adachi, M

1999-07-01

We have developed a tele-medicine system to monitor the airway status at home for patients with poorly controlled asthma, whereby a nurse provides instructions to individuals via the telephone to help them manage exacerbation under the supervision of their physicians. We examined the effectiveness of this system with a randomized control study. Patients with high hospitalization risk were enrolled in the study by screening patients for those with multiple previous emergency room visits and randomly assigned to either the tele-medicine or control group. After six months of participation in the program, the number of emergency room visits decreased significantly and the activities of daily living were improved in the tele-medicine group. Most of the patients in the tele-medicine group were able to continue measuring and transmitting peak expiratory flow (PEF) value successfully, and at six months had noticed an improvement in PEF. We therefore conclude that the system effectively contributes to the management of poorly controlled asthma. In addition, further consideration suggests that the reduction of emergency room visits may lead to reduction in hospitalization since we found a good correlation between number of emergency room visits and hospitalization from the studies published previously.

The impact of reducing financial barriers on utilisation of a primary health care facility in Rwanda.

PubMed

Dhillon, Ranu S; Bonds, Matthew H; Fraden, Max; Ndahiro, Donald; Ruxin, Josh

2012-01-01

This study investigates the impact of subsidising community-based health insurance (mutuelle) enrolment, removing point-of-service co-payments, and improving service delivery on health facility utilisation rates in Mayange, a sector of rural Rwanda of approximately 25,000 people divided among five 'imidugudu' or small villages. While comprehensive service upgrades were introduced in the Mayange Health Centre between April 2006 and February 2007, utilisation rates remained similar to comparison sites. Between February 2007 and April 2007, subsidies for mutuelle enrolment established virtually 100% coverage. Immediately after co-payments were eliminated in February 2007, patient visits levelled at a rate triple the previous value. Regression analyses using data from Mayange and two comparison sites indicate that removing financial barriers resulted in about 0.6 additional annual visits for curative care per capita. Although based on a single local pilot, these findings suggest that in order to achieve improved health outcomes, key short-term objectives include improved service delivery and reduced financial barriers. Based on this pilot, higher utilisation rates may be affected if broader swaths of the population are enrolled in mutuelle and co-payments are eliminated. Health leaders in Rwanda should consider further studies to determine if the impact of eliminating co-payments and increasing subsidies for mutuelle enrolment as seen in Mayange holds at greater levels of scale. Broader studies to better elucidate the impact of enrolment subsidies and co-payment subsidies on utilisation, health outcomes, and costs would also provide policy insights.

An observational study of the initial management of hypothyroidism in France: the ORCHIDÉE study

PubMed Central

Delemer, Brigitte; Aubert, Jean-Pierre; Nys, Pierre; Landron, Frédéric; Bouée, Stéphane

2012-01-01

Objective To document the initial management of hypothyroidism in France with respect to diagnostic setting, investigations, and therapeutic approach. Design Observational study of the management by primary care practitioners (PCPs) and endocrinologists of patients diagnosed with, and treated for, hypothyroidism during the enrollment period or the previous 6 months. Methods A representative sample of PCPs and endocrinologists enrolled up to five consecutive patients and reported sociodemographic, clinical, therapeutic, and laboratory data. Data were submitted at baseline and at the first measurement of TSH after starting the treatment. Results The analysis population comprised 1255 patients (mean (s.d.) age 52.8 (16.3) years; 84% female). Hypothyroidism was suspected on clinical grounds in 77% of patients, with goiter in 16%. Autoimmune thyroiditis, supported by positive anti-thyroid antibodies, was the most frequent diagnosis (59%), followed by iatrogenic causes (28%), of which thyroidectomy was the most common. The median baseline TSH was 8.6 mIU/l, suggesting a high incidence of subclinical hypothyroidism. Imaging studies were requested in over 75% of patients, with ultrasound performed in 98% and scintigraphy performed in 19% of these patients. Both groups of physicians treated their patients almost exclusively with levothyroxine. Endocrinologists were more likely than PCPs to provide counseling on how to take medication correctly. Conclusions This observational study of a large cohort of patients with newly diagnosed hypothyroidism in France illustrates current practice and indicates some areas where physician education may be required to optimize adherence to guidelines and cost-effectiveness. PMID:23034782

Cost effectiveness of using surgery versus skeletal traction in management of femoral shaft fractures at Thika level 5 hospital, Kenya.

PubMed

Opondo, Everisto; Wanzala, Peter; Makokha, Ansellimo

2013-01-01

A prospective quasi experimental study was undertaken at the Thika level 5 hospital. The study aimed to compare the costs of managing femoral shaft fracture by surgery as compared to skeletal traction. Sixty nine (46.6%) patients were enrolled in group A and managed surgically by intramedullary nailing while 79 (53.4%) patients were enrolled in group B and managed by skeletal traction. Exclusion criteria included patients with pathological fractures and previous femoral fractures. Data was collected by evaluation of patients in patient bills using a standardized questionnaire. The questionnaire included cost of haematological and radiological tests, bed fees, theatre fees and physiotherapy costs. The data was compiled and analyzed using SPSS version 16. Person's chi square and odds ratios were used to measure associations and risk analysis respectively. A higher proportion of patients (88.4%) in group A were hospitalized for less than one month compared to 20 patients (30.4%) in group B (p, 0.001).Total cost of treatment in group A was significantly lower than in group B. Nineteen (27.9%) patients who underwent surgery paid a total bill of Ksh 5000-7500 compared to 7(10.4%) who were treated by traction. The financial cost benefit of surgery was further complimented by better functional outcomes. The data indicates a cost advantage of managing femoral shaft fracture by surgery compared to traction. Furthermore the longer hospital stay in the traction group is associated with more malunion, limb deformity and shortening.

Physician-directed heart failure transitional care program: a retrospective case review.

PubMed

Ota, Ken S; Beutler, David S; Gerkin, Richard D; Weiss, Jessica L; Loli, Akil I

2013-10-01

Despite a variety of national efforts to improve transitions of care for patients at risk for rehospitalization, 30-day rehospitalization rates for patients with heart failure have remained largely unchanged. This is a retrospective review of 73 patients enrolled in our hospital-based, physican-directed Heart Failure Transitional Care Program (HFTCP). This study evaluated the 30- and 90- day readmission rates before and after enrollment in the program. The Transitionalist's services focused on bedside consultation prior to hospital discharge, follow-up home visits within 72 hours of discharge, frequent follow-up phone calls, disease-specific education, outpatient intravenous diuretic therapy, and around-the-clock telephone access to the Transitionalist. The pre-enrollment 30-day readmission rates for acute decompensated heart failure (ADHF) and all-cause readmission was 26.0% and 28.8%, respectively, while the post-enrollment rates for ADHF and all-cause readmission were 4.1% (P < 0.001) and 8.2% (P = 0.002), respectively. The pre-enrollment 90-day all-cause and ADHF readmission rates were 69.8%, and 58.9% respectively, while the post-enrollment rates for all-cause and ADHF were 27.3% (P < 0.001) and 16.4% (P < 0.001) respectively. Our physician-implemented HFTCP reduced rehospitalization risk for patients enrolled in the program. This program may serve as a model to assist other hospital systems to reduce readmission rates of patients with HF.

Upper Tract Urothelial Carcinomas Accompanied by Previous or Synchronous Nonmuscle-Invasive Bladder Cancer and Preoperative Hydronephrosis Might Have Worse Oncologic Outcomes After Radical Nephroureterectomy.

PubMed

Liang, Chengcai; Chi, Runmin; Huang, Liqun; Wang, Jinliang; Liu, Hailong; Xu, Ding; Qian, Subo; Qian, Xiaoqiang; Qi, Jun

2016-10-01

The purpose of the study was to identify predictors of clinicopathologic features and oncologic outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy (RNU). The medical records of 172 patients treated with RNU from January 2001 to September 2014 were retrospectively reviewed. Logistic regression and survival analysis methodology were respectively used to evaluate predictors of clinicopathologic features and oncologic outcomes. Of the enrolled 172 patients, 80 (46.5%) had renal pelvic tumors, 67 (39%) had ureteral tumors, and the remaining 25 (14.5%) patients had multifocal tumors. Compared with patients with renal pelvic tumors, those with ureteral and multifocal tumors were more likely to have previous or synchronous nonmuscle-invasive bladder cancer (NMIBC) and severe hydronephrosis (P = .001 and P < .001, respectively). Logistic regression analysis showed that previous or synchronous NMIBC was significantly associated with worse renal function and high grade (P = .034 and P = .014, respectively), and severe hydronephrosis independently predicted worse renal function and positive lymph node or lymphovascular invasion status (P = .001 and P = .007, respectively). Moreover, severe hydronephrosis was an independent risk factor for overall survival and cancer-specific survival in multivariate analysis (P = .025 and P = .045, respectively). Multifocality and previous or synchronous NMIBC were significantly associated with bladder-recurrence-free survival (P = .023 and P = .001, respectively). Upper tract urothelial carcinoma accompanied by previous or synchronous NMIBC and preoperative severe hydronephrosis could have worse oncologic outcomes after RNU. These common accompanied diagnoses could be valuable for guiding preoperative planning and postoperative adjuvant therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Prospective Observational Study of Implantable Cardioverter‐Defibrillators in Primary Prevention of Sudden Cardiac Death: Study Design and Cohort Description

PubMed Central

Cheng, Alan; Dalal, Darshan; Butcher, Barbara; Norgard, Sanaz; Zhang, Yiyi; Dickfeld, Timm; Eldadah, Zayd A.; Ellenbogen, Kenneth A.; Guallar, Eliseo; Tomaselli, Gordon F.

2013-01-01

Background Primary‐prevention implantable cardioverter‐defibrillators (ICDs) reduce total mortality in patients with severe left ventricular systolic function. However, only a minority of patients benefit from these devices. We designed the Prospective Observational Study of Implantable Cardioverter‐Defibrillators (PROSE‐ICD) to identify risk factors and enhance our understanding of the biological mechanisms that predispose to arrhythmic death in patients undergoing ICD implantation for primary prevention of sudden death. Methods and Results This is a multicenter prospective cohort study with a target enrollment of 1200 patients. The primary end point is ICD shocks for adjudicated ventricular tachyarrhythmias. The secondary end point is total mortality. All patients undergo a comprehensive evaluation including history and physical examination, signal‐averaged electrocardiograms, and blood sampling for genomic, proteomic, and metabolomic analyses. Patients are evaluated every 6 months and after every known ICD shock for additional electrocardiographic and blood sampling. As of December 2011, a total of 1177 patients have been enrolled with more nonwhite and female patients compared to previous randomized trials. A total of 143 patients have reached the primary end point, whereas a total of 260 patients died over an average follow‐up of 59 months. The PROSE‐ICD study represents a real‐world cohort of individuals with systolic heart failure receiving primary‐prevention ICDs. Conclusions Extensive electrophysiological and structural phenotyping as well as the availability of serial DNA and serum samples will be important resources for evaluating novel metrics for risk stratification and identifying patients at risk for arrhythmic sudden death. Clinical Trial Registration URL: http://clinicaltrials.gov/ Unique Identifier: NCT00733590. PMID:23525420

The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinson's disease.

PubMed

Giladi, Nir; Boroojerdi, Babak; Surmann, Erwin

2013-09-01

This open-label extension (SP716; NCT00599196) of a 6-month, double-blind, randomized study (SP513) investigated the safety and tolerability of rotigotine transdermal system over up to ~6 years in patients with Parkinson's disease (PD; early-stage PD at double-blind enrollment). Eligible patients completing the 6-month study received optimal dose open-label rotigotine (≤ 16 mg/24 h) for up to ~6 years. Adjunctive levodopa was permitted. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Analysis of adjunctive levodopa use, dyskinesias [unified Parkinson's disease rating scale (UPDRS) IV], and efficacy (UPDRS II + III total score) were also assessed. Of 381 patients enrolled in the open-label extension, 52 % were still in the study at time of closure; 24 % withdrew because of AEs and 6 % because of lack of efficacy. Patients received rotigotine for a median duration of 1,564.5 days (~4 years, 3 months; range 5-2, 145 days). 69 % of patients started supplemental levodopa; median time to levodopa was 485 days (~1 year, 4 months). Most common AEs (% per patient-year) were somnolence (18 %), application site reactions (12 %), nausea (9 %), peripheral edema (7 %), and fall (7 %). AEs indicative of impulsive-compulsive behavior were recorded in 25 (7 %) patients. Dyskinesias were experienced by 65 (17 %) patients; the majority [47 of 65 (72 %)] reported first dyskinesia after starting levodopa. Mean UPDRS II + III total scores remained below double-blind baseline for 4 years (assessment of all patients). In conclusion, rotigotine was generally well tolerated for up to ~6 years in patients with early-stage PD. The AEs reported were in line with previous studies of rotigotine transdermal system, with typical dopaminergic side effects and application site reactions seen.

Encouraging Patient Portal Use in the Patient-Centered Medical Home: Three Stakeholder Perspectives.

PubMed

Fix, Gemmae M; Hogan, Timothy P; Amante, Daniel J; McInnes, D Keith; Nazi, Kim M; Simon, Steven R

2016-11-22

Health care organizations are increasingly offering patients access to their electronic medical record and the ability to communicate with their providers through Web-based patient portals, thus playing a prominent role within the patient-centered medical home (PCMH). However, despite enthusiasm, adoption remains low. We examined factors in the PCMH context that may affect efforts to improve enrollment in a patient portal. Using a sociotechnical approach, we conducted qualitative, semistructured interviews with patients and providers from 3 primary care clinics and with national leaders from across a large integrated health care system. We gathered perspectives and analyzed data from 4 patient focus groups and one-on-one interviews with 1 provider from each of 3 primary care clinics and 10 program leaders. We found that leaders were focused on marketing in primary care, whereas patients and providers were often already aware of the portal. In contrast, both patients and providers cited administrative and logistical barriers impeding enrollment. Further, although leadership saw the PCMH as the logical place to focus enrollment efforts, providers and patients were more circumspect and expressed concern about how the patient portal would affect their practice and experience of care. Further, some providers expressed ambivalence about patients using the portal. Despite absence of consensus on how and where to encourage portal adoption, there was wide agreement that promoting enrollment was a worthwhile goal. Patients, clinicians, and national leaders agreed that efforts were needed to increase enrollment in the patient portal. Opinions diverged regarding the suitability of the PCMH and, specifically, the primary care clinic for promoting patient portal enrollment. Policymakers should consider diverse stakeholder perspectives in advance of interventions to increase technology adoption. ©Gemmae M Fix, Timothy P Hogan, Daniel J Amante, D Keith McInnes, Kim M Nazi, Steven R Simon. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.11.2016.

Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report.

PubMed

Wang, C H; Wang, H M; Chen, J S; Chang, W J; Lai, G M

1997-01-01

Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemotherapy. The major limiting toxicity was myelotoxicity. Recently, the role of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced neutropenic sepsis has been well established. In this study, we tested whether recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow function in both previously untreated and pretreated metastatic NPC patients receiving intensive chemotherapy. Twelve patients with distant metastatic disease, 5 newly diagnosed (group A) and 7 pretreated patients (group B), were enrolled to receive BEC (bleomycin, epirubicin and cisplatin), followed by rhG-CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles. Four patients in group A completed the treatment as scheduled while only 2 patients in group B did. After the first treatment cycle, 6 patients (50%) had grade III-IV myelosuppression. Five of the patients were from group B. The mean values of the white cell count nadir were 2,680 (range 1,200-3,700) in group A and 1,343 (range 400-2,900) in group B (p = 0.0386). Neutropenia-associated fever occurred in 7 patients, 6 of whom had received previous treatment. There were 2 deaths due to toxicity, and both patients had liver metastases within 6 months following radiation. After 24 months of follow-up, only 1 patient is still alive. Our preliminary results suggest that in previously treated metastatic NPC patients, bone marrow suppression is still the major limiting toxic side effect of aggressive chemotherapy, especially for those patients with liver recurrences within 6 months after irradiation and despite rhG-CSF support.

Coverage Gains After the Affordable Care Act Among the Uninsured in Minnesota.

PubMed

Call, Kathleen Thiede; Lukanen, Elizabeth; Spencer, Donna; Alarcón, Giovann; Kemmick Pintor, Jessie; Baines Simon, Alisha; Gildemeister, Stefan

2015-11-01

We determined whether and how Minnesotans who were uninsured in 2013 gained health insurance coverage in 2014, 1 year after the Affordable Care Act (ACA) expanded Medicaid coverage and enrollment. Insurance status and enrollment experiences came from the Minnesota Health Insurance Transitions Study (MH-HITS), a follow-up telephone survey of children and adults in Minnesota who had no health insurance in the fall of 2013. ACA had a tempered success in Minnesota. Outreach and enrollment efforts were effective; one half of those previously uninsured gained coverage, although many reported difficulty signing up (nearly 62%). Of the previously uninsured who gained coverage, 44% obtained their coverage through MNsure, Minnesota's insurance marketplace. Most of those who remained uninsured heard of MNsure and went to the Web site. Many still struggled with the enrollment process or reported being deterred by the cost of coverage. Targeting outreach, simplifying the enrollment process, focusing on affordability, and continuing funding for in-person assistance will be important in the future.

Coverage Gains After the Affordable Care Act Among the Uninsured in Minnesota

PubMed Central

Lukanen, Elizabeth; Spencer, Donna; Alarcón, Giovann; Kemmick Pintor, Jessie; Baines Simon, Alisha; Gildemeister, Stefan

2015-01-01

Objectives. We determined whether and how Minnesotans who were uninsured in 2013 gained health insurance coverage in 2014, 1 year after the Affordable Care Act (ACA) expanded Medicaid coverage and enrollment. Methods. Insurance status and enrollment experiences came from the Minnesota Health Insurance Transitions Study (MH-HITS), a follow-up telephone survey of children and adults in Minnesota who had no health insurance in the fall of 2013. Results. ACA had a tempered success in Minnesota. Outreach and enrollment efforts were effective; one half of those previously uninsured gained coverage, although many reported difficulty signing up (nearly 62%). Of the previously uninsured who gained coverage, 44% obtained their coverage through MNsure, Minnesota’s insurance marketplace. Most of those who remained uninsured heard of MNsure and went to the Web site. Many still struggled with the enrollment process or reported being deterred by the cost of coverage. Conclusions. Targeting outreach, simplifying the enrollment process, focusing on affordability, and continuing funding for in-person assistance will be important in the future. PMID:26447912

What Fraction of Medicaid Enrollees Have Private Insurance Coverage at the Time of Enrollment? Estimates from Administrative Data

PubMed Central

DeLeire, Thomas; Friedsam, Donna; Leininger, Lindsey; Meier, Sarah; Voskuil, Kristen

2014-01-01

We use administrative data from Wisconsin to determine the fraction of new Medicaid enrollees who have private health insurance at the time of enrollment in the program. Through the linkage of several administrative data sources not previously used for research, we are able to observe coverage status directly for a large fraction of enrollees and indirectly for the remainder. We provide strict bounds for the percentages in each status and find that the percentage of new enrollees with private insurance coverage at the time of enrollment lies between 16 percent and 29 percent, and the percentage that dropped private coverage in favor of public insurance lies between 4 percent and 18 percent. Our point estimates indicate that, among all new enrollees, 21 percent had private health insurance at the time of enrollment and that 10 percent dropped this coverage. Our results show substantially lower rates than previous studies of crowd-out following public health insurance expansions and significant rates of dual coverage, whereby new enrollees into public insurance retain their previously held private insurance coverage. PMID:25316718

State of Kansas: K-12 Enrollment Projection Report

ERIC Educational Resources Information Center

Carter, Ted

2015-01-01

This document contains headcount enrollment projections for the State of Kansas for the 2015-16 school year through the 2019-20 school year. These projections are based on resident live births in Kansas and the headcount enrollment data for previous school years. Based on the available data related to resident live births by county and previous…

Interinstitutional Collaboration Practices between Virginia Community Colleges and High Schools Involved in Dual Enrollment Articulation Agreements

ERIC Educational Resources Information Center

Caradona, Sally Lynn

2012-01-01

The purpose of this study was to build on the previous work of articulation practices of Virginia's public school divisions and community colleges participating in dual enrollment partnerships, and to understand the role of the community college in initiating, developing, and implementing dual enrollment programs. The primary focus involved…

Effect of improved access to antiretroviral therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania.

PubMed

Mugusi, Sabina F; Mwita, Julius C; Francis, Joel M; Aboud, Said; Bakari, Muhammad; Aris, Eric A; Swai, Andrew B; Mugusi, Ferdinand M; Pallangyo, Kisali; Sandstrom, Eric

2010-05-28

Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004-Dec 2005 compared to those enrolled between 2006 and September 2008. Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/microl) with 65.7% having below 200 cells/microl. Females had higher CD4 cell counts (150 cells/microl) than males (109 cells/microl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/microl) compared to CD4 of 167 cells/microl in those seen later (2006-8) (p < 0.001). Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease.

Validity of subjective smoking status in orthopedic patients.

PubMed

Bender, Daniel; Haubruck, Patrick; Boxriker, Sonja; Korff, Sebastian; Schmidmaier, Gerhard; Moghaddam, Arash

2015-01-01

In this level 1 diagnostic study, we analyzed the validity of subjective smoking status and, as secondary research question, the smoking cessation adherence in orthopedic patients during a routine hospital stay of nonunion patients by measuring serum cotinine. We included patients undergoing revision surgery due to nonunion of long bones. Patients were interviewed about their smoking status. Blood samples were taken from all the patients prior to surgery and for an additional 6 weeks following surgery. Serum levels of cotinine were measured, and coherence between subjective smoking status and objective cotinine analysis was evaluated. Between March 2012 and August 2014, we enrolled 136 patients. Six of the 26 "previous smokers" (23%) and four of the 65 "nonsmokers" (6%) had serum cotinine above cutoff levels. In self-labeled smokers, serum cotinine levels averaged at 2,367.4±14,885.9 ng/mL (with a median of 100 ng/mL), whereas in previous smokers the levels averaged at 4,270±19,619.4 ng/mL (with a median of 0 ng/mL) and in the nonsmokers group the levels averaged at 12±53.9 ng/mL (with a median of 0.03 ng/mL). Overall, the subjective smoking status matched serum cotinine testing in 88% of the cases. Sensitivity was 79.6% and specificity was 93.1%. Ninety-one percent of the patients with preoperative positive serum values were still positive at follow-up. In this study, we could show that subjective smoking status in orthopedic patients is predominantly reliable as validated by objective cotinine measurements; however, patients who declare themselves as "previous smokers" are at elevated risk for underreporting continued smoking and patients who smoked preoperatively are at high risk for continuing their habit. In the future, caregivers should consider introducing effective treatments for smoking cessation to smokers and furthermore offer effective treatments to maintain smoking cessation in previous smokers during their routine consultation prior to orthopedic and trauma surgery.

Reduced cost and mortality using home telehealth to promote self-management of complex chronic conditions: a retrospective matched cohort study of 4,999 veteran patients.

PubMed

Darkins, Adam; Kendall, Stephen; Edmonson, Ellen; Young, Michele; Stressel, Pamela

2015-01-01

This retrospective analysis of 2009-2012 Veterans Health Administration (VHA) administrative data assessed the efficacy of care coordination home telehealth (CCHT), a model of care designed to reduce institutional care. Outcomes for 4,999 CCHT-non-institutional care (NIC) patients were compared with usual (non-CCHT) care in a matched cohort group (MCG) of 183,872 Veterans. Both cohorts were comprised of patients with complex chronic conditions with statistically similar baseline (pre-CCHT enrollment) healthcare costs, when adjusted for age, sex, chronic disease, emergency room (ER) visits, hospital admissions, hospital lengths of stay, and pharmacy costs. Subsequent analyses after 12 months of CCHT-NIC enrollment showed mean annual healthcare costs for CCHT-NIC patients fell 4%, from $21,071 to $20,206, whereas the corresponding costs for MCG patients increased 48%, from $20,937 to $31,055. Higher mean annual pharmacy expenditure of 22% ($470 over baseline) for CCHT-NIC patients versus 15% for MCG patients ($326 over baseline) was attributable to the medication compliance effect of better care coordination. Several healthcare cost drivers (e.g., ER visits and admissions) had sizable declines in the CCHT-NIC group. Medicare usage review in both cohorts excluded this as a confounding factor in cost analyses. Prefinal case selection criteria analysis of both cohorts yielded a 9.8% mortality rate in CCHT patients versus 16.58% in non-CCHT patients. This study corroborates previous positive VHA analyses of CCHT but contradicts results from recent non-VHA studies, highlighting the efficacy of the VHA's standardized CCHT model, which incorporates a biopsychosocial approach to care that emphasizes patient self-management.

Characterizing the course of back pain after osteoporotic vertebral fracture: a hierarchical cluster analysis of a prospective cohort study.

PubMed

Toyoda, Hiromitsu; Takahashi, Shinji; Hoshino, Masatoshi; Takayama, Kazushi; Iseki, Kazumichi; Sasaoka, Ryuichi; Tsujio, Tadao; Yasuda, Hiroyuki; Sasaki, Takeharu; Kanematsu, Fumiaki; Kono, Hiroshi; Nakamura, Hiroaki

2017-09-23

This study demonstrated four distinct patterns in the course of back pain after osteoporotic vertebral fracture (OVF). Greater angular instability in the first 6 months after the baseline was one factor affecting back pain after OVF. Understanding the natural course of symptomatic acute OVF is important in deciding the optimal treatment strategy. We used latent class analysis to classify the course of back pain after OVF and identify the risk factors associated with persistent pain. This multicenter cohort study included 218 consecutive patients with ≤ 2-week-old OVFs who were enrolled at 11 institutions. Dynamic x-rays and back pain assessment with a visual analog scale (VAS) were obtained at enrollment and at 1-, 3-, and 6-month follow-ups. The VAS scores were used to characterize patient groups, using hierarchical cluster analysis. VAS for 128 patients was used for hierarchical cluster analysis. Analysis yielded four clusters representing different patterns of back pain progression. Cluster 1 patients (50.8%) had stable, mild pain. Cluster 2 patients (21.1%) started with moderate pain and progressed quickly to very low pain. Patients in cluster 3 (10.9%) had moderate pain that initially improved but worsened after 3 months. Cluster 4 patients (17.2%) had persistent severe pain. Patients in cluster 4 showed significant high baseline pain intensity, higher degree of angular instability, and higher number of previous OVFs, and tended to lack regular exercise. In contrast, patients in cluster 2 had significantly lower baseline VAS and less angular instability. We identified four distinct groups of OVF patients with different patterns of back pain progression. Understanding the course of back pain after OVF may help in its management and contribute to future treatment trials.

Patient-centered disease management (PCDM) for heart failure: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Chronic heart failure (HF) disease management programs have reported inconsistent results and have not included comorbid depression management or specifically focused on improving patient-reported outcomes. The Patient Centered Disease Management (PCDM) trial was designed to test the effectiveness of collaborative care disease management in improving health status (symptoms, functioning, and quality of life) in patients with HF who reported poor HF-specific health status. Methods/design Patients with a HF diagnosis at four VA Medical Centers were identified through population-based sampling. Patients with a Kansas City Cardiomyopathy Questionnaire (KCCQ, a measure of HF-specific health status) score of < 60 (heavy symptom burden and impaired quality of life) were invited to enroll in the PCDM trial. Enrolled patients were randomized to receive usual care or the PCDM intervention, which included: (1) collaborative care management by VA clinicians including a nurse, cardiologist, internist, and psychiatrist, who worked with patients and their primary care providers to provide guideline-concordant care management, (2) home telemonitoring and guided patient self-management support, and (3) screening and treatment for comorbid depression. The primary study outcome is change in overall KCCQ score. Secondary outcomes include depression, medication adherence, guideline-based care, hospitalizations, and mortality. Discussion The PCDM trial builds on previous studies of HF disease management by prioritizing patient health status, implementing a collaborative care model of health care delivery, and addressing depression, a key barrier to optimal disease management. The study has been designed as an ‘effectiveness trial’ to support broader implementation in the healthcare system if it is successful. Trial registration Unique identifier: NCT00461513 PMID:23837415

Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program.

PubMed

Gangadhar, Tara C; Hwu, Wen-Jen; Postow, Michael A; Hamid, Omid; Daud, Adil; Dronca, Roxana; Joseph, Richard; O'Day, Steven J; Hodi, F S; Pavlick, Anna C; Kluger, Harriet; Oxborough, Romina P; Yang, Aiming; Gazdoiu, Mihaela; Kush, Debra A; Ebbinghaus, Scot; Salama, April K S

KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. Of the 947 evaluable patients, 621 (65.6%) remained on treatment and transitioned to receive commercial pembrolizumab following approval by the Food and Drug Administration, whereas 326 (34.4%) discontinued, most commonly for disease progression (39.6%) or death (26.4%). Objective response rate was 14.5% (95% confidence interval, 12.2%-16.8%) in the treated population (n=947) and 22.1% (95% confidence interval, 18.8%-25.5%) in patients who had ≥1 response assessment reported (n=619). Twelve patients achieved complete response. One hundred eighty-one (19.1%) patients experienced ≥1 treatment-related AE, most commonly general disorders (8.0%), skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%); 29 (3.1%) patients experienced ≥1 grade 3/4 treatment-related AE. Immune-mediated AEs were also reported. There were no treatment-related deaths. The safety and efficacy observed in this expanded access program were consistent with those previously reported for similar populations and support the use of pembrolizumab for patients with advanced melanoma.

Results of a Phase II Trial of Carboplatin, Pemetrexed, and Bevacizumab for the Treatment of Never or Former/Light Smoking Patients With Stage IV Non-Small Cell Lung Cancer.

PubMed

Weiss, Jared M; Villaruz, Liza C; O'Brien, Jonathon; Ivanova, Anastasia; Lee, Carrie; Olson, Juneko Grilley; Pollack, Gregory; Gorman, Richard; Socinski, Mark A; Stinchombe, Thomas E

2016-03-01

Bevacizumab- and pemetrexed-based therapies have demonstrated activity in patients with non-small-cell lung cancer (NSCLC) and nonsquamous histologic features. Patients with history of never or light smoking might derive greater benefit from these therapies. The included patients had stage IIIB (malignant pleural effusion) or IV NSCLC with nonsquamous histologic features, adequate organ function, no contraindications to bevacizumab, and no previous cytotoxic therapy. The patients had also never smoked or had smoked ≤ 10 pack years and had quit ≥ 1 year before enrollment. The patients had received 4 cycles of carboplatin (area under the curve, 6), pemetrexed 500 mg/m(2), and bevacizumab 15 mg/kg. Patients without disease progression initiated maintenance therapy with pemetrexed and bevacizumab. A single-arm phase II trial with the primary endpoint of progression-free survival (PFS) was performed. The secondary endpoints were the objective response rate (ORR), overall survival (OS), and toxicity. From March 2010 to November 2013, 38 eligible patients were enrolled and treated in the trial. The most common histologic type was adenocarcinoma (97%). Most of the patients were women (66%) and never smokers (63%). The median PFS was 12.6 months (95% confidence interval [CI], 8.0-23.9 months). The ORR and OS were 47% (95% CI, 31%-64%) and 20.3 months (95% CI, 15.8-30.5 months). The grade 3 or 4 toxicities occurring at rate of ≥ 10% were neutropenia (18%), anemia (16%), fatigue (16%), hypertension (16%), and thrombocytopenia (11%). The combination of the carboplatin, pemetrexed, and bevacizumab demonstrated activity with acceptable toxicity in patients with a clinical history of never or light smoking. Copyright © 2016 Elsevier Inc. All rights reserved.

Quality of life in the actinic neoplasia syndrome: The VA Topical Tretinoin Chemoprevention (VATTC) Trial

PubMed Central

Weinstock, Martin A.; Lee, Kachiu C.; Chren, Mary-Margaret; Marcolivio, Kimberly

2013-01-01

Background Keratinocyte carcinomas (KCs) are the most common malignancies of the skin. As lesions have a low mortality rate, understanding quality-of-life (QoL) factors is necessary in their management. Objective To assess QoL and associated patient characteristics in those with a history of keratinocyte carcinomas. Methods We conducted a cross-sectional study of veterans with a history of KCs enrolled in a randomized controlled trial for chemoprevention of keratinocyte carcinomas. Study dermatologists counted actinic keratoses (AKs) and assessed for skin photodamage. QoL was assessed using Skindex-29 and KC-specific questions. Demographics were self-reported. Results Participants (n = 931) enrolled at 5 clinical sites had worse QoL on all subscales (emotions, functioning, and symptoms) compared to a reference group of patients without skin disease. Univariate analysis demonstrated worse QoL associated with higher AK count, past 5-fluorouracil (5-FU) use, and greater sun sensitivity. Multivariate analysis demonstrated that higher AK count and past 5-FU use were independently related to diminished QoL. Higher comorbidities showed modest associations on the symptoms and functioning subscales. Number of previous KCs was not independently associated with any QoL differences. Limitations Study population may not be generalizable to the general population. Counting of AKs is of limited reliability. Previous 5-FU use is self reported. Conclusions A history of ever use of 5-FU and present AKs was strongly associated with worse QoL. We find it more useful to consider these patients as having the chronic condition “actinic neoplasia syndrome,” whose burden may be best measured by factors other than their history of KCs. PMID:19398145

Risk factors for lung function decline in a large cohort of young cystic fibrosis patients.

PubMed

Cogen, Jonathan; Emerson, Julia; Sanders, Don B; Ren, Clement; Schechter, Michael S; Gibson, Ronald L; Morgan, Wayne; Rosenfeld, Margaret

2015-08-01

To identify novel risk factors and corroborate previously identified risk factors for mean annual decline in FEV1% predicted in a large, contemporary, United States cohort of young cystic fibrosis (CF) patients. Retrospective observational study of participants in the EPIC Observational Study, who were Pseudomonas-negative and ≤12 years of age at enrollment in 2004-2006. The associations between potential demographic, clinical, and environmental risk factors evaluated during the baseline year and subsequent mean annual decline in FEV1 percent predicted were evaluated using generalized estimating equations. The 946 participants in the current analysis were followed for a mean of 6.2 (SD 1.3) years. Mean annual decline in FEV1% predicted was 1.01% (95%CI 0.85-1.17%). Children with one or no F508del mutations had a significantly smaller annual decline in FEV1 compared to F508del homozygotes. In a multivariable model, risk factors during the baseline year associated with a larger subsequent mean annual lung function decline included female gender, frequent or productive cough, low BMI (<66th percentile, median in the cohort), ≥1 pulmonary exacerbation, high FEV1 (≥115% predicted, in the top quartile), and respiratory culture positive for methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus, or Stenotrophomonas maltophilia. We have identified a range of risk factors for FEV1 decline in a large cohort of young, CF patients who were Pa negative at enrollment, including novel as well as previously identified characteristics. These results could inform the design of a clinical trial in which rate of FEV1 decline is the primary endpoint and identify high-risk groups that may benefit from closer monitoring. © 2015 Wiley Periodicals, Inc.

Applying Sequential Analytic Methods to Self-Reported Information to Anticipate Care Needs.

PubMed

Bayliss, Elizabeth A; Powers, J David; Ellis, Jennifer L; Barrow, Jennifer C; Strobel, MaryJo; Beck, Arne

2016-01-01

Identifying care needs for newly enrolled or newly insured individuals is important under the Affordable Care Act. Systematically collected patient-reported information can potentially identify subgroups with specific care needs prior to service use. We conducted a retrospective cohort investigation of 6,047 individuals who completed a 10-question needs assessment upon initial enrollment in Kaiser Permanente Colorado (KPCO), a not-for-profit integrated delivery system, through the Colorado State Individual Exchange. We used responses from the Brief Health Questionnaire (BHQ), to develop a predictive model for cost for receiving care in the top 25 percent, then applied cluster analytic techniques to identify different high-cost subpopulations. Per-member, per-month cost was measured from 6 to 12 months following BHQ response. BHQ responses significantly predictive of high-cost care included self-reported health status, functional limitations, medication use, presence of 0-4 chronic conditions, self-reported emergency department (ED) use during the prior year, and lack of prior insurance. Age, gender, and deductible-based insurance product were also predictive. The largest possible range of predicted probabilities of being in the top 25 percent of cost was 3.5 percent to 96.4 percent. Within the top cost quartile, examples of potentially actionable clusters of patients included those with high morbidity, prior utilization, depression risk and financial constraints; those with high morbidity, previously uninsured individuals with few financial constraints; and relatively healthy, previously insured individuals with medication needs. Applying sequential predictive modeling and cluster analytic techniques to patient-reported information can identify subgroups of individuals within heterogeneous populations who may benefit from specific interventions to optimize initial care delivery.

Biomarkers of Tuberculosis Severity and Treatment Effect: A Directed Screen of 70 Host Markers in a Randomized Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sigal, G. B.; Segal, M. R.; Mathew, A.

More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers withmore » baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8 weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study. Keywords: host immune response; tuberculosis; biomarkers; clinical trials« less

Factors associated with and impact of pain persistence in Asian patients with depression: a 3-month, prospective observational study.

PubMed

Novick, Diego; Montgomery, William; Aguado, Jaume; Peng, Xiaomei; Haro, Josep Maria

2017-03-01

We investigated the depression outcomes and the factors associated with pain persistence in Asian patients treated for major depressive disorder (MDD). This observational study enrolled 909 Asian adult inpatients and outpatients. The presence or absence of painful physical symptoms and severity of depression were assessed at baseline and after three months of treatment. Factors associated with pain persistence and outcome of depression were investigated using regression methods. Of the 909 patients enrolled, 684 were included in the analysis and evaluated at three months. Of them, 335 (49%) had no pain at baseline nor follow up, 198 (29%) at baseline but not at follow up and 151 (22%) in both assessments. Pain more frequently persisted in patients who were divorced/widowed/separated, with >1 comorbidity, aged <40 years, with previous MDD episodes, taking pain medications, and with greater depression severity. At three months, response/remission were 84%/73% in the no pain group, 83%/63% in the remitted pain group and 46%/25% in the persistent pain group (differences all p < .0001; all bivariate comparisons were statistically significant with p < .05 except response between no pain and remitted pain). Persistent pain was also associated with less improvement in quality of life and health state. Pain should be taken into account when diagnosing MDD and when tailoring therapy.

Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years.

PubMed

Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

2014-12-01

Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained. Copyright © 2014 Elsevier Inc. All rights reserved.

Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results

PubMed Central

Akbar, Ayesha; Hart, Ailsa; Subramanian, Sreedhar; Bommelaer, Gilles; Baumgart, Daniel C.; Grimaud, Jean-Charles; Cadiot, Guillaume; Makins, Richard; Hoque, Syed; Bouguen, Guillaume; Bonaz, Bruno

2016-01-01

Background and Aims: Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup. Methods: This single-arm, open-label, multicentre trial [ART] was conducted at 18 centres across the UK, France, and Germany. Eligible patients were 18–75 years old with moderate-to-severe, steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received ≥ 5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate [clinical activity index ≤ 4] at Week 12. Results: In all, 86 patients were enrolled. At Week 12, 33/84 [39.3%] of patients in the intention-to-treat population achieved clinical remission, with 47/84 [56.0%] achieving a clinical response [clinical activity index reduction of ≥ 3]. Clinical remission was achieved in 30.0% of patients with previous immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life [Short Health Scale] significantly improved at Week 12 [p < 0.0001]. The majority of adverse events were of mild/moderate intensity. Conclusions: At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup. PMID:26818659

Sporadic Legionnaires' disease: the role of domestic electric hot-water tanks.

PubMed

Dufresne, S F; Locas, M C; Duchesne, A; Restieri, C; Ismaïl, J; Lefebvre, B; Labbé, A C; Dion, R; Plante, M; Laverdière, M

2012-01-01

Sporadic community-acquired legionellosis (SCAL) can be acquired through contaminated aerosols from residential potable water. Electricity-dependent hot-water tanks are widely used in the province of Quebec (Canada) and have been shown to be frequently contaminated with Legionella spp. We prospectively investigated the homes of culture-proven SCAL patients from Quebec in order to establish the proportion of patients whose domestic potable hot-water system was contaminated with the same Legionella isolate that caused their pneumonia. Water samples were collected in each patient's home. Environmental and clinical isolates were compared using pulsed-field gel electrophoresis. Thirty-six patients were enrolled into the study. Legionella was recovered in 12/36 (33%) homes. The residential and clinical isolates were found to be microbiologically related in 5/36 (14%) patients. Contaminated electricity-heated domestic hot-water systems contribute to the acquisition of SCAL. The proportion is similar to previous reports, but may be underestimated.

Diffuse thyroid 18F-FDG uptake after R-CHOP therapy predicts favorable outcome in patients with DLBCL.

PubMed

Song, Moo-Kon; Chung, Joo-Seop; Kim, Seong-Jang; Kim, Sang-Soo; Shin, Ho-Jin

2015-06-01

Therapy-induced autoimmunity may mediate the destruction of cancer cells. Previous studies have demonstrated that presence of autoimmune thyroid disorder is associated with favorable outcome in patients with solid cancer. Patients with diffuse large B cell lymphoma (DLBCL) who achieved complete response on positron emission tomography/computed tomography (PET/CT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were enrolled in this study. The patients with and without diffuse thyroid uptake (DTU) were classified by PET/CT. A total of 270 patients were enrolled in this study. DTU related to autoimmune thyroiditis was present in 61 patients. The median time to DTU detection was 5.7 months (range, 0-21.3 months). High International Prognostic Index (IPI) score (progression-free survival [PFS], p = 0.001; overall survival [OS], p = 0.008), bulky mass ≥10 cm (PFS, p = 0.001; OS, p = 0.001), bone marrow involvement (PFS, p < 0.001; OS, p = 0.001), and DTU after R-CHOP therapy (PFS, p < 0.001; OS, p = 0.001) were significantly associated with PFS and OS. High IPI score (PFS, p = 0.003; OS, p = 0.014), BM involvement (PFS, p = 0.009; OS, p = 0.039), and DTU after R-CHOP therapy (PFS, p = 0.002; OS, p = 0.002) were independently associated with PFS and OS. DTU after R-CHOP therapy independently predicted favorable outcomes in patients with DLBCL.

A prospective analysis of the influence of older age on physician and patient decision-making when considering enrollment in breast cancer clinical trials (SWOG S0316).

PubMed

Javid, Sara H; Unger, Joseph M; Gralow, Julie R; Moinpour, Carol M; Wozniak, Antoinette J; Goodwin, J Wendall; Lara, Primo N; Williams, Pamela A; Hutchins, Laura F; Gotay, Carolyn C; Albain, Kathy S

2012-01-01

Patients older than 65 years are underrepresented in clinical trials. We conducted a prospective study (SWOG S0316) to determine physician- and patient-perceived barriers to breast cancer clinical trial enrollment for older patients. Eight geographically diverse SWOG institutions participated. The study assessed patients' and physicians' decisions to enroll in or decline clinical treatment trials, including demographics, trial availability, and eligibility. Patient and physician questionnaires elicited concerns related to treatment, medical status, age, family, and financial or transportation concerns. A total of 1,079 patients were registered and eligible and 909 (84%) returned for follow-up. The major reason for nonaccrual was either trial unavailability or ineligibility (60%). Older patients were less likely to be eligible for trials (65% for age ≥65 years vs. 78% for age <65 years). If eligible, trial participation rates did not differ significantly by age (34% for age ≥65 years vs. 40% for age <65 years). Patients ≥65 years more often were concerned about side effects, had friends opposed to participation, or believed that participation would not benefit other generations. When trials were available and patients were eligible, physicians discussed trial participation with 76% of patients <65 years versus 58% of patients ≥65 years of age. For patients ≥65 years, 11% of physicians indicated age as a reason they did not enroll a patient in a clinical trial. Trial unavailability or patient ineligibility were the major reasons for lack of enrollment in breast cancer clinical trials for patients of all ages in this prospective study. Older patients were less likely to be eligible for trials, but if eligible they participated at similar rates to younger patients.

Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes

PubMed Central

Pecorelli, S.; Ray-Coquard, I.; Tredan, O.; Colombo, N.; Parma, G.; Tisi, G.; Katsaròs, D.; Lhommé, C.; Lissoni, A. A.; Vermorken, J. B.; du Bois, A.; Poveda, A.; Frigerio, L.; Barbieri, P.; Carminati, P.; Brienza, S.; Guastalla, J. P.

2010-01-01

Background: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. Patients and methods: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m2/cycle (0.8 mg/m2/day from day 1 to day 5) was administered, repeated every 28 days. Results: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. Conclusion: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity. PMID:19906760

Physician-Directed Heart Failure Transitional Care Program: A Retrospective Case Review

PubMed Central

Ota, Ken S.; Beutler, David S.; Gerkin, Richard D.; Weiss, Jessica L.; Loli, Akil I.

2013-01-01

Background Despite a variety of national efforts to improve transitions of care for patients at risk for rehospitalization, 30-day rehospitalization rates for patients with heart failure have remained largely unchanged. Methods This is a retrospective review of 73 patients enrolled in our hospital-based, physican-directed Heart Failure Transitional Care Program (HFTCP). This study evaluated the 30- and 90- day readmission rates before and after enrollment in the program. The Transitionalist’s services focused on bedside consultation prior to hospital discharge, follow-up home visits within 72 hours of discharge, frequent follow-up phone calls, disease-specific education, outpatient intravenous diuretic therapy, and around-the-clock telephone access to the Transitionalist. Results The pre-enrollment 30-day readmission rates for acute decompensated heart failure (ADHF) and all-cause readmission was 26.0% and 28.8%, respectively, while the post-enrollment rates for ADHF and all-cause readmission were 4.1% (P < 0.001) and 8.2% (P = 0.002), respectively. The pre-enrollment 90-day all-cause and ADHF readmission rates were 69.8%, and 58.9% respectively, while the post-enrollment rates for all-cause and ADHF were 27.3% (P < 0.001) and 16.4% (P < 0.001) respectively. Conclusions Our physician-implemented HFTCP reduced rehospitalization risk for patients enrolled in the program. This program may serve as a model to assist other hospital systems to reduce readmission rates of patients with HF. PMID:23976905

Low prevalence of work disability in early inflammatory arthritis (EIA) and early rheumatoid arthritis at enrollment into a multi-site registry: results from the catch cohort.

PubMed

Mussen, Lauren; Boyd, Tristan; Bykerk, Vivian; de Leon, Faye; Li, Lihua; Boire, Gilles; Hitchon, Carol; Haraoui, Boulos; Thorne, J Carter; Pope, Janet

2013-02-01

We determined the prevalence of work disability in early rheumatoid arthritis (ERA) and undifferentiated early inflammatory arthritis (EIA) patients at first enrollment into the Canadian Early Arthritis Cohort (CATCH) who met the 2010 ACR criteria versus those not meeting criteria, to determine the impact of meeting new criteria on work disability status. Data at first visit into the cohort were analyzed. Descriptive statistics and logistic regression analyses were performed to investigate the association of other variables in our database with work disability. 1,487 patients were enrolled in the CATCH study, a multi-site observational, prospective cohort of patients with EIA. 934 patients were excluded (505 based on missing criteria for ACR 2010 classification, as anti-CCP was absent, and 429 were not working for other reasons). Of the 553 patients included, 71 % were female with mean disease duration of 6.4 months. 524 (94.8 %) were employed while 29 (5.2 %) reported work disability at first visit. There were no differences between those meeting 2010 ACR criteria versus those who did not. Baseline characteristics associated with work disability were male gender, age, education, income, HAQ, and positive RF status. The mean HAQ score in work disabled patients was 1.4 versus 0.9 in those who were working (p < 0.001). Disease activity score (DAS28) was not associated with work disability (p = 0.069), nor was tender joint count, swollen joint count, anti-CCP, patient global assessment, or SF-12v2. In the regression model, work disability was associated with lower income levels (p = 0.01) and worse HAQ scores (OR 2.33; p = 0.001), but not significantly associated with male gender (p = 0.08), older age (>50 years; p = 0.3), lower education (p = 0.3) or RF positivity (p = 0.6). We found rates of work disability to be low at entry into this EIA cohort compared to previous studies. There may be potential for intervention in ERA to prevent the development of work disability.

Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial.

PubMed

Jennings, Paul A; Cameron, Peter; Bernard, Stephen; Walker, Tony; Jolley, Damien; Fitzgerald, Mark; Masci, Kevin

2014-10-01

Improved early pain control may affect the longer-term prevalence of persistent pain. In a previous randomised, controlled trial, we found that the administration of ketamine on hospital arrival decreased pain scores to a greater extent than morphine alone in patients with prehospital traumatic pain. In this follow-up study, we sought to determine the prevalence of persistent pain and whether there were differences in patients who received ketamine or morphine. This study was a long-term follow-up study of the prehospital, prospective, randomised, controlled, open-label study comparing ketamine with morphine in patients with trauma and a verbal pain score of >5 after 5 mg intravenous morphine. Patients were followed-up by telephone 6-12 months after enrollment, and a questionnaire including the SF-36 (V.2) health-related quality of life survey and the Verbal Numerical Rating Scale for pain was administered. A total of 97/135 (72%) patients were able to be followed-up 6-12 months after enrollment between July 2008 and July 2010. Overall, 44/97 (45%) participants reported persistent pain related to their injury, with 3/97 (3%) reporting persistent severe pain. The prevalence of persistent pain was the same between study groups (22/50 (44%) for the ketamine group vs 22/47 (46%) for the morphine group). There was no difference in the SF-36 scores between study arms. There is a high incidence of persistent pain after traumatic injury, even in patients with relatively minor severity of injury. Although decreased pain scores at hospital arrival are achieved with ketamine compared with morphine, this difference does not affect the prevalence of persistent pain or health-related quality of life 6 months after injury. Further larger studies are required to confirm this finding. Australian and New Zealand Clinical Trials Registry (ACTRN12607000441415). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Contemporary outcomes of seminal tract re-anastomoses for obstructive azoospermia: a nationwide Japanese survey.

PubMed

Taniguchi, Hisanori; Iwamoto, Teruaki; Ichikawa, Tomohiko; Nagai, Atsushi; Okada, Hiroshi; Fujisawa, Masato; Tsujimura, Akira; Shiraishi, Koji; Hibi, Hatsuki; Nagao, Koichi; Iwasaki, Akira; Kamba, Tomomi; Tomomasa, Hiroshi; Takada, Shingo; Matsuda, Tadashi

2015-02-01

To evaluate current outcomes of seminal tract re-anastomoses in Japan, and to compare them with historical data. A total of 213 patients with obstructive azoospermia who underwent seminal tract re-anastomosis from April 2008 to March 2012 at 25 institutions were enrolled in the present study. The outcomes of the procedure were compared with those reported in a previous multi-institutional study carried out in 2000. The percentage of partners aged over 35 years was 37%. A microsurgical double-layer anastomosis was carried out 83.0% of the time. Sperm were observed in ejaculate postoperatively in 68.9% and 41.5% of patients who underwent a vasovasostomy or a vasoepididymostomy, respectively. Natural conception occurred in 27.5% of patients after a vasectomy and 32.3% of patients with an epididymal obstruction. Except for the ratio of natural conception in patients with vasal obstruction after herniorrhaphies, there were no significant differences in final ratios of sperm appearance and natural conception between the previously reported study and the present study. Compared with historical data, contemporary seminal tract re-anastomosis in Japan seems to provide equivalent or better outcomes, depending on the cause of obstruction. Seminal tract re-anastomosis is a valid treatment option for patients with obstructive azoospermia. © 2014 The Japanese Urological Association.

Longitudinal Studies of a B Cell Derived Signature of Tolerance in Renal Transplant Recipients

PubMed Central

Newell, Kenneth A.; Asare, Adam; Sanz, Ignacio; Wei, Chungwen; Rosenberg, Alexander; Gao, Zhong; Kanaparthi, Sai; Asare, Smita; Lim, Noha; Stahly, Michael; Howell, Michael; Knechtle, Stuart; Kirk, Allan; Marks, William H.; Kawai, Tatsuo; Spitzer, Thomas; Tolkoff-Rubin, Nina; Sykes, Megan; Sachs, David H.; Cosimi, A. Benedict; Burlingham, William J.; Phippard, Deborah; Turka, Laurence A.

2016-01-01

Biomarkers of transplant tolerance would enhance the safety and feasibility of clinical tolerance trials and potentially facilitate management of patients receiving immunosuppression. To this end, we examined blood from spontaneously tolerant renal transplant recipients and patients enrolled in two interventional tolerance trials using flow cytometry and gene expression profiling. Using a previously reported tolerant cohort as well as newly identified tolerant patients we confirmed our previous finding that tolerance was associated with increased expression of B cell-associated genes relative to immunosuppressed patients. This was not accounted for merely by an increase in total B cell numbers, but was associated with the increased frequencies of transitional and naïve B cells. Moreover, serial measurements of gene expression demonstrated that this pattern persisted over several years although patients receiving immunosuppression also displayed an increase in the two most dominant tolerance-related B cell genes, IGKV1D-13 and IGLL-1, over time. Importantly, patients rendered tolerant via induction of transient mixed chimerism, and those weaned to minimal immunosuppression, showed similar increases in IGKV1D-13 as did spontaneously tolerant individuals. Collectively, these findings support the notion that alterations in B cells may be a common theme for tolerant kidney transplant recipients, and a useful monitoring tool in prospective trials. PMID:26461968

Delayed nausea and vomiting from carboplatin doublet chemotherapy

PubMed Central

Waqar, Saiama N.; Mann, Janelle; Baggstrom, Maria Q.; Waqar, Muhammad Atif; Chitneni, Pooja; Williams, Kristina; Gao, Feng; Morgensztern, Daniel; Govindan, Ramaswamy

2016-01-01

Background Delayed nausea and vomiting following administration of carboplatin containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis comprising of a 5-HT3 antagonist and dexamethasone. We performed a prospective study to define the incidence and risk factors for delayed chemotherapy induced nausea and vomiting (CINV). Methods Previously untreated patients with newly diagnosed cancer scheduled to receive carboplatin containing chemotherapy (AUC 5 or above), but no prophylactic aprepitant were enrolled in the study. The primary endpoint was the incidence of delayed CINV after cycle 1 of chemotherapy. Secondary endpoints included the incidence of CINV with the third chemotherapy cycle and gender differences in incidence of CINV. Patients completed the Functional Living Index Emesis (FLIE) questionnaires 24, 48, 72 and 96 hours after receiving chemotherapy. Telephone interviews were conducted 24–48 hours following chemotherapy to assess the severity and need for breakthrough medications for CINV. Results Between December 2006 and July 2009, 105 patients were enrolled onto this study. Delayed emesis following cycle 1 of carboplatin was observed in 30% of patients. Of these, 14.1%, 22.4% and 23.5% of patients described CINV at 48 hours, 72 hours, and 96 hours respectively. The incidence of delayed CINV following cycle 3 dropped to 12.8%, 14.6% and 16% of patients at 48 hours, 72 hours and 96 hours respectively. No differences were observed in the incidence of CINV between men and women. A total of 20% of patients required use of breakthrough antiemetics with cycle 1. Conclusions Without prophylactic aprepitant administration, 30% of patients receiving carboplatin containing regimen had moderate to severe delayed CINV. PMID:27145068

Regionalization of post-cardiac arrest care: implementation of a cardiac resuscitation center.

PubMed

Heffner, Alan C; Pearson, David A; Nussbaum, Marcy L; Jones, Alan E

2012-10-01

Guidelines recommend standardized treatment of post-cardiac arrest patients to improve outcomes. However, the infrastructure, resources, and personnel required to meet the complex needs of cardiac arrest victims remain a barrier to care. Given that regionalization of time-dependent high-acuity illness is an emerging paradigm, the aim of the present study was to develop and implement a regionalized approach to post-cardiac arrest care. We performed a prospective observational study on all patients treated in a regionalized clinical pathway from November 2007 through June 2011. All patients were enrolled after admission to an urban academic medical center. Clinical data including arrest and treatment variables, complications, and outcome were collected on consecutive patients with the use of a preformatted standard data collection tool using Utstein criteria. A total of 220 patients were enrolled; 127 (58%) patients were local direct admissions from our community, and 93 (42%) were transferred from 1 of 24 outlying referral hospitals. One hundred six (48%, 95% CI 38%-53%) patients survived to hospital discharge. The primary outcome of hospital survival with good neurologic function was observed in 94 (43%, 95% CI 32%-48%). There was no difference in survival with good neurologic outcome among local and referred patients. Overall 1-year survival was 44% (95% CI 38%-51%). Among patients discharged from the hospital with good neurologic function, 93% (95% CI 85%-97%) remained alive at 1 year. Development of a regionalized approach to post-cardiac arrest care using previously established referral relationships is feasible, and implementation of such an approach was clinically effective in our region. Copyright © 2012 Mosby, Inc. All rights reserved.

Safety and effectiveness of room temperature stable recombinant factor VIIa in patients with haemophilia A or B and inhibitors: Results of a multinational, prospective, observational study.

PubMed

Kavakli, K; Demartis, F; Karimi, M; Eshghi, P; Neme, D; Chambost, H; Sommer, L; Zak, M; Benson, G

2017-07-01

A room temperature stable formulation of recombinant activated factor VII (NovoSeven ® ), allowing convenient storage and therefore improved treatment access, has been developed. Bioequivalence to the previous NovoSeven ® was demonstrated in healthy humans, leading to European approval (2008). Although no confirmed cases of neutralising antibodies to rFVIIa in patients with haemophilia A or B have been observed with the original formulation, changes in formulation or storage condition may alter immunogenicity. SMART-7™ was designed to investigate the safety of NovoSeven ® in a real-world setting in patients with haemophilia A or B with inhibitors. Study medication was not provided by the sponsor, and treatment was at the discretion of the treating physician, in accordance with the local label. Patient baseline information was collected at enrolment. Information on safety, drug exposure and bleeding episodes was collected and FVII antibody screening was encouraged at baseline and performed at the investigator's discretion. Fifty-one patients were enrolled and 31 completed the study. Forty-one adverse events (AEs) were reported in 23 patients; 25 AEs in 14 patients were serious. No thromboembolic events were observed. Although four cases of reduced therapeutic response were reported, FVII antibody screening was negative. Forty-eight patients experienced 618 bleeding episodes and 93.4% of 609 evaluated bleeds were stopped by treatment. Of the 538 bleeding episodes treated with NovoSeven ® monotherapy, 94.2% stopped by end of treatment. Data collected during the SMART-7™ study revealed no treatment-related safety issues and no FVII-binding antibodies for patients treated with NovoSeven ® under real-world conditions. © 2017 John Wiley & Sons Ltd.

Clinical Benefit of Long-Term Adalimumab Treatment in Patients With Crohn's Disease Following Loss of Response or Intolerance to Infliximab: 96-Week Efficacy Data From GAIN/ADHERE Trials.

PubMed

Panaccione, Remo; Sandborn, William J; D'Haens, Geert; Wolf, Douglas C; Berg, Sofie; Maa, Jen-Fue; Petersson, Joel; Robinson, Anne M

2018-04-25

In the 4-week GAIN clinical trial, adalimumab was efficacious in inducing remission in patients with moderate to severe Crohn's disease (CD) who had prior loss of response/intolerance to infliximab. The efficacy and safety of adalimumab in these patients are reported here up to 96 weeks or for 3 years, respectively, in ADHERE open-label extension study. Patients who completed GAIN could enrol in ADHERE and receive open-label adalimumab 40 mg every other week. Efficacy variables included clinical response (Crohn's Disease Activity Index [CDAI] decrease from baseline ≥70/≥100 points [CR-70/CR-100]) and remission (CDAI<150), steroid discontinuation and fistula remission (absence of drainage). Data were reported using hybrid non-responder imputation (hNRI), last observation carried forward and as-observed analysis. Subgroup analyses were performed by randomised group in GAIN and by Week 4 efficacy in GAIN. Safety was also assessed. A total of 310 patients from GAIN enrolled in ADHERE. CR-70, CR-100 and remission rates at Week 96 were 39.0%, 35.5% and 26.5% (hNRI), respectively. Of the patients with CR-70 response or remission at Week 4 of GAIN, 45.5% and 44.4% (hNRI), respectively, maintained effect at Week 96. Steroid discontinuation and steroid-free remission rates increased from Week 12 to 96 in patients using corticosteroids at GAIN baseline. Long-term adalimumab maintenance therapy led to sustained clinical remission and response, and steroid discontinuation in a considerable proportion of patients with CD previously treated with infliximab. No new safety signals were observed in this patient population.

Does phase 1 trial enrollment preclude quality end-of-life care? Phase 1 trial enrollment and end-of-life care characteristics in children with cancer.

PubMed

Levine, Deena R; Johnson, Liza-Marie; Mandrell, Belinda N; Yang, Jie; West, Nancy K; Hinds, Pamela S; Baker, Justin N

2015-05-01

End-of-life care (EOLC) discussions and treatment-related decisions, including phase 1 trial enrollment, in patients with incurable disease are complex and can influence the quality of EOLC received. The current study was conducted in pediatric oncology patients to determine whether end-of-life characteristics differed between those who were and were not enrolled in a phase 1 trial. The authors reviewed the medical records of 380 pediatric oncology patients (aged <22 years at the time of death) who died during a 3.5-year period. Of these, 103 patients with hematologic malignancies were excluded. A total of 277 patients with a diagnosis of a brain tumor or other solid tumor malignancy were divided into 2 groups based on phase 1 trial enrollment: a phase 1 cohort (PIC; 120 patients) and a non-phase 1 cohort (NPIC; 157 patients). The EOLC characteristics of these 2 cohorts were compared using regression analysis and chi-square testing. A comparison of patients in the PIC and NPIC revealed no significant differences in either demographic characteristics (including sex, race, religious affiliation, referral origin, diagnosis, or age at diagnosis, with the exception of age at the time of death [P =.03]) or in EOLC indices (such as use or timing of do not attempt resuscitation orders, hospice use or length of stay, forgoing life-sustaining therapies, location of death, time from first EOLC discussion to death, and total number of EOLC discussions). The results of the current study of a large cohort of deceased pediatric cancer patients indicate that enrollment on a phase 1 trial does not affect EOLC characteristics, suggesting that quality EOLC can be delivered regardless of phase 1 trial participation. © 2014 American Cancer Society.

Effect of treatment course of comprehensive intervention with Traditional Chinese Medicine on mortality of acquired immunodeficiency syndrome patients treated with combined antiretroviral therapy.

PubMed

Guo, Huijun; Wang, Jian; Li, Zhengwei; Jiang, Ziqiang; Xu, Qianlei; Xu, Liran

2016-08-01

To investigate the effect of a treatment course of comprehensive intervention with Traditional Chinese Medicine (TCM) on the mortality of patients with acquired immunodeficiency syndrome (AIDS) treated with combined antiretroviral therapy (cART). AIDS patients who had taken cART in a national TCM human immunodeficiency virus treatment trial program (NTCMTP) before 2009 were enrolled in this study and followed for 36 months from November 2009. Patients enrolled in the NTCMTP in 2004 were taken as the first group, those enrolled in 2006 as the second group, and those enrolled in 2009 as the third group. Cumulative survival rates were calculated by the life table method. Survival curves for subgroups were compared by the log-rank test. Hazard ratios were calculated with a Cox proportional hazards model. A total of 1443 AIDS patients were followed for 3 years (4198 person-years). During this period, 91 (6.3%) patients died and 13 (0.9%) were lost to follow-up. The total mortality rate was 2.17/ 100 person-years. The mortality rate of patients enrolled in the NTCMTP in 2004 was 1.49/100 person- years, which was lower than that of patients enrolled in 2006 (2.23/100 person-years) and 2009 (3.48/100 person-years). After adjusting for other factors, a shorter time of treatment with TCM, male sex, older age, lower CD4 + T-cell counts, and long-term treatment with cART were risk factors of mortality. Long-term treatment with TCM decreased the mortality risk of AIDS patients. Factors such as being male, older age, CD4 + T-cell counts, and time of treatment with TCM and cART were correlated with mortality.

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial.

PubMed

Patel, Manish R; Ellerton, John; Infante, Jeffrey R; Agrawal, Manish; Gordon, Michael; Aljumaily, Raid; Britten, Carolyn D; Dirix, Luc; Lee, Keun-Wook; Taylor, Mathew; Schöffski, Patrick; Wang, Ding; Ravaud, Alain; Gelb, Arnold B; Xiong, Junyuan; Rosen, Galit; Gulley, James L; Apolo, Andrea B

2018-01-01

The approval of anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 agents has expanded treatment options for patients with locally advanced or metastatic urothelial carcinoma. Avelumab, a human monoclonal anti-PD-L1 antibody, has shown promising antitumour activity and safety in this disease. We aimed to assess the safety profile in patients (both post-platinum therapy and cisplatin-naive) treated with avelumab and to assess antitumour activity of this drug in post-platinum patients. In this pooled analysis of two cohorts from the phase 1 dose-expansion JAVELIN Solid Tumor study, patients aged 18 years and older with histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma that had progressed after at least one previous platinum-based chemotherapy were enrolled from 80 cancer treatment centres or hospitals in the USA, Europe, and Asia. Eligible patients had adequate end-organ function, an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and at least one measurable lesion. Cisplatin-ineligible patients who might have been previously treated in the perioperative setting, including platinum-naive patients, were also eligible. Patients unselected for PD-L1 expression received avelumab (10 mg/kg, 1 h intravenous infusion) every 2 weeks until confirmed disease progression, unacceptable toxicity, or other criterion for withdrawal. The primary endpoint for this efficacy expansion cohort was confirmed best overall response (according to RECIST version 1.1), adjudicated by independent review. Safety analysis was done in all patients who received at least one dose of avelumab. Antitumour activity was assessed in post-platinum patients who received at least one dose of avelumab. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort of patients with metastatic urothelial carcinoma is closed and the trial is ongoing. Between Sept 3, 2014, and March 15, 2016, 329 patients with advanced metastatic urothelial carcinoma were screened for enrolment into this study; 249 patients were eligible and received treatment with avelumab for a median of 12 weeks (IQR 6·0-19·7) and followed up for a median of 9·9 months (4·3-12·1). Safety and antitumour activity were evaluated at data cutoff on June 9, 2016. In 161 post-platinum patients with at least 6 months of follow-up, a best overall response of complete or partial response was recorded in 27 patients (17%; 95% CI 11-24), including nine (6%) complete responses and 18 (11%) partial responses. The most frequent treatment-related adverse events (any grade in ≥10% patients) were infusion-related reaction (73 [29%]; all grade 1-2) and fatigue (40 [16%]). Grade 3 or worse treatment-related adverse events occurred in 21 (8%) of 249 patients, the most common of which were fatigue (four [2%]), and asthenia, elevated lipase, hypophosphataemia, and pneumonitis in two (1%) patients each. 19 (8%) of 249 patients had a serious adverse event related to treatment with avelumab, and one treatment-related death occurred (pneumonitis). Avelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients. These data provide the rationale for therapeutic use of avelumab in metastatic urothelial carcinoma and it has received accelerated US FDA approval in this setting on this basis. Merck KGaA, and Pfizer Inc. Copyright © 2018 Elsevier Ltd. All rights reserved.

Treatment consumption and treatment re-enrollment in GHB-dependent patients in The Netherlands.

PubMed

van Noorden, Martijn S; Mol, Ton; Wisselink, Jeroen; Kuijpers, Wil; Dijkstra, Boukje A G

2017-07-01

The objective of this study was to assess treatment consumption and re-enrollment in treatment in patients with gamma-hydroxybutyrate (GHB)-dependence in Dutch Addiction Treatment Centers (ATCs) in comparison with other addictions. A cohort-study using nationwide administrative data from regular Dutch ATCs associated with the Dutch National Alcohol and Drugs Information System (LADIS), covering an estimated 95% of ATCs. We selected in- and out-patients with alcohol, drug and/or behavioral addictions with a first treatment episode in 2008-2011 and consecutive treatments until 2013 (n=71,679). Patients still in treatment at that date (n=3686; 5.1%), forensic patients (n=1949; 2.7%) and deceased patients (n=570; 0.8%) were excluded, leaving 65,474 patients (91.3%). Of those, 596 (0.9%) patients had GHB dependence. We analyzed number of treatment contacts, treatment duration, admissions and admission duration of the first treatment episode, and re-enrollment (defined as having started a second treatment episode in the study period). GHB-dependent patients showed the highest number of treatment contacts, duration of treatment and chance of being admitted. Re-enrollment rates were 2-5 times higher in GHB-dependent patients than other patients with adjusted HR of other addictions ranging from 0.18 (95% confidence interval [CI]: 0.15-0.21) to 0.53 (95% CI: 0.47-0.61). This study demonstrates high levels of treatment consumption and high rates of treatment re-enrollment in GHB-dependent patients. These findings highlight the urgency of developing effective relapse prevention interventions for GHB-dependent patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The Impact of Continuous Medicaid Enrollment on Diagnosis, Treatment, and Survival in Six Surgical Cancers

PubMed Central

Dawes, Aaron J; Louie, Rachel; Nguyen, David K; Maggard-Gibbons, Melinda; Parikh, Punam; Ettner, Susan L; Ko, Clifford Y; Zingmond, David S

2014-01-01

Objective To examine the effect of Medicaid enrollment on the diagnosis, treatment, and survival of six surgically relevant cancers among poor and underserved Californians. Data Sources California Cancer Registry (CCR), California's Patient Discharge Database (PDD), and state Medicaid enrollment files between 2002 and 2008. Study Design We linked clinical and administrative records to differentiate patients continuously enrolled in Medicaid from those receiving coverage at the time of their cancer diagnosis. We developed multivariate logistic regression models to predict death within 1 year for each cancer after controlling for sociodemographic and clinical variables. Data Collection/Extraction Methods All incident cases of six cancers (colon, esophageal, lung, pancreas, stomach, and ovarian) were identified from CCR. CCR records were linked to hospitalizations (PDD) and monthly Medicaid enrollment. Principal Findings Continuous enrollment in Medicaid for at least 6 months prior to diagnosis improves survival in three surgically relevant cancers. Discontinuous Medicaid patients have higher stage tumors, undergo fewer definitive operations, and are more likely to die even after risk adjustment. Conclusions Expansion of continuous insurance coverage under the Affordable Care Act is likely to improve both access and clinical outcomes for cancer patients in California. PMID:25256223

Real-Time Pretreatment Review Limits Unacceptable Deviations on a Cooperative Group Radiation Therapy Technique Trial: Quality Assurance Results of RTOG 0933

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai, E-mail: vgondi@chicagocancer.org; University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin; Cui, Yunfeng

2015-03-01

Purpose: RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients. Methods and Materials: Before enrolling patients, all treating physicians and sites were required to successfully complete a “dry-run” credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging–computed tomography image fusion and hippocampal andmore » normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment. Results: In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations. Conclusions: Although >95% of the cases passed the pre-enrollment credentialing, the pretreatment centralized review disqualified 5.7% of reviewed cases, prevented unacceptable deviations in 24% of reviewed cases, and limited the final unacceptable deviation rate to 5%. Thus, pretreatment review is deemed necessary in future hippocampal avoidance trials and is potentially useful in other similarly challenging radiation therapy technique trials.« less

Patients' views of consent in clinical trials for acute myocardial infarction: impact of trial design.

PubMed

Dickert, Neal W; Hendershot, Kristopher A; Speight, Candace D; Fehr, Alexandra E

2017-08-01

Seeking prospective informed consent is difficult in clinical trials for emergent conditions such as acute myocardial infarction (AMI). Prior data suggest that enrolment decisions of patients are often poorly informed in AMI trials but that patients prefer to be asked permission before enrolment. It is unknown whether this is true across trial designs or in comparative effectiveness research (CER) with approved treatments. Structured interviews were conducted with 30 patients with AMI. Participants considered three scenarios: (1) a CER trial of approved antiplatelet drugs; (2) a placebo-controlled trial of a novel drug to reduce myocardial injury and (3) a CER trial of an intra-aortic balloon pump versus medication. Participants were asked their desired involvement in enrolment decisions and willingness to participate. Descriptive analysis was performed of Likert scale data, and qualitative descriptive analysis was performed of textual data. Across scenarios, most participants (73%-80%) preferred to be asked permission prior to trial enrolment. Reasons for involvement included wanting to be the decision maker and a desire for transparency. Willingness to enrol was affected by trial type. Fewer participants stated they would likely enrol in a CER procedural trial than in a CER trial of approved medications (p=0.012). These findings suggest that patients prefer prospective involvement in enrolment decisions to enrolment without consent across trial types. However, their desire to participate was affected by trial type. There is a need to develop and evaluate context-sensitive approaches to consent in AMI trials that account for both the acuity of the situation and trial characteristics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Another Simple yet Effective Best Practice for Increasing Enrollments at an Extended Campus

ERIC Educational Resources Information Center

Christensen, Steven S.; Howell, Scott L.; Hall, C. Giles

2016-01-01

This article is a follow-up to a previous article, "Six Ways to Increase Enrollments at an Extended Campus," published in this journal (vol. 17, no. 4, winter 2015), wherein a seventh best practice to increase course offerings and increase enrollments at an extended campus is presented. This best practice seeks to identify those areas of…

Sentinel Node Mapping Using a Fluorescent Dye and Visible Light During Laparoscopic Gastrectomy for Early Gastric Cancer: Result of a Prospective Study From a Single Institute.

PubMed

Lee, Chang Min; Park, Sungsoo; Park, Seong-Heum; Jung, Sung Woo; Choe, Jung Wan; Sul, Ji-Young; Jang, You Jin; Mok, Young-Jae; Kim, Jong-Han

2017-04-01

The aim of this study was to investigate the feasibility of sentinel node mapping using a fluorescent dye and visible light in patients with gastric cancer. Recently, fluorescent imaging technology offers improved visibility with the possibility of better sensitivity or accuracy in sentinel node mapping. Twenty patients with early gastric cancer, for whom laparoscopic distal gastrectomy with standard lymphadenectomy had been planned, were enrolled in this study. Before lymphadenectomy, the patients received a gastrofiberoscopic peritumoral injection of fluorescein solution. The sentinel basin was investigated via laparoscopic fluorescent imaging under blue light (wavelength of 440-490 nm) emitted from an LED curing light. The detection rate and lymph node status were analyzed in the enrolled patients. In addition, short-term clinical outcomes were also investigated. No hypersensitivity to the dye was identified in any enrolled patients. Sentinel nodes were detected in 19 of 20 enrolled patients (95.0%), and metastatic lymph nodes were found in 2 patients. The latter lymph nodes belonged to the sentinel basin of each patient. Meanwhile, 1 patient (5.0%) experienced a postoperative complication that was unrelated to sentinel node mapping. No mortality was recorded among enrolled cases. Sentinel node mapping with visible light fluorescence was a feasible method for visualizing sentinel nodes in patients with early gastric cancer. In addition, this method is advantageous in terms of visualizing the concrete relationship between the sentinel nodes and surrounding structures.

Accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation: results of a phase II study.

PubMed

Cai, Gang; Zhu, Ji; Hu, Weigang; Zhang, Zhen

2014-12-11

This study was conducted to investigate the local effects and toxicity of accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation. Twenty-two patients with recurrent/unresectable rectal cancer who previously received pelvic irradiation were enrolled in our single-center trial between January 2007 and August 2012. Reirradiation was scheduled for up to 39 Gy in 30 fractions using intensity-modulated radiotherapy plans. The dose was delivered via a hyperfractionation schedule of 1.3 Gy twice daily. Patient follow-up was performed by clinical examination, CT/MRI, or PET/CT every 3 months for the first 2 years and every 6 months thereafter. Tumor response was evaluated 1 month after reirradiation by CT/MRI based on the RECIST criteria. Adverse events were assessed using the National Cancer Institute (NCI) common toxicity criteria (version 3.0). The median time from the end of the initial radiation therapy to reirradiation was 30 months (range, 18-93 months). Overall local responses were observed in 9 patients (40.9%). None of the patients achieved a complete response (CR), and 9 patients (40.9%) had a partial response (PR). Thirteen patients failed to achieve a clinical response: 12 (54.5%) presented with stable disease (SD) and 1 (4.5%) with progressive disease (PD). Among all the patients who underwent reirradiation, partial or complete symptomatic relief was achieved in 6 patients (27.3%) and 13 patients (59.1%), respectively. Grade 4 acute toxicity and treatment-related deaths were not observed. The following grade 3 acute toxicities were observed: diarrhea (2 patients, 9.1%), cystitis (1 patient, 4.5%), dermatitis (1 patient, 4.5%), and intestinal obstruction (1 patient, 4.5%). Late toxicity was infrequent. Chronic severe diarrhea, small bowel obstruction, and dysuria were observed in 2 (9.1%), 1 (4.5%) and 2 (9.1%) of the patients, respectively. This study showed that accelerated hyperfractionated intensity-modulated radiotherapy significantly relieved local symptoms and led to a promising local response with an acceptable toxicity profile in patients with recurrent/unresectable rectal cancer and previous pelvic irradiation. Innovative treatment regimens should be evaluated in future studies to improve the clinical outcome while avoiding excessive toxicity in patients with recurrent rectal cancer and previous pelvic irradiation.

HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment.

PubMed

Baker, A; Kochan, N; Dixon, J; Wodak, A; Heather, N

1995-04-01

This study compares the injecting and sexual risk-taking behaviour among injecting drug users (IDUs) currently, previously and never enrolled in methadone maintenance treatment (MMT). All subjects had injected during the 6 months prior to the day of interview. The current MMT group showed significantly lower injecting risk-taking behaviour subscale scores on the HIV Risk-taking Behaviour Scale (HRBS) of the Opiate Treatment Index than the previous MMT and non-MMT groups together. The current MMT group differed from the other two groups in the frequency of injecting and cleaning of injection equipment with bleach. There was no difference between the current MMT group and the other two groups combined in sexual risk-taking behaviour scores on the HRBS. There were no differences between the previous MMT and non-MMT groups in injecting and sexual risk-taking behaviour. HIV seroprevalence was low and there was no difference in seroprevalence between groups. Thus, IDUs currently enrolled in MMT are at reduced risk for HIV infection when compared with IDUs who have previously or never been enrolled in MMT. However, the absence of a difference between the current MMT and other two groups in frequency of sharing behaviours suggests the need for additional strategies among MMT clients to reduce needle-sharing. Possible strategies include the application of relapse prevention interventions and the availability of sterile injecting equipment in MMT clinics. Further research is needed to identify factors which increase attraction and retention of IDUs to MMT.

"Design characteristics of the CORRONA CERTAIN study: a comparative effectiveness study of biologic agents for rheumatoid arthritis patients".

PubMed

Pappas, Dimitrios A; Kremer, Joel M; Reed, George; Greenberg, Jeffrey D; Curtis, Jeffrey R

2014-04-01

Comparative effectiveness research has recently attracted considerable attention. The Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) is an ongoing prospective cohort study of adult patients with Rheumatoid Arthritis (RA). CERTAIN uses the existing Consortium of Rheumatology Researchers of North America (CORRONA) network of participating private and academic sites in order to recruit patients fulfilling the 1987 ACR criteria that have at least moderate disease activity. Patients starting or switching biologic agents either anti-TNF therapy or a non anti-TNF biologic are eligible for enrollment, depending on the treatment selected by their physician. Enrollment is expected to be completed by March of 2014, and 2711 patients will participate in the study. As of October 7th 2013, 2234 patients have been enrolled. Patient visits and laboratory blood work are mandated every three months for one year. Safety data is collected through one year and beyond. The primary comparative effectiveness endpoint is attainment of low RA disease activity at one year among patients who have been exposed to at least one prior TNF-α inhibitor agent prior to enrollment. Multiple secondary effectiveness and safety endpoints will be addressed by investigating the entire population enrolled (naïve and biologic experienced). The unique design features of CERTAIN will inform comparative effectiveness and safety questions for choosing biologic agents for the management of RA.

Impact of Pharmacist Involvement in Early Identification and Enrollment in Patient Assistance Programs on CMV Outcomes in Transplantation.

PubMed

Byrns, Jennifer S; Pilch, Nicole W; Taber, David J

2016-04-01

No data exist evaluating the utilization of patient assistance programs (PAPs) on cytomegalovirus (CMV)-related outcomes. To determine whether early identification and enrollment in PAPs can prevent CMV-related events. Retrospective analysis of patients at risk of CMV reactivation who received kidney and/or pancreas transplants. Two groups were evaluated with patients receiving oral valganciclovir for CMV prophylaxis through enrollment in PAPs or oral acyclovir with preemptive CMV monitoring. Primary outcomes include the incidence of CMV infection. Secondary outcomes include a cost benefit analysis, incidence of rejection, patient/graft survival, and time to CMV infection. There were 97 patients identified; valganciclovir through PAPs (n = 39) and preemptive CMV quantitative nucleic acid testing monitoring (n = 58). The incidence of CMV viremia was lower in the PAP group (12.8% vs 36.2%, respectively; P = .021). There were no significant differences in CMV syndrome/disease, acute rejection, graft loss, or death between the groups. The time to CMV infection was shorter in the preemptive group. Cost benefit analysis found that hiring a full time pharmacy employee for enrolling patients in PAPs was cost beneficial for the institution/health care system. Early identification and enrollment of patients in PAPs reduces the incidence of CMV viremia. Pharmacists play a crucial role in this process. © The Author(s) 2014.

A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.

PubMed

Siegel, Abby B; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Flaig, Thomas W; Tsai, Wei Yann; Wu, David P H; Lee, Valerie; Greenlee, Heather

2014-01-01

To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.

Retinoic acid plus arsenic trioxide, the ultimate panacea for acute promyelocytic leukemia?

PubMed

Lallemand-Breitenbach, Valérie; de Thé, Hugues

2013-09-19

Rarely in the field of cancer treatment did we experience as many surprises as with acute promyelocytic leukemia (APL). Yet, the latest clinical trial reported by Lo-Coco et al in the New England Journal of Medicine is a practice-changing study, as it reports a very favorable outcome of virtually all enrolled low-intermediate risk patients with APL without any DNA-damaging chemotherapy. Although predicted from previous small pilot studies, these elegant and stringently controlled results open a new era in leukemia therapy.

Recruitment and Enrollment for the Simultaneous Conduct of 2 Randomized Controlled Trials for Patients with Subacute and Chronic Low Back Pain at a CAM Research Center

PubMed Central

Long, Cynthia R.; Haan, Andrea G.; Spencer, Lori Byrd; Meeker, William C.

2008-01-01

Abstract Objective To describe recruitment and enrollment experiences of 2 low back pain (LBP) randomized controlled trials (RCTs). Design Descriptive report. Setting Chiropractic research center in the midwest United States that is not a fee-for-service clinic. Participants Both trials enrolled participants with subacute or chronic LBP without neurologic signs who had not received spinal manipulative care during the previous month. For study 1 we screened 1940 potential participants to enroll 192 participants (89 women and 103 men), mean age 40.0 ± 9.4 years (range, 21–54 years). For study 2 we screened 1849 potential participants to enroll 240 participants (105 women and 135 men) at least 55 years old (mean, 63.1 ± 6.7 years). Interventions Study 1 randomly assigned participants to 2 weeks of 2 different chiropractic techniques or a wait list control group. Study 2 randomly assigned participants to 6 weeks of 2 different chiropractic techniques or medical care consisting of 3 provider visits for medications. Outcome measures Recruitment source costs and yield, and baseline characteristics of enrolled versus nonparticipants were recorded. Results We conducted 3789 telephone screens for both trials to enroll 432 (11%) participants, at a cost in excess of $156,000 for recruitment efforts. The cost per call for all callers averaged $41, ranging from $4 to $300 based on recruitment method; for enrolled participants, the cost per call was $361, ranging from $33 to $750. Direct mail efforts accounted for 62% of all callers, 57% for enrolled participants, and had the second lowest cost per call for recruitment efforts. Conclusions It is important that complementary and alternative medicine (CAM) research can be successfully conducted at CAM institutions. However, the costs associated with recruitment efforts for studies conducted at CAM institutions may be higher than expected and many self-identified participants are users of the CAM therapy. Therefore, strategies for efficient recruitment methods and targeting nonusers of CAM therapies should be developed early for CAM trials. PMID:18990046

Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.

PubMed

Han, MeiLan K; Quibrera, Pedro M; Carretta, Elizabeth E; Barr, R Graham; Bleecker, Eugene R; Bowler, Russell P; Cooper, Christopher B; Comellas, Alejandro; Couper, David J; Curtis, Jeffrey L; Criner, Gerard; Dransfield, Mark T; Hansel, Nadia N; Hoffman, Eric A; Kanner, Richard E; Krishnan, Jerry A; Martinez, Carlos H; Pirozzi, Cheryl B; O'Neal, Wanda K; Rennard, Stephen; Tashkin, Donald P; Wedzicha, Jadwiga A; Woodruff, Prescott; Paine, Robert; Martinez, Fernando J

2017-08-01

Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time. In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40-80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1-4) on the basis of post-bronchodilator FEV 1 . Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe. Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test. This trial is registered with ClinicalTrials.gov, number NCT01969344. 2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas 567 (51%) had none. 82 (7%) of 1105 patients had at least one acute exacerbation each year, whereas only 23 (2%) had two or more acute exacerbations in each year. An inconsistent pattern (both years with and without acute exacerbations) was common (456 [41%] of the group), particularly among GOLD stages 3 and 4 patients (256 [56%] of 456). In logistic regression, consistent acute exacerbations (≥1 event per year for 3 years) were associated with higher baseline symptom burden, previous exacerbations, greater evidence of small airway abnormality on CT, lower interleukin-15 concentrations, and higher interleukin-8 concentrations, than were no acute exacerbations. Although acute exacerbations are common, the exacerbation status of most individuals varies markedly from year to year. Among patients who had any acute exacerbation over 3 years, very few repeatedly had two or more events per year. In addition to symptoms and history of exacerbations in the year before study enrolment, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, and interleukin-15 and interleukin-8 concentrations. National Institutes of Health, and National Heart, Lung, and Blood Institute. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute Q fever in febrile patients in northwestern of Iran.

PubMed

Esmaeili, Saber; Golzar, Farhad; Ayubi, Erfan; Naghili, Behrooz; Mostafavi, Ehsan

2017-04-01

Q fever is an endemic disease in different parts of Iran. This study aimed to investigate the prevalence of acute Q fever disease among at-risk individuals in northwestern Iran. An etiological study was carried out in 2013 in Tabriz County. A total of 116 individuals who were in contact with livestock and had a nonspecific febrile illness were enrolled in the study. IgG phase II antibodies against Coxiella burnetii were detected using ELISA. The prevalence of acute Q fever was 13.8% (95% confidence interval [CI]: 8.0, 21.0%). Headache (87.5%) and fatigue and weakness (81.3%) were the dominant clinical characteristics among patients whit acute Q fever. Acute lower respiratory tract infection and chills were poorly associated with acute Q fever. Furthermore, 32% (95% CI: 24, 41%) of participants had a history of previous exposure to Q fever agent (past infection). Consumption of unpasteurized dairy products was a weak risk factor for previous exposure to C. burnetii. This study identified patients with acute Q fever in northwestern of Iran. The evidence from this study and previous studies conducted in different regions of Iran support this fact that Q fever is one of the important endemic zoonotic diseases in Iran and needs due attention by clinical physicians and health care system.

Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial.

PubMed

Magnano, Laura; Montoto, Silvia; González-Barca, Eva; Briones, Javier; Sancho, Juan Manuel; Muntañola, Ana; Salar, Antonio; Besalduch, Joan; Escoda, Lourdes; Moreno, Carol; Domingo-Domenech, Eva; Estany, Cristina; Oriol, Albert; Altés, Albert; Pedro, Carmen; Gardella, Santiago; Asensio, Antoni; Vivancos, Pilar; Fernández de Sevilla, Alberto; Ribera, Josep María; Colomer, Dolors; Campo, Elias; López-Guillermo, Armando

2017-04-01

Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.

Hospice Enrollment in Patients With Advanced Heart Failure Decreases Acute Medical Service Utilization.

PubMed

Yim, Cindi K; Barrón, Yolanda; Moore, Stanley; Murtaugh, Chris; Lala, Anuradha; Aldridge, Melissa; Goldstein, Nathan; Gelfman, Laura P

2017-03-01

Patients with advanced heart failure (HF) enroll in hospice at low rates, and data on their acute medical service utilization after hospice enrollment is limited. We performed a descriptive analysis of Medicare fee-for-service beneficiaries, with at least one home health claim between July 1, 2009, and June 30, 2010, and at least 2 HF hospitalizations between July 1, 2009, and December 31, 2009, who subsequently enrolled in hospice between July 1, 2009, and December 31, 2009. We estimated panel-negative binomial models on a subset of beneficiaries to compare their acute medical service utilization before and after enrollment. Our sample size included 5073 beneficiaries: 55% were female, 45% were ≥85 years of age, 13% were non-white, and the mean comorbidity count was 2.38 (standard deviation 1.22). The median number of days between the second HF hospital discharge and hospice enrollment was 45. The median number of days enrolled in hospice was 15, and 39% of the beneficiaries died within 7 days of enrollment. During the study period, 11% of the beneficiaries disenrolled from hospice at least once. The adjusted mean number of hospital, intensive care unit, and emergency room admissions decreased from 2.56, 0.87, and 1.17 before hospice enrollment to 0.53, 0.19, and 0.76 after hospice enrollment. Home health care Medicare beneficiaries with advanced HF who enrolled in hospice had lower acute medical service utilization after their enrollment. Their pattern of hospice use suggests that earlier referral and improved retention may benefit this population. Further research is necessary to understand hospice referral and palliative care needs of advanced HF patients. © 2017 American Heart Association, Inc.

Hospice Enrollment in Patients with Advanced Heart Failure Decreases Acute Medical Service Utilization

PubMed Central

Yim, Cindi K.; Barrón, Yolanda; Moore, Stanley; Murtaugh, Chris; Lala, Anuradha; Aldridge, Melissa; Goldstein, Nathan; Gelfman, Laura P.

2017-01-01

Background Patients with advanced heart failure (HF) enroll in hospice at low rates and data on their acute medical service utilization following hospice enrollment is limited. Methods and Results We performed a descriptive analysis of Medicare fee-for-service beneficiaries, with at least one home health claim between 07/01/2009 and 06/30/2010, and at least two HF hospitalizations between 07/01/2009 and 12/31/2009, who subsequently enrolled in hospice between 07/01/2009 and 12/31/2009. We estimated panel negative binomial models on a subset of beneficiaries to compare their acute medical service utilization before and after enrollment. Our sample size included 5,073 beneficiaries: 55% were female, 45% were ≥ 85 years of age, 13% were non-white, and the mean comorbidity count was 2.38 (STD 1.22). The median number of days between the second HF hospital discharge and hospice enrollment was 45. The median number of days enrolled in hospice was 15, and 39% of the beneficiaries died within 7 days of enrollment. During the study period, 11% of the beneficiaries disenrolled from hospice at least once. The adjusted mean number of hospital, ICU, and ER admissions decreased from 2.56, 0.87, and 1.17 before hospice enrollment to 0.53, 0.19, and 0.76 after hospice enrollment. Conclusions Home health care Medicare beneficiaries with advanced HF who enrolled in hospice had lower acute medical service utilization following their enrollment. Their pattern of hospice use suggests that earlier referral and improved retention may benefit this population. Further research is necessary to understand hospice referral and palliative care needs of advanced HF patients. PMID:28292824

Hospice Enrollment, Local Hospice Utilization Patterns, and Rehospitalization in Medicare Patients

PubMed Central

Holden, Timothy R.; Smith, Maureen A.; Bartels, Christie M.; Campbell, Toby C.; Yu, Menggang

2015-01-01

Abstract Background: Rehospitalizations are prevalent and associated with decreased quality of life. Although hospice has been advocated to reduce rehospitalizations, it is not known how area-level hospice utilization patterns affect rehospitalization risk. Objectives: The study objective was to examine the association between hospice enrollment, local hospice utilization patterns, and 30-day rehospitalization in Medicare patients. Methods: With a retrospective cohort design, 1,997,506 hospitalizations were assessed between 2005 and 2009 from a 5% national sample of Medicare beneficiaries. Local hospice utilization was defined using tertiles representing the percentage of all deaths occurring in hospice within each Hospital Service Area (HSA). Cox proportional hazard models were used to assess the relationship between 30-day rehospitalization, hospice enrollment, and local hospice utilization, adjusting for patient sociodemographics, medical history, and hospital characteristics. Results: Rates of patients dying in hospice were 27% in the lowest hospice utilization tertile, 41% in the middle tertile, and 53% in the highest tertile. Patients enrolled in hospice had lower rates of 30-day rehospitalization than those not enrolled (2.2% versus 18.8%; adjusted hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.118–0.131). Patients residing in areas of low hospice utilization were at greater rehospitalization risk than those residing in areas of high utilization (19.1% versus 17.5%; HR, 1.05; 95% CI, 1.04–1.06), which persisted beyond that accounted for by individual hospice enrollment. Conclusions: Area-level hospice utilization is inversely proportional to rehospitalization rates. This relationship is not fully explained by direct hospice enrollment, and may reflect a spillover effect of the benefits of hospice extending to nonenrollees. PMID:25879990

Comparison of a hydrogel corneal inlay and monovision laser in situ keratomileusis in presbyopic patients: focus on visual performance and optical quality.

PubMed

Verdoorn, Cornelis

2017-01-01

To compare the visual performance and optical quality after Raindrop Near Vision Inlay implantation or monovision LASIK for the correction of presbyopia. In this retrospective case-series study, patients previously treated in the nondominant eye with monovision LASIK were compared with patients previously implanted with Raindrop Near Vision Inlay. The study enrolled 16 inlay and 15 monovision LASIK patients. Uncorrected near visual acuity, uncorrected distance visual acuity, binocular stereopsis, patient satisfaction, and patient task performance were assessed. Postoperatively, the mean spherical equivalent was -0.66 D (0.78 SD) for the inlay group and -1.03 D (0.56 SD) for the monovision LASIK group. Monocularly, at uncorrected near distances, 60% of inlay patients and 47% of monovision LASIK patients achieved ≥20/20. Monocularly, at uncorrected far distances, 75% of inlay patients and 40% of monovision LASIK patients achieved ≥20/32 vision. Binocularly, at near distances, 79% of inlay patients and 53% of monovision LASIK patients obtained ≥20/20 vision. All patients achieved ≥20/20 binocularly for distance. On average, inlay patients obtained 98 seconds of arc and monovision LASIK patients obtained 286 seconds of arc for stereopsis. Most (79%) of the inlay patients and 66% of monovision LASIK patients were satisfied with their near vision, while 86% of inlay patients and 67% of monovision LASIK patients were satisfied with their distance vision. Patients receiving corneal inlays demonstrated better near and distance visual acuities, binocular stereopsis, task performance, and satisfaction, when compared to patients treated with monovision LASIK.

The Carotid Revascularization Endarterectomy vs. Stenting Trial completes randomization: lessons learned and anticipated results.

PubMed

Lal, Brajesh K; Brott, Thomas G

2009-11-01

The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) completed randomization on July 18, 2008. Sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), the trial has enrolled 2,522 participants across North America and is the largest randomized clinical trial (RCT) comparing the efficacy of carotid artery stenting (CAS) to carotid endarterectomy (CEA). It is also the largest RCT to assess carotid revascularization in both symptomatic and asymptomatic patients with carotid artery stenosis. Conventional-risk patients with symptomatic carotid stenosis (> or =50% by angiography, > or =70% by ultrasound) or asymptomatic carotid stenosis (> or =60% by angiography, > or =70% by ultrasound) were randomized to both treatment arms in a 1:1 ratio. Eligibility criteria for CREST were similar to those of the previous NINDS-sponsored CEA RCTs. The investigational devices used in the CAS arm of the study are the RX Acculink stent and the RX Accunet embolic protection system, (Abbott Vascular, Santa Clara, Calif). The primary aim is to contrast the efficacy of CAS versus CEA in preventing stroke, myocardial infarction, and all-cause mortality during a 30-day peri-procedural period, and ipsilateral stroke over the follow-up period (extending up to four years). The secondary aims are to contrast the efficacy of CAS and CEA in men and women, the restenosis rates of the two procedures, health-related quality of life, and cost effectiveness of CAS and CEA. The conclusion of enrollment in CREST marks the end of a long recruitment period from 117 community and academic hospital centers across the United States and Canada. Each surgeon and interventionalist underwent a rigorous credentialing process that included performance-assessment of prior CEA and CAS procedures. Credentialing of interventionalists also included a review of additional CAS procedures enrolled into a CREST lead-in phase prior to entering patients into the randomized trial; 1564 patients were enrolled in the lead-in, the final pathway for the largest credentialing effort to date for any clinical trial. CREST will provide long-term follow-up after carotid revascularization based on systematic ultrasonographic and neurologic surveillance, and on quality of life and cost-effectiveness comparisons between CAS and CEA in the setting of a RCT. We present a brief description of the CREST protocol, impediments that were overcome during the trial, salient results from the lead-in phase of the trial, a summary of enrollment activities and characteristics of the final cohort, and a timeline for anticipated results from the randomized phase.

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

PubMed

Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

2016-02-01

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial.

PubMed

van den Eertwegh, Alfons J M; Versluis, Jurjen; van den Berg, H Pieter; Santegoets, Saskia J A M; van Moorselaar, R Jeroen A; van der Sluis, Tim M; Gall, Helen E; Harding, Thomas C; Jooss, Karin; Lowy, Israel; Pinedo, Herbert M; Scheper, Rik J; Stam, Anita G M; von Blomberg, B Mary E; de Gruijl, Tanja D; Hege, Kristen; Sacks, Natalie; Gerritsen, Winald R

2012-05-01

The granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells vaccine (GVAX) has antitumour activity against prostate cancer; preclinical studies have shown potent synergy when combined with ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen 4. We aimed to assess the safety of combined treatment with GVAX and ipilimumab in patients with metastatic castration-resistant prostate cancer (mCRPC). We did an open-labelled, single-centre, dose-escalation study of ipilimumab concurrent with a fixed dose of GVAX, with a subsequent expansion phase, both at the VU University Medical Centre (Amsterdam, Netherlands). Eligible patients had documented mCRPC and had not been previously treated with chemotherapy. All patients received a 5×10(8) cell priming dose of GVAX intradermally on day 1 with subsequent intradermal injections of 3×10(8) cells every 2 weeks for 24 weeks. The vaccinations were combined with intravenous ipilimumab every 4 weeks. We enrolled patients in cohorts of three; each cohort received an escalating dose of ipilimumab at 0·3, 1·0, 3·0, or 5·0 mg/kg. Our primary endpoint was safety. This study is registered with ClinicalTrials.gov, number NCT01510288. We enrolled 12 patients into our dose-escalation cohort. We did not record any severe immune-related adverse events at the first two dose levels. At the 3·0 mg/kg dose level, one patient had grade 2 and two patients grade 3 hypophysitis; at the 5·0 mg/kg dose level, two patients had grade 3 hypophysitis and one patient developed grade 4 sarcoid alveolitis (a dose-limiting toxic effect). Due to observed clinical activity and toxic events, we decided to expand the 3·0 mg/kg dose level, rather than enrol a further three patients at the 5·0 mg/kg level. 16 patients were enrolled in the expansion cohort, two of whom developed grade 2 hypophysitis, three colitis (one grade 1 and two grade 2), and one grade 3 hepatitis--all immune-related adverse events. The most common adverse events noted in all 28 patients were injection-site reactions (grade 1-2 events seen in all patients), fatigue (grade 1-2 in 20 patients, grade 3 in two), and pyrexia (grade 1-2 in 15 patients, grade 3 in one). 50% or greater declines in prostate-specific antigen from baseline was recorded in seven patients (25%); all had received 3·0 mg/kg or 5·0 mg/kg ipilimumab. GVAX combined with 3·0 mg/kg ipilimumab is tolerable and safe for patients with mCRPC. Further research on the combined treatment of patients with mCRPC with vaccination and ipilimumab is warranted. Cell Genesys Inc, Prostate Cancer Foundation, Dutch Cancer Society (KWF-VU 2006-3697), and Foundation Stichting VUmc Cancer Center Amsterdam. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pharmaceutical industry research and cost savings in community-acquired pneumonia.

PubMed

Kessler, Lori A; Waterer, Grant W; Barca, Robin; Wunderink, Richard G

2002-09-01

To provide financial justification for continuing pharmaceutical research in an environment that has met with increasing resistance from insurance carriers to paying for the care of patients enrolled in research studies. Matched case-control study of patients enrolled into inpatient community-acquired pneumonia (CAP) pharmaceutical research protocols. Case patients were enrolled into a CAP pharmaceutical research trial. Control patients were obtained from a prospective cohort study of CAP. Cases were matched to controls on the basis of age, sex, pneumonia severity index (PSI) grade, and comorbid illnesses as measured by the PSI and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scoring systems. Financial data were obtained from hospital billing records. Twenty-five cases were identified and matched to appropriate controls. There was no statistically significant difference in mean PSI and APACHE II scores between cases and controls. There was a significant reduction in the total charges for hospital care of patients enrolled into a pharmaceutical industry trial ($6267 vs $9979; P = .03). As expected, the most dramatic reduction was in pharmacy charges ($642 vs $1797; P = .002), but there were trends toward lower charges in all cost subgroups. Interestingly, there was also a strong trend toward reduced length of hospital stay associated with enrollment in a pharmaceutical trial (4.5 vs 6.0 days; P = .06). Enrollment in a pharmaceutical research protocol results in significant cost savings in patients admitted to the hospital with CAP and may lead to earlier hospital discharge.

Angular Stable Miniplate Fixation of Chronic Unstable Scaphoid Nonunion.

PubMed

Schormans, Philip M J; Brink, Peter R G; Poeze, Martijn; Hannemann, Pascal F W

2018-02-01

Background  Around 5 to 15% of all scaphoid fractures result in nonunion. Treatment of long-lasting scaphoid nonunion remains a challenge for the treating surgeon. Healing of scaphoid nonunion is essential for prevention of scaphoid nonunion advanced collapse and the subsequent predictable pattern of radiocarpal osteoarthritis. Purpose  The purpose of this study was to investigate the feasibility of fixation of the scaphoid nonunion with a volar angular stable miniplate and cancellous bone grafting. We hypothesized that this technique could be successful, even in patients with previous surgery for nonunion and in patients with a long duration of nonunion. Patients and Methods  A total of 21 patients enrolled in a single-center prospective cohort study. Healing of nonunion was assessed on multiplanar computed tomography scan of the wrist at a 3-month interval. Functional outcome was assessed by measuring grip strength, range of motion, and by means of the patient-rated wrist and hand evaluation (PRWHE) questionnaire. Results  During follow-up, 19 out of 21 patients (90%) showed radiological healing of the nonunion. The range of motion did not improve significantly. Postoperative PRWHE scores decreased by 34 points. Healing occurred regardless of the length of time of the nonunion (range: 6-183 months) and regardless of previous surgery (38% of patients). Conclusion  Volar angular stable miniplate fixation with autologous cancellous bone grafting is a successful technique for the treatment of chronic unstable scaphoid nonunion, even in patients with long-lasting nonunion and in patients who underwent previous surgery for a scaphoid fracture. Rotational interfragmentary stability might be an important determining factor for the successful treatment of unstable scaphoid nonunion. Level of Evidence  Level IV.

Internal validation of the prognostic index for spine metastasis (PRISM) for stratifying survival in patients treated with spinal stereotactic radiosurgery.

PubMed

Jensen, Garrett; Tang, Chad; Hess, Kenneth R; Bishop, Andrew J; Pan, Hubert Y; Li, Jing; Yang, James N; Tannir, Nizar M; Amini, Behrang; Tatsui, Claudio; Rhines, Laurence; Brown, Paul D; Ghia, Amol J

2017-01-01

We sought to validate the Prognostic Index for Spinal Metastases (PRISM), a scoring system that stratifies patients into subgroups by overall survival.Methods and materials: The PRISM was previously created from multivariate Cox regression with patients enrolled in prospective single institution trials of stereotactic spine radiosurgery (SSRS) for spinal metastasis. We assess model calibration and discrimination within a validation cohort of patients treated off-trial with SSRS for metastatic disease at the same institution. The training and validation cohorts consisted of 205 and 249 patients respectively. Similar survival trends were shown in the 4 PRISM. Survival was significantly different between PRISM subgroups (P<0.0001). C-index for the validation cohort was 0.68 after stratification into subgroups. We internally validated the PRISM with patients treated off-protocol, demonstrating that it can distinguish subgroups by survival, which will be useful for individualizing treatment of spinal metastases and stratifying patients for clinical trials.

Umbilical Hernia in Peritoneal Dialysis Patients: Surgical Treatment and Risk Factors.

PubMed

Banshodani, Masataka; Kawanishi, Hideki; Moriishi, Misaki; Shintaku, Sadanori; Ago, Rika; Hashimoto, Shinji; Nishihara, Masahiro; Tsuchiya, Shinichiro

2015-12-01

No previous reports have focused on surgical treatments and risk factors of umbilical hernia alone in peritoneal dialysis (PD) patients. Herein, we evaluated the treatments and risk factors. A total of 411 PD patients were enrolled. Of the 15 patients with umbilical hernia (3.6%), six underwent hernioplasty. There was no recurrence in five patients treated with tension-free hernioplasty. The mean PD vintage after onset of hernia in the hernioplasty group tended to be longer than that in the non-hernioplasty group. An incarcerated hernia occurred in one non-hernioplasty patient. Although the incidence was significantly higher among women (P = 0.02), female sex was not a risk factor for umbilical hernia (P = 0.08). Our findings suggest that umbilical hernias should be repaired for continuing PD. Furthermore, there were no significant risk factors for umbilical hernia in PD patients. Future studies with larger sample groups are required to elucidate these risk factors. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Burden incurred by patients and their caregivers after outpatient surgery: a prospective observational study.

PubMed

Manohar, Asha; Cheung, Kristin; Wu, Christopher L; Stierer, Tracey S

2014-05-01

The burden of patients and their caregivers after outpatient surgery has not been fully examined. The number of outpatient surgeries has dramatically increased in the last several years, particularly in the orthopaedic sector. Patients undergoing outpatient orthopaedic procedures may be expected to have more postdischarge pain than those undergoing nonorthopaedic outpatient procedures. In light of this, assessment of patient and caregiver expectations and actual burden after discharge is of importance. We assessed the impact of outpatient surgery on recovery of patients and their caregivers in the postoperative period by determining (1) expected versus actual time to resume daily activities, including work; (2) expected versus actual recovery at 7 and 30 days postoperatively; and (3) the number of caregivers that felt emotional or physical disturbances from caring for outpatients. Forty-four adult patients undergoing outpatient surgical procedures and their primary caregivers were enrolled in this prospective survey study, of which 30% were orthopaedic patients. Surveys assessing postoperative recovery were given to patients at six time points, on Postoperative Days 0 to 3, 7, and 30. Surveys assessing the burden of informal caregiving were given to each patient's primary caregiver at four time points, on Postoperative Days 1 to 3 and 7. The enrollment rate was 79% (44 enrolled of 56 approached) and the survey response rate was 100% for patients and 93% (41 of 44) for caregivers. We found that 16 of 44 patients (36%) needed more time than originally anticipated to resume their daily activities and three of 29 patients (10%) needed more time off from work than originally anticipated. Patients were approximately 66% and 88% fully recovered 7 and 30 days after surgery, respectively. The primary caregivers noted disturbances in emotional (nine of 43, 21%) and physical (17 of 43, 40%) aspects of their daily lives while providing care for patients. Our surveyed patients were from multiple surgical services; however, our results may be generalized to an orthopaedic population, although they may underestimate actual results for this population given their generally higher pain scores. Patients may take longer to recover from outpatient surgery than previously recognized. As increased pain and prolonged recovery may be associated with increased caregiver burden, these data are of particular significance to the outpatient orthopaedic surgical population. Informal caregiving after outpatient surgery may be an unrecognized physical and psychologic burden and may have a significant societal impact. Level II, prognostic study. See Instructions for Authors for a complete description of levels of evidence.

Clinical Outcomes Following Transcatheter Aortic Valve Replacement in Asian Population.

PubMed

Yoon, Sung-Han; Ahn, Jung-Min; Hayashida, Kentaro; Watanabe, Yusuke; Shirai, Shinichi; Kao, Hsien-Li; Yin, Wei-Hsian; Lee, Michael Kang-Yin; Tay, Edgar; Araki, Motoharu; Yamanaka, Futoshi; Arai, Takahide; Lin, Mao-Shin; Park, Jun-Bean; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Lee, Cheol Whan; Park, Seong-Wook; Muramatsu, Toshiya; Hanyu, Michiya; Kozuma, Ken; Kim, Hyo-Soo; Saito, Shigeru; Park, Seung-Jung

2016-05-09

This study describes the characteristics of a real-world Asian patient population treated with transcatheter aortic valve replacement (TAVR) and evaluates their clinical outcomes. No previously reported randomized or observational studies adequately assess the safety and efficacy of TAVR in an Asian population. The Asian TAVR registry is an international multicenter study that enrolled patients with aortic stenosis who underwent TAVR in Asian countries. In total, 848 patients with mean STS score of 5.2 ± 3.8% were enrolled between March 2010 and September 2014 at 11 centers in 5 countries. The Edwards Sapien or Medtronic CoreValve was implanted in 64.7% and 35.3% of patients, respectively. The procedural success rate was 97.5%. The 30-day and 1-year mortality rates were 2.5% and 10.8%, respectively. There was no difference in 1-year mortality between devices (Sapien: 9.4%; CoreValve: 12.2%; log-rank p = 0.40). The rates of stroke, life-threatening bleeding, major vascular complications and acute kidney injury (stage 2 to 3) were 3.8%, 6.4%, 5.0% and 3.3%, respectively. Moderate or severe paravalvular leakage was significantly more common with the CoreValve than Sapien (14.4% vs. 7.3%; p = 0.001). According to the multivariate model, a higher STS score, lower body mass index, New York Heart Association functional class III-IV symptoms, diabetes mellitus, prior cerebrovascular accident, low mean gradient at baseline, and moderate or severe paravalvular leakage were significantly associated with reduced survival. Despite anatomical features of concern, the clinical outcomes of TAVR in our Asian population were favorable in comparison with those of previously published trials and observational studies. (The Asian Transcatheter Aortic Valve Replacement Registry [Asian TAVR]; NCT02308150). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The impact of reducing financial barriers on utilisation of a primary health care facility in Rwanda

PubMed Central

Dhillon, Ranu S.; Bonds, Matthew H.; Fraden, Max; Ndahiro, Donald; Ruxin, Josh

2011-01-01

This study investigates the impact of subsidising community-based health insurance (mutuelle) enrolment, removing point-of-service co-payments, and improving service delivery on health facility utilisation rates in Mayange, a sector of rural Rwanda of approximately 25,000 people divided among five ‘imidugudu’ or small villages. While comprehensive service upgrades were introduced in the Mayange Health Centre between April 2006 and February 2007, utilisation rates remained similar to comparison sites. Between February 2007 and April 2007, subsidies for mutuelle enrolment established virtually 100% coverage. Immediately after co-payments were eliminated in February 2007, patient visits levelled at a rate triple the previous value. Regression analyses using data from Mayange and two comparison sites indicate that removing financial barriers resulted in about 0.6 additional annual visits for curative care per capita. Although based on a single local pilot, these findings suggest that in order to achieve improved health outcomes, key short-term objectives include improved service delivery and reduced financial barriers. Based on this pilot, higher utilisation rates may be affected if broader swaths of the population are enrolled in mutuelle and co-payments are eliminated. Health leaders in Rwanda should consider further studies to determine if the impact of eliminating co-payments and increasing subsidies for mutuelle enrolment as seen in Mayange holds at greater levels of scale. Broader studies to better elucidate the impact of enrolment subsidies and co-payment subsidies on utilisation, health outcomes, and costs would also provide policy insights. PMID:21732708

Clinical Characteristic Picture and Impact of Symptoms on Quality of Life of Interstitial Cystitis Patients in Taiwan.

PubMed

Lee, Ming-Huei; Lin, Alex Tong-Long; Kuo, Hann-Chorng; Chen, Yung-Fu

2014-01-01

No clinical characteristic picture and impact of symptoms on quality of life (QOL) of interstitial cystitis (IC) patients in Taiwan had been reported. This paper is intended to provide preliminary descriptive results of IC research in Taiwan. A total of 319 patients, based on National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK) criteria, were enrolled in the study from February 2004 through March 2006. Evaluation data included baseline demographic information, patient and family medical history, dietary effects, pregnancy data, sexual relationships with symptoms, and impact of symptoms on quality of life. The main responsibility of the hospitals discussed was patient care and data collection. Taichung Hospital presents the results. The Interstitial Cystitis Database (ICDB) patients were predominantly female, that is, 86% of the total, with an average enrollment age of 46. The analysis of various symptoms indicates the following distribution: (i) 94% frequency; (ii) 80% pain; (iii) 53% nocturia; (iv) 43% urgency; and (v) 10% associated incontinence. Approximately 83% reported pain over the bladder while in full stage, and 74% reported pain relief after voiding. The predominant characteristic of pain was full sensation (54%) with the predominant position on low abdominal area (52%). Moreover, 80% reported sleeping disturbance due to disease, and 66% reported difficulty in performing daily work. Interstitial cystitis patients in Taiwan have lower economic status but lower impact on QOL than Western patients. However, the sexual-related pain and sleeping disorder were higher than previously thought and deserve our attention. Accordingly, this research provides a foundation for further investigations of baseline associations and longitudinal trends. © 2013 Wiley Publishing Asia Pty Ltd.

Diagnostic performance of a biomarker panel as a negative predictor for acute appendicitis in adult ED patients with abdominal pain.

PubMed

Huckins, David S; Copeland, Karen; Self, Wesley; Vance, Cheryl; Hendry, Phyllis; Borg, Keith; Gogain, Joseph

2017-03-01

Evaluate the diagnostic accuracy of the APPY1TM biomarker panel, previously described for use in pediatric patients, for identifying adult ED patients with abdominal pain who are at low risk of acute appendicitis. This study prospectively enrolled subjects >18years of age presenting to seven U.S. emergency departments with <72hours of abdominal pain suggesting possible acute appendicitis. The APPY1 panel was performed on blood samples drawn from each patient at the time of initial evaluation and results were correlated with the final diagnosis either positive or negative for acute appendicitis. 431 patients were enrolled with 422 completing all aspects of the study. The APPY1 biomarker panel exhibited a sensitivity of 97.5% (95% CI, 91.3-99.3%), a negative predictive value of 98.4% (95% CI, 94.4-99.6%), a negative likelihood ratio of 0.07 (95% CI, 0.02-0.27), with a specificity of 36.5% (95% CI, 31.6-41.8%) for acute appendicitis. The panel correctly identified 125 of 342 (36.6%) patients who did not have appendicitis with 2 (2.5%) false negatives. The CT utilization rate in this population was 72.7% (307/422). Of 307 CT scans, 232 were done for patients who did not have appendicitis and 79 (34%) of these patients were correctly identified as negative with "low risk" biomarker panel results, representing 26% (79/307) of all CT scans performed. This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this prospective adult cohort, thereby potentially reducing the dependence on CT for the evaluation of possible acute appendicitis. Copyright © 2016 Elsevier Inc. All rights reserved.

The cancer anorexia/weight loss syndrome: exploring associations with single nucleotide polymorphisms (SNPs) of inflammatory cytokines in patients with non-small cell lung cancer

PubMed Central

Jatoi, Aminah; Qi, Yingwei; Kendall, Glenda; Jiang, Ruoxiang; McNallan, Sheila; Cunningham, Julie; Mandrekar, Sumithra; Yang, Ping

2010-01-01

Objective The cancer anorexia/weight loss syndrome commonly occurs in patients with non-small cell lung cancer (NSCLC) and is characterized by loss of weight and appetite as well as diminished survival. The current study explored whether any of 22 single nucleotide polymorphisms (SNPs) of certain previously implicated inflammatory cytokines (interleukin-1 beta, interleukin-1RN, interleukin-6, and tumor necrosis factor) are associated with this syndrome. Patients and Methods All NSCLC patients who had been enrolled in the Mayo Clinic Lung Cancer Cohort, had completed a health-related questionnaire approximately 6 months after enrollment, and had blood drawn were included in this study, thus yielding a sample size of 471 patients. Results Sixty-six (14%) patients manifested weight loss shortly after diagnosis, and 152 (32%) reported appetite loss. Only tumor necrosis factor alpha rs800629 was associated with anorexia (odds ratio: 0.46; 95% confidence interval: 0.29, 0.72; p<0.001); patients who were heterozygous and minor homozygous were less likely to suffer anorexia. Otherwise, there were no statistically significant associations between any of the other 21 SNPs and weight loss and/or anorexia. In univariate analyses, weight loss, anorexia, more advanced cancer stage, and interleukin-1 beta rs1143627 were associated with a worse survival, and interleukin-6 rs2069835 was associated with better survival. However, in multivariate analyses, cancer stage and patient age were the only statistically significant predictors of worse survival. Conclusion No specific SNP was associated with all aspects of the cancer anorexia/weight loss syndrome, but rs800629 may merit further study in cancer-associated anorexia. PMID:20012999

Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy

PubMed Central

Rockey, Don C; Vierling, John M; Mantry, Parvez; Ghabril, Marwan; Brown, Robert S; Alexeeva, Olga; Zupanets, Igor A; Grinevich, Vladimir; Baranovsky, Andrey; Dudar, Larysa; Fadieienko, Galyna; Kharchenko, Nataliya; Klaryts'ka, Iryna; Morozov, Vyacheslav; Grewal, Priya; McCashland, Timothy; Reddy, K Gautham; Reddy, K Rajender; Syplyviy, Vasyl; Bass, Nathan M; Dickinson, Klara; Norris, Catherine; Coakley, Dion; Mokhtarani, Masoud; Scharschmidt, Bruce F

2014-01-01

Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetyl glutamine, which is excreted in urine. This randomized, double-blind, placebo-controlled phase II trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the previous 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days, and safety. GPB, at 6 mL orally twice-daily, significantly reduced the proportion of patients who experienced an HE event (21% versus 36%; P = 0.02), time to first event (hazard ratio [HR] = 0.56; P < 0.05), as well as total events (35 versus 57; P = 0.04), and was associated with fewer HE hospitalizations (13 versus 25; P = 0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P < 0.01), time to first event (HR = 0.29; P < 0.01), and total events (7 versus 31; P < 0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. Conclusion: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167). (Hepatology 2014;59:1073-1083) PMID:23847109

Revisiting the “Golden Hour”: An Evaluation of Out-of-Hospital Time in Shock and Traumatic Brain Injury

PubMed Central

Newgard, Craig D.; Meier, Eric N.; Bulger, Eileen M.; Buick, Jason; Sheehan, Kellie; Lin, Steve; Minei, Joseph P.; Barnes-Mackey, Roxy A.; Brasel, Karen

2015-01-01

Study Objective We evaluated shock and traumatic brain injury (TBI) patients previously enrolled in an out-of-hospital clinical trial to test the association between out-of-hospital time and outcome. Methods This was a secondary analysis of shock and TBI patients ≥ 15 years enrolled in a Resuscitation Outcomes Consortium out-of-hospital clinical trial by 81 EMS agencies transporting to 46 Level I and II trauma centers in 11 sites (May 2006 through May 2009). Inclusion criteria were: SBP ≤ 70 mmHg or SBP 71 - 90 mmHg with heart rate ≥ 108 beats per minute (shock cohort) and Glasgow Coma Scale score ≤ 8 (TBI cohort); patients meeting both criteria were placed in the shock cohort. Primary outcomes were 28-day mortality (shock cohort) and 6-month Glasgow Outcome Scale - Extended (GOSE) ≤ 4 (TBI cohort). Results There were 778 patients in the shock cohort (26% 28-day mortality) and 1,239 patients in the TBI cohort (53% 6-month GOSE ≤ 4). Out-of-hospital time > 60 minutes was not associated with worse outcomes after accounting for important confounders in the shock cohort (adjusted odds ratio [aOR] 1.42, 95% CI 0.77-2.62) or TBI cohort (aOR 0.80, 95% CI 0.52-1.21). However, shock patients requiring early critical hospital resources and arriving > 60 minutes had higher 28-day mortality (aOR 2.37, 95% CI 1.05-5.37); this finding was not observed among a similar TBI subgroup. Conclusions Among out-of-hospital trauma patients meeting physiologic criteria for shock and TBI, there was no association between time and outcome. However, the subgroup of shock patients requiring early critical resources arriving after 60 minutes had higher mortality. PMID:25596960

Evaluation of Mediterranean diet adherence in patients with a history of coronary revascularization.

PubMed

Acar, B; Gucuk Ipek, E; Unal, S; Yayla, C; Karanfil, M; Burak, C; Kara, M; Bayraktar, F; Kuyumcu, M S; Aydogdu, S

Lifestyle modification is an important component of the secondary prevention strategies; and a healthy diet is one of the cornerstones in management of the coronary heart disease. We aimed to investigate the dietary habits of the patients with history of coronary revascularization, characteristics of the ones with good adherence by using alternate MedDiet questionnaire. We included outpatients who had a history of coronary revascularization at least 6 months prior to enrollment. Each participant filled out a questionnaire to collect the data of demographics and clinical characteristics. Alternate MedDiet score was calculated to evaluate the Mediterranean style dietary adherence. Alternate MedDiet was originally based on 14-item questionnaire; we adjusted it to our population (max 13 points). We enrolled 226 consecutive outpatients (age 61.7±10.9 years, 72% males). The median duration after revascularization was 60 months. A total of 112 (49.6%) patients had previous percutaneous coronary intervention (PCI), 77 (34.1%) had coronary by-pass graft surgery (CABG), and 36 (15.9%) had both revascularization procedures. The median MedDiet score was 6. Patients were stratified into two subgroups (MedDiet score ≥7 vs. <7). A total of 61 (26.9%) patients had MedDiet score ≥7. By univariate analysis, good MedDiet scores were associated with older age, waist circumference, body mass index, high education level, regular follow-up, duration after first revascularization and revascularization with CABG+PCI. In the multivariate analysis, high education level (P=.002, OR=8.212, 95%CI: 2.155-31.291) and duration after revascularization (P=.034, OR=1.007, 95%CI: 1.001-1.013) were independent predictors of good MedDiet scores. The adherence rate to a healthy diet was low in patients with previous coronary revascularization. MedDiet score seems to be practical and useful item to evaluate the dietary habits in outpatient setting. Mediterranean diet adherence rates were associated with high education level, and duration after revascularization. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Social disparities in Disease Management Programmes for coronary heart disease in Germany: a cross-classified multilevel analysis

PubMed Central

Bozorgmehr, Kayvan; Maier, Werner; Brenner, Hermann; Saum, Kai-Uwe; Stock, Christian; Miksch, Antje; Holleczek, Bernd; Szecsenyi, Joachim; Razum, Oliver

2015-01-01

Background Disease Management Programmes (DMPs) aim to improve effectiveness and equity of care but may suffer from selective enrolment. We analysed social disparities in DMP enrolment among elderly patients with coronary heart disease (CHD) in Germany, taking into account contextual effects at municipality and primary care practice levels. Methods Cross-sectional analysis of effects of educational attainment and regional deprivation on physician-reported DMP enrolment in a subsample of a large population-based cohort study in Germany, adjusting for individual-level, practice-level and area-level variables. We calculated OR and their 95% CIs (95% CI) in cross-classified, multilevel logistic regression models. Results Among N=1280 individuals with CHD (37.3% women), DMP enrolment rates were 22.2% (women) and 35% (men). The odds of DMP enrolment were significantly higher for male patients (OR=1.98 (1.50 to 2.62)), even after adjustment for potential confounding by individual-level, practice-level and area-level variables (range: OR=1.60 (1.08 to 2.36) to 2.16 (1.57 to 2.98)). Educational attainment was not significantly associated with DMP enrolment. Compared to patients living in least-deprived municipalities, the adjusted propensity of DMP enrolment was statistically significantly lower for patients living in medium-deprived municipalities (OR=0.41 (0.24 to 0.71)), and it also tended to be lower for patients living in the most-deprived municipalities (OR=0.70 (0.40 to 1.21)). Models controlling for the social situation (instead of health-related behaviour) yielded comparable effect estimates (medium-deprived/most-deprived vs least-deprived areas: OR=0.45 (0.26 to 0.78)/OR=0.68 (0.33 to 1.19)). Controlling for differences in comorbidity attenuated the deprivation effect estimates. Conclusions We found evidence for marked gender, but not educational disparities in DMP enrolment among patients with CHD. Small-area deprivation was associated with DMP enrolment, but the effects were partly explained by differences in comorbidity. Future studies on DMPs should consider contextual effects when analysing programme effectiveness or impacts on equity and efficiency. PMID:26082518

Lung Transplantation in the Management of Patients with LAM:Baseline Data from the NHLBI LAM Registry

PubMed Central

Ryu, Jay; Beck, Gerald; Moss, Joel; Lee, Jar-Chi; Finlay, Geraldine; Brown, Kevin; Chapman, Jeffrey; McMahan, June; Olson, Eric; Ruoss, Stephen; Sherer, Susan; Maurer, Janet R; Ryu, Jay; Beck, Gerald; Moss, Joel; Lee, Jar-Chi; Finlay, Geraldine; Brown, Kevin; Chapman, Jeffrey; McMahan, June; Olson, Eric; Ruoss, Steven

2008-01-01

Background In 1997, the National Heart, Lung, and Blood Institute of the National Institutes of Health established a Registry to better characterize the demographic, clinical, physiologic and radiographic features of patients with LAM. We report here data collected at enrollment from patients who had either undergone transplant prior to enrollment, underwent transplant during the 5-year study, or were evaluated/waitlisted for lung transplant during the 5-year study. Methods The LAM Registry enrolled patients from six clinical centers between August 1998 and October 2001. On entry patients filled out questionnaires covering medical history, symptoms, treatment and quality of life (SF-36 and St. George’s Respiratory Questionnaire). Enrollees underwent blood laboratory work, arterial blood gases and pulmonary function testing. Follow-up was at six month and/or yearly intervals. Diagnoses were confirmed by biopsy or typical clinical presentation plus CT findings confirmed by independent expert radiologists. A total of 243 women were enrolled. Of those 13 (5.3%) had been transplanted at time of entry (Group A), 21 (8.6%) were transplanted during the study (Group B) and 48 (19.8%) were either waitlisted for transplant or underwent evaluation after enrollment during the study period (Group C). The remaining 161 (66.3%) registrants were neither considered for nor listed for transplant during the Registry period (Group D). Results One-third of patients in a large sample of LAM patients had either been transplanted or were being considered for transplant. At enrollment, patients who had already been transplanted and those not in need of transplant (Groups A and D) had better pulmonary function and quality of life scores compared to patients who subsequently underwent lung transplant during the Registry period (Group B). Conclusion In this large registry of LAM patients, lung transplantation appears to be associated both with significantly improved lung function and quality of life compared to patients with advanced disease. PMID:18096481

Patient Navigation for Patients Frequently Visiting the Emergency Department: A Randomized, Controlled Trial.

PubMed

Seaberg, David; Elseroad, Stanton; Dumas, Michael; Mendiratta, Sudave; Whittle, Jessica; Hyatte, Cheryl; Keys, Jan

2017-11-01

Emergency department (ED) superutilizers (patients with five or more visits/year) comprise only 5% of the patients seen yet comprise 25% of total ED visits. Although the reasons for this are multifactorial, the cost to the patient and the community is exceedingly high. The cost is not just monetary; care of these patients is inappropriately fragmented and their presence in the ED may contribute to overcrowding affecting the community's emergency readiness. Previous studies using staff trained to help patients navigate their care options have had conflicting results. The objective was to determine whether a trained patient navigator (PN) can reduce ED use and costs in superutilizers over a 1-year period. Superutilizers were enrolled in a prospective randomized controlled clinical trial. Patients were randomized into the treatment arm and met with a PN who reviewed their diagnosis and associated care plan and identified proper primary care services and community resources for follow-up. The remaining control group was provided standard care. Both groups were given a follow-up call and survey by the PN within 7 days of their visit who assessed primary care follow-up and patient satisfaction using a 4-point Likert scale. After 12 months, the patients' return ED visits and ED costs were compared to the year prior and primary care compliance and satisfaction were measured using Student's t-tests with Bonferroni correction or Mann-Whitney U-tests. A total of 282 patients were enrolled (148 in navigation treatment group, 134 controls). Patients were similarly matched in age, race, sex, insurance, and chief complaints. Overall ED visits decreased during the 12-month study period, compared to the 12 months prior to enrollment (2,249 visits prior to 2,050 visits during study period, -8.8%). There was a greater decrease in ED visits from the preenrollment year to postenrollment year in the treatment group (1,148 visits to 996 visits, -13.2%) compared to the control group (1,101 visits to 1,054 visits, -4.3%; p < 0.05). Overall health care costs (ED and hospital) for all 282 patients decreased in the year after compared to the 12 months prior to enrollment ($3.9M to $3.1M) with a greater decrease in the navigation treatment group (-26.6%) compared to the control group (-17.5%). Patient surveys found no difference in patient satisfaction in the pre- and postenrollment periods but there was an increase in primary care physician (PCP) use over the 12-month follow-up period in the treatment group (6.42 visits/patient) compared to the control group (4.07 visits/patient; p < 0.05). Our data showed that the overall number of return ED visits and costs did decrease for both groups, potentially inferring a placebo effect for the use of a PN; however, the decrease in ED visits and costs were greater in the treatment group. One-year follow-up noted an increase in PCP visits in the navigation group. Use of a PN may be cost-effective. © 2017 by the Society for Academic Emergency Medicine.

Understanding Motivations to Participate in an Observational Research Study: Why do Patients Enroll?

PubMed Central

Soule, Michael C.; Beale, Eleanor E.; Suarez, Laura; Beach, Scott R.; Mastromauro, Carol A.; Celano, Christopher M; Moore, Shannon V; Huffman, Jeff C.

2016-01-01

By understanding common motivations for participating in observational research studies, clinicians may better understand the perceived benefits of research participation from their clients’ perspective. We enrolled 164 cardiac patients in a study about the effects of gratitude and optimism. Two weeks post-enrollment, participants completed a four-item questionnaire regarding motivations for study enrollment. Altruistic motivation ranked highest, while intellectual, health-related, and financial motivations rated lower. Four subgroups of participants emerged, each with distinct characteristics and different priorities for participating. These findings may help front-line clinicians to understand which motivations for participation apply to their clients who enroll in non-treatment-based research projects. PMID:26933943

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.

PubMed

Lee, Daniel W; Kochenderfer, James N; Stetler-Stevenson, Maryalice; Cui, Yongzhi K; Delbrook, Cindy; Feldman, Steven A; Fry, Terry J; Orentas, Rimas; Sabatino, Marianna; Shah, Nirali N; Steinberg, Seth M; Stroncek, Dave; Tschernia, Nick; Yuan, Constance; Zhang, Hua; Zhang, Ling; Rosenberg, Steven A; Wayne, Alan S; Mackall, Crystal L

2015-02-07

Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells. This phase 1, dose-escalation trial consecutively enrolled children and young adults (aged 1-30 years) with relapsed or refractory acute lymphoblastic leukaemia or non-Hodgkin lymphoma. Autologous T cells were engineered via an 11-day manufacturing process to express a CD19-CAR incorporating an anti-CD19 single-chain variable fragment plus TCR zeta and CD28 signalling domains. All patients received fludarabine and cyclophosphamide before a single infusion of CD19-CAR T cells. Using a standard 3 + 3 design to establish the maximum tolerated dose, patients received either 1 × 10(6) CAR-transduced T cells per kg (dose 1), 3 × 10(6) CAR-transduced T cells per kg (dose 2), or the entire CAR T-cell product if sufficient numbers of cells to meet the assigned dose were not generated. After the dose-escalation phase, an expansion cohort was treated at the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT01593696. Between July 2, 2012, and June 20, 2014, 21 patients (including eight who had previously undergone allogeneic haematopoietic stem-cell transplantation) were enrolled and infused with CD19-CAR T cells. 19 received the prescribed dose of CD19-CAR T cells, whereas the assigned dose concentration could not be generated for two patients (90% feasible). All patients enrolled were assessed for response. The maximum tolerated dose was defined as 1 × 10(6) CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3·0-36·3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients). CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur. National Institutes of Health Intramural funds and St Baldrick's Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The utility of prescreening for hepatitis A in military recruits prior to vaccination.

PubMed

Hirota, William K; Duncan, Marten B; Hirota, William K; Tsuchida, Amy

2002-11-01

The U.S. Army administers the hepatitis A virus (HAV) vaccination for prophylaxis against HAV infection. There is little comparative data as to whether prescreening for previous HAV infection before immunization is less costly than universal vaccination. We designed a study to determine the prevalence of previous HAV infection in U.S. Army recruits and then perform a cost analysis. The cost analysis compared selective vaccination versus universal vaccination. Basic demographic information, including age, gender, geographic origin, and ethnicity, were collected after which patients were tested for HAV antibodies. A total of 1,332 individuals was prospectively enrolled with 183 individuals (13.74%) having evidence of previous HAV infection. Minority recruits were found to have a higher prevalence than Caucasian recruits (p = 0.0451. The cost analysis demonstrates that vaccination without prescreening was the least costly of two vaccination strategies for this cohort. To achieve current vaccination goals, all U.S. military recruits should be vaccinated without evaluation for previous HAV immunity.

Dual Enrollment Policies and Undergraduate Rates in the United States: An Institutional and Cohert Approach Using the 2006-2014 IPEDS

ERIC Educational Resources Information Center

Myers, Carrie B.; Myers, Scott M.

2017-01-01

Previous studies have found that freshmen who enter college with dual enrollment credits earned during high school have higher 6-year graduation rates. Yet, we do not know if institutional graduation rates benefit in the aggregate from their practice of accepting dual enrollment credits among incoming freshman cohorts. In this study, we used…

Seroprotection for hepatitis B in children with nephrotic syndrome.

PubMed

Mantan, Mukta; Pandharikar, Nagaraj; Yadav, Sangeeta; Chakravarti, Anita; Sethi, Gulshan Rai

2013-11-01

Children with nephrotic syndrome have been shown to have lower seroconversion to various vaccines due to immune dysregulation, prolonged immunosuppressive treatment and recurrent prolonged proteinuria.The primary aim of this study was to determine hepatitis B surface antibody (anti-HBs) titers in children with nephrotic syndrome who had been previously vaccinated against hepatitis B. The secondary aim was to study the association of anti-HBs titers with type of disease, schedule and dose of vaccination, and type of immunosuppressive therapy. This cross-sectional study was conducted in the Department of Pediatrics in a tertiary care hospital between January 2011 and January 2012). All children (aged 1-18 years) with nephrotic syndrome who tested negative for hepatitis B surface antigen and who had previously been vaccinated against hepatitis B, with the last dose being at least 1 month prior to being included in the study. A form consisting of history and clinical details was filled in, and the schedule and dose of vaccination(s) received was noted. A blood sample was taken from all patients for biochemical assessment and determination of anti-HBs titer. The patient cohort comprised 75 children (51 males; 24 females) of whom 42 (56%) had steroid-resistant nephrotic syndrome (SRNS) and 33 (44%) had steroid-sensitive nephrotic syndrome (SSNS). Most patients enrolled in the study (96%) were in remission at the time of the biochemical and serological assessment. Twenty-one (28%) patients had received only steroids, while 72 % also received other immunosuppressants. Forty-six (61.3%) patients had received a double dose of vaccine. Of the 75 children enrolled, 36 (48%) and 39 (52%) had an anti-HBs titer of ≥10 mIU/mL (seroprotected) and <10 mIU/mL (unprotected), respectively. The mean titer among all patients was 143.58 mIU/mL. The seroprotection rates were 63.6% in SSNS patients and 35.7% in SRNS subjects (P = 0.016). Based on our results, we conclude that children with SRNS are less likely to seroconvert with vaccination. A higher dose (double) of hepatitis B vaccine should be used for vaccinating such patients. Anti-HBs titers should be monitored in SRNS patients post-vaccination, and a booster should be given if titers fall to <10 mIU/mL.

Subclinical atherosclerosis and history of cardiovascular events in Italian patients with rheumatoid arthritis: Results from a cross-sectional, multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.

PubMed

Ruscitti, Piero; Margiotta, Domenico Paolo Emanuele; Macaluso, Federica; Iacono, Daniela; D'Onofrio, Francesca; Emmi, Giacomo; Atzeni, Fabiola; Prete, Marcella; Perosa, Federico; Sarzi-Puttini, Piercarlo; Emmi, Lorenzo; Cantatore, Francesco Paolo; Triolo, Giovanni; Afeltra, Antonella; Giacomelli, Roberto; Valentini, Gabriele

2017-10-01

Several studies have pointed out a significant association between rheumatoid arthritis (RA) and accelerated atherosclerosis. At the best of our knowledge, no such study has been carried out in a large Italian series and, in this study, we aimed to investigate the prevalence of both subclinical atherosclerosis and history of cardiovascular events (CVEs), in patients consecutively admitted from January 1, 2015 to December 31, 2015 to Rheumatology Units throughout the whole Italy.Centers members of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) were invited to enrol patients consecutively admitted from January 1, 2015 to December 31, 2015 and satisfying American College of Rheumatology/ European League Against Rheumatism criteria for RA and to investigate each of them for: traditional cardiovascular risk factors: sex, age, smoking habit, total cholesterol, triglycerides, glycaemia, high blood pressure, metabolic syndrome (MS), type 2 diabetes (T2D); RA features: disease duration as assessed from the first symptom, disease activity as evaluated by DAS28, radiographic damage as assessed by hands and feet x-ray, and previous joint surgery; prevalence of both subclinical atherosclerosis and history of CVEs.Eight centers participated to the study. From January 1, 2015 to December 31, 2015, the 1176 patients, who had been investigated for all the items, were enrolled in the study. They were mostly women (80.52%), with a median age of 60 years (range, 18-91 years), a median disease duration of 12 years (range, 0.8-25 years), seropositive in 69.21%. Nineteen percent were in remission; 17.51% presented low disease activity; 39.45% moderate disease activity; 22.61% high disease activity.Eighty-two patients (6.9%) had a history for CVEs (58 myocardial infarction, 38 heart failure, 10 ischemic transitory attack, and 7 stroke). This figure appears to be lower than that reported worldwide (8.5%). After excluding the 82 patients with a history of CV events, subclinical atherosclerosis was detected in 16% of our patients, (176 patients), a figure lower than that reported worldwide (32.7%) and in previous Italian studies.This is the first Italian multicenter study on subclinical and clinical atherosclerosis in patients with RA. We pointed out a low prevalence of both subclinical atherosclerosis and history of CV events.

Informed consent as an ethical requirement in clinical trials: an old, but still unresolved issue. An observational study to evaluate patient's informed consent comprehension.

PubMed

Sanchini, Virginia; Reni, Michele; Calori, Giliola; Riva, Elisabetta; Reichlin, Massimo

2014-04-01

We explored the comprehension of the informed consent in 77 cancer patients previously enrolled in randomised phase II or phase III clinical trials, between March and July 2011, at the San Raffaele Scientific Institute in Milano. We asked participants to complete an ad hoc questionnaire and analysed their answers. Sixty-two per cent of the patients understood the purpose and nature of the trial they were participating in; 44% understood the study procedures and 40% correctly listed at least one of the major risks or complications related to their participation in the trial. We identified three factors associated with comprehension of the informed consent: age, education and type of tumour/investigator team. We suggest several possible improvements of how to obtain informed consent that will increase patient awareness, as well as the validity and effectiveness of the clinical trials.

A comparison of patients with major depressive disorder recruited through newspaper advertising versus consultation referrals for clinical drug trials.

PubMed

Miller, C A; Hooper, C L; Bakish, D

1997-01-01

Difficulties in recruiting patients for clinical trials have plagued investigators for many years. One concern is the generalizability of clinical trial results to community practice, that is, whether volunteers recruited through advertising are homogeneous with those seeking treatment in a clinical setting. This article retrospectively compares the baseline characteristics of patients recruited through newspaper advertisements with those recruited through consultation referrals by reviewing the charts of 54 patients enrolled in two clinical trials for major depressive disorder (MDD). We examined demographic data, background information, clinical histories, and baseline status. Results indicated homogeneity for most variables. The consultation group was significantly more likely to have had previous treatment for the current episode of depression. These results suggest that, although the advertisement and consultation groups were very similar, the drug naivety of the advertisement group may make them a preferred source in terms of generalizability to community practice.

Wisconsin's BadgerCare Plus reform: impact on low-income families' enrollment and retention in public coverage.

PubMed

Leininger, Lindsey Jeanne; Friedsam, Donna; Dague, Laura; Mok, Shannon; Hynes, Emma; Bergum, Alison; Aksamitauskas, Milda; Oliver, Thomas; DeLeire, Thomas

2011-02-01

To examine the impact of a Wisconsin health care reform enacted in early 2008 on public insurance enrollment and retention. Administrative data covering the period January 2007 to November 2009. We calculate unadjusted enrollment trends and exit rates stratified by age, income group, and enrollment mode. Kaplan-Meier curves and Cox proportional hazards models are estimated to assess the impact of the reform on program exits. Overall enrollment increased by approximately one-third and exit rates decreased by approximately one-fifth. The majority of new enrollment came from the previously income eligible. Wisconsin's enactment of eligibility expansions coupled with administrative simplification and targeted marketing and outreach efforts were successful in enrolling and retaining low-income children and families in public coverage. © Health Research and Educational Trust.

Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia

PubMed Central

Sikazwe, Izukanji; Wa Mwanza, Mwanza; Savory, Theodora; Sikombe, Kombatende; Somwe, Paul; Roy, Monika; Padian, Nancy

2018-01-01

Background Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia’s HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/μL to anticipate effects of current global efforts to treat all PLWHs. Methods and findings We analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/μL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28–41], median CD4 268 cells/μL [IQR 134–430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/μL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%–16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%–6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%–13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%–49.9%), 13.6% increase in retention at six months (95% CI, 7.3%–20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%–41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%–46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome. Conclusions In this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/μL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/μL) by expanding treatment without undermining existing care standards. PMID:29870531

Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia.

PubMed

Mody, Aaloke; Sikazwe, Izukanji; Czaicki, Nancy L; Wa Mwanza, Mwanza; Savory, Theodora; Sikombe, Kombatende; Beres, Laura K; Somwe, Paul; Roy, Monika; Pry, Jake M; Padian, Nancy; Bolton-Moore, Carolyn; Holmes, Charles B; Geng, Elvin H

2018-06-01

Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia's HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/μL to anticipate effects of current global efforts to treat all PLWHs. We analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/μL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28-41], median CD4 268 cells/μL [IQR 134-430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/μL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%-16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%-6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%-13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%-49.9%), 13.6% increase in retention at six months (95% CI, 7.3%-20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%-41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%-46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome. In this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/μL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/μL) by expanding treatment without undermining existing care standards.

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

PubMed

Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars; Alings, Marco; Goto, Shinya; Lewis, Basil S; Rosenqvist, Mårten; Hanna, Michael; Mohan, Puneet; Alexander, John H; Diener, Hans-Christoph

2012-06-01

In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. Bristol-Myers Squibb and Pfizer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Heart rate variability during hemodialysis is an indicator for long-term vascular access survival in uremic patients

PubMed Central

Huang, Ya-Ting; Chang, Yu-Ming; Chen, I-Ling; Yang, Chuan-Lan; Leu, Show-Chin; Su, Hung-Li; Kao, Jsun-Liang; Tsai, Shih-Ching; Jhen, Rong-Na; Tang, Woung-Ru

2017-01-01

Background Vascular access (VA) is the lifeline of hemodialysis patients. Although the autonomic nervous system might be associated with VA failure (VAF), it has never been addressed in previous studies. This study aimed to evaluate the predictive values of the heart rate variability (HRV) indices for long-term VA outcomes. Methods This retrospective study was conducted using a prospectively established cohort enrolling 175 adult chronic hemodialysis patients (100 women, mean age 65.1 ± 12.9 years) from June 2010 to August 2010. Each participant received a series of HRV measurements at enrollment. After a 60-month follow-up period, we retrospectively reviewed all events and therapeutic procedures of the VAs which existed at the enrollment and during the follow-up period. Results During the 60-month follow-up period, 37 (26.8%) had VAF but 138 (73.2%) didn’t. The values of most HRV indices were statistically increased during hemodialysis since initiation in the non-VAF group, but not in the VAF group. Among all participants, the independent indicators for VAF included higher normalized high-frequency (nHF) activity [hazard ratio (HR) 1.04, p = 0.005], lower low-frequency/high-frequency (LF/HF) ratio (HR 0.80, p = 0.015), experience of urokinase therapy (HR 11.18, p = 0.002), percutaneous transluminal angioplasty (HR 2.88, p = 0.003) and surgical thrombectomy (HR 2.36, p = 0.035), as well as higher baseline serum creatinine (HR 1.07, p = 0.027) and potassium level (HR 1.58, p = 0.037). In subgroup analysis, a lower sympathetic activity indicated by lower LF/HF ratio was an independent indicator for VAF (HR 0.61, p = 0.03) for tunneled cuffed catheter, but conversely played a protective role against VAF (HR 1.27, p = 0.002) for arteriovenous fistula. Conclusions HRV is a useful tool for predicting long-term VAF among hemodialysis patients. PMID:28249028

Identification and characterization of near-fatal asthma phenotypes by cluster analysis.

PubMed

Serrano-Pariente, J; Rodrigo, G; Fiz, J A; Crespo, A; Plaza, V

2015-09-01

Near-fatal asthma (NFA) is a heterogeneous clinical entity and several profiles of patients have been described according to different clinical, pathophysiological and histological features. However, there are no previous studies that identify in a unbiased way--using statistical methods such as clusters analysis--different phenotypes of NFA. Therefore, the aim of the present study was to identify and to characterize phenotypes of near fatal asthma using a cluster analysis. Over a period of 2 years, 33 Spanish hospitals enrolled 179 asthmatics admitted for an episode of NFA. A cluster analysis using two-steps algorithm was performed from data of 84 of these cases. The analysis defined three clusters of patients with NFA: cluster 1, the largest, including older patients with clinical and therapeutic criteria of severe asthma; cluster 2, with an high proportion of respiratory arrest (68%), impaired consciousness level (82%) and mechanical ventilation (93%); and cluster 3, which included younger patients, characterized by an insufficient anti-inflammatory treatment and frequent sensitization to Alternaria alternata and soybean. These results identify specific asthma phenotypes involved in NFA, confirming in part previous findings observed in studies with a clinical approach. The identification of patients with a specific NFA phenotype could suggest interventions to prevent future severe asthma exacerbations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparing quantitative values of two generations of laser-assisted indocyanine green dye angiography systems: can we predict necrosis?

PubMed

Phillips, Brett T; Fourman, Mitchell S; Rivara, Andrew; Dagum, Alexander B; Huston, Tara L; Ganz, Jason C; Bui, Duc T; Khan, Sami U

2014-01-01

Several devices exist today to assist the intraoperative determination of skin flap perfusion. Laser-Assisted Indocyanine Green Dye Angiography (LAICGA) has been shown to accurately predict mastectomy skin flap necrosis using quantitative perfusion values. The laser properties of the latest LAICGA device (SPY Elite) differ significantly from its predecessor system (SPY 2001), preventing direct translation of previous published data. The purpose of this study was to establish a mathematical relationship of perfusion values between these 2 devices. Breast reconstruction patients were prospectively enrolled into a clinical trial where skin flap evaluation and excision was based on quantitative SPY Q values previously established in the literature. Initial study patients underwent mastectomy skin flap evaluation using both SPY systems simultaneously. Absolute perfusion unit (APU) values at identical locations on the breast were then compared graphically. 210 data points were identified on the same patients (n = 4) using both SPY systems. A linear relationship (y = 2.9883x + 12.726) was identified with a high level or correlation (R(2) = 0.744). Previously published values using SPY 2001 (APU 3.7) provided a value of 23.8 APU on the SPY Elite. In addition, postoperative necrosis in these patients correlated to regions of skin identified with the SPY Elite with APU less than 23.8. Intraoperative comparison of LAICGA systems has provided direct correlation of perfusion values predictive of necrosis that were previously established in the literature. An APU value of 3.7 from the SPY 2001 correlates to a SPY Elite APU value of 23.8.

Comparing Quantitative Values of Two Generations of Laser-Assisted Indocyanine Green Dye Angiography Systems: Can We Predict Necrosis?

PubMed Central

Fourman, Mitchell S.; Rivara, Andrew; Dagum, Alexander B.; Huston, Tara L.; Ganz, Jason C.; Bui, Duc T.; Khan, Sami U.

2014-01-01

Objective: Several devices exist today to assist the intraoperative determination of skin flap perfusion. Laser-Assisted Indocyanine Green Dye Angiography (LAICGA) has been shown to accurately predict mastectomy skin flap necrosis using quantitative perfusion values. The laser properties of the latest LAICGA device (SPY Elite) differ significantly from its predecessor system (SPY 2001), preventing direct translation of previous published data. The purpose of this study was to establish a mathematical relationship of perfusion values between these 2 devices. Methods: Breast reconstruction patients were prospectively enrolled into a clinical trial where skin flap evaluation and excision was based on quantitative SPY Q values previously established in the literature. Initial study patients underwent mastectomy skin flap evaluation using both SPY systems simultaneously. Absolute perfusion unit (APU) values at identical locations on the breast were then compared graphically. Results: 210 data points were identified on the same patients (n = 4) using both SPY systems. A linear relationship (y = 2.9883x + 12.726) was identified with a high level or correlation (R2 = 0.744). Previously published values using SPY 2001 (APU 3.7) provided a value of 23.8 APU on the SPY Elite. In addition, postoperative necrosis in these patients correlated to regions of skin identified with the SPY Elite with APU less than 23.8. Conclusion: Intraoperative comparison of LAICGA systems has provided direct correlation of perfusion values predictive of necrosis that were previously established in the literature. An APU value of 3.7 from the SPY 2001 correlates to a SPY Elite APU value of 23.8. PMID:25525483

Sitagliptin on carotid intima-media thickness in type 2 diabetes patients receiving primary or secondary prevention of cardiovascular disease: A subgroup analysis of the PROLOGUE study.

PubMed

Tanaka, Atsushi; Yoshida, Hisako; Nanasato, Mamoru; Oyama, Jun-Ichi; Ishizu, Tomoko; Ajioka, Masayoshi; Ishiki, Ryoji; Saito, Makoto; Shibata, Yoshisato; Kaku, Kohei; Maemura, Koji; Higashi, Yukihito; Inoue, Teruo; Murohara, Toyoaki; Node, Koichi

2018-05-19

Whether a dipeptidyl peptidase-4 (DPP-4) inhibitor can attenuate atherosclerosis is still controversial. Some clinical trials reported that DPP-4 inhibitors in diabetes patients without a previous history of cardiovascular (CV) events could reduce carotid intima-media thickness (IMT). However, in the PROLOGUE study, which enrolled diabetes patients both with and without previous CV events, sitagliptin failed to slow the progression of carotid IMT relative to conventional therapy. We hypothesized that the effect of DPP-4 inhibitors on carotid atherosclerosis might be different between the primary and secondary prevention groups. We performed a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in carotid IMT in subgroups with or without previous CV events. No significant difference in the IMT changes between the treatment groups was found in the secondary prevention subgroup (sitagliptin, N = 102; conventional, 111). However, in the primary prevention subgroup (sitagliptin, 120; conventional, 109), we found significant inhibitory effects of sitagliptin on mean and max internal carotid artery IMT [estimated group difference: -0.096 mm (95% CI -0.175 to -0.018, p = 0.017) and -0.162 mm (95% CI -0.272 to -0.052, p = 0.004), respectively], although there was no significant difference in the common carotid artery IMT. Our data suggest that there is a favorable effect of DPP-4 inhibitor treatment on carotid atherosclerosis in diabetes patients without previous CV events. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Outcomes of FP-7/8 Ahmed Glaucoma Valves in the Management of Refractory Glaucoma in the Mainland Chinese Population

PubMed Central

Yang, Xuejiao; Deng, Shuifeng; Li, Zuohong; Li, Fei; Zhuo, Yehong

2015-01-01

Background To evaluate the efficacy and safety of the Ahmed glaucoma valve (AGV) and the risk factors associated with AGV implantation failure in a population of Chinese patients with refractory glaucoma. Method In total, 79 eyes with refractory glaucoma from 79 patients treated in our institution from November 2007 to November 2010 were enrolled in this retrospective study. The demographic data, preoperative and postoperative intraocular pressures (IOPs), best corrected visual acuity (BCVA), number of anti-glaucoma medications used, completed and qualified surgery success rates and postoperative complications were recorded to evaluate the outcomes of AGV implantation. Factors that were associated with implant failure were determined using Cox proportional hazard regression model analysis and multiple linear regression analysis. Principle Findings The average follow-up time was 12.7±5.8 months (mean±SD). We observed a significant reduction in the mean IOP from 39.9±12.6 mm Hg before surgery to 19.3±9.6 mm Hg at the final follow-up. The complete success rate was 59.5%, and the qualified success rate was 83.5%. The number of previous surgeries was negatively correlated with qualified success rate (P<0.05, OR=0.736, 95% CI 0.547-0.99). Patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control IOP (P<0.01). The primary complication was determined to be a flat anterior chamber (AC). Conclusion AGV implantation was safe and effective for the management of refractory glaucoma. Patients with a greater number of previous surgeries were more likely to experience surgical failure, and patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control postoperative IOP. PMID:25996991

Clinical Outcomes of FP-7/8 Ahmed Glaucoma Valves in the Management of Refractory Glaucoma in the Mainland Chinese Population.

PubMed

Zhu, Yingting; Wei, Yantao; Yang, Xuejiao; Deng, Shuifeng; Li, Zuohong; Li, Fei; Zhuo, Yehong

2015-01-01

To evaluate the efficacy and safety of the Ahmed glaucoma valve (AGV) and the risk factors associated with AGV implantation failure in a population of Chinese patients with refractory glaucoma. In total, 79 eyes with refractory glaucoma from 79 patients treated in our institution from November 2007 to November 2010 were enrolled in this retrospective study. The demographic data, preoperative and postoperative intraocular pressures (IOPs), best corrected visual acuity (BCVA), number of anti-glaucoma medications used, completed and qualified surgery success rates and postoperative complications were recorded to evaluate the outcomes of AGV implantation. Factors that were associated with implant failure were determined using Cox proportional hazard regression model analysis and multiple linear regression analysis. The average follow-up time was 12.7±5.8 months (mean±SD). We observed a significant reduction in the mean IOP from 39.9±12.6 mm Hg before surgery to 19.3±9.6 mm Hg at the final follow-up. The complete success rate was 59.5%, and the qualified success rate was 83.5%. The number of previous surgeries was negatively correlated with qualified success rate (P<0.05, OR=0.736, 95% CI 0.547-0.99). Patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control IOP (P<0.01). The primary complication was determined to be a flat anterior chamber (AC). AGV implantation was safe and effective for the management of refractory glaucoma. Patients with a greater number of previous surgeries were more likely to experience surgical failure, and patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control postoperative IOP.

A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer.

PubMed

Ho, Alan L; Lipson, Brynna L; Sherman, Eric J; Xiao, Han; Fury, Matthew G; Apollo, Arlyn; Seetharamu, Nagashree; Sima, Camelia S; Haque, Sofia; Lyo, John K; Sales, Roberta; Cox, Lisa; Pfister, David G

2014-06-01

Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan.

PubMed

Suzuki, Kenshi; Ri, Masaki; Chou, Takaaki; Sugiura, Isamu; Takezako, Naoki; Sunami, Kazutaka; Ishida, Tadao; Izumi, Tohru; Ozaki, Shuji; Shumiya, Yoshihisa; Ota, Kenji; Iida, Shinsuke

2017-03-01

This is the first study in which the carfilzomib, lenalidomide and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM) patients. The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics of the regimen. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m 2 , followed by 27 mg/m 2 . Lenalidomide and dexamethasone were administered at 25 mg (days 1-21) and 40 mg (days 1, 8, 15 and 22), respectively. Twenty-six patients were enrolled. Patients had received a median of four prior regimens and 88.5% and 61.5% received previous bortezomib and lenalidomide, respectively. High-risk cytogenetics were seen in 53.8% of patients. The overall response rate was 88.5%. A higher rate of hyperglycemia was observed than in a previous carfilzomib monotherapy study, but this was attributed to dexamethasone. Carfilzomib pharmacokinetics were not affected by lenalidomide and dexamethasone. The KRd regimen was well tolerated and showed efficacy in Japanese RRMM patients. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Clinical characteristics of severe congenital neutropenia caused by novel ELANE gene mutations.

PubMed

Shu, Zhou; Li, Xiao-Hui; Bai, Xiao-Ming; Zhang, Zhi-Yong; Jiang, Li-ping; Tang, Xue-Mei; Zhao, Xiao-dong

2015-02-01

Mutations within the ELANE gene, which encodes human neutrophil elastase, are the most common genetic causes of severe congenital neutropenia (SCN). No cases of SCN have been previously described from a Chinese population. Herein, we describe the clinical, hematologic and molecular characteristics of 7 Chinese SCN cases with novel ELANE mutations. Seven Chinese pediatric patients (4 males and 3 females) with suspected SCN were enrolled in this study. Clinical data, peripheral blood, bone marrow and immune function were evaluated for SCN. ELANE genomic DNA and cDNA sequences from patients and potential carriers were analyzed using polymerase chain reaction (PCR) and direct sequencing. All the7 patients experienced recurrent infection (soft tissue, lung, oral cavity) during a period of 120 days. Noninfectious conditions such as anemia and osteopenia were found in most patients, and absolute peripheral neutrophil counts varied. DNA and cDNA sequencing demonstrated that the patients harbored a range of heterozygous ELANE gene mutations, including substitution, deletion, insertion and frame shift alterations. All the mutations had not been reported previously; however, no mutation carriers were identified among the parents or siblings, even in a family with 2 affected offspring. SCN cases were identified for the first time in China, and all patients carried novel ELANE mutations. Granulocyte-colony stimulating factor (G-CSF) was an effective treatment for most of the SCN patients and prevented life-threatening bacterial infections.

Effect of Improved access to Antiretroviral Therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania

PubMed Central

2010-01-01

Background Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. Methods A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004 - Dec 2005 compared to those enrolled between 2006 and September 2008. Results Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/μl) with 65.7% having below 200 cells/μl. Females had higher CD4 cell counts (150 cells/μl) than males (109 cells/μl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/μl) compared to CD4 of 167 cells/μl in those seen later (2006-8) (p < 0.001). Conclusion Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease. PMID:20509892

Tailoring Care to Vulnerable Populations by Incorporating Social Determinants of Health: the Veterans Health Administration's "Homeless Patient Aligned Care Team" Program.

PubMed

O'Toole, Thomas P; Johnson, Erin E; Aiello, Riccardo; Kane, Vincent; Pape, Lisa

2016-03-31

Although the clinical consequences of homelessness are well described, less is known about the role for health care systems in improving clinical and social outcomes for the homeless. We described the national implementation of a "homeless medical home" initiative in the Veterans Health Administration (VHA) and correlated patient health outcomes with characteristics of high-performing sites. We conducted an observational study of 33 VHA facilities with homeless medical homes and patient- aligned care teams that served more than 14,000 patients. We correlated site-specific health care performance data for the 3,543 homeless veterans enrolled in the program from October 2013 through March 2014, including those receiving ambulatory or acute health care services during the 6 months prior to enrollment in our study and 6 months post-enrollment with corresponding survey data on the Homeless Patient Aligned Care Team (H-PACT) program implementation. We defined high performance as high rates of ambulatory care and reduced use of acute care services. More than 96% of VHA patients enrolled in these programs were concurrently receiving VHA homeless services. Of the 33 sites studied, 82% provided hygiene care (on-site showers, hygiene kits, and laundry), 76% provided transportation, and 55% had an on-site clothes pantry; 42% had a food pantry and provided on-site meals or other food assistance. Six-month patterns of acute-care use pre-enrollment and post-enrollment for 3,543 consecutively enrolled patients showed a 19.0% reduction in emergency department use and a 34.7% reduction in hospitalizations. Three features were significantly associated with high performance: 1) higher staffing ratios than other sites, 1) integration of social supports and social services into clinical care, and 3) outreach to and integration with community agencies. Integrating social determinants of health into clinical care can be effective for high-risk homeless veterans.

Tailoring Care to Vulnerable Populations by Incorporating Social Determinants of Health: the Veterans Health Administration’s “Homeless Patient Aligned Care Team” Program

PubMed Central

Johnson, Erin E.; Aiello, Riccardo; Kane, Vincent; Pape, Lisa

2016-01-01

Introduction Although the clinical consequences of homelessness are well described, less is known about the role for health care systems in improving clinical and social outcomes for the homeless. We described the national implementation of a “homeless medical home” initiative in the Veterans Health Administration (VHA) and correlated patient health outcomes with characteristics of high-performing sites. Methods We conducted an observational study of 33 VHA facilities with homeless medical homes and patient- aligned care teams that served more than 14,000 patients. We correlated site-specific health care performance data for the 3,543 homeless veterans enrolled in the program from October 2013 through March 2014, including those receiving ambulatory or acute health care services during the 6 months prior to enrollment in our study and 6 months post-enrollment with corresponding survey data on the Homeless Patient Aligned Care Team (H-PACT) program implementation. We defined high performance as high rates of ambulatory care and reduced use of acute care services. Results More than 96% of VHA patients enrolled in these programs were concurrently receiving VHA homeless services. Of the 33 sites studied, 82% provided hygiene care (on-site showers, hygiene kits, and laundry), 76% provided transportation, and 55% had an on-site clothes pantry; 42% had a food pantry and provided on-site meals or other food assistance. Six-month patterns of acute-care use pre-enrollment and post-enrollment for 3,543 consecutively enrolled patients showed a 19.0% reduction in emergency department use and a 34.7% reduction in hospitalizations. Three features were significantly associated with high performance: 1) higher staffing ratios than other sites, 1) integration of social supports and social services into clinical care, and 3) outreach to and integration with community agencies. Conclusion Integrating social determinants of health into clinical care can be effective for high-risk homeless veterans. PMID:27032987

Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial.

PubMed

Shaw, Alice T; Gandhi, Leena; Gadgeel, Shirish; Riely, Gregory J; Cetnar, Jeremy; West, Howard; Camidge, D Ross; Socinski, Mark A; Chiappori, Alberto; Mekhail, Tarek; Chao, Bo H; Borghaei, Hossein; Gold, Kathryn A; Zeaiter, Ali; Bordogna, Walter; Balas, Bogdana; Puig, Oscar; Henschel, Volkmar; Ou, Sai-Hong Ignatius

2016-02-01

Alectinib--a highly selective, CNS-active, ALK inhibitor-showed promising clinical activity in crizotinib-naive and crizotinib-resistant patients with ALK-rearranged (ALK-positive) non-small-cell lung cancer (NSCLC). We aimed to assess the safety and efficacy of alectinib in patients with ALK-positive NSCLC who progressed on previous crizotinib. We did a phase 2 study at 27 centres in the USA and Canada. We enrolled patients aged 18 years or older with stage IIIB-IV, ALK-positive NSCLC who had progressed after crizotinib. Patients were treated with oral alectinib 600 mg twice daily until progression, death, or withdrawal. The primary endpoint was the proportion of patients achieving an objective response by an independent review committee using Response Evaluation Criteria in Solid Tumors, version 1.1. Response endpoints were assessed in the response-evaluable population (ie, patients with measurable disease at baseline who received at least one dose of study drug), and efficacy and safety analyses were done in the intention-to-treat population (all enrolled patients). This study is registered with ClinicalTrials.gov, number NCT01871805. The study is ongoing and patients are still receiving treatment. Between Sept 4, 2013, and Aug 4, 2014, 87 patients were enrolled into the study (intention-to-treat population). At the time of the primary analysis (median follow-up 4·8 months [IQR 3·3-7·1]), 33 of 69 patients with measurable disease at baseline had a confirmed partial response; thus, the proportion of patients achieving an objective response by the independent review committee was 48% (95% CI 36-60). Adverse events were predominantly grade 1 or 2, most commonly constipation (31 [36%]), fatigue (29 [33%]), myalgia 21 [24%]), and peripheral oedema 20 [23%]). The most common grade 3 and 4 adverse events were changes in laboratory values, including increased blood creatine phosphokinase (seven [8%]), increased alanine aminotransferase (five [6%]), and increased aspartate aminotransferase (four [5%]). Two patients died: one had a haemorrhage (judged related to study treatment), and one had disease progression and a history of stroke (judged unrelated to treatment). Alectinib showed clinical activity and was well tolerated in patients with ALK-positive NSCLC who had progressed on crizotinib. Therefore, alectinib could be a suitable treatment for patients with ALK-positive disease who have progressed on crizotinib. F Hoffmann-La Roche. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prescription Drug Utilization and Reimbursement Increased Following State Medicaid Expansion in 2014.

PubMed

Mahendraratnam, Nirosha; Dusetzina, Stacie B; Farley, Joel F

2017-03-01

The Affordable Care Act (ACA) expanded health care and medication insurance coverage through Medicaid expansion in select states. Expansion has the potential to increase the availability of health services to patients, including prescription medications. However, limited studies have examined how expansion affected prescription drug utilization and reimbursement. To compare prescription drug utilization (number of prescriptions filled) and reimbursement trends between states that did and did not expand Medicaid coverage in 2014, while accounting for known effects of expansion on Medicaid enrollment. We conducted a comparative interrupted time series using retrospective Medicaid state drug utilization data from 2011 to 2014. After inclusion/exclusion criteria, 8 states that expanded Medicaid in 2014 and 10 states that did not expand Medicaid were studied. Primary outcomes were changes in quarterly prescription drug utilization and quarterly total prescription drug reimbursement before and after expansion. To account for increases in enrollment in expansion states, secondary outcomes were per-member-per-quarter (PMPQ) utilization and reimbursement before and after expansion. Expansion states experienced a 1.4 million prescriptions per quarter and $163 million per quarter increase in utilization and reimbursement above the change in rates observed in nonexpansion states after expansion (P < 0.001). Specifically, 1 year after ACA implementation, expansion states used 17.0% more prescriptions and spent 36.1% more in reimbursement than the quarter preceding expansion. Expansion and nonexpansion states experienced significant drops in PMPQ prescriptions immediately after expansion (P < 0.001), but PMPQ prescriptions and reimbursement trends increased by the end of the postexpansion period in expansion states (P < 0.029 and P < 0.001, respectively). Study results suggest that Medicaid expansion offers vulnerable patients who were previously uninsured increased access to health care resources, specifically prescription drugs. Although this hypothesis would benefit from further testing, it aligns with previous studies that have shown that Medicaid expansion has led to increased access to coverage and care. While enrollment contributes to the increase in prescription utilization and reimbursement, the drop in PMPQ utilization suggests that the patients entering the program are healthier than existing patients. This shows that risk pooling is working. However, the increase in PMPQ reimbursement suggests that new enrollment may not be the only factor driving reimbursement changes. Factors such as changes in product mix, risk pool composition, and drug pricing and their effects on total and per-member reimbursement should be evaluated in future studies. No outside funding supported this study. Mahendraratnam is currently a Worldwide Health Economics and Outcomes Research Pre-doctoral Fellow at Bristol-Myers Squibb and previously provided advisory services to public and private sector clients while employed at Avalere Health, an Inovalon Company, as well as completed an internship at Genentech, a member of the Roche Group. Farley and Dusetzina have no conflicts of interest to report. Preliminary results of this study were presented at the 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 21st Annual Meeting in Washington, DC, on May 21-25, 2016, and the 2016 AcademyHealth Annual Research Meeting (ARM) in Boston, Massachusetts, on June 26-28, 2016. Study concept and design were contributed by Farley, Mahendraratnam, and Dusetzina. Mahendraratnam, Farley, and Dusetzina collected the data, and data interpretation was performed by all the authors. The manuscript was written by Mahendraratnam, Farley, and Dusetzina and revised by Farley, Dusetzina, and Mahendraratnam.

Selective enrollment in Disease Management Programs for coronary heart disease in Germany - An analysis based on cross-sectional survey and administrative claims data.

PubMed

Röttger, Julia; Blümel, Miriam; Busse, Reinhard

2017-04-04

In 2002, Disease Management Programs (DMPs) were introduced within the German healthcare system with the aim to increase the quality of chronic disease care. Due to the enrollment procedures, it can be assumed a) that only certain patients actively decide to enroll in a DMP and/or b) that only certain patients get the recommendation for DMP enrollment from their physician. How strong this assumed effect of self- and/or professional selection is, is still unclear. We used data from a cross-sectional postal-survey linked on individual level with administrative claims data from a German sickness fund. The sample consisted of individuals suffering from coronary heart disease (CHD) who i) were either enrolled in the respective DMP or ii) fulfilled the disease related criteria for enrollment but were not enrolled. We applied multivariate logistic regression analyses to assess factors on patient level associated with DMP enrollment. We included 7070 individuals in our analyses. Male sex, higher age and receiving old age pension, a higher Charlson Score and a diagnosis of type 2 diabetes increased the odds for DMP-CHD enrollment significantly. Individuals with a diagnosed myocardial infarction (MI) were also more likely to be enrolled in the DMP-CHD. We found a significant interaction effect for MI and sex, indicating that the association between MI and DMP enrollment is stronger for women than for men. DMP-enrollees and non-enrollees differ in various factors. Studies analyzing the effectiveness of DMP-CHD should carefully take into account these group differences. Furthermore, the results suggest that the DMP-CHD assessed reaches men better than women.

77 FR 8667 - Summary of Benefits and Coverage and Uniform Glossary

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... group health plans and health insurance coverage in the group and individual markets under the Patient... to participants and beneficiaries who enroll or re-enroll in group health coverage through an open... beneficiaries who enroll in group health plan coverage other than through an open enrollment period (including...

Effective Strategies for Affordable Care Act Enrollment in Immigrant-Serving Safety Net Clinics in New Mexico.

PubMed

Getrich, Christina M; García, Jacqueline M; Solares, Angélica; Kano, Miria

2017-01-01

In the new Affordable Care Act (ACA) health care environment, safety-net institutions continue to serve as important sources of culturally appropriate care for different groups of immigrant patients. This article reports on a qualitative study examining the early ACA enrollment experiences of a range of health care providers (n = 29) in six immigrant-serving safety-net clinics in New Mexico. The six clinics configured their ACA enrollment strategies differently with regard to operations, staffing, and outreach. Providers reported a generally chaotic rollout overall and expressed frustration with strategies that did not accommodate patients, provided little training for providers, and engaged in minimal outreach. Conversely, providers lauded strategies that flexibly met patient needs, leveraged trust through strategic use of staff, and prioritized outreach. Findings underscore the importance of using and funding concerted strategies for future enrollment of immigrant patients, such as featuring community health workers and leveraging trust for outreach.

Pentostatin and Rituximab Therapy for Previously Untreated B-CLL

PubMed Central

Kay, Neil E.; Wu, Wenting; Kabat, Brian; LaPlant, Betsy; Lin, Thomas S.; Byrd, John C.; Jelinek, Diane F.; Grever, Michael R.; Zent, Clive S.; Call, Timothy G.; Shanafelt, Tait D.

2010-01-01

We have shown that the combination of pentostatin (P), cyclophosphamide (C) and rituximab (R) achieves an overall response (OR) rate >90% with more than 40% complete responses (CR) in patients with untreated CLL. To evaluate if the tolerability of this regimen could be enhanced without sacrificing efficacy, we conducted a phase II trial of P and R without cyclophosphamide, using a higher P dose (4 mg/m2). Among the 33 patients enrolled, 82% were male, median age was 65 (9 patients ≥70 years) and 64% were Rai stage III-IV. The OR rate was 76% with 9 CR (27%), 5 nPR, and 11 PRs. At the time of this analysis, 29/33 patients are still alive and the median follow up for patients still alive is 14 months (range: 1-34.8 months). Four (12%) patients experienced grade 3 or higher hematologic toxicity and 5 (15%) experienced grade 3 or higher non-hematologic toxicity. Comparison of this trial to our previous PCR trial showed that patients treated with PCR had a higher OR rate (91% vs. 76%) and CR rate (41% vs. 27%) compared to patients treated with PR. Median treatment-free survival for all accrued patients was notably longer in PCR treated patients compared to PR (30 vs. 16 months). These findings suggest that increasing the dose of the purine nucleoside analogue does not eliminate the need for cyclophosphamide in chemoimmunotherapy for treatment of CLL. PMID:20187101

Impact of individual clinical outcomes on trial participants' perspectives on enrollment in emergency research without consent.

PubMed

Whitesides, Louisa W; Baren, Jill M; Biros, Michelle H; Fleischman, Ross J; Govindarajan, Prasanthi R; Jones, Elizabeth B; Pancioli, Arthur M; Pentz, Rebecca D; Scicluna, Victoria M; Wright, David W; Dickert, Neal W

2017-04-01

Evidence suggests that patients are generally accepting of their enrollment in trials for emergency care conducted under exception from informed consent. It is unknown whether individuals with more severe initial injuries or worse clinical outcomes have different perspectives. Determining whether these differences exist may help to structure post-enrollment interactions. Primary clinical data from the Progesterone for the Treatment of Traumatic Brain Injury trial were matched to interview data from the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study. Answers to three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study were analyzed in the context of enrolled patients' initial injury severity (initial Glasgow Coma Scale and Injury Severity Score) and principal clinical outcomes (Extended Glasgow Outcome Scale and Extended Glasgow Outcome Scale relative to initial injury severity). The three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study addressed participants' general attitude toward inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial (general trial inclusion), their specific attitude toward being included in Progesterone for the Treatment of Traumatic Brain Injury trial under the exception from informed consent (personal exception from informed consent enrollment), and their attitude toward the use of exception from informed consent in the Progesterone for the Treatment of Traumatic Brain Injury trial in general (general exception from informed consent enrollment). Qualitative analysis of interview transcripts was performed to provide contextualization and to determine the extent to which respondents framed their attitudes in terms of clinical experience. Clinical data from Progesterone for the Treatment of Traumatic Brain Injury trial were available for all 74 patients represented in the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study (including 46 patients for whom the surrogate was interviewed due to the patient's cognitive status or death). No significant difference was observed regarding acceptance of general trial inclusion or acceptance of general exception from informed consent enrollment between participants with favorable neurological outcomes and those with unfavorable outcomes relative to initial injury. Agreement with personal enrollment in Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent, however, was significantly higher among participants with favorable outcomes compared to those with unfavorable outcomes (89% vs 59%, p = 0.003). There was also a statistically significant relationship between more severe initial injury and increased acceptance of personal exception from informed consent enrollment ( p = 0.040) or general exception from informed consent use ( p = 0.034) in Progesterone for the Treatment of Traumatic Brain Injury trial. Many individuals referenced personal experience as a basis for their attitudes, but these references were not used to support negative views. Patients and surrogates of patients with unfavorable clinical outcomes were somewhat less accepting of their own inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent than were patients or surrogates of patients with favorable clinical outcomes. These findings suggest a need to identify optimal strategies for communicating with patients and their surrogates regarding exception from informed consent enrollment when clinical outcomes are poor.

Changes in symptoms and pain intensity of cancer patients after enrollment in palliative care at home.

PubMed

Dumitrescu, Luminita; van den Heuvel-Olaroiu, Marinela; van den Heuvel, Wim J A

2007-11-01

This study describes the activities and interventions carried out by an at-home palliative care team treating cancer patients who died within two years of being enrolled in a palliative care program. It analyzes which changes in symptoms and pain occurred and which sociodemographic and medical characteristics were related to these changes. The analysis is based on 102 cancer patients. Data were collected through systematic registration during the palliative care process. At enrollment, patients were interviewed by the coordinating general practitioner concerning their sociodemographic background, medical history, psychological status, and symptoms. During the palliative care process, symptoms and functioning of the patients were recorded by the physician and nurses. The results show that cancer patients enrolled in palliative care at home have many symptoms, often associated with metastatic disease and comorbidities. The palliative care teams delivered frequent and various interventions. The number of symptoms decreased considerably, as did pain intensity and the intensity of other symptoms. Patients living in urban areas and with low income particularly benefited from a reduction in the number of symptoms they displayed. Cancer patients who needed palliative care benefited significantly from this at-home palliative care service.

A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

PubMed Central

Siegel, Abby B.; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S.; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Flaig, Thomas W.; Tsai, Wei Yann; Wu, David P. H.; Lee, Valerie; Greenlee, Heather

2013-01-01

Purpose To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests. PMID:23757319

Pancreatic cancer clinical trials and accrual in the United States.

PubMed

Hoos, William A; James, Porsha M; Rahib, Lola; Talley, Anitra W; Fleshman, Julie M; Matrisian, Lynn M

2013-09-20

Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer. Pancreatic cancer-specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors. The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual. Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.

[TECAR therapy for Peyronie’s disease: a phase-one prospective study. Great evidence in patients with erectile dysfunction].

PubMed

Pavone, Carlo; Castrianni, Davide; Romeo, Salvatore; Napoli, Enrica; Usala, Manuela; Gambino, Giuseppa; Scaturro, Dalila; Letizia Mauro, Giulia

2013-01-01

Our phase-one prospective study wants to evaluate the safety and tolerability of TECAR therapy in the treatment of Peyronie’s disease. From June 2011 to September 2012 we enrolled 70 patients. Each patient had been previously subjected to andrological examination, to a questionnaire for the evaluation of IPP and ED, and the SF-36 (V1) for the evaluation of the general state of health. The evaluation of pain was made using the VAS scale of pain. Every patient was subjected to TECAR treatment of the fibrotic plaque (both in resistive mode and in capacitive mode) for a total of three sessions carried out on consecutive days. We recorded a good compliance by patients; none of them reported side effects. Pain was decreased by the technique in 80% of the cases.The whole sample completed the study. Surprisingly enough those patients who complained also of erectile dysfunction, reported an improvement in sexual potency.

Conventional Vs Digital Impressions: Acceptability, Treatment Comfort and Stress Among Young Orthodontic Patients.

PubMed

Mangano, Alessandro; Beretta, Matteo; Luongo, Giuseppe; Mangano, Carlo; Mangano, Francesco

2018-01-01

The objective of the present study was to compare patients' acceptability, comfort and stress with conventional and digital impressions. Thirty young orthodontic patients (15 males and 15 females) who had no previous experience of impressions were enrolled in this study. Conventional impressions for orthodontic study models of the dental arches were taken using an alginate impression material (Hydrogum ® , Zhermack Spa, Badia Polesine, Rovigo, Italy). Fifteen days later, digital impressions of both arches were acquired using an intraoral scanner (CS3600 ® , Carestream Dental, Rochester, NY, USA). Immediately after impression taking, patients' acceptability, comfort and stress were measured using two questionnaires and the State anxiety scale. Data showed no difference in terms of anxiety and stress; however, patients preferred the use of digital impressions systems instead of conventional impression techniques. Alginate impressions resulted as fast as digital impressions. Digital impressions resulted the most accepted and comfortable impression technique in young orthodontic patients, when compared to conventional techniques.

Characteristics of Latinas in Puerto Rico and the US mainland receiving teriparatide in the DANCE observational study.

PubMed

Ruff, Valerie A; Acosta, Agaph; Soto-Raices, Oscar; Sierra-Zorita, Radamés; Toro-Torres, Ramón; Rodríguez-Ginorio, Henry; Comulada, Angel; Chiang, Alan Y; Krohn, Kelly; Taylor, Kathleen A

2014-09-01

The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study investigated the use of teriparatide in men and women with osteoporosis in the United States (US) and Puerto Rico (PR). In a sub-analysis, we evaluated whether the baseline characteristics of Latinas differed from those of white women in the study population and whether any patient attributes affected physicians' decisions to prescribe teriparatide. We assessed 3 patient cohorts treated with teriparatide 20 microg once daily for up to 24 months: 1) PR Latinas, 2) US Latinas, and 3) white women on the US mainland (white women). We analyzed differences related to ethnicity (Latina vs. white) and geography (PR vs. US mainland). Overall, 302 of the 3243 women (9%) enrolled in DANCE were Latina (205 of these 302 Latinas resided in PR). Significant differences were observed in 7 of 11 baseline characteristics. White women had more prior fragility fractures and family history of hip fracture than Latinas, while PR Latinas were generally older than US Latinas and had more comorbid conditions. A similar proportion of subjects in each cohort had received prior osteoporosis therapy. Physicians prescribed teriparatide more often for Latinas based on multiple risk factors for fracture and intolerance to previous osteoporosis therapy and to white women based on inadequate response to previous therapy or new (incident) fractures. Overall, Latinas were less persistent with teriparatide therapy than white women. We observed significant differences related to ethnicity and geography in the baseline demographics of Latinas enrolled in the DANCE study, criteria cited by physicians for initiating teriparatide therapy, and treatment persistence.

Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials.

PubMed

D'Angelo, Sandra P; Mahoney, Michelle R; Van Tine, Brian A; Atkins, James; Milhem, Mohammed M; Jahagirdar, Balkrishna N; Antonescu, Cristina R; Horvath, Elise; Tap, William D; Schwartz, Gary K; Streicher, Howard

2018-03-01

Patients with metastatic sarcoma have limited treatment options. Nivolumab and ipilimumab are monoclonal antibodies targeting PD-1 and CTLA-4, respectively. We investigated the activity and safety of nivolumab alone or in combination with ipilimumab in patients with locally advanced, unresectable, or metastatic sarcoma. We did a multicentre, open-label, non-comparative, randomised, phase 2 study that enrolled patients aged 18 years or older and had central pathology confirmation of sarcoma with at least one measurable lesion by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, evidence of metastatic, locally advanced or unresectable disease, an ECOG performance status of 0-1, and received at least one previous line of systemic therapy. Patients were assigned to treatment in an unblinded manner, as this trial was conducted as two independent, non-comparative phase 2 trials. Enrolled patients were assigned (1:1) via a dynamic allocation algorithm to intravenous nivolumab 3 mg/kg every 2 weeks, or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses. Thereafter, all patients received nivolumab monotherapy (3 mg/kg) every 2 weeks for up to 2 years. The primary endpoint was the proportion of patients with locally advanced, unresectable or metastatic soft tissue sarcoma achieving a confirmed objective response. Analysis was per protocol. This study is ongoing although enrolment is closed. It is registered with ClinicalTrials.gov, number NCT02500797. Between Aug 13, 2015, and March 17, 2016, 96 patients from 15 sites in the USA underwent central pathology review for eligibility and 85 eligible patients, including planned over-enrolment, were allocated to receive either nivolumab monotherapy (43 patients) or nivolumab plus ipilimumab (42 patients). The primary endpoint analysis was done according to protocol specifications in the first 76 eligible patients (38 patients per group). The number of confirmed responses was two (5% [92% CI 1-16] of 38 patients) in the nivolumab group and six (16% [7-30] of 38 patients) in the nivolumab plus ipilimumab group. The most common grade 3 or worse adverse events were anaemia (four [10%] patients), decreased lymphocyte count (three [7%]), and dehydration, increased lipase, pain, pleural effusion, respiratory failure, secondary benign neoplasm, and urinary tract obstruction (two [5%] patients each) among the 42 patients in the nivolumab group and anaemia (eight [19%] patients), hypotension (four [10%] patients), and pain and urinary tract infection (three [7%] patients each) among the 42 patients in the nivolumab plus ipilimumab group. Serious treatment-related adverse events occurred in eight (19%) of 42 patients receiving monotherapy and 11 (26%) of 42 patients receiving combination therapy, and included anaemia, anorexia, dehydration, decreased platelet count, diarrhoea, fatigue, fever, increased creatinine, increased alanine aminotransferase, increased aspartate aminotransferase, hyponatraemia, pain, pleural effusion, and pruritus. There were no treatment-related deaths. Nivolumab alone does not warrant further study in an unselected sarcoma population given the limited efficacy. Nivolumab combined with ipilimumab demonstrated promising efficacy in certain sarcoma subtypes, with a manageable safety profile comparable to current available treatment options. The combination therapy met its predefined primary study endpoint; further evaluation of nivolumab plus ipilimumab in a randomised study is warranted. Alliance Clinical Trials in Oncology, National Cancer Institute Cancer Therapy Evaluation Program, Bristol-Myers Squibb, Cycle for Survival. Copyright © 2018 Elsevier Ltd. All rights reserved.

The cancer anorexia/weight loss syndrome: exploring associations with single nucleotide polymorphisms (SNPs) of inflammatory cytokines in patients with non-small cell lung cancer.

PubMed

Jatoi, Aminah; Qi, Yingwei; Kendall, Glenda; Jiang, Ruoxiang; McNallan, Sheila; Cunningham, Julie; Mandrekar, Sumithra; Yang, Ping

2010-10-01

The cancer anorexia/weight loss syndrome commonly occurs in patients with non-small cell lung cancer (NSCLC) and is characterized by loss of weight and appetite as well as diminished survival. The current study explored whether any of 22 single nucleotide polymorphisms (SNPs) of certain previously implicated inflammatory cytokines (interleukin-1 beta, interleukin-1RN, interleukin-6, and tumor necrosis factor) are associated with this syndrome. All NSCLC patients who had been enrolled in the Mayo Clinic Lung Cancer Cohort, had completed a health-related questionnaire approximately 6 months after enrollment, and had blood drawn were included in this study, thus yielding a sample size of 471 patients. Sixty-six (14%) patients manifested weight loss shortly after diagnosis, and 152 (32%) reported appetite loss. Only tumor necrosis factor alpha rs800629 was associated with anorexia (odds ratio: 0.46; 95% confidence interval: 0.29, 0.72; p < 0.001); patients who were heterozygous and minor homozygous were less likely to suffer anorexia. Otherwise, there were no statistically significant associations between any of the other 21 SNPs and weight loss and/or anorexia. In univariate analyses, weight loss, anorexia, more advanced cancer stage, and interleukin-1 beta rs1143627 were associated with a worse survival, and interleukin-6 rs2069835 was associated with better survival. However, in multivariate analyses, cancer stage and patient age were the only statistically significant predictors of worse survival. No specific SNP was associated with all aspects of the cancer anorexia/weight loss syndrome, but rs800629 may merit further study in cancer-associated anorexia.

Prevalence of Fabry Disease in Young Patients with Stroke in Argentina.

PubMed

Reisin, Ricardo C; Mazziotti, Julieta; Cejas, Luciana León; Zinnerman, Alberto; Bonardo, Pablo; Pardal, Manuel Fernández; Martínez, Alejandra; Riccio, Patricia; Ameriso, Sebastián; Bendersky, Eduardo; Nofal, Pedro; Cairola, Patricia; Jure, Lorena; Sotelo, Andrea; Rozenfeld, Paula; Ceci, Romina; Casas-Parera, Ignacio; Sánchez-Luceros, Analía

2018-03-01

Fabry disease (FD) is an underdiagnosed cause of stroke in young adults, but the frequency of this association is largely unknown. We estimated the prevalence of FD in a nationwide cohort of young adults who had stroke and transient ischemic attack (TIA) in Argentina. This was a prospective, multicenter study of stroke and FD in young adults (18-55 years) conducted in Argentina between 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemic or hemorrhagic stroke within the previous 180 days. FD was diagnosed by measuring α-galactosidase A activity (males) and through genetic studies (females). We enrolled 311 patients (54% men, mean age: 41 years). Ischemic events occurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in 11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes) had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene. Her only other manifestation of FD was angiokeratoma. Eighteen females had nonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients had the nonpathogenic mutation D313Y, while a third had the likely benign mutation S126G. FD was identified in 1 patient (.3%) in this first Latin American study. The patient presented with a late-onset oligo-symptomatic form of the disease. A large number of nonpathogenic mutations were present in our cohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Influence of Prior Heart Failure Hospitalization on Cardiovascular Events in Patients with Reduced and Preserved Ejection Fraction

PubMed Central

Bello, Natalie A.; Claggett, Brian; Desai, Akshay S.; McMurray, John J.V.; Granger, Christopher B.; Yusuf, Salim; Swedberg, Karl; Pfeffer, Marc A.; Solomon, Scott D.

2014-01-01

Background Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between prior HF hospitalization and randomization in the CHARM trials on clinical outcomes in patients with both reduced and preserved ejection fraction. Methods and Results CHARM enrolled 7,599 patients with NYHA class II-IV heart failure, of whom 5,426 had a history of prior HF hospitalization. Cox proportional hazards regression models were utilized to assess the association between time from prior HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF over a median of 36.6 months. For patients with HF and reduced (HFrEF) or preserved (HFpEF) ejection fraction, rates of CV mortality and HF hospitalization were higher among patients with prior HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for HFrEF patients within each category. Event rates for those with HFpEF and a HF hospitalization in the 6 months prior to randomization were comparable to the rate in HFrEF patients with no prior HF hospitalization. Conclusions Rates of CV death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high risk population for future clinical trials in HFrEF and HFpEF. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00634400. PMID:24874200

Screening for Cryptococcal Antigenaemia in Patients Accessing an Antiretroviral Treatment Program in South Africa

PubMed Central

Jarvis, Joseph N; Lawn, Stephen D; Vogt, Monica; Bangani, Nonzwakazi; Wood, Robin; Harrison, Thomas S

2009-01-01

Background Cryptococcal meningitis is a leading cause of death in AIDS patients and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. Screening for cryptococcal antigen (CRAG) in patients enrolling in ART programs may identify those at risk of cryptococcal meningitis and permit targeted use of pre-emptive therapy. Methods In this retrospective study, CRAG was measured in stored plasma samples obtained from patients as they enrolled in a well characterised ART cohort in South Africa. The predictive value of screening for CRAG prior to ART for development of microbiologically confirmed cryptococcal meningitis or death during the first year of follow-up was determined. Results Of 707 participants with a baseline median CD4 count of 97 (IQR 46-157) cells/μL, 46 (7%) had a positive CRAG. Antigenaemia was 100% sensitive for predicting development of cryptococcal meningitis during the first year of ART and in multivariate analysis was an independent predictor of mortality (AHR 3.2, 95%CI 1.5-6.6). Most (92%) cases of cryptococcal meningitis developed in patients with a CD4 count ≤100 cells/μL. In this sub-set of patients, a CRAG titre ≥1 in 8 was 100% sensitive and 96% specific for predicting incident cryptococcal meningitis during the first year of ART in those with no previous history of the disease. Conclusions CRAG screening prior to commencing ART in patients with a CD4 count ≤100 cells/μL is highly effective at identifying those at risk of cryptococcal meningitis and death and might permit implementation of a targeted pre-emptive treatment strategy. PMID:19222372

Immunogenicity of the meningococcal polysaccharide conjugate vaccine in pediatric kidney transplant patients.

PubMed

Nelson, Delphine R; Fadrowski, Jeffrey; Neu, Alicia

2018-06-01

Immunosuppressed kidney transplant patients may have suboptimal response to vaccinations. The aim of this study was to determine antibody response to a quadrivalent meningococcal conjugate vaccine (MenACWY-D) in adolescents with a kidney transplant. This was a prospective, single-center, cohort study. Adolescent patients (11-22 years old) with a functioning kidney transplant for at least 3 months and no previous meningococcal vaccination were eligible for enrollment. Antibody levels to all serogroups were measured before vaccination (baseline) and at 4 weeks and 1, 2 and 3 years after vaccination. Seropositivity was defined as a titer ≥ 1:8 at baseline, and seroconversion as a fourfold or greater increase in antibody titer from baseline at 4 weeks post-vaccination. Geometric mean titers (GMTs) were calculated at each time point and compared to published GMTs from vaccinated healthy adolescents. Nineteen patients were enrolled. No patient had seroprotective titers against all four serogroups at baseline. At 4 weeks post-vaccination 41% of patients seroconverted to all four serogroups, with seroconversion rates of 88, 53, 71 and 94% for serogroups A, C, W and Y, respectively. GMTs were significantly lower in adolescents with a kidney transplant than in healthy adolescents at 1 month (p = 0.02) and 3 years (p = 0.04) post-vaccination. There were no significant adverse events, episodes of rejection or death in any patient. Adolescents with a kidney transplant may not respond adequately to MenACWY-D and may experience more rapid declines in antibody titers than healthy adolescents. Further study is needed to determine if alternative dosing schedules can improve antibody response in this population.

Quality of life in patients referring to private osteopathic clinical practice: a prospective observational study.

PubMed

Cerritelli, Francesco; Verzella, Marco; Barlafante, Gina

2014-08-01

Health improvement is one of the main priorities of both public and private health systems. In recent years, more attention has been given to the use of complementary and alternative medicines, including osteopathic manipulative treatment (OMT), as possible effective interventions in increasing patients' health reported outcomes. With regard to OMT, very little research was focused on its effectiveness in enhancing health in the general population. To explore the extent to which OMT is effective in improving quality of life in referring patients. Cohort study. Private osteopathic clinical practices in Italy. 25 osteopaths from Central and Southern Italy participated in the study. Self-referred patients, with a diagnosed musculo-skeletal disorder and older than 18 years of age, who did not undergo any OMT session in the previous 12 months and/or contemporarily additional manual therapies were enrolled. Changing from baseline SF36 general health sub-domain scores was used as the study primary outcomes. 1000 patients with primary diagnosis of musculo-skeletal disorder were initially enrolled. 988 patients completed the study. After 4 weeks, mean general health score was 14.7 points higher (95% CI 13.9-15.6; Cohen's d=0.84). Similarly, physical and mental component scores increased (11.5; 95% CI 10.8-12.1; d=0.87 and 9.6; 95% CI 8.6-10.5; d=0.61 respectively). No association between SF36 domains and socio-demographic exposures was found to be statistically significant. Positive changes on various quality of life dimensions were reported by patients receiving osteopathic treatment. The trial was registered on clinicaltrials.gov (identifier NCT01965678). Copyright © 2014 Elsevier Ltd. All rights reserved.

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Improved body weight and metabolic outcomes in overweight or obese psychiatric patients switched to amisulpride from other atypical antipsychotics.

PubMed

Lin, Chao-Cheng; Bai, Ya-Mei; Wang, Ying-Chieh; Chen, Tzu-Ting; Lai, I-Ching; Chen, Jen-Yeu; Chen, Shiow-Yi; Gau, Susan S F; Liou, Ying-Jay

2009-12-01

Switching to a different second-generation antipsychotic (SGA) with a lower risk of weight gain is recommended for overweight or obese psychiatric patients undergoing SGA treatment. However, there have been no complete reports regarding the long-term metabolic effects of switching to amisulpride. In this open-label 1-year study, we investigated the effects on body weight and other metabolic profiles when psychiatric patients treated with another SGA were switched to amisulpride treatment. Forty-six schizophrenia or schizoaffective inpatients with a body mass index greater than 27 kg/m were enrolled in the switch group. These patients were cross-titrated to amisulpride treatment and followed up for 1 year prospectively. Another 46 inpatients matched with the baseline body mass index of those in the switch group were enrolled as the control group retrospectively. The results showed that the switch group had greater weight loss than the control group (7.80 +/- 6.67 vs 2.60 +/- 6.23 kg, respectively; repeated-measure analysis of variance, P < 0.0005). During the treatment course, the amisulpride-treated patients showed significantly decreased fasting triglyceride, total cholesterol, glucose, and insulin resistance levels; decreased diastolic blood pressure and pulse rate; and a significant increase in high-density lipoprotein cholesterol levels after switching to amisulpride (all with a P < 0.05). The prevalence of metabolic syndrome in amisulpride-treated patients also decreased significantly from 65.2% to 30.4% (McNemar test, P < 0.0005). These findings suggest that switching to amisulpride could be an effective treatment of overweight or obese psychiatric patients treated previously with other SGAs.

Oropharyngeal acid reflux and motility abnormalities of the proximal esophagus.

PubMed

Passaretti, Sandro; Mazzoleni, Giorgia; Vailati, Cristian; Testoni, Pier Alberto

2016-10-28

To investigate the relationship between pathological oropharyngeal (OP) acid exposure and esophageal motility in patients with extra-esophageal syndromes. In this prospective study we enrolled consecutive outpatients with extra-esophageal symptoms suspected to be related to gastroesophageal reflux disease (GERD). We enrolled only patients with a reflux symptom index (RSI) score-higher than 13 and with previous lung, allergy and ear, nose and throat evaluations excluding other specific diagnoses. All patients underwent 24-h OP pH-metry with the Dx probe and esophageal high-resolution manometry (HRM). Patients were divided into two groups on the basis of a normal or pathological pH-metric finding (Ryan Score) and all manometric characteristics of the two groups were compared. We examined 135 patients with chronic extra-esophageal syndromes. Fifty-one were considered eligible for the study. Of these, 42 decided to participate in the protocol. Patients were divided into two groups on the basis of normal or pathological OP acid exposure. All the HRM parameters were compared for the two groups. Significant differences were found in the median upper esophageal sphincter resting pressure (median 71 mmHg vs 126 mmHg, P = 0.004) and the median proximal contractile integral (median 215.5 cm•mmHg•s vs 313.5 cm•mmHg•s, P = 0.039), both being lower in the group with pathological OP acid exposure, and the number of contractions with small or large breaks, which were more frequent in the same group. This group also had a larger number of peristaltic contractions with breaks in the 20 mmHg isobaric contour (38.7% vs 15.38%, P < 0.0001). In patients with suspected GERD-related extra-esophageal syndromes pathological OP acid exposure was associated with weaker proximal esophageal motility.

A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wuthrick, Evan J., E-mail: evan.wuthrick@osumc.edu; Curran, Walter J.; Camphausen, Kevin

Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acutemore » toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival.« less

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.

PubMed

Morris, Van K; Salem, Mohamed E; Nimeiri, Halla; Iqbal, Syma; Singh, Preet; Ciombor, Kristen; Polite, Blase; Deming, Dustin; Chan, Emily; Wade, James L; Xiao, Lianchun; Bekaii-Saab, Tanios; Vence, Luis; Blando, Jorge; Mahvash, Armeen; Foo, Wai Chin; Ohaji, Chimela; Pasia, Manolo; Bland, Gail; Ohinata, Aki; Rogers, Jane; Mehdizadeh, Amir; Banks, Kimberly; Lanman, Richard; Wolff, Robert A; Streicher, Howard; Allison, James; Sharma, Padmanee; Eng, Cathy

2017-04-01

Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study

PubMed Central

Morris, Van K; Salem, Mohamed E; Nimeiri, Halla; Iqbal, Syma; Singh, Preet; Ciombor, Kristen; Polite, Blase; Deming, Dustin; Chan, Emily; Wade, James L; Xiao, Lianchun; Bekaii-Saab, Prof Tanios; Vence, Luis; Blando, Jorge; Mahvash, Armeen; Foo, Wai Chin; Ohaji, Chimela; Pasia, Manolo; Bland, Gail; Ohinata, Aki; Rogers, Jane; Mehdizadeh, Amir; Banks, Kimberly; Lanman, Richard; Wolff, Robert A; Streicher, Howard; Allison, Prof James; Sharma, Prof Padmanee; Eng, Prof Cathy

2018-01-01

Summary Background Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. Methods We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. Findings We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15–33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. Interpretation To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. Funding National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor. PMID:28223062

Baseline Characteristics of the Autosomal Dominant Polycystic Kidney Disease Subcohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

PubMed

Kim, Hyunsuk; Koh, Junga; Park, Sue K; Oh, Kook Hwan; Kim, Yeong Hoon; Kim, Yaeni; Ahn, Curie; Oh, Yun Kyu

2018-05-24

The aim of this study was to describe the baseline characteristics of autosomal dominant polycystic kidney disease (ADPKD) in a cohort of Korean patients with chronic kidney disease (CKD). From April 2011 to February 2016, patients with CKD stage 1 to 5 (pre-dialysis) were enrolled as an ADPKD subcohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease. Baseline characteristics, the correlation of kidney and liver volume and kidney function, and the factors associated with kidney function were analyzed. A total of 364 ADPKD patients with a mean estimated glomerular filtration rate (eGFR) of 68.1 ± 33.3 mL/min/1.73 m 2 (50.5% male with a mean age of 47.0 ± 10.6 years) were enrolled from nine hospitals in Korea. Initially, 55.8% of the patients were asymptomatic, and pain was the most common symptom (12.9%); 87.6% and 77.5% of the patients had hypertension and hepatic cysts, respectively. The height-adjusted total kidney volumes (htTKV) were higher in male patients than in female patients. In contrast, the height-adjusted total liver volumes were higher in female patients than in male patients. The decrease rate of eGFR depending on Log(htTKV) was larger in the group aged between 41 and 50 than the other age groups. Older age, a higher 24-hour urine protein excretion, larger htTKV, and hyperuricemia were independently associated with lower eGFR, whereas using febuxostat was independently associated with higher eGFR. This subcohort will provide clinical characteristics and outcomes of Korean ADPKD patients and can compare with those of other previous cohorts. We have identified factors associated with advanced-stage CKD in Korean patients with ADPKD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Talking About Trials: Overcoming Bottlenecks in Clinical Communication

Cancer.gov

Participation in clinical trials by adult patients is dismally low. No one knows how many patients are offered the opportunity to enroll in trials. NCI researchers are studying how patients hear about trials, whether they discuss enrollment with their providers, and the roles they play in deciding to participate in a trial.

Drier Air, Lower Temperatures, and Triggering of Paroxysmal Atrial Fibrillation

PubMed Central

Nguyen, Jennifer L.; Link, Mark S.; Luttmann-Gibson, Heike; Laden, Francine; Schwartz, Joel; Wessler, Benjamin S.; Mittleman, Murray A.; Gold, Diane R.; Dockery, Douglas W.

2015-01-01

Background The few previous studies on the onset of paroxysmal atrial fibrillation and meteorologic conditions have focused on outdoor temperature and hospital admissions, but hospital admissions are a crude indicator of atrial fibrillation incidence, and studies have found other weather measures in addition to temperature to be associated with cardiovascular outcomes. Methods Two hundred patients with dual chamber implantable cardioverter-defibrillators were enrolled and followed prospectively from 2006 to 2010 for new onset episodes of atrial fibrillation. The date and time of arrhythmia episodes documented by the implanted cardioverter-defibrillators were linked to meteorologic data and examined using a case-crossover analysis. We evaluated associations with outdoor temperature, apparent temperature, air pressure, and three measures of humidity (relative humidity, dew point, and absolute humidity). Results Of the 200 enrolled patients, 49 patients experienced 328 atrial fibrillation episodes lasting ≥30 seconds. Lower temperatures in the prior 48 hours were positively associated with atrial fibrillation. Lower absolute humidity (ie, drier air) had the strongest and most consistent association: each 0.5 g/m3 decrease in the prior 24 hours increased the odds of atrial fibrillation by 4% (95% confidence interval [CI]: 0%, 7%) and by 5% (95% CI: 2%, 8%) for exposure in the prior 2 hours. Results were similar for dew point but slightly weaker. Conclusions Recent exposure to drier air and lower temperatures were associated with the onset of atrial fibrillation among patients with known cardiac disease, supporting the hypothesis that meteorologic conditions trigger acute cardiovascular episodes. PMID:25756220

Cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis in China.

PubMed

Fitzpatrick, Christopher; Hui, Zhang; Lixia, Wang; Renzhong, Li; Yunzhou, Ruan; Mingting, Chen; Yanlin, Zhao; Jin, Zhao; Wei, Su; Caihong, Xu; Cheng, Chen; Alston, Timothy; Yan, Qu; Chengfei, Lv; Yunting, Fu; Shitong, Huan; Qiang, Sun; Scano, Fabio; Chin, Daniel P; Floyd, Katherine

2015-11-01

To investigate the cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis launched in four sites in China in 2011. In 2011-2012, we reviewed the records of 172 patients with drug-resistant tuberculosis who enrolled in the comprehensive programme and we collected relevant administrative data from hospitals and China's public health agency. For comparison, we examined a cohort of 81 patients who were treated for drug-resistant tuberculosis in 2006-2009. We performed a cost-effectiveness analysis, from a societal perspective, that included probabilistic uncertainty. We measured early treatment outcomes based on three-month culture results and modelled longer-term outcomes to facilitate estimation of the comprehensive programme's cost per disability-adjusted life-year (DALY) averted. The comprehensive programme cost 8837 United States dollars (US$) per patient treated. Low enrolment rates meant that some fixed costs were higher, per patient, than expected. Although the comprehensive programme appeared 30 times more costly than the previous one, it resulted in greater health benefits. The comprehensive programme, which cost US$ 639 (95% credible interval: 112 to 1322) per DALY averted, satisfied the World Health Organization's criterion for a very cost-effective intervention. The comprehensive programme, which included rapid screening, standardized care and financial protection, improved individual outcomes for MDR tuberculosis in a cost-effective manner. To support post-2015 global heath targets, the comprehensive programme should be expanded to non-residents and other areas of China.

Screening for comorbid conditions in patients enrolled in the SODA registry: a 2-year observational analysis.

PubMed

Woodmansee, Whitney W; Gordon, Murray B; Molitch, Mark E; Ioachimescu, Adriana G; Carver, Don W; Mirakhur, Beloo; Cox, David; Salvatori, Roberto

2018-05-16

This 2-year analysis assessed frequency of comorbidities and comorbidity screening in the Somatuline ® (lanreotide, LAN) Depot for Acromegaly (SODA) registry. Patient data collected included pituitary hormone deficiencies, sleep studies, echocardiograms, gallbladder sonographies, colonoscopies, and glycated hemoglobin (HbA1c) levels. Insulin-like growth factor-1 (IGF-1) and growth hormone levels in patients with (DM) and without (non-DM) diabetes mellitus were analyzed. There were 241 patients enrolled. Pituitary hormone deficiencies were reported more frequently at enrollment in male (56.9%) vs female patients (32.0%; p < 0.001). TSH deficiency was the most common endocrine deficiency (69.8%), followed by gonadotropin deficiency (62.3%). Screening tests reported at enrollment: sleep studies in 29.9% (79.2% had sleep apnea), echocardiogram in 46.1% (46.8% abnormal), gallbladder sonography in 18.7% (17.8% had gallstones), and colonoscopy in 48.1% (35.3% had polyps). Follow-up studies were reported less frequently at 1 and 2 years. HbA1c data were reported in 30.8% and 41.2% after 1 and 2 years. HbA1c levels were similar at 1 and 2 years of LAN therapy among DM and non-DM patients with available data. Fewer DM vs non-DM patients achieved IGF-1 below upper limit of normal at Month 24 (58.3% vs 80.6%; p = 0.033). Fewer than half of patients in SODA had screening results reported at enrollment for sleep apnea, cardiomyopathy, and colon polyps. Gallbladder imaging was reported in a minority of patients. Lower IGF-1 control rates were observed in DM vs non-DM patients at Month 24. These data suggest a need for better monitoring of comorbidities in US acromegaly patients.

Proactive recruitment of cancer patients’ social networks into a smoking cessation trial

PubMed Central

Bastian, Lori A.; Fish, Laura J.; Peterson, Bercedis L.; Biddle, Andrea K.; Garst, Jennifer; Lyna, Pauline; Molner, Stephanie; Bepler, Gerold; Kelley, Mike; Keefe, Francis J.; McBride, Colleen M.

2011-01-01

Background This report describes the characteristics associated with successful enrollment of smokers in the social networks (i.e., family and close friends) of patients with lung cancer into a smoking cessation intervention. Methods Lung cancer patients from four clinical sites were asked to complete a survey enumerating their family members and close friends who smoke, and provide permission to contact these potential participants. Family members and close friends identified as smokers were interviewed and offered participation in a smoking cessation intervention. Repeated measures logistic regression model examined characteristics associated with enrollment. Results A total of 1,062 eligible lung cancer patients were identified and 516 patients consented and completed the survey. These patients identified 1,325 potentially eligible family and close friends. Of these, 496 consented and enrolled in the smoking cessation program. Network enrollment was highest among patients who were white and had late-stage disease. Social network members enrolled were most likely to be female, a birth family, immediate family, or close friend, and live in close geographic proximity to the patient. Conclusions Proactive recruitment of smokers in the social networks of lung cancer patients is challenging. In this study, the majority of family members and friends declined to participate. Enlisting immediate female family members and friends, who live close to the patient as agents to proactively recruit other network members into smoking cessation trials could be used to extend reach of cessation interventions to patients’ social networks. Moreover, further consideration should be given to the appropriate timing of approaching network smokers to consider cessation. PMID:21382509

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

PubMed Central

2013-01-01

Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169. PMID:23388612

Factors associated with loss to clinic among HIV patients not yet known to be eligible for antiretroviral therapy (ART) in Mozambique

PubMed Central

Pati, Rituparna; Lahuerta, Maria; Elul, Batya; Okamura, Mie; Alvim, Maria Fernanda; Schackman, Bruce; Bang, Heejung; Fernandes, Rufino; Assan, Americo; Lima, Josue; Nash, Denis

2013-01-01

Introduction Retention in HIV care prior to ART initiation is generally felt to be suboptimal, but has not been well-characterized. Methods We examined data on 37,352 adult pre-ART patients (ART ineligible or unknown eligibility) who enrolled in care during 2005–2008 with >1 clinical visit at 23 clinics in Mozambique. We defined loss to clinic (LTC) as >12 months since the last visit among those not known to have died/transferred. Cox proportional-hazards models were used to examine factors associated with LTC, accounting for clustering within sites. Results Of 37,352 pre-ART patients, 61% had a CD4 count within three months of enrolment (median CD4: 452, IQR: 345–611). 17,598 (47.1%) were ART ineligible and 19,754 (52.9%) were of unknown eligibility status at enrolment because of missing information on CD4 count and/or WHO stage. Kaplan-Meier estimates for LTC at 12 months were 41% (95% CI: 40.2–41.8) and 48% (95% CI: 47.2–48.8), respectively. Factors associated with LTC among ART ineligible patients included male sex (AHRmen_vs_non-pregnant women: 1.5; 95% CI: 1.4–1.6) and being pregnant at enrolment (AHRpregnant_vs_non-pregnant women: 1.3; 95% CI: 1.1–1.5). Older age, more education, higher weight and more advanced WHO stage at enrolment were independently associated with lower risks of LTC. Similar findings were observed among patients whose ART eligibility status was unknown at enrolment. Conclusions Substantial LTC occurred prior to ART initiation among patients not yet known to be eligible for ART, including nearly half of patients without documented ART eligibility assessment. Interventions are needed to target pre-ART patients who may be at higher risk for LTC, including pregnant women and patients with less advanced HIV disease. PMID:23755857

The Cancer Research Network: a platform for epidemiologic and health services research on cancer prevention, care, and outcomes in large, stable populations.

PubMed

Chubak, Jessica; Ziebell, Rebecca; Greenlee, Robert T; Honda, Stacey; Hornbrook, Mark C; Epstein, Mara; Nekhlyudov, Larissa; Pawloski, Pamala A; Ritzwoller, Debra P; Ghai, Nirupa R; Feigelson, Heather Spencer; Clancy, Heather A; Doria-Rose, V Paul; Kushi, Lawrence H

2016-11-01

The ability to collect data on patients for long periods prior to, during, and after a cancer diagnosis is critical for studies of cancer etiology, prevention, treatment, outcomes, and costs. We describe such data capacities within the Cancer Research Network (CRN), a cooperative agreement between the National Cancer Institute (NCI) and organized health care systems across the United States. Data were extracted from each CRN site's virtual data warehouse using a centrally written and locally executed program. We computed the percent of patients continuously enrolled ≥1, ≥5, and ≥10 years before cancer diagnosis in 2012-2015 (year varied by CRN site). To describe retention after diagnosis, we computed the cumulative percentages enrolled, deceased, and disenrolled each year after the diagnosis for patients diagnosed in 2000. Approximately 8 million people were enrolled in ten CRN health plans on December 31, 2014 or 2015 (year varied by CRN site). Among more than 30,000 recent cancer diagnoses, 70 % were enrolled for ≥5 years and 56 % for ≥10 years before diagnosis. Among 25,274 cancers diagnosed in 2000, 28 % were still enrolled in 2010, 45 % had died, and 27 % had disenrolled from CRN health systems. Health plan enrollment before cancer diagnosis was generally long in the CRN, and the proportion of patients lost to follow-up after diagnosis was low. With long enrollment histories among cancer patients pre-diagnosis and low post-diagnosis disenrollment, the CRN provides an excellent platform for epidemiologic and health services research on cancer incidence, outcomes, and costs.

Under-representation of racial minorities in prostate cancer studies submitted to the US Food and Drug Administration to support potential marketing approval, 1993-2013.

PubMed

Wissing, Michel D; Kluetz, Paul G; Ning, Yang-Min; Bull, Jonca; Merenda, Christine; Murgo, Anthony J; Pazdur, Richard

2014-10-01

US Food and Drug Administration (FDA) approval of new drugs depends on results from clinical trials that must be generalized to the US population. However, racial minorities are frequently under-represented in clinical studies. The enrollment of racial minorities was compared in key clinical studies submitted to the FDA in the last 10 years in support of potential marketing approval for prostate cancer (PCa) prevention or treatment. Patient demographic data were obtained from archival data sets of large registration trials submitted to the FDA to support proposed PCa indications. Six countries/regions were analyzed: the United States, Canada, Australia, Europe, the United Kingdom, and Eastern Europe. Background racial demographics were collected from national census data. Seventeen key PCa clinical trials were analyzed. These trials were conducted in the past 20 years, comprising 39,574 patients with known racial information. Most patients were enrolled in the United States, but there appeared to be a trend toward increased non-US enrollment over time. In all countries, racial minorities were generally under-represented. There was no significant improvement in racial minority enrollment over time. The United States enrolled the largest nonwhite population (7.1%). Over the past 20 years, racial minorities were consistently under-represented in key PCa trials. There is a need for effective measures that will improve enrollment of racial minorities. With increased global enrollment, drug developers should aim to recruit a patient population that resembles the racial demographics of the patient population to which drug use will be generalized upon approval. © 2014 American Cancer Society.

The Cancer Research Network: a platform for epidemiologic and health services research on cancer prevention, care, and outcomes in large, stable populations

PubMed Central

Chubak, Jessica; Ziebell, Rebecca; Greenlee, Robert T.; Honda, Stacey; Hornbrook, Mark C.; Epstein, Mara; Nekhlyudov, Larissa; Pawloski, Pamala A.; Ritzwoller, Debra P.; Ghai, Nirupa R.; Feigelson, Heather Spencer; Clancy, Heather A.; Doria-Rose, V. Paul; Kushi, Lawrence H.

2018-01-01

Purpose The ability to collect data on patients for long periods prior to, during, and after a cancer diagnosis is critical for studies of cancer etiology, prevention, treatment, outcomes and costs. We describe such data capacities within the Cancer Research Network (CRN), a cooperative agreement between the National Cancer Institute (NCI) and organized health care systems across the United States. Methods Data were extracted from each CRN site’s virtual data warehouse using a centrally-written and locally-executed program. We computed the percent of patients continuously enrolled ≥1, ≥5, and ≥10 years before cancer diagnosis in 2012–2015 (year varied by CRN site). To describe retention after diagnosis, we computed the cumulative percentages enrolled, deceased, and disenrolled each year after diagnosis for patients diagnosed in 2000. Results Approximately 8 million people were enrolled in ten CRN health plans on December 31, 2014 or 2015 (year varied by CRN site). Among more than 30,000 recent cancer diagnoses, 70% were enrolled for ≥5 years and 56% for ≥10 years before diagnosis. Among 25,274 cancers diagnosed in 2000, 28% were still enrolled in 2010, 45% had died, and 27% had disenrolled from CRN health systems. Conclusions Health plan enrollment before cancer diagnosis was generally long in the CRN, and the proportion of patients lost to follow-up after diagnosis was low. With long enrollment histories among cancer patients pre-diagnosis and low post-diagnosis disenrollment, the CRN provides an excellent platform for epidemiologic and health services research on cancer incidence, outcomes, and costs. PMID:27639398

Wisconsin's BadgerCare Plus Reform: Impact on Low-Income Families' Enrollment and Retention in Public Coverage

PubMed Central

Leininger, Lindsey Jeanne; Friedsam, Donna; Dague, Laura; Mok, Shannon; Hynes, Emma; Bergum, Alison; Aksamitauskas, Milda; Oliver, Thomas; DeLeire, Thomas

2011-01-01

Objectives To examine the impact of a Wisconsin health care reform enacted in early 2008 on public insurance enrollment and retention. Data Sources Administrative data covering the period January 2007 to November 2009. Study Design We calculate unadjusted enrollment trends and exit rates stratified by age, income group, and enrollment mode. Kaplan–Meier curves and Cox proportional hazards models are estimated to assess the impact of the reform on program exits. Principal Findings Overall enrollment increased by approximately one-third and exit rates decreased by approximately one-fifth. The majority of new enrollment came from the previously income eligible. Conclusions Wisconsin's enactment of eligibility expansions coupled with administrative simplification and targeted marketing and outreach efforts were successful in enrolling and retaining low-income children and families in public coverage. PMID:21143476

GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS

PubMed Central

Bartlett, Jaclyn R.; Friedman, Kenneth J.; Ling, Simon C.; Pace, Rhonda G.; Bell, Scott C.; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L.; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J.; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B.; Phillips, M. James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M.; Drumm, Mitchell L.; Wright, Fred A.; Lange, Ethan M.; Durie, Peter R.; Knowles, Michael R.

2013-01-01

Context A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients. Design, Setting, and Participants A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls. Main Outcome Measures We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83). Conclusion The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension. PMID:19738092

FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin in the EPIC³ program.

PubMed

Poynard, Thierry; Munteanu, Mona; Colombo, Massimo; Bruix, Jordi; Schiff, Eugene; Terg, Ruben; Flamm, Steven; Moreno-Otero, Ricardo; Carrilho, Flair; Schmidt, Warren; Berg, Thomas; McGarrity, Thomas; Heathcote, E Jenny; Gonçales, Fernando; Diago, Moises; Craxi, Antonio; Silva, Marcelo; Boparai, Navdeep; Griffel, Louis; Burroughs, Margaret; Brass, Clifford; Albrecht, Janice

2011-02-01

EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon-alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy. Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3, and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2=0.80 (p<0.00001). Five baseline factors were associated (p<0.001) with SVR in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), previous treatment with non-PEG-IFN (2.6/2.0). These same factors were associated (p ≤ 0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis (p ≤ 0.001): genotype 2/3 (odds ratio=2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5). FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12 weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

MRI versus breast-specific gamma imaging (BSGI) in newly diagnosed ductal cell carcinoma-in-situ: a prospective head-to-head trial.

PubMed

Keto, Jessica L; Kirstein, Laurie; Sanchez, Diana P; Fulop, Tamara; McPartland, Laura; Cohen, Ilona; Boolbol, Susan K

2012-01-01

Mammography remains the standard imaging technique for the diagnosis of ductal carcinoma-in-situ (DCIS). Functional breast imaging, including breast magnetic resonance imaging (MRI), has known limitations in evaluating DCIS. To date, there are limited data on the utility of breast-specific gamma imaging (BSGI) in DCIS. We sought to prospectively compare the sensitivity of BSGI to MRI in newly diagnosed DCIS patients. Patients with newly diagnosed DCIS from June 1, 2009, through May 31, 2010, underwent a protocol with both breast MRI and BSGI. Each imaging study was read by a separate dedicated breast radiologist. Patients were excluded if excisional biopsy was performed for diagnosis, if their MRI was performed at an outside facility, or if final pathology revealed invasive carcinoma. There were 18 patients enrolled onto the study that had both MRI and BSGI for newly diagnosed DCIS. The sensitivity for MRI was 94% and for BSGI was 89% (P > 0.5, NS). There was one index tumor not seen on either MRI or BSGI, and one index tumor seen on MRI but not visualized on BSGI. Although BSGI has previously been shown to be as sensitive as MRI for detecting known invasive breast carcinoma, this study shows that BSGI is equally as sensitive as MRI at detecting newly diagnosed DCIS. As a result of the limited number of patients enrolled onto the study, larger prospective studies need to be performed to determine the true sensitivity and specificity of BSGI.

Dentist and practice characteristics associated with restorative treatment of enamel caries in permanent teeth: multiple-regression modeling of observational clinical data from The National Dental PBRN

PubMed Central

Fellows, Jeffrey L; Gordan, Valeria V.; Gilbert, Gregg H.; Rindal, D. Brad; Qvist, Vibeke; Litaker, Mark S.; Benjamin, Paul; Flink, Håkan; Pihlstrom, Daniel J.; Johnson, Neil

2014-01-01

Purpose Current evidence in dentistry recommends non-surgical treatment to manage enamel caries lesions. However, surveyed practitioners report they would restore enamel lesions that are confined to the enamel. We used actual clinical data to evaluate patient, dentist, and practice characteristics associated with restoration of enamel caries, while accounting for other factors. Methods We combined data from a National Dental Practice-Based Research Network observational study of consecutive restorations placed in previously unrestored permanent tooth surfaces and practice/demographic data from 229 participating network dentists. Analysis of variance and logistic regression, using generalized estimating equations (GEE) and variable selection within blocks, were used to test the hypothesis that patient, dentist, and practice characteristics were associated with variations in enamel restorations of occlusal and proximal caries compared to dentin lesions, accounting for dentist and patient clustering. Results Network dentists from 5 regions placed 6,891 restorations involving occlusal and/or proximal caries lesions. Enamel restorations accounted for 16% of enrolled occlusal caries lesions and 6% of enrolled proximal caries lesions. Enamel occlusal restorations varied significantly (p<0.05) by patient age and race/ethnicity, dentist use of caries risk assessment, network region, and practice type. Enamel proximal restorations varied significantly (p<0.05) by dentist race/ethnicity, network region, and practice type. CLINICAL SIGNIFICANCE Identifying patient, dentist, and practice characteristics associated with enamel caries restorations can guide strategies to improve provider adherence to evidence-based clinical recommendations. PMID:25000667

Comparison of two contraceptive pills containing drospirenone and 20 μg or 30 μg ethinyl estradiol for polycystic ovary syndrome.

PubMed

Bhattacharya, Sudhindra M; Jha, Ayan; DasMukhopadhyay, Lipika

2016-02-01

To compare the effects of 30 μg and 20 μg ethinyl estradiol (EE) among women with polycystic ovary syndrome (PCOS). In a randomized study, patients with PCOS, a history of six or fewer menstrual cycles in the previous 12 months, and abnormal body hair growth were enrolled at a center in Kolkata, India, between May 1, 2012, and January 31, 2014. Participants were randomly assigned (1:1) using a computer-generated randomization table to receive an oral contraceptive pill containing 3mg drospirenone and either 30 μg EE or 20 μg EE. Patients were followed up after 6 and 12 months. The primary outcome was the absolute change in the free androgen index. Participants were masked to group assignment but investigators were not. Analyses were by intention to treat. Overall, 112 patients were enrolled. At 6 months, the free androgen index had decreased by 4.96±6.01 among patients receiving 30 μg (n=55) and by 4.81±6.03 among those receiving 20 μg (n=57; P=0.89). At 12 months, the decrease from baseline was 5.23±5.79 with 30 μg and 4.99±5.86 with 20 μg (P=0.82). Among patients with PCOS, an oral contraceptive pill containing 20 μg EE has similar effects on androgen levels to those of a pill containing 30 μg. CTRI/2012/04/002571. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Comparison of superior vena cava and femoroiliac vein pressure according to intra-abdominal pressure.

PubMed

Ait-Oufella, Hafid; Boelle, Pierre-Yves; Galbois, Arnaud; Baudel, Jean-Luc; Margetis, Dimitri; Alves, Mikael; Offenstadt, Georges; Maury, Eric; Guidet, Bertrand

2012-06-28

Previous studies have shown a good agreement between central venous pressure (CVP) measurements from catheters placed in superior vena cava and catheters placed in the abdominal cava/common iliac vein. However, the influence of intra-abdominal pressure on such measurements remains unknown. We conducted a prospective, observational study in a tertiary teaching hospital. We enrolled patients who had indwelling catheters in both superior vena cava (double lumen catheter) and femoroiliac veins (dialysis catheter) and into the bladder. Pressures were measured from all the sites, CVP, femoroiliac venous pressure (FIVP), and intra-abdominal pressure. A total of 30 patients were enrolled (age 62 ± 14 years; SAPS II 62 (52-76)). Fifty complete sets of measurements were performed. All of the studied patients were mechanically ventilated (PEP 3 cmH20 (2-5)). We observed that the concordance between CVP and FIVP decreased when intra-abdominal pressure increased. We identified 14 mmHg as the best intra-abdominal pressure cutoff, and we found that CVP and FIVP were significantly more in agreement below this threshold than above (94% versus 50%, P = 0.002). We reported that intra-abdominal pressure affected agreement between CVP measurements from catheter placed in superior vena cava and catheters placed in the femoroiliac vein. Agreement was excellent when intra-abdominal pressure was below 14 mmHg.

Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)

PubMed Central

Preston, Ioana R.; Roberts, Kari E.; Miller, Dave P.; Sen, Ginny P.; Selej, Mona; Benton, Wade W.; Hill, Nicholas S.

2015-01-01

Background— Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Methods and Results— Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. Conclusions— No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. PMID:26510696

Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

PubMed

Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

2015-12-22

Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

Effect of a chronic disease management service for patients with diabetes on hospitalisation and acute care costs.

PubMed

Rasekaba, Tshepo M; Lim, W Kwang; Hutchinson, Anastasia F

2012-05-01

To evaluate the effect of a diabetes-management program for patients with type 2 diabetes and related comorbidities on acute healthcare utilisation and costs. This was a retrospective administrative dataset analysis using data for patients enrolled from 2007 to 2008. Inpatient admissions for diabetes-related conditions were compared before, during and following enrolment. Costs per episode were estimated from Weighted Inlier Equivalent Separations (WIES) funding. A cost model was then developed based on admission rates per 100 patients. Data were retrieved for 357 patients; 49% males, mean age 62 years. The mean per-patient cost of the program was AU$524 (s.d. $213). The mean cost of an inpatient admission was $4357(95% CI 2743-5971) pre-enrolment and $4396 (95% CI 2888-5904) post-enrolment. Following program completion the annual costs (per 100 patients) for managing 'diabetes with multiple complications' and hypoglycaemia decreased from $10181 to $1710 and $9947 to $7800. In contrast, the annual cost of cardiovascular disorders increased from $14485 to $40071 per 100 patients. In the short-term diabetes-management programs for patients with comorbid vascular disease may reduce hospital utilisation for diabetes but not for cardiovascular disease. Longer-term follow-up is needed to determine whether intensive management of vascular complications can reduce costs.

Oral administration of forskolin and rutin contributes to intraocular pressure control in primary open angle glaucoma patients under maximum tolerated medical therapy.

PubMed

Vetrugno, Michele; Uva, Maurizio G; Russo, Vincenzo; Iester, Michele; Ciancaglini, Marco; Brusini, Paolo; Centofanti, Marco; Rossetti, Luca M

2012-10-01

Tight control of intraocular pressure (IOP) is still the only therapeutic approach available for the treatment of primary open angle glaucoma (POAG). However, some patients do not respond adequately to hypotonising drugs, and despite multiple drug combinations they cannot reach their target IOP. Forskolin is a natural compound that has already shown efficacy in IOP reduction following topical application. The aim of this study was to evaluate the effects on the IOP of a food supplement containing forskolin and rutin when administered to POAG patients under maximum tolerated medical therapy (MTMT) and on a waiting list for filtrating surgery to further decrease their IOP. The design of the study was open and case-controlled. Ninety-seven (52 in the treatment group, and 45 in the reference group) patients were enrolled in 8 different glaucoma centers in Italy, all under MTMT and with IOP enrollment values above their target pressure. During the 30 days before surgery, patients in the treatment group were prescribed 2 tablets per day of a food supplement containing rutin and forskolin in addition to their usual topical drug treatment. Their IOP values were measured at 3 time points during the day, at enrollment and once a week until surgery. Control patients continued only with their normal topical therapy. All patients in the treatment group, independently of the combination drug therapy that they were taking, showed a further 10% decrease (P<0.01) of their IOP, starting from 1 week after introduction of the oral supplement and lasting until the last evaluation before surgery. This decrease was more evident (15% of the enrollment value; P<0.01) in those subjects with high (IOP≥21 mmHg) enrollment values rather than in those with low (IOP<21) enrollment values (9%; P<0.01). On the contrary, IOP values in the control group remained stable from the beginning to the end of the observation period, independently of their enrollment values. Forskolin and rutin given as oral treatment appear to contribute to a better control and a further small reduction of IOP in patients who were poorly responsive to multitherapy treatment.

Patient Recruitment into a Multicenter Randomized Clinical Trial 
for Kidney Disease: Report of the Focal Segmental Glomerulosclerosis Clinical Trial (FSGS CT)

PubMed Central

Ferris, Maria; Norwood, Victoria; Radeva, Milena; Gassman, Jennifer J.; Al‐Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey‐Mims, Marva

2012-01-01

Abstract We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open‐label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web‐based anonymous survey of site investigators revealed site‐related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start‐up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. Clin Trans Sci 2013; Volume 6: 13–20 PMID:23399084

Patient recruitment into a multicenter randomized clinical trial for kidney disease: report of the focal segmental glomerulosclerosis clinical trial (FSGS CT).

PubMed

Ferris, Maria; Norwood, Victoria; Radeva, Milena; Gassman, Jennifer J; Al-Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey-Mims, Marva; Trachtman, Howard

2013-02-01

We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. © 2013 Wiley Periodicals, Inc.

Patients’ Perspectives of Enrollment in Research Without Consent- The Patients’ Experiences in Emergency Research- ProTECT Study (PEER-ProTECT)

PubMed Central

Dickert, Neal W; Scicluna, Victoria M; Baren, Jill M; Biros, Michelle H; Fleischman, Ross J; Govindarajan, Prasanthi R; Jones, Elizabeth B; Pancioli, Arthur M; Wright, David W; Pentz, Rebecca D

2016-01-01

Objective Research in acute illness often requires an exception from informed consent (EFIC). Few studies have assessed the views of patients enrolled in EFIC trials. This study was designed to assess the views of patients and their surrogates of EFIC enrollment in a randomized, placebo-controlled trial of an investigational agent for traumatic brain injury. Design Interactive interview study. Setting Nested within the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT III) trial, a Phase III randomized controlled trial in acute traumatic brain injury (TBI). Participants Patients and surrogates (for patients incapable of being interviewed) enrolled in ProTECT III under EFIC at 12 sites. Measurements Interviews focused on respondents’ acceptance of EFIC enrollment in ProTECT, use of placebo and randomization, understanding of major study elements, and views regarding regulatory protections. Descriptive statistical analysis was performed; textual data were analyzed thematically. Main Results 85 individuals were interviewed. 84% had positive attitudes toward ProTECT III inclusion. 78% found their inclusion under EFIC acceptable, and 72% found use of EFIC in ProTECT III acceptable in general. Only 2 respondents clearly disagreed with both personal and general EFIC enrollment. The most common concerns (26%) related to absence of consent. 80% and 92% were accepting of placebo use and randomization, respectively. Though there were few black respondents (n=11), they were less accepting of personal EFIC enrollment than white respondents (55% vs 83%, p= 0.0494). Conclusions Acceptance of EFIC in this placebo-controlled trial of an investigational agent was high and exceeded acceptance among community consultation participants. EFIC enrollment appears generally consistent with patients’ preferences. PMID:25574795

Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial.

PubMed

Shi, Yuankai; Zhang, Li; Liu, Xiaoqing; Zhou, Caicun; Zhang, Li; Zhang, Shucai; Wang, Dong; Li, Qiang; Qin, Shukui; Hu, Chunhong; Zhang, Yiping; Chen, Jianhua; Cheng, Ying; Feng, Jifeng; Zhang, Helong; Song, Yong; Wu, Yi-Long; Xu, Nong; Zhou, Jianying; Luo, Rongcheng; Bai, Chunxue; Jin, Yening; Liu, Wenchao; Wei, Zhaohui; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Dai, Hong; Jiao, Shunchang; Wang, Jie; Liang, Li; Zhang, Weimin; Sun, Yan

2013-09-01

Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

What do patients with urothelial cancer know about the association of their tumor disease with smoking habits? Results of a German survey study

PubMed Central

Fritsche, Hans-Martin; Gilfrich, Christian; Dombrowski, Mirja; Maurer, Odilo; Spachmann, Philipp; Kumar, Manju Ganesh; Bjurlin, Marc; Burger, Maximilian; Brookman-May, Sabine

2018-01-01

Purpose Smoking represents a primary risk factor for the development of urothelial carcinoma (UC) and a relevant factor impacting UC-specific prognosis. Data on the accordant knowledge of UC-patients in this regard and the significance of physicians in the education of UC-patients is limited. Materials and Methods Eighty-eight UC-patients were enrolled in a 23-items-survey-study aimed to analyse patient knowledge and awareness of their tumor disease with smoking along with physician smoking cessation counselling. Results The median age of the study patients was 69 years; 26.1% (n=23), 46.6% (n=41), and 27.3% (n=24), respectively, were non-smokers, previous, and active smokers. Exactly 50% of active smokers reported a previous communication with a physician about the association of smoking and their tumor disease; however, only 25.0% were aware of smoking as main risk factor for UC development. Merely 33% of the active smokers had been prompted directly by their physicians to quit smoking. About 42% of active smokers had received the information that maintaining smoking could result in a tumor-specific impairment of their prognosis. Closely 29% of active and about 5% of previous smokers (during the time-period of active smoking) had been offered support from physicians for smoking cessation. No association was found between smoking anamnesis (p=0.574) and pack-years (p=0.912), respectively, and tumor stage of UC. Conclusions The results of this study suggest that the medical conversation of physicians with UC-patients about the adverse significance of smoking is limited. Implementation of structured educational programs for smoking cessation may be an opportunity to further enhance comprehensive cancer care. PMID:29520384

Different impact of aspirin on renal progression in patients with predialysis advanced chronic kidney disease with or without previous stroke.

PubMed

Hsiao, Kuang-Chih; Huang, Jing-Yang; Lee, Chun-Te; Hung, Tung-Wei; Liaw, Yung-Po; Chang, Horng-Rong

2017-04-01

The benefit of reducing the risk of stroke against increasing the risk of renal progression associated with antiplatelet therapy in patients with advanced chronic kidney disease (CKD) is controversial. We enrolled 1301 adult patients with advanced CKD treated with erythropoiesis stimulating agents from January 1, 2002 to June 30, 2009 from the 2005 Longitudinal Health Insurance Database in Taiwan. All of the patients were followed until the development of the primary or secondary endpoints, or the end of the study (December 31, 2011). The primary endpoint was the development of ischemic stroke, and the secondary endpoints included hospitalization for bleeding events, cardiovascular mortality, all-cause mortality, and renal failure. The adjusted cumulative probability of events was calculated using multivariate Cox proportional regression analysis. Adjusted survival curves showed that the usage of aspirin was not associated with ischemic stroke, hospitalization for bleeding events, cardiovascular mortality or all-cause mortality, however, it was significantly associated with renal failure. In subgroup analysis, aspirin use was associated with renal failure in the patients with no history of stroke (HR, 1.41; 95% CI, 1.14-1.73), and there was a borderline interaction between previous stroke and the use of aspirin on renal failure (interaction p=0.0565). There was no significant benefit in preventing ischemic stroke in the patients with advanced CKD who received aspirin therapy. Furthermore, the use of aspirin was associated with the risk of renal failure in the patients with advanced CKD without previous stroke. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Novel infrastructure for sepsis biomarker research in critically ill neonates and children.

PubMed

Juskewitch, Justin E; Enders, Felicity T; Abraham, Roshini S; Huskins, W Charles

2013-02-01

Sepsis biomarker research requires an infrastructure to identify septic patients efficiently and to collect and store specimens properly. We developed a novel infrastructure to study biomarkers of sepsis in children. Patients in pediatric and neonatal intensive care units were enrolled prospectively; enrollment information was stored in a secure, remotely accessible database. Researchers were notified of electronic medical record (EMR) orders for blood cultures (a surrogate for a diagnostic evaluation of suspected sepsis) by a page triggered by the order. Staff confirmed patient enrollment and remotely submitted an EMR order for collection of study specimens simultaneous with the blood culture. Specimens were processed and stored by a mobile clinical research unit. Over 2 years, 2029 patients were admitted; 138 were enrolled. Staff received pages for 95% of blood cultures collected from enrolled patients. The median time between the blood culture order and collection was 34 minutes (range 9-241). Study specimens were collected simultaneously with 41 blood cultures. The median times between specimen collection and storage for flow cytometry and cytokine analysis were 33 minutes (range 0-82) and 52 minutes (range 28-98), respectively. This novel infrastructure facilitated prompt, proper collection and storage of specimens for sepsis biomarker analysis. © 2013 Wiley Periodicals, Inc.

Nurse and patient factors that influence nursing time in chest tube management early after open heart surgery: A descriptive, correlational study.

PubMed

Cook, Myra; Idzior, Laura; Bena, James F; Albert, Nancy M

2017-10-01

Determine nurse characteristics and patient factors that affect nurses' time in managing chest tubes in the first 24-hours of critical-care stay. Prospective, descriptive. Cardiovascular critical-care nurses and post-operative heart surgery patients with chest tubes were enrolled from a single center in Ohio. Nurses completed case report forms about themselves, comfort and time in managing chest tubes, chest tube placement and management factors. Analysis included correlational and comparative statistics; Bonferroni corrections were applied, as appropriate. Of 29 nurses, 86.2% were very comfortable managing chest tubes and oozing/non-secure dressings, but only 41.4% were very comfortable managing clogged chest tubes. Of 364 patients, mean age was 63.1 (±12.3) years and 36% had previous heart surgery. Total minutes of chest tube management was higher with≥3 chest tubes, tube size <28 French, and when both mediastinal and pleural tubes were present (all p<0.001). In the first 4-hours, time spent on chest tubes was higher when patients had previous cardiac surgeries (p≤0.002), heart failure (p<0.001), preoperative anticoagulant medications (p=0.031) and reoperation for postoperative bleeding/tamponade (p=0.005). Time to manage chest tubes can be anticipated by patient characteristics. Nurse comfort with chest tube-related tasks affected time spent on chest tube management. Published by Elsevier Ltd.

“Design characteristics of the CORRONA CERTAIN study: a comparative effectiveness study of biologic agents for rheumatoid arthritis patients”

PubMed Central

2014-01-01

Background Comparative effectiveness research has recently attracted considerable attention. The Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) is an ongoing prospective cohort study of adult patients with Rheumatoid Arthritis (RA). Methods/Design CERTAIN uses the existing Consortium of Rheumatology Researchers of North America (CORRONA) network of participating private and academic sites in order to recruit patients fulfilling the 1987 ACR criteria that have at least moderate disease activity. Patients starting or switching biologic agents either anti-TNF therapy or a non anti-TNF biologic are eligible for enrollment, depending on the treatment selected by their physician. Enrollment is expected to be completed by March of 2014, and 2711 patients will participate in the study. As of October 7th 2013, 2234 patients have been enrolled. Patient visits and laboratory blood work are mandated every three months for one year. Safety data is collected through one year and beyond. The primary comparative effectiveness endpoint is attainment of low RA disease activity at one year among patients who have been exposed to at least one prior TNF-α inhibitor agent prior to enrollment. Multiple secondary effectiveness and safety endpoints will be addressed by investigating the entire population enrolled (naïve and biologic experienced). Discussion The unique design features of CERTAIN will inform comparative effectiveness and safety questions for choosing biologic agents for the management of RA. PMID:24690143

Newly Diagnosed Hepatitis C in the US Commercially Insured Population Before and After the 2012 Implementation of Expanded Screening Guidelines.

PubMed

Pyenson, Bruce S; Dieguez, Gabriela; Ferro, Christine; Mavinkurve, Maushumi; Gonzalez, Yuri Sanchez

2018-02-01

In the United States in 2014, more than 3 million individuals were estimated to have chronic hepatitis C virus (HCV) infection, including many undiagnosed individuals. In 2012, the Centers for Disease Control and Prevention expanded its HCV testing recommendations to target all adults born between 1945 and 1965, in addition to at-risk individuals, which has led to an increase in newly diagnosed patients. Few studies have explored the medical cost or clinical status of patients who are newly diagnosed with HCV. To compare the demographics, comorbidities, and medical costs of patients who are newly diagnosed and those who were previously diagnosed with HCV infection. We conducted a retrospective study using 2013 claims data from the Truven Health MarketScan Commercial database to compare patients newly diagnosed with HCV infection in 2013 and patients who were diagnosed before 2013. The patients were divided into 2 cohorts based on the time of diagnosis before and after 2013. All patients were classified by disease stage and by comorbidities, and were required to have continuous health plan enrollment between January 2010 and December 2013. The full-year costs were tabulated for every patient, regardless of the date of diagnosis. Of the 9193 patients with an HCV diagnosis in 2013 in the database, approximately 26% (N = 2428) were newly diagnosed in 2013, of whom 12% (N = 299) had advanced-stage HCV. The average age of the newly diagnosed patients was 49.5 years versus 54.1 years for previously diagnosed patients. Patients who were previously diagnosed had a higher prevalence of HIV, diabetes, and more severe cancers than patients who were newly diagnosed with HCV. Patients who were newly diagnosed with HCV had a higher prevalence of acute liver failure and drug-induced psychosis. The average annual per-patient per-month (PPPM) medical costs for both groups was approximately $2200 in 2013. The annual medical cost for a patient who was newly diagnosed increased sharply in the year before diagnosis, from approximately $588 PPPM for the 3 years before the diagnosis to approximately $854 PPPM in the year before diagnosis. In 2013, the healthcare costs of patients who were newly diagnosed with HCV were similar in their first year of diagnosis to the costs of patients who had been diagnosed previously, although patients who were previously diagnosed had more advanced-stage disease. Patients who were newly diagnosed had 3-fold the healthcare costs in their first year of diagnosis versus the costs in the 3 years before their diagnosis.

Urinary NGAL deficiency in recurrent urinary tract infections.

PubMed

Forster, Catherine S; Johnson, Kathryn; Patel, Viral; Wax, Rebecca; Rodig, Nancy; Barasch, Jonathan; Bachur, Richard; Lee, Richard S

2017-06-01

Children with recurrent urinary tract infections (rUTI) often show no identifiable cause of their infections. Neutrophil gelatinase-associated lipocalin (NGAL) is known to be upregulated within the uroepithelium and kidney of patients with UTI and exhibits a localized bacteriostatic effect through iron chelation. We hypothesize that some patients with rUTI without an identifiable cause of their recurrent infections have locally deficient NGAL production. We therefore explored whether a lack of NGAL production may be a factor in the pathogenesis of rUTI. Patients seen in the urology clinic for rUTI who were <21 years of age were enrolled. Patients were excluded if they had UTI at the time of enrollment, evidence of renal disease, decreased renal function, known anatomic abnormality of the genitourinary tract, or other reasons that predispose to UTI, such as neurogenic bladder, the need for intermittent catheterization, or unrepaired posterior urethral valves. Control patients were healthy children enrolled from the emergency department with no history of UTI or renal dysfunction, normal urinalysis at the time of enrollment, and presenting no diagnosis associated with increased NGAL levels, such as acute kidney injury or infection. NGAL was measured by immunoblot. Fifteen cases and controls were enrolled. Median urinary NGAL levels were significantly decreased in rUTI patients compared with controls [15 (14-29) ng/ml vs 30 (27-61) ng/ml; p = 0.002)] Although comparatively diminished, measurable NGAL levels were present in all patients with rUTI. Urinary NGAL is significantly decreased in patients with compared with patients without rUTI. These data suggest that some patients with rUTI may be predisposed to UTI because of a relative local deficiency in urinary NGAL production.

Can a tailored knowledge translation strategy improve short term outcomes? A pilot study to increase compliance with bowel preparation recommendations in general surgery.

PubMed

Eskicioglu, Cagla; Gagliardi, Anna; Fenech, Darlene S; Victor, Charles J; McLeod, Robin S

2011-07-01

Previous studies have shown that practices supported by level I evidence may take up to 20 years before they are adopted. Although mechanical bowel preparation (MBP) has been a routine practice in colorectal surgery, there is strong evidence dating back to the early 1990s suggesting that in most patients MBP before elective colorectal surgery is not required. The objective of this study was to determine if surgical practices pertaining to bowel preparation could be altered using a tailored knowledge translation strategy. A multi-faceted strategy including guideline development, consensus, education by opinion leaders, audit and feedback, and reminder cards was used in this before-after study. The primary outcome was compliance with the recommendations presented in the guideline regarding MBP, normal diet on the day prior to surgery, and enemas. Two-hundred eighty-two patients were enrolled in the study with 111 enrolled before the intervention and 171 enrolled after the intervention. Demographic and clinical characteristics between the 2 groups were similar. Overall, there was a 7.8% increase in compliance with MBP recommendations (81.1% vs 88.4%, P = .038), a 10.2% increase in compliance with diet recommendations (45.6% vs 55.8%, P = .080), and a 5.6% increase in compliance with enema recommendations (88.5% vs 94.2%, P < .001). The results of this study reveal that a tailored, multi-faceted knowledge translation strategy is effective in changing surgeon behavior. Copyright © 2011 Mosby, Inc. All rights reserved.

Sedation protocol with fasting and shorter sleep leads to magnetic resonance imaging success.

PubMed

Kimiya, Takahisa; Sekiguchi, Shinichiro; Yagihashi, Tatsuhiko; Arai, Mie; Takahashi, Hirotaka; Takahashi, Takao

2017-10-01

Young children undergoing magnetic resonance imaging (MRI) require sedation. In June 2013, Tokyo Metropolitan Ohtsuka Hospital (TMOH) introduced an oral sedation protocol for young children undergoing MRI; the protocol included instructions on fasting before sedation, and recommended a shorter duration of sleep the night before MRI. We compared the MRI success rate before and after the introduction of this protocol. The eligible subjects were children under 3 years old who underwent MRI by appointment at TMOH between October 2012 and March 2014, under sedation with triclofos sodium. All those who underwent MRI in or after June 2013 were enrolled prospectively as a post-protocol group. All patients who underwent MRI before June 2013 were enrolled retrospectively as a pre-protocol group, with data collected from chart review. Seventy-four patients were enrolled in the post-protocol group, and 42 in the pre-protocol group. The MRI success rate was significantly higher in the post-protocol group than in the pre-protocol group (98.7% vs 88.1%), as was the rate of on-time starting of MRI (86.5% vs 71.4%). The post-protocol group woke up earlier on the day of examination (6:18 a.m. vs 6:43 a.m.), resulting in a significantly longer time between awakening and the beginning of sedation (289.8 min vs 265.9 min), and a significantly shorter average duration of sleep on the previous night (504.8 min vs 532.3 min). Implementation of a hospital-wide sedation protocol for young children undergoing MRI significantly improved the MRI success rate. © 2017 Japan Pediatric Society.

Statistical Abstract of Tennessee Higher Education, 1982-1983.

ERIC Educational Resources Information Center

Tennessee Higher Education Commission, Nashville.

Statistics are presented on higher education in Tennessee for 1982-1983 and previous years. Attention is directed to: enrollment trends, undergraduate transfers, student finances, degrees conferred, faculty salaries, institutional finances, and actions of the Tennessee Higher Education Commission. Tables include: student headcount enrollment by…

Statistical Abstract of Tennessee Higher Education, 1984-85.

ERIC Educational Resources Information Center

Tennessee Higher Education Commission, Nashville.

Statistics are presented on higher education in Tennessee for 1984-1985 and previous years. Attention is directed to: enrollment trends, undergraduate transfers, student finances, degrees conferred, faculty salaries, institutional finances, and actions of the Tennessee Higher Education Commission. Tables include: student headcount enrollment by…

Social disparities in Disease Management Programmes for coronary heart disease in Germany: a cross-classified multilevel analysis.

PubMed

Bozorgmehr, Kayvan; Maier, Werner; Brenner, Hermann; Saum, Kai-Uwe; Stock, Christian; Miksch, Antje; Holleczek, Bernd; Szecsenyi, Joachim; Razum, Oliver

2015-11-01

Disease Management Programmes (DMPs) aim to improve effectiveness and equity of care but may suffer from selective enrolment. We analysed social disparities in DMP enrolment among elderly patients with coronary heart disease (CHD) in Germany, taking into account contextual effects at municipality and primary care practice levels. Cross-sectional analysis of effects of educational attainment and regional deprivation on physician-reported DMP enrolment in a subsample of a large population-based cohort study in Germany, adjusting for individual-level, practice-level and area-level variables. We calculated OR and their 95% CIs (95% CI) in cross-classified, multilevel logistic regression models. Among N=1280 individuals with CHD (37.3% women), DMP enrolment rates were 22.2% (women) and 35% (men). The odds of DMP enrolment were significantly higher for male patients (OR=1.98 (1.50 to 2.62)), even after adjustment for potential confounding by individual-level, practice-level and area-level variables (range: OR=1.60 (1.08 to 2.36) to 2.16 (1.57 to 2.98)). Educational attainment was not significantly associated with DMP enrolment. Compared to patients living in least-deprived municipalities, the adjusted propensity of DMP enrolment was statistically significantly lower for patients living in medium-deprived municipalities (OR=0.41 (0.24 to 0.71)), and it also tended to be lower for patients living in the most-deprived municipalities (OR=0.70 (0.40 to 1.21)). Models controlling for the social situation (instead of health-related behaviour) yielded comparable effect estimates (medium-deprived/most-deprived vs least-deprived areas: OR=0.45 (0.26 to 0.78)/OR=0.68 (0.33 to 1.19)). Controlling for differences in comorbidity attenuated the deprivation effect estimates. We found evidence for marked gender, but not educational disparities in DMP enrolment among patients with CHD. Small-area deprivation was associated with DMP enrolment, but the effects were partly explained by differences in comorbidity. Future studies on DMPs should consider contextual effects when analysing programme effectiveness or impacts on equity and efficiency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

What about money? Effect of small monetary incentives on enrollment, retention, and motivation to change behaviour in an HIV/STD prevention counselling intervention. The Project RESPECT Study Group.

PubMed

Kamb, M L; Rhodes, F; Hoxworth, T; Rogers, J; Lentz, A; Kent, C; MacGowen, R; Peterman, T A

1998-08-01

We studied the effect of small monetary incentives and non-monetary incentives of similar value on enrollment and participation in clinic based HIV/STD prevention counselling. We examined incident STDs to try to assess whether participants offered money may be less motivated to change risky behaviours than those offered other incentives. Patients from five US STD clinics were invited to enroll in a multisession risk reduction counselling intervention and, based on their enrollment date, were offered either $15 for each additional session or non-monetary incentives worth $15. The two incentive groups were compared on participants' enrollment, completion of intervention sessions, and new STDs over the 24 months after enrollment. Of 648 patients offered money, 198 (31%) enrolled compared with 160 (23%) of 696 patients offered other incentives (p = 0.002). Enrollees in the two incentive groups had similar baseline characteristics, including condom use. Of the 198 participants offered money, 109 (55%) completed all sessions compared with 59 (37%) of the participants offered other incentives (p < 0.0001). Comparing those offered money with those offered other incentives STD rates were similar after 6, 12, and 24 months. Small monetary incentives enhanced enrollment and participation compared with other incentives of similar value. Regardless of incentive offered, participants had similar post-enrollment STD rates, suggesting that the type of incentive does not adversely affect motivation to change behaviour. Money may be useful in encouraging high risk individuals to participate in and complete counselling or other public health interventions.

Roster of Physics Departments with Enrollment and Degree Data, 2016: Results from the 2016 Survey of Enrollments and Degrees. Roster

ERIC Educational Resources Information Center

Nicholson, Starr; Mulvey, Patrick J.

2017-01-01

The physics bachelor's class of 2016 represents yet another all-time high. There were 8,432 bachelor's degrees conferred, an increase of 4% from the previous year and a 131% increase from the recent low in 1999. First-year graduate physics student enrollments have remained at about 3,200 students for the last 5 years. The number of physics PhDs…

Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.

PubMed

Shaverdian, Narek; Lisberg, Aaron E; Bornazyan, Krikor; Veruttipong, Darlene; Goldman, Jonathan W; Formenti, Silvia C; Garon, Edward B; Lee, Percy

2017-07-01

Preclinical studies have found radiotherapy enhances antitumour immune responses. We aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab. We assessed patients with advanced NSCLC treated on the phase 1 KEYNOTE-001 trial at a single institution (University of California, Los Angeles, CA, USA). Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 1 or less, had adequate organ function, and no history of pneumonitis. Patients received pembrolizumab at a dose of either 2 mg/kg of bodyweight or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks, until disease progression, unacceptable toxicity, or other protocol-defined reasons for discontinuation. Disease response and pulmonary toxicity were prospectively assessed by Immune-related Response Criteria and Common Terminology Criteria for Adverse Events version 4.0. The primary objective of the KEYNOTE-001 trial was to assess the safety, side-effect profile, and antitumour activity of pembrolizumab. For our secondary analysis, patients were divided into subgroups to compare patients who previously received radiotherapy with patients who had not. Our primary objective was to determine whether previous radiotherapy affected progression-free survival, overall survival, and pulmonary toxicity in the intention-to-treat population. The KEYNOTE-001 trial was registered with ClinicalTrials.gov, number NCT01295827. Between May 22, 2012, and July 11, 2014, 98 patients were enrolled and received their first cycle of pembrolizumab. One patient was lost to follow-up. 42 (43%) of 97 patients had previously received any radiotherapy for the treatment of NSCLC before the first cycle of pembrolizumab. 38 (39%) of 97 patients received extracranial radiotherapy and 24 (25%) of 97 patients received thoracic radiotherapy. Median follow-up for surviving patients was 32·5 months (IQR 29·8-34·1). Progression-free survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (hazard ratio [HR] 0·56 [95% CI 0·34-0·91], p=0·019; median progression-free survival 4·4 months [95% CI 2·1-8·6] vs 2·1 months [1·6-2·3]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (HR 0·50 [0·30-0·84], p=0·0084; median progression-free survival 6·3 months [95% CI 2·1-10·4] vs 2·0 months [1·8-2·1]). Overall survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (HR 0·58 [95% CI 0·36-0·94], p=0·026; median overall survival 10·7 months [95% CI 6·5-18·9] vs 5·3 months [2·7-7·7]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (0·59 [95% CI 0·36-0·96], p=0·034; median overall survival 11·6 months [95% CI 6·5-20·5] vs 5·3 months [3·0-8·5]). 15 (63%) of 24 patients who had previously received thoracic radiotherapy had any recorded pulmonary toxicity versus 29 (40%) of 73 patients with no previous thoracic radiotherapy. Three (13%) patients with previous thoracic radiotherapy had treatment-related pulmonary toxicity compared with one (1%) of those without; frequency of grade 3 or worse treatment-related pulmonary toxicities was similar (one patient in each group). Our data suggest that previous treatment with radiotherapy in patients with advanced NSCLC results in longer progression-free survival and overall survival with pembrolizumab treatment than that seen in patients who did not have previous radiotherapy, with an acceptable safety profile. Further clinical trials investigating this combination are needed to determine the optimal treatment strategy for patients with advanced NSCLC. US National Institutes of Health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Feasibility and outcomes of screening for cardiovascular risk factors in the emergency department.

PubMed

Tan, Natalie; Taylor, David McDonald

2013-04-01

The present study aimed to determine the prevalence of undiagnosed and undertreated hypercholesterolaemia and hypertension (HT) among ED patients and to evaluate the effects of a formal referral back to the general practitioner (GP) for further management. This was a cross-sectional study of ED patients with follow up, if indicated. Patients aged ≥35 years, without substantial illness or communication difficulties, were enrolled. Data were collected using a researcher-administered questionnaire, a point-of-care Accutrend® Plus System machine (Roche Diagnostic Australia Pty Ltd, Castle Hill, NSW, Australia) and digital sphygmomanometer. Patients with total cholesterol (TC) ≥6.0 mmol/L and/or BP ≥140/90 were given a referral letter and advised to consult their GP. The investigators made follow-up telephone calls 5 weeks later. Of 827 presentations, 534 patients were enrolled (mean age 56.7 ± 13.3 years, 300 [56.2%] male). One hundred and eleven patients (20.7%, 95% CI 17.5-24.5) had TC ≥6.0 mmol/L. Patients with/without elevated TC differed significantly (P < 0.05) in regard to age, gender, GP ownership and attendance, and previous screening. Sixty-six patients consulted with their GP. Thirty had their TC levels retested, 18 received dietary/lifestyle advice and four had lipid-lowering medication prescribed or adjusted. Ninety-six patients (18.0%, 95% CI 14.9-21.6) had HT. Whereas 53 consulted their GP, no action was taken in 43 cases. Investigations were ordered for three and nine had antihypertensive medication prescribed or adjusted. Substantial proportions of ED patients have undiagnosed and undertreated hypercholesterolaemia and/or HT. GP referral initiated interventions for many patients with hypercholesterolaemia, but fewer with HT. The ED has potential as a useful venue for the opportunistic screening of hypercholesterolaemia. © 2013 The Authors. EMA © 2013 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

The Utility of a Wireless Implantable Hemodynamic Monitoring System in Patients Requiring Mechanical Circulatory Support.

PubMed

Feldman, David S; Moazami, Nader; Adamson, Philip B; Vierecke, Juliane; Raval, Nir; Shreenivas, Satya; Cabuay, Barry M; Jimenez, Javier; Abraham, William T; O'Connell, John B; Naka, Yoshifumi

Proper timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients is not well established and is an area of intense interest. In addition, optimizing LVAD performance after implantation remains difficult and represents a significant clinical need. Implantable hemodynamic monitoring systems may provide physicians with the physiologic information necessary to improve the timing of LVAD implantation as well as LVAD performance when compared with current methods. The CardioMEMS Heart sensor Allows for Monitoirng of Pressures to Improve Outcomes in NYHA Class III heart failure patients (CHAMPION) Trial enrolled 550 previously hospitalized patients with New York Heart Association (NYHA) class III heart failure. All patients were implanted with a pulmonary artery (PA) pressure monitoring system and randomized to a treatment and control groups. In the treatment group, physicians used the hemodynamic information to make heart failure management decisions. This information was not available to physicians for the control group. During an average of 18 month randomized follow-up, 27 patients required LVAD implantation. At the time of PA pressure sensor implantation, patients ultimately requiring advanced therapy had higher PA pressures, lower systemic pressure, and similar cardiac output measurements. Treatment and control patients in the LVAD subgroup had similar clinical profiles at the time of enrollment. There was a trend toward a shorter length of time to LVAD implantation in the treatment group when hemodynamic information was available. After LVAD implantation, most treatment group patients continued to provide physicians with physiologic information from the hemodynamic monitoring system. As expected PA pressures declined significantly post LVAD implant in all patients, but the magnitude of decline was higher in patients with PA pressure monitoring. Implantable hemodynamic monitoring appeared to improve the timing of LVAD implantation as well as optimize LVAD performance when compared with current methods. Further studies are necessary to evaluate these findings in a prospective manner.

Exploration of adherence and patient experiences with DOACs one year after switching from vitamin-K antagonists- insights from the switching study.

PubMed

Bartoli-Abdou, John K; Patel, Jignesh P; Crawshaw, Jacob; Vadher, Bipin; Brown, Alison; Roberts, Lara N; Patel, Raj K; Arya, Roopen; Auyeung, Vivian

2018-02-01

Current UK and European guidelines recommend anticoagulated patients prescribed warfarin with time in therapeutic range (TTR) <65% be considered for DOAC therapy. There has been considerable concern that adherence with DOACs may be poor compared with warfarin. Little is known about the patient experience of switching from warfarin to DOAC and how patients manage their DOAC long term. Our aim was to conduct focus groups exploring patient's previous experiences with warfarin, their current experience with DOACs, their adherence to DOACs and the long-term service provision they envisage. Patients enrolled on the Switching Study who had been switched from warfarin to a DOAC >1year previously were invited to participate in focus groups. Two focus groups for atrial fibrillation (AF) and two for secondary prevention of venous thromboembolism (VTE) patients were held at anticoagulation clinics in South London, UK. Data was analysed using framework analysis to extract dominant themes. Five VTE patients and 15 AF patients attended the focus groups. Dominant themes that emerged were: indication specific anticoagulation prioritisation, warfarin as a necessary inconvenience, DOACs as the anticoagulant of choice, concerns regarding DOAC monitoring, high adherence to DOACs and desire for long-term access to specialist anticoagulation services. VTE patients prioritised anticoagulation over other therapies whereas AF patients did not. All participants reported high levels of adherence to DOACs. Patients derived confidence from long-term management in specialist anticoagulation clinics stating a preference to be managed in such a service. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial.

PubMed

Diéras, Véronique; Miles, David; Verma, Sunil; Pegram, Mark; Welslau, Manfred; Baselga, José; Krop, Ian E; Blackwell, Kim; Hoersch, Silke; Xu, Jin; Green, Marjorie; Gianni, Luca

2017-06-01

The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane. Enrolled patients were randomly assigned (1:1) via a hierarchical, dynamic randomisation scheme and an interactive voice response system to trastuzumab emtansine (3·6 mg/kg intravenously every 3 weeks) or control (capecitabine 1000 mg/m 2 self-administered orally twice daily on days 1-14 on each 21-day cycle, plus lapatinib 1250 mg orally once daily on days 1-21). Randomisation was stratified by world region (USA vs western Europe vs or other), number of previous chemotherapy regimens for unresectable, locally advanced, or metastatic disease (0 or 1 vs >1), and disease involvement (visceral vs non-visceral). The coprimary efficacy endpoints were progression-free survival (per independent review committee assessment) and overall survival. Efficacy was analysed in the intention-to-treat population; safety was analysed in all patients who received at least one dose of study treatment, with patients analysed according to the treatment actually received. On May 30, 2012, the study protocol was amended to allow crossover from control to trastuzumab emtansine after the second interim overall survival analysis crossed the prespecified overall survival efficacy boundary. This study is registered with ClinicalTrials.gov, number NCT00829166. Between Feb 23, 2009, and Oct 13, 2011, 991 eligible patients were enrolled and randomly assigned to either trastuzumab emtansine (n=495) or capecitabine and lapatinib (control; n=496). In this final descriptive analysis, median overall survival was longer with trastuzumab emtansine than with control (29·9 months [95% CI 26·3-34·1] vs 25·9 months [95% CI 22·7-28·3]; hazard ratio 0·75 [95% CI 0·64-0·88]). 136 (27%) of 496 patients crossed over from control to trastuzumab emtansine after the second interim overall survival analysis (median follow-up duration 24·1 months [IQR 19·5-26·1]). Of those patients originally randomly assigned to trastuzumab emtansine, 254 (51%) of 495 received capecitabine and 241 [49%] of 495 received lapatinib (separately or in combination) after study drug discontinuation. In the safety population (488 patients treated with capecitabine plus lapatinib, 490 patients treated with trastuzumab emtansine), fewer grade 3 or worse adverse events occurred with trastuzumab emtansine (233 [48%] of 490) than with capecitabine plus lapatinib control treatment (291 [60%] of 488). In the control group, the most frequently reported grade 3 or worse adverse events were diarrhoea (103 [21%] of 488 patients) followed by palmar-plantar erythrodysaesthesia syndrome (87 [18%]), and vomiting (24 [5%]). The safety profile of trastuzumab emtansine was similar to that reported previously; the most frequently reported grade 3 or worse adverse events in the trastuzumab emtansine group were thrombocytopenia (70 [14%] of 490), increased aspartate aminotransferase levels (22 [5%]), and anaemia (19 [4%]). Nine patients died from adverse events; five of these deaths were judged to be related to treatment (two in the control group [coronary artery disease and multiorgan failure] and three in the trastuzumab emtansine group [metabolic encephalopathy, neutropenic sepsis, and acute myeloid leukaemia]). This descriptive analysis of final overall survival in the EMILIA trial shows that trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive metastatic breast cancer even in the presence of crossover treatment. The safety profile was similar to that reported in previous analyses, reaffirming trastuzumab emtansine as an efficacious and tolerable treatment in this patient population. F Hoffmann-La Roche/Genentech. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mixed-Methods Analysis of Factors Impacting Use of a Postoperative mHealth App

PubMed Central

Scott, Aaron R; Alore, Elizabeth A; Naik, Aanand D; Berger, David H

2017-01-01

Background Limited communication and care coordination following discharge from hospitals may contribute to surgical complications. Smartphone apps offer a novel mechanism for communication and care coordination. However, factors which may affect patient app use in a postoperative, at-home setting are poorly understood. Objective The objectives of this study were to (1) gauge interest in smartphone app use among patients after colorectal surgery and (2) better understand factors affecting patient app use in a postoperative, at-home setting. Methods A prospective feasibility study was performed at a hospital that principally serves low socioeconomic status patients. After colorectal surgery, patients were enrolled and given a smartphone app, which uses previously validated content to provide symptom-based recommendations. Patients were instructed to use the app daily for 14 days after discharge. Demographics and usability data were collected at enrollment. Usability was measured with the System Usability Scale (SUS). At follow-up, the SUS was repeated and patients underwent a structured interview covering ease of use, willingness to use, and utility of use. Two members of the research team independently reviewed the field notes from follow-up interviews and extracted the most consistent themes. Chart and app log reviews identified clinical endpoints. Results We screened 115 patients, enrolled 20 patients (17.4%), and completed follow-up interviews with 17 patients (85%). Reasons for nonenrollment included: failure to meet inclusion criteria (47/115, 40.9%), declined to participate (26/115, 22.6%), and other reasons (22/115, 19.1%). There was no difference in patient ratings between usability at first-use and after extended use, with SUS scores greater than the 95th percentile at both time points. Despite high usability ratings, 6/20 (30%) of patients never used the app at home after hospital discharge and 2/20 (10%) only used the app once. Interviews revealed three themes related to app use: (1) patient-related barriers could prevent use even though the app had high usability scores; (2) patients viewed the app as a second opinion, rather than a primary source of information; and (3) many patients viewed the app as an external burden. Conclusions Use patterns in this study, and response rates after prompts to contact the operative team, suggest that apps need to be highly engaging to be adopted by patients. The growing penetration of smartphones and the proliferation of app-based interventions are unlikely to improve care coordination and communication, unless apps address the barriers and patient perceptions identified in this study. This study shows that high usability alone is not sufficient to motivate patients to use smartphone apps in the postoperative period. PMID:28179215

Enrollment into a time sensitive clinical study in the critical care setting: results from computerized septic shock sniffer implementation.

PubMed

Herasevich, Vitaly; Pieper, Matthew S; Pulido, Juan; Gajic, Ognjen

2011-01-01

Recruitment of patients into time sensitive clinical trials in intensive care units (ICU) poses a significant challenge. Enrollment is limited by delayed recognition and late notification of research personnel. The objective of the present study was to evaluate the effectiveness of the implementation of electronic screening (septic shock sniffer) regarding enrollment into a time sensitive (24 h after onset) clinical study of echocardiography in severe sepsis and septic shock. We developed and tested a near-real time computerized alert system, the septic shock sniffer, based on established severe sepsis/septic shock diagnostic criteria. A sniffer scanned patients' data in the electronic medical records and notified the research coordinator on call through an institutional paging system of potentially eligible patients. The performance of the septic shock sniffer was assessed. The septic shock sniffer performed well with a positive predictive value of 34%. Electronic screening doubled enrollment, with 68 of 4460 ICU admissions enrolled during the 9 months after implementation versus 37 of 4149 ICU admissions before sniffer implementation (p<0.05). Efficiency was limited by study coordinator availability (not available at nights or weekends). Automated electronic medical records screening improves the efficiency of enrollment and should be a routine tool for the recruitment of patients into time sensitive clinical trials in the ICU setting.

Enrollment into a time sensitive clinical study in the critical care setting: results from computerized septic shock sniffer implementation

PubMed Central

Pieper, Matthew S; Pulido, Juan; Gajic, Ognjen

2011-01-01

Objective Recruitment of patients into time sensitive clinical trials in intensive care units (ICU) poses a significant challenge. Enrollment is limited by delayed recognition and late notification of research personnel. The objective of the present study was to evaluate the effectiveness of the implementation of electronic screening (septic shock sniffer) regarding enrollment into a time sensitive (24 h after onset) clinical study of echocardiography in severe sepsis and septic shock. Design We developed and tested a near-real time computerized alert system, the septic shock sniffer, based on established severe sepsis/septic shock diagnostic criteria. A sniffer scanned patients' data in the electronic medical records and notified the research coordinator on call through an institutional paging system of potentially eligible patients. Measurement The performance of the septic shock sniffer was assessed. Results The septic shock sniffer performed well with a positive predictive value of 34%. Electronic screening doubled enrollment, with 68 of 4460 ICU admissions enrolled during the 9 months after implementation versus 37 of 4149 ICU admissions before sniffer implementation (p<0.05). Efficiency was limited by study coordinator availability (not available at nights or weekends). Conclusions Automated electronic medical records screening improves the efficiency of enrollment and should be a routine tool for the recruitment of patients into time sensitive clinical trials in the ICU setting. PMID:21508415

Does Participation in a Randomized Clinical Trial Change Outcomes? An Evaluation of Patients Not Enrolled in the SPRINT Trial.

PubMed

Lin, Carol Alice; Bhandari, Mohit; Guyatt, Gordon; Walter, Stephen D; Schemitsch, Emil H; Swiontkowski, Marc; Sanders, David; Tornetta, Paul

2016-03-01

To determine the extent to which knowledge from clinical trial protocols is transferred to nonparticipating patients. Retrospective review of prospectively collected data from a large clinical trial. Six level-1 international trauma centers. We compared rates and timing of reoperation in a subset of patients enrolled in the Study to Prospectively evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT) to concurrent patients who were eligible but not enrolled. This was a retrospective review of prospectively collected trial data. The records of 6 of the original SPRINT centers were searched for non-SPRINT patients who underwent intramedullary nailing of a closed tibial fracture. The rate and timing of reoperation were compared. A P < 0.05 was considered significant. One hundred fourteen non-SPRINT patients were compared with 328 patients enrolled in SPRINT from those same sites. There were 7 reoperations (6.1%) in non-SPRINT patients versus 18 (5.2%) in SPRINT patients [odds ratio (OR) 1.19, 95% confidence interval (CI) 0.41 to 3.13; P = 0.811]. There was no difference in the time to reoperation between the SPRINT and non-SPRINT patients (6.2 vs. 6.8 months, 95% CI of the difference -3.8 to 2.6; P = 0.685) or in the proportion of patients who underwent reoperation before 6 months (29% vs. 43%; OR 1.75; 95% CI 0.18 to 15.41; P = 0.647). Patients not enrolled in SPRINT had similarly low rates of reoperation for nonunion, and the average time to reoperation for both groups was longer than 6 months. A 6-month waiting period may have allowed slow-to-heal fractures adequate time to heal, thereby reducing the rate of diagnosis of nonunion. As such, this waiting period could contribute to lower-than-expected reoperation rates for nonunion. It is possible that clinical trials may beneficially influence the care of nonenrolled patients.

HCV viraemia in anti-HCV-negative haemodialysis patients: Do we need HCV RNA detection test?

PubMed

Papadopoulos, Nikolaos; Griveas, Ioannis; Sveroni, Eirini; Argiana, Vasiliki; Kalliaropoulos, Antonios; Martinez-Gonzalez, Beatriz; Deutsch, Melanie

2018-03-01

Hepatitis C virus (HCV) infection is still common among dialysis patients, but the natural history of HCV in this group is not completely understood. The KDIGO HCV guidelines of 2009 recommend that chronic haemodialysis patients be screened for HCV antibody upon admission to the dialysis clinic and every 6 months thereafter if susceptible to HCV infection. However, previous studies have shown the presence of HCV viraemia in anti-HCV-negative haemodialysis patients as up to 22%. To evaluate the presence of HCV viraemia, using HCV RNA detection, among anti-HCV-negative haemodialysis patients from a tertiary dialysis unit in Athens. We enrolled 41 anti-HCV-negative haemodialysis patients diagnosed with third-generation enzyme immunoassay. HCV viraemia was evaluated using a sensitive (cut-off: 12 IU/mL) reverse transcriptase polymerase chain reaction (COBAS AmpliPrep/TaqMan system) for HCV RNA. None of the 41 anti-HCV-negative haemodialysis patients were shown to be viraemic. Routine HCV RNA testing appears not to be necessary in anti-HCV-negative haemodialysis patients.

Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers

PubMed Central

Yap, Timothy A.; Yan, Li; Patnaik, Amita; Tunariu, Nina; Biondo, Andrea; Fearen, Ivy; Papadopoulos, Kyriakos P.; Olmos, David; Baird, Richard; Delgado, Liliana; Tetteh, Ernestina; Beckman, Robert A.; Lupinacci, Lisa; Riisnaes, Ruth; Decordova, Shaun; Heaton, Simon P.; Swales, Karen; deSouza, Nandita M; Leach, Martin O.; Garrett, Michelle D.; Sullivan, Daniel M.; de Bono, Johann S.; Tolcher, Anthony W.

2014-01-01

Purpose Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60mg on alternate days (QOD). Due to a long half-life (60-80h), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Experimental Design Patients with advanced cancers were enrolled onto a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers, and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy and intrinsic susceptibility-weighted MRI. Results Seventy-one patients were enrolled; 38 patients had 60mg MK-2206 QOD, while 33 received MK-2206 at 90mg, 135mg, 150mg, 200mg, 250mg, and 300mg QW. The QW MK-2206 MTD was established at 200mg following dose-limiting rash at 250mg and 300mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially-obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial. Conclusions MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200mg QW is currently used in phase II MK-2206 monotherapy and combination studies. PMID:25239610

Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial.

PubMed

Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

2017-01-01

Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied. The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients. Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders. The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283). The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

An open-label extension long-term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan.

PubMed

Ichikawa, Hironobu; Hiratani, Michio; Yasuhara, Akihiro; Tsujii, Noa; Oshimo, Takashi; Ono, Hiroaki; Tadori, Yoshihiro

2018-02-01

The purpose of this study was to evaluate the long-term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6-17 years) with autistic disorder (AD) in Japan. In this open-label extension study, patients who had completed a previous randomized, double-blind, placebo-controlled 8-week study were enrolled and were flexibly dosed with aripiprazole (1-15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan. Seventy (81%) out of 86 enrolled patients completed week-48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment-emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was -6.3 in prior placebo patients and -2.6 in prior aripiprazole patients. Aripiprazole was generally safe, well tolerated, and effective in the long-term treatment of irritability associated with AD in Japanese pediatric patients. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Drug-related problems at discharge: results on the Spanish pharmacy discharge programme CONSULTENOS.

PubMed

López, Maángeles Pardo; Saliente, Ma Teresa Aznar; Company, Enrique Soler; Monsalve, Ana Garcia; Cueva, Marta Aparício; Domingo, Elena Arroyo; Hernández, Monica Montero; Carrión, Carmen Carrión; Martí, Monica Climente; Querejeta, Nuria Bujaldón; Blasco, Joaquín Borrás; Milá, Amparo Rocher

2010-10-01

The aim of this study was to describe the most common drug-related problems (DRPs) found after discharge, pharmacist interventions and their results for the patients enrolled on the CONSULTENOS programme. An observational, prospective, multicentre study was conducted to evaluate the results of a pharmaceutical care programme at discharge. Patients from 10 hospitals participating in the CONSULTENOS programme were enrolled. Pharmacists conducting this programme were newly graduated and worked under the supervision of a pharmacy staff member; only two pharmacists had previous hospital pharmacy experience. DRPs were identified and classified according to the Iaser methodology. Frequencies, types of DRP, interventions and outcomes were registered prospectively, at discharge and during a follow-up call 7 days after leaving the hospital. A total of 7711 patients were included in the study. DRPs were detected in 23.7% of the patients, with a total of 2120 DRPs (1788 at discharge and 332 in the follow-up). The most common problems identified at discharge were twofold: firstly the need of an additional treatment (34.1%) and secondly an unnecessary treatment (18.1%). In the follow-up phone call the most frequent DRPs were adverse effects (29.2%). Besides the standard educational interventions at discharge, 3313 extra interventions were performed, of which 85% were accepted. The outcomes for the patients were positive in 80% of the cases, although documentation with objective or subjective data was rare. DRPs occur frequently after patient discharge. A pharmaceutical care programme can identify and solve DRPs in this scenario. The clinical impact of the pharmacists' interventions should be better addressed. © 2010 The Authors. IJPP © 2010 Royal Pharmaceutical Society of Great Britain.

Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.

PubMed

Yap, Timothy A; Yan, Li; Patnaik, Amita; Tunariu, Nina; Biondo, Andrea; Fearen, Ivy; Papadopoulos, Kyriakos P; Olmos, David; Baird, Richard; Delgado, Liliana; Tetteh, Ernestina; Beckman, Robert A; Lupinacci, Lisa; Riisnaes, Ruth; Decordova, Shaun; Heaton, Simon P; Swales, Karen; deSouza, Nandita M; Leach, Martin O; Garrett, Michelle D; Sullivan, Daniel M; de Bono, Johann S; Tolcher, Anthony W

2014-11-15

Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60 mg on alternate days (QOD). Due to a long half-life (60-80 hours), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Patients with advanced cancers were enrolled in a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy, and intrinsic susceptibility-weighted MRI. A total of 71 patients were enrolled; 38 patients had 60 mg MK-2206 QOD, whereas 33 received MK-2206 at 90, 135, 150, 200, 250, and 300 mg QW. The QW MK-2206 MTD was established at 200 mg following dose-limiting rash at 250 and 300 mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial. Treatment with MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200 mg QW is currently used in phase II MK-2206 monotherapy and combination studies (NCT00670488). ©2014 American Association for Cancer Research.

Comparable pharmacodynamics, efficacy, and safety of linagliptin 5 mg among Japanese, Asian and white patients with type 2 diabetes.

PubMed

Sarashina, Akiko; Friedrich, Christian; Crowe, Susanne; Patel, Sanjay; Graefe-Mody, Ulrike; Hayashi, Naoyuki; Horie, Yoshiharu

2016-09-01

The efficacy and safety of drugs can vary between different races or ethnic populations because of differences in the relationship of dose to exposure, pharmacodynamic response or clinical efficacy and safety. In the present post-hoc analysis, we assessed the influence of race on the pharmacokinetics, pharmacodynamics, efficacy and safety of monotherapy with the dipeptidyl peptidase-4 inhibitor, linagliptin, in patients with type 2 diabetes enrolled in two comparable, previously reported randomized phase III trials. Study 1 (with a 12-week placebo-controlled phase) recruited Japanese patients only (linagliptin, n = 159; placebo, n = 80); study 2 (24-week trial) enrolled Asian (non-Japanese; linagliptin, n = 156; placebo, n = 76) and white patients (linagliptin, n = 180; placebo, n = 90). Linagliptin trough concentrations were equivalent across study and race groups, and were higher than half-maximal inhibitory concentration, resulting in dipeptidyl peptidase-4 inhibition >80% at trough. Linagliptin inhibited plasma dipeptidyl peptidase-4 activity to a similar degree in study 1 and study 2. Linagliptin reduced fasting plasma glucose concentrations by a similar magnitude across groups, leading to clinically relevant reductions in glycated hemoglobin in all groups. Glycated hemoglobin levels decreased to a slightly greater extent in study 1 (Japanese) and in Asian (non-Japanese) patients from study 2. Linagliptin had a favorable safety profile in each race group. Trough exposure, pharmacodynamic response, and efficacy and safety of linagliptin monotherapy were comparable among Japanese, Asian (non-Japanese) and white patients, confirming that the recommended 5-mg once-daily dose of linagliptin is appropriate for use among different race groups. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Characteristics That Predict Physician Participation in a Web-Based CME Activity: The MI-Plus Study

PubMed Central

Schoen, Michael J.; Tipton, Edmond F.; Houston, Thomas K.; Funkhouser, Ellen; Levine, Deborah A.; Estrada, Carlos A.; Allison, Jeroan J.; Williams, O. Dale; Kiefe, Catarina I.

2011-01-01

Introduction Physician use of the Internet for practice improvement has increased dramatically over the last decade, but research shows that many physicians choose not to participate. The current study investigated the association of specific physician characteristics with enrollment rates and intensity of participation in a specific Internet-delivered educational intervention to improve care to post–myocardial infarction (MI) patients. Methods Primary-care physicians were recruited for participation in a randomized controlled trial designed to compare effectiveness of an intervention Web site versus a control Web site in the management of adult chronic disease. Physicians were informed that the intervention focused on ambulatory post–myocardial infarction patients. Physician characteristics were obtained from a commercial vendor with data merged from the American Medical Association and Alabama State Licensing Board. Enrollment and Web use were tracked electronically. Results Out of a sample of 1337 eligible physicians, 177 (13.2%) enrolled in the study. Enrollment was higher for physicians with more post-MI patients (≥20 vs < 20 patients, 15.3% vs 9.3%, P = .002) and for those practicing in rural compared to urban areas (16.3% vs 12.1%, P = .046). Intensity of use of the Internet courses after initial enrollment was not predicted by physician characteristics in the current sample. Discussion Physicians with more post-MI patients and rural practice location were found to predict enrollment in an Internet-delivered continuing medical education (CME) intervention designed to improve care for post-MI patients. These factors predicted program interest but not program use. More research is needed to replicate these findings to investigate variables that determine physician engagement in Internet CME. PMID:19998447

Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

PubMed

Ghedini, Pietro; Bossert, I; Zanoni, L; Ceci, F; Graziani, T; Castellucci, P; Ambrosini, V; Massari, F; Nobili, E; Melotti, B; Musto, A; Zoboli, S; Antunovic, L; Kirienko, M; Chiti, A; Mosconi, C; Ardizzoni, A; Golfieri, R; Fanti, S; Nanni, C

2018-05-01

During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry.

PubMed

Guillevin, Loïc; Hunsche, Elke; Denton, Christopher P; Krieg, Thomas; Schwierin, Barbara; Rosenberg, Daniel; Matucci-Cerinic, Marco

2013-01-01

Digital ulcers (DUs) are frequent manifestations of systemic scleroderma (SSc). This study assessed functional limitations due to DUs among patients enrolled in the Digital Ulcer Outcome (DUO) Registry, an international, multicentre, observational registry of SSc patients with DU disease. Patients completed at enrolment a DU-specific functional assessment questionnaire with a 1-month recall period, measuring impairment in work and daily activities, and hours of help needed from others. Physician-reported clinical parameters were used to describe the population. For patients who completed at least part of the questionnaire, descriptive analyses were performed for overall results, and stratified by number of DUs at enrolment. This study included 2327 patients who completed at least part of the questionnaire. For patients with 0, 1-2, and ≥3 DUs at enrolment, mean overall work impairment during the prior month among employed/self-employed patients was 28%, 42%, and 48%, respectively. Across all included patients, ability to perform daily activities was impaired on average by 35%, 54%, and 63%, respectively. Patients required a mean of 2.0, 8.7, and 8.8 hours of paid help and 17.0, 35.9, and 63.7 hours of unpaid help, respectively, due to DUs in the prior month. Patients with DUs had more complications and medication use than patients with no DUs. With increasing number of DUs, SSc patients reported more impairment in work and daily activities and required more support from others.

Acute Q fever in febrile patients in northwestern of Iran

PubMed Central

Esmaeili, Saber; Golzar, Farhad; Ayubi, Erfan; Naghili, Behrooz; Mostafavi, Ehsan

2017-01-01

Background Q fever is an endemic disease in different parts of Iran. This study aimed to investigate the prevalence of acute Q fever disease among at-risk individuals in northwestern Iran. Methodology An etiological study was carried out in 2013 in Tabriz County. A total of 116 individuals who were in contact with livestock and had a nonspecific febrile illness were enrolled in the study. IgG phase II antibodies against Coxiella burnetii were detected using ELISA. Principal findings The prevalence of acute Q fever was 13.8% (95% confidence interval [CI]: 8.0, 21.0%). Headache (87.5%) and fatigue and weakness (81.3%) were the dominant clinical characteristics among patients whit acute Q fever. Acute lower respiratory tract infection and chills were poorly associated with acute Q fever. Furthermore, 32% (95% CI: 24, 41%) of participants had a history of previous exposure to Q fever agent (past infection). Consumption of unpasteurized dairy products was a weak risk factor for previous exposure to C. burnetii. Conclusion This study identified patients with acute Q fever in northwestern of Iran. The evidence from this study and previous studies conducted in different regions of Iran support this fact that Q fever is one of the important endemic zoonotic diseases in Iran and needs due attention by clinical physicians and health care system. PMID:28394892

Factors associated with African Americans' enrollment in a national cancer genetics registry.

PubMed

Skinner, C S; Schildkraut, J M; Calingaert, B; Hoyo, C; Crankshaw, S S; Fish, L; Susswein, L; Jasper, C; Reid, L

2008-01-01

This study explored whether reactions to the Cancer Genetics Network (CGN) or CGN enrollment differed by receipt of a standard informational brochure versus a targeted version addressing factors previously associated with African Americans' health behavior decisions and research participation. The 262 participants, identified through tumor registries or clinic contacts, were mailed brochures and completed phone interviews. When asked whether - based on the brochure - they were or were not 'leaning toward' CGN enrollment, about 75% of both standard and targeted groups reported leaning toward. When given the opportunity at the end of the interview, 68% enrolled in the CGN. Trust was strongly related to enrollment. Less education, less satisfaction with cancer care, and individualistic rather than collective orientation were associated with lower trust. Education was also bivariately associated with enrollment, but mediation analysis indicated that the operational mechanism of education's influence on enrollment was through trust. Copyright 2008 S. Karger AG, Basel.

Docetaxel Alone or in Combination With a Therapeutic Cancer Vaccine (PANVAC) in Patients With Metastatic Breast Cancer: A Randomized Clinical Trial.

PubMed

Heery, Christopher R; Ibrahim, Nuhad K; Arlen, Philip M; Mohebtash, Mahsa; Murray, James L; Koenig, Kimberly; Madan, Ravi A; McMahon, Sheri; Marté, Jennifer L; Steinberg, Seth M; Donahue, Renee N; Grenga, Italia; Jochems, Caroline; Farsaci, Benedetto; Folio, Les R; Schlom, Jeffrey; Gulley, James L

2015-11-01

Previous phase 1 and 2 trials of PANVAC, a poxviral-based cancer vaccine, have suggested clinical efficacy in some patients with breast, ovarian, and colorectal cancer and have shown evidence of immunologic activity. Preclinical data have shown that docetaxel can modify tumor phenotype, making tumor cells more amenable to T cell-mediated killing. The goal of this study was to determine if the treatment combination of docetaxel and PANVAC improves clinical outcomes in patients with metastatic breast cancer compared with docetaxel treatment alone. Between May 2006 and February 2012, this open-label, phase 2 randomized clinical trial enrolled 48 patients with metastatic breast cancer of all subtypes, without limitation on other lines of previous therapy, to receive treatment with either docetaxel with PANVAC (arm A) or docetaxel alone (arm B). Final clinical data were collected on September 16, 2013. All patients were treated at either the National Cancer Institute or the Department of Breast Medical Oncology, MD Anderson Cancer Center. The primary end point was progression-free survival (PFS), using a phase 2.5 statistical design, with the intent of identifying a trend toward benefit (defined as 1-sided P≤.10) to guide a larger trial design. Secondary end points included safety and immunologic correlative studies. Forty-eight participants were enrolled: 25 were randomized to the combination treatment arm A, and 23 to arm B. No patient remained in the study at the time of the final analysis. Patient and tumor characteristics were well matched. Analysis of adverse events in both treatment arms demonstrated very little difference between the 2 groups. In the combination treatment arm (arm A), statistically significant increases were noted in the frequency of grades 1 and 2 edema (P=.02, likely related to greater median number of docetaxel cycles) and injection-site reactions (P<.001). In the final data analysis, median PFS was 7.9 months in arm A vs 3.9 months in arm B (hazard ratio, 0.65 [95% CI, 0.34-1.14]; P=.09). The results suggest that the combination of PANVAC with docetaxel in metastatic breast cancer may provide a clinical benefit. This study was hypothesis generating and provides both rationale and statistical assumptions for a larger definitive randomized study. clinicaltrials.gov Identifier: NCT00179309.

Patient navigation for American Indians undergoing cancer treatment: utilization and impact on care delivery in a regional healthcare center.

PubMed

Guadagnolo, B Ashleigh; Boylan, Amy; Sargent, Michele; Koop, David; Brunette, Deb; Kanekar, Shalini; Shortbull, Vanessa; Molloy, Kevin; Petereit, Daniel G

2011-06-15

A study was undertaken to assess patient navigation utilization and its impact on treatment interruptions and clinical trial enrollment among American Indian cancer patients. Between February 2004 and September 2009, 332 American Indian cancer patients received patient navigation services throughout cancer treatment. The patient navigation program provided culturally competent navigators to assist patients with navigating cancer therapy, obtaining medications, insurance issues, communicating with medical providers, and travel and lodging logistics. Data on utilization and trial enrollment were prospectively collected. Data for a historical control group of 70 American Indian patients who did not receive patient navigation services were used to compare treatment interruptions among those undergoing patient navigation during curative radiation therapy (subgroup of 123 patients). The median number of contacts with a navigator was 12 (range, 1-119). The median time spent with the navigator at first contact was 40 minutes (range, 10-250 minutes), and it was 15 minutes for subsequent contacts. Patients treated with radiation therapy with curative intent who underwent patient navigation had fewer days of treatment interruption (mean, 1.7 days; 95% confidence interval [CI], 1.1-2.2 days) than historical controls who did not receive patient navigation services (mean, 4.9 days; 95% CI, 2.9-6.9 days). Of the 332 patients, 72 (22%; 95% CI, 17%-26%) were enrolled on a clinical treatment trial or cancer control protocol. Patient navigation was associated with fewer treatment interruptions and relatively high rates of clinical trial enrollment among American Indian cancer patients compared with national reports. Copyright © 2010 American Cancer Society.

Evaluating the patient experience after implantation of a 0.4 mg sustained release dexamethasone intracanalicular insert (Dextenza™): results of a qualitative survey.

PubMed

Gira, Joseph P; Sampson, Reginald; Silverstein, Steven M; Walters, Thomas R; Metzinger, Jamie Lynne; Talamo, Jonathan H

2017-01-01

The purpose of this study is to evaluate the patient experience of sustained release dexamethasone intracanalicular insert (Dextenza™) following cataract surgery as part of a Phase III clinical trial program. This cross-sectional, qualitative evaluation involved individual interviews lasting approximately 45 minutes. Patients from four US investigational study sites who had previously received an insert were enrolled. There were no predesignated end points; this was a qualitative survey seeking a deeper understanding of patient experience. Twenty-five patients were interviewed. Most patients (92%) reported the highest level of satisfaction grade with regard to overall product satisfaction. All patients described the insert as comfortable. Most patients (96%) described their overall experience with the insert as very convenient or extremely convenient. Twenty-two of 23 (96%) participants rated their experience with the insert as "very" or "extremely convenient", compared to previous topical therapy, and 88% of patients stated that if they were to undergo cataract surgery again, they would request the insert. When asked if they would recommend the insert to family members or friends, 92% stated they would. The survey found that 84% of participants would be willing to pay more for the insert than for eye drop therapy. The dexamethasone insert was found by patients to be highly favorable with regard to overall satisfaction, convenience, and comfort. The insert was well received and largely preferred over topical therapy alternatives following surgery. More extensive evaluation of the patient experience is warranted, and future studies should help inform design of the next generation of sustained release drug delivery systems.

Validating and updating a prediction rule for serious bacterial infection in patients with fever without source.

PubMed

Bleeker, S E; Derksen-Lubsen, G; Grobbee, D E; Donders, A R T; Moons, K G M; Moll, H A

2007-01-01

To externally validate and update a previously developed rule for predicting the presence of serious bacterial infections in children with fever without apparent source. Patients, 1-36 mo, presenting with fever without source, were prospectively enrolled. Serious bacterial infection included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, bacterial gastroenteritis, osteomyelitis/ethmoiditis. The generalizability of the original rule was determined. Subsequently, the prediction rule was updated using all available data of the patients with fever without source (1996-1998 and 2000-2001, n = 381) using multivariable logistic regression. the generalizability of the rule appeared insufficient in the new patients (n = 150). In the updated rule, independent predictors from history and examination were duration of fever, vomiting, ill clinical appearance, chest-wall retractions and poor peripheral circulation (ROC area (95%CI): 0.69 (0.63-0.75)). Additional independent predictors from laboratory were serum white blood cell count and C-reactive protein, and in urinalysis > or = 70 white bloods (ROC area (95%CI): 0.83 (0.78-0.88). A previously developed prediction rule for predicting the presence of serious bacterial infection in children with fever without apparent source was updated. Its clinical score can be used as a first screening tool. Additional laboratory testing may specify the individual risk estimate (range: 4-54%) further.

Evaluation of nonprescription syringe sales in San Francisco.

PubMed

Rose, Valerie J; Raymond, H Fisher

2010-01-01

To determine the experiences, practices, and challenges associated with nonprescription syringe sales (NPSS) among pharmacists whose pharmacies were enrolled in the Disease Prevention Demonstration Project in San Francisco, CA. Self-administered survey mailed to 69 pharmacies and interviews with pharmacists and technicians. A total of 55 of 69 pharmacies (80%) returned the survey, and eight pharmacy managers and three pharmacy technicians were interviewed in person. Of pharmacists, 72% reported none or very few problems with NPSS in the previous year, although surveys and interviews illustrated challenges associated with NPSS in terms of time management, educating patients about syringe disposal, and understanding patient preferences for syringes. Of pharmacists, 62% reported NPSS to no more than 10 to 20 patients per week and 67% collected more than 400 syringes in the previous year. One-third of pharmacists perceived that their pharmacies were located in areas where drug activity was high and that the majority of NPSS patients injected illegal drugs. Access to sterile syringes is a prominent public health issue, and pharmacists can play an important role in injection drug user (IDU) education and disease prevention. This evaluation suggests that pharmacies are selling nonprescription syringes to individuals perceived to be IDUs with no major problems. Additional evaluations from health department programs are needed to demonstrate the efficacy of NPSS in California.

A prospective study of proton reirradiation for recurrent and secondary soft tissue sarcoma.

PubMed

Guttmann, David M; Frick, Melissa A; Carmona, Ruben; Deville, Curtiland; Levin, William P; Berman, Abigail T; Chinniah, Chidambaram; Hahn, Stephen M; Plastaras, John P; Simone, Charles B

2017-08-01

Proton reirradiation for sarcoma has not been previously described. We hypothesized that this strategy would provide favorable toxicity and survival outcomes. Patients with soft tissue sarcoma in a previously-irradiated field were enrolled on a prospective trial of proton reirradiation. The primary endpoint was provider-reported acute toxicity. Secondary endpoints included late toxicities, local control, and overall survival. 23 patients underwent proton reirradiation. Median time between radiation courses was 40.7months (range 10-272). No grade 4-5 toxicities were observed. One patient (4%) experienced acute grade 3 dysphagia. Common grade 2 acute toxicities were fatigue (26%), anorexia (17%), and urinary incontinence (13%). There were two grade 3 late wound infections (10%) and one grade 3 late wound complication (5%). Grade 2 late complications included lymphedema (10%), fracture (5%), and fibrosis (5%). At a median follow-up of 36months, the 3-year cumulative incidence of local failure was 41% (95% CI [20-63%]). Median overall survival and progression-free survival were 44 and 29months, respectively. In extremity patients, amputation was spared in 7/10 (70%). Proton reirradiation of recurrent/secondary soft tissue sarcomas is well tolerated. While longer follow-up is needed, early survival outcomes in this high-risk population are encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study.

PubMed

Huang, Jing; Fan, Qingxia; Lu, Ping; Ying, Jianming; Ma, Changwu; Liu, Wei; Liu, Ying; Tan, Fenlai; Sun, Yan

2016-06-01

Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR overexpression or amplification. For this phase 2, single-arm, multicenter trial undertaken at six hospitals in China, we included Chinese patients with previously treated, histologically confirmed advanced ESCC and EGFR overexpression (immunohistochemical staining sore of 3+) or amplification (positive fluorescence in situ hybridization result). These patients received oral icotinib (250 mg, three times daily).The primary end point was the proportion of patients with objective responses as assessed by an independent radiology review committee. Between December 5, 2013, and May 28, 2015, a total of 281 patients were screened. Fifty-four eligible patients were enrolled. Nine responses were observed, including one complete response and eight partial responses, and 16 patients had stable disease, resulting in a 16.7% objective response rate (95% confidence interval [CI]: 6.7-26.6) and 46.3% disease control rate (95% CI: 33.0-59.6). The median progression-free survival and overall survival times were 52 (95% CI: 40-95) days and 153 (95% CI: 139-218) days, respectively. A total of 43 patients experienced at least one adverse event, but most were only grade 1 to 2 in severity. The most frequent was rash (48.1%), followed by diarrhea (22.2%). Icotinib showed favorable activity in patients with advanced, previously treated ESCC with EGFR overexpression or amplification. These findings suggest further research into EGFR overexpression or amplification for selecting responsive patients. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Subtypes in clinical burnout patients enrolled in an employee rehabilitation program: differences in burnout profiles, depression, and recovery/resources-stress balance.

PubMed

Bauernhofer, Kathrin; Bassa, Daniela; Canazei, Markus; Jiménez, Paulino; Paechter, Manuela; Papousek, Ilona; Fink, Andreas; Weiss, Elisabeth M

2018-01-17

Burnout is generally perceived a unified disorder with homogeneous symptomatology across people (exhaustion, cynicism, and reduced professional efficacy). However, increasing evidence points to intra-individual patterns of burnout symptoms in non-clinical samples such as students, athletes, healthy, and burned-out employees. Different burnout subtypes might therefore exist. Yet, burnout subtypes based on burnout profiles have hardly been explored in clinical patients, and the samples investigated in previous studies were rather heterogeneous including patients with various physical, psychological, and social limitations, symptoms, and disabilities. Therefore, the aim of this study is to explore burnout subtypes based on burnout profiles in clinically diagnosed burnout patients enrolled in an employee rehabilitation program, and to investigate whether the subtypes differ in depression, recovery/resources-stress balance, and sociodemographic characteristics. One hundred three patients (66 women, 37 men) with a clinical burnout diagnosis, who were enrolled in a 5 week employee rehabilitation program in two specialized psychosomatic clinics in Austria, completed a series of questionnaires including the Maslach Burnout Inventory - General Survey (MBI-GS), the Beck Depression Inventory, and the Recovery-Stress-Questionnaire for Work. Cluster analyses with the three MBI-GS subscales as clustering variables were used to identify the burnout subtypes. Subsequent multivariate/univariate analysis of variance and Pearson chi-square tests were performed to investigate differences in depression, recovery/resources-stress balance, and sociodemographic characteristics. Three different burnout subtypes were discovered: the exhausted subtype, the exhausted/cynical subtype, and the burned-out subtype. The burned-out subtype and the exhausted/cynical subtype showed both more severe depression symptoms and a worse recovery/resources-stress balance than the exhausted subtype. Furthermore, the burned-out subtype was more depressed than the exhausted/cynical subtype, but no difference was observed between these two subtypes with regard to perceived stress, recovery, and resources. Sociodemographic characteristics were not associated with the subtypes. The present study indicates that there are different subtypes in clinical burnout patients (exhausted, exhausted/cynical, and burned-out), which might represent patients at different developmental stages in the burnout cycle. Future studies need to replicate the current findings, investigate the stability of the symptom patterns, and examine the efficacy of rehabilitation interventions in different subtypes.

"I struggle to count my blessings": recovery after hip fracture from the patients' perspective.

PubMed

Bruun-Olsen, Vigdis; Bergland, Astrid; Heiberg, Kristi Elisabeth

2018-01-19

Recovery outlooks of physical functioning and quality of life after hip fracture have not changed significantly over the past 25 years. Previous research has mainly dealt with causalities and acute treatment, while the recovery process from the patients' perspective has been less comprehensively described. Expanded knowledge of what the patients consider important in their recovery process may have important consequences for how these patients are treated in the future and thereby on future patient outcomes. The aim presently is therefore to explore how elderly patients with hip fracture enrolled in an ongoing RCT have experienced their recovery process. The study was qualitative in design. Eight frail elderly in recovery after hip fracture (aged 69-91) were interviewed in their home four months after their fracture. The interviews covered issues related to their experiences of facilitators and barriers throughout the different stages in the recovery process. The patients were already enrolled in an ongoing randomized controlled trial, examining the effects of habitual functional training during their short term stays at nursing homes. The patients were chosen strategically according to age, gender, and participation in rehabilitation. The interviews were recorded, transcribed and subjected to a method of systematic text condensation inspired by Giorgi's phenomenological method. The results revealed that the patients' experiences of the recovery process fell into three main themes: "Feeling vulnerable", "A span between self-reliance and dependency" and "Disruption from a normal life". The feeling of gloominess and vulnerability persisted throughout. Being in recovery was also experienced as a tension between self-reliance and dependency; a disrupted life where loss of mobility and the impact of age was profoundly present. Being in recovery after hip fracture was experienced as a life breaking event. Based on these findings, increased focus on individualized treatment to each patient through each stage of the recovery process should be emphasized.

A prospective observational study of techniques to remove corneal foreign body in the emergency department.

PubMed

Quirke, Michael; Mullarkey, Caitriona; Askoorum, Shakti; Coffey, Norma; Binchy, James

2014-06-01

Patients  with corneal foreign bodies (CFBs) often present to the emergency department (ED). However, removal techniques vary among emergency physicians (EPs). A prospective, single-blinded, observational study was performed to compare slit-lamp-aided (SLA) versus non-slit-lamp-aided (NSLA) CFB removal by EPs. Five EPs enrolled consecutive patients with a CFB over 3 months. One blinded EP reviewed patients after 3 days. The study end points were: change in visual acuity; visual analogue pain scale (VAS) score at 12 and 24 h; satisfaction rating; symptoms at follow-up; and rate of complications. 54 patients were enrolled: 28 had SLA removal and 26 NSLA removal; 52 were male; 22 had undergone previous CFB removal; six were wearing eye protection at the time of injury. Forty-three patients were reviewed: 26 by attendance and 18 by telephone. There was no difference in any end points at review. However, patients in the SLA group had median VAS scores that were 1.5 cm lower after 24 h than patients in the NSLA group (p=0.43, 95% CI -2.0 to 1.0). One patient in the SLA group developed keratitis. We show that patient satisfaction ratings, complications and visual acuity were similar for the two methods. There was a trend for increased pain in the NSLA group at 12 and 24 h. Slit-lamp biomicroscopy and the use of magnification to remove CFBs remains the gold standard of care, and more intensive training should be given to EPs at the departmental level, particularly in EDs that receive patients with eye injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults.

PubMed

Setyawan, Juliana; Hodgkins, Paul; Guérin, Annie; Gauthier, Geneviève; Cloutier, Martin; Wu, Eric; Erder, M Haim

2013-10-01

To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically significant when compared to OROS MPH and MPH LA patients. This study did not control for ADHD severity. Overall, compared to LDX-treated patients, patients initiated on other ADHD medications were equally or more likely to have a therapy augmentation and more likely to deviate from the recommended once-daily dosing regimen.

Efficacy and safety profile of boceprevir- or telaprevir-based triple therapy or dual peginterferon alfa-2a or alfa-2b plus ribavirin therapy in chronic hepatitis C: the real-world PegBase observational study.

PubMed

Mangia, Alessandra; Foster, Graham R; Berg, Christoph P; Curescu, Manuela; Ledinghen, Victor De; Habersetzer, François; Manolakopoulos, Spilios; Negri, Elisa; Papatheodoridis, George; Ahlers, Silke; Castillo, Marco; Bakalos, Georgios; Mauss, Stefan

2017-01-01

The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.

Reasons for non-participation in an international multicenter trial of a new drug for tuberculosis treatment.

PubMed

Lamunu, D; Chapman, K N; Nsubuga, P; Muzanyi, G; Mulumba, Y; Mugerwa, M A; Goldberg, S; Bozeman, L; Engle, M; Saukkonen, J; Mastranunzio, S; Mayanja-Kizza, H; Johnson, J L

2012-04-01

Clinical trials can provide a high standard of patient care and contribute to scientific knowledge; however, only a fraction of the patients screened participate and receive treatment as part of a trial. To explore reasons why patients were not enrolled in an international tuberculosis (TB) treatment trial and to compare experiences among study sites. An analysis of reasons why patients were not enrolled was conducted among patients screened for a TB clinical trial at 26 sites in North and South America, Africa, and Europe. Staff at study sites screened 1119 potential candidates for the trial: 61% (n = 686) were not enrolled due to 1) failure to meet eligibility criteria (n = 405, 59%), 2) site's decision (n = 168, 24%), or 3) candidate's choice (n = 113, 16%). Study staff recorded a total of 144 reasons for why they believed patients chose not to participate, including concerns over research (28%), conflicts with work or school (21%), and lifestyle and family issues (20%). Socio-demographic and geographic factors also influenced participation. Increased evaluation of screening outcomes and of specific interventions, such as improved education and communication about trial procedures, may increase the efficiency of screening and enrollment in clinical trials.

Effectiveness of a transitional home care program in reducing acute hospital utilization: a quasi-experimental study.

PubMed

Low, Lian Leng; Vasanwala, Farhad Fakhrudin; Ng, Lee Beng; Chen, Cynthia; Lee, Kheng Hock; Tan, Shu Yun

2015-03-14

Improving healthcare utilization is essential as health systems around the world grapple with the escalating demands for acute hospital resources. Evidence suggests that transitional care programs are effective to improve utilization of healthcare. However, the evidence for transitional care programs that enhance the home medical care model and provide multi-disciplinary patient-centered care is not well established. We evaluated if a transitional home care program operated by the Singapore General Hospital was effective in reducing acute hospital utilization. We performed a quasi-experimental study using a pre-post design to evaluate the effectiveness of a transitional home care program in reducing hospital admissions and emergency department attendances of medically complex patients enrolled into the program in a tertiary hospital in Singapore. Patients received a comprehensive needs assessment performed by the physician and a nurse case manager in the home setting, followed by an individualized care plan that included medical and nursing care, patient education and coordination of care with hospital specialists and community services. Primary study outcomes were emergency department attendances and hospital admissions to all hospitals. These were extracted from hospital administrative data and national health records. Wilcoxon Signed Ranks Test was used for assess differences in pre and post continuous data. Overall, 262 patients were enrolled into the program and 259 were analyzed. Patients had a 51.6% and 52.8% reduction in hospital admissions in the three-month and six-month post enrollment, respectively. Similarly, a 47.1% and 48.2% reduction was observed for emergency department attendances in the three and six months post enrollment, respectively. The average difference in per patient hospital bed days in the pre- and post-enrollment periods were 12.05 days and 20.03 days at the 3-month and 6-month periods, respectively. Patients enrolled in the transitional home care program had significantly lower acute hospital utilization through the reduction of emergency department attendances and hospital admissions. A comprehensive assessment of patients' medical and social needs in the home setting and formulation of an individualized care plan optimized post-discharge care for medically complex patients.

Evaluation of a new pediatric positive airway pressure mask.

PubMed

Kushida, Clete A; Halbower, Ann C; Kryger, Meir H; Pelayo, Rafael; Assalone, Valerie; Cardell, Chia-Yu; Huston, Stephanie; Willes, Leslee; Wimms, Alison J; Mendoza, June

2014-09-15

The choice and variety of pediatric masks for continuous positive airway pressure (CPAP) is limited in the US. Therefore, clinicians often prescribe modified adult masks. Until recently a mask for children aged < 7 years was not available. This study evaluated apnea-hypopnea index (AHI) equivalence and acceptability of a new pediatric CPAP mask for children aged 2-7 years (Pixi; ResMed Ltd, Sydney, Australia). Patients aged 2-7 years were enrolled and underwent in-lab baseline polysomnography (PSG) using their previous mask, then used their previous mask and the VPAP III ST-A flow generator for ≥ 10 nights at home. Thereafter, patients switched to the Pixi mask for ≥ 2 nights before returning for a PSG during PAP therapy via the Pixi mask. Patients then used the Pixi mask at home for ≥ 21 nights. Patients and their parents/guardians returned to the clinic for follow-up and provided feedback on the Pixi mask versus their previous mask. AHI with the Pixi mask was 1.1 ± 1.5/h vs 2.6 ± 5.4/h with the previous mask (p = 0.3538). Parents rated the Pixi mask positively for: restfulness of the child's sleep, trouble in getting the child to sleep, and trouble in having the child stay asleep. The Pixi mask was also rated highly for leaving fewer or no marks on the upper lip and under the child's ears, and being easy to remove. The Pixi mask is suitable for children aged 2-7 years and provides an alternative to other masks available for PAP therapy in this age group. © 2014 American Academy of Sleep Medicine.

Factors and Regional Differences Associated with Endometriosis: A Multi-Country, Case-Control Study.

PubMed

Chapron, Charles; Lang, Jing-He; Leng, Jin-Hua; Zhou, Yingfang; Zhang, Xinmei; Xue, Min; Popov, Alexander; Romanov, Vladimir; Maisonobe, Pascal; Cabri, Patrick

2016-08-01

The present study aimed to investigate clinical, lifestyle, and environmental factors associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) as determined by case-control comparison [women with superficial peritoneal endometriosis (SUP) or no endometriosis], and compare differences between factor associated with endometriosis at a national level. This was three countries (China, Russia, and France), case-control study in 1008 patients. Patients were identified and enrolled during their first routine appointment with their physician post-surgery for a benign gynecologic indication, excluding pregnancy. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. For every DIE patient recruited (n = 143), two women without endometriosis (n = 288), two SUP patients (n = 288), and two OMA patients (n = 288) were recruited. For the overall population, factors significantly associated (P ≤ 0.05) with DIE or OMA [Odds ratio (OR) >1] were: previous use of hormonal treatment for endometriosis [OR 6.66; 95% confidence interval (CI) 4.05-10.93]; previous surgery for endometriosis (OR 1.95; 95% CI 1.11-3.43); and living or working in a city or by a busy area (OR 1.66; 95% CI 1.09-2.52). Differences between regions with regard to the diagnosis, symptomatology, and treatment of endometriosis exist. The findings provide insight into potential risk factors for endometriosis and differences between regions in terms of endometriosis management and symptomatology. Further investigations are required to confirm the associations found in this study. ClinicalTrials.gov identifier, NCT01351051. Ipsen.

Strategies to Recruit a Diverse Low-Income Population to Child Weight Management Programs From Primary Care Practices.

PubMed

Barlow, Sarah E; Butte, Nancy F; Hoelscher, Deanna M; Salahuddin, Meliha; Pont, Stephen J

2017-12-21

Primary care practices can be used to engage children and families in weight management programs. The Texas Childhood Obesity Research Demonstration (TX CORD) study targeted patients at 12 primary care practices in diverse and low-income areas of Houston, Texas, and Austin, Texas for recruitment to a trial of weight management programs. This article describes recruitment strategies developed to benefit both families and health care practices and the modification of electronic health records (EHRs) to reflect recruitment outcomes. To facilitate family participation, materials and programs were provided in English and Spanish, and programs were conducted in convenient locations. To support health care practices, EHRs and print materials were provided to facilitate obesity recognition, screening, and study referral. We provided brief training for providers and their office staffs that covered screening patients for obesity, empathetic communication, obesity billing coding, and use of counseling materials. We collected EHR data from 2012 through 2014, including demographics, weight, and height, for all patients aged 2 to 12 years who were seen in the 12 provider practices during the study's recruitment phase. The data of patients with a body mass index (BMI) at or above the 85th percentile were compared with the same data for patients who were referred to the study and patients who enrolled in the study. We also examined reasons that patients referred to the study declined to participate. Overall, 26% of 7,845 patients with a BMI at or above the 85th percentile were referred to the study, and 27% of referred patients enrolled. Enrollment among patients with a BMI at or above the 85th percentile was associated with being Hispanic and with more severe obesity than with patients of other races/ethnicities or less severe obesity, respectively. Among families of children aged 2 to 5 years who were referred, 20% enrolled, compared with 30% of families of older children (>5 y to 12 y). Referral rates varied widely among the 12 primary care practices, and referral rates were not associated with EHR modifications. Engagement and recruitment strategies for enrolling families in primary care practice in weight management programs should be strengthened. Further study of factors associated with referral and enrollment, better systems for EHR tools, and data on provider and office adherence to study protocols should be examined. EHRs can track referral and enrollment to capture outcomes of recruitment efforts.

Strategies to Recruit a Diverse Low-Income Population to Child Weight Management Programs From Primary Care Practices

PubMed Central

Butte, Nancy F.; Hoelscher, Deanna M.; Salahuddin, Meliha; Pont, Stephen J.

2017-01-01

Purpose and Objectives Primary care practices can be used to engage children and families in weight management programs. The Texas Childhood Obesity Research Demonstration (TX CORD) study targeted patients at 12 primary care practices in diverse and low-income areas of Houston, Texas, and Austin, Texas for recruitment to a trial of weight management programs. This article describes recruitment strategies developed to benefit both families and health care practices and the modification of electronic health records (EHRs) to reflect recruitment outcomes. Intervention Approach To facilitate family participation, materials and programs were provided in English and Spanish, and programs were conducted in convenient locations. To support health care practices, EHRs and print materials were provided to facilitate obesity recognition, screening, and study referral. We provided brief training for providers and their office staffs that covered screening patients for obesity, empathetic communication, obesity billing coding, and use of counseling materials. Evaluation Methods We collected EHR data from 2012 through 2014, including demographics, weight, and height, for all patients aged 2 to 12 years who were seen in the 12 provider practices during the study’s recruitment phase. The data of patients with a body mass index (BMI) at or above the 85th percentile were compared with the same data for patients who were referred to the study and patients who enrolled in the study. We also examined reasons that patients referred to the study declined to participate. Results Overall, 26% of 7,845 patients with a BMI at or above the 85th percentile were referred to the study, and 27% of referred patients enrolled. Enrollment among patients with a BMI at or above the 85th percentile was associated with being Hispanic and with more severe obesity than with patients of other races/ethnicities or less severe obesity, respectively. Among families of children aged 2 to 5 years who were referred, 20% enrolled, compared with 30% of families of older children (>5 y to 12 y). Referral rates varied widely among the 12 primary care practices, and referral rates were not associated with EHR modifications. Implications for Public Health Engagement and recruitment strategies for enrolling families in primary care practice in weight management programs should be strengthened. Further study of factors associated with referral and enrollment, better systems for EHR tools, and data on provider and office adherence to study protocols should be examined. EHRs can track referral and enrollment to capture outcomes of recruitment efforts. PMID:29267156

The efficacy of radiographic anatomical measurement methods in predicting success after extracorporeal shockwave lithotripsy for lower pole kidney stones.

PubMed

Arpali, Emre; Altinel, Mert; Sargin, Semih Yasar

2014-01-01

To assess the impact of lower pole calyceal anatomy on clearace of lower pole stones after extracorporeal shockwave lithotripsy (ESWL) by means of a new and previously defined radiographic measurement method. Sixty-four patients with solitary radiopaque lower pole kidney stones were enrolled in the study. Infundibulopelvic angle (IPA), infundibulotransverse angle (ITA), infundibular lenght(IL), and infundibular width (IW) were measured on the intravenous urographies which were taken before the procedure. 48 of 64 patients (75%) were stone-free after a follow-up period of 3 months. The IPA,ITA,IL and IW were determined as statistically significant factors, while age,gender and stone area were found to have no impact on clearance. By the help of radiographic measurement methods related to lower pole kidney anatomy, appropriate patient selection and increment in success after ESWL may be achieved.

The pharmacovigilance program on natalizumab in Italy: 2 years of experience.

PubMed

Tedeschi, G; Amato, M P; D'Alessandro, R; Drago, F; Milanese, C; Popoli, P; Rossi, P; Savettieri, G; Tola, M R; Vanacore, N; Covezzoli, A; De Rosa, M; Comi, G; Pozzilli, Carlo; Bertolotto, Antonio; Marrosu, Maria Giovanna; Grimaldi, Luigi M E; Piccinni, C; Montanaro, N; Periotto, Laura; Iommelli, Rosamaria; Addis, Antonio; Martini, Nello; Provinciali, L; Mancardi, G L

2009-10-01

At the end of 2006 a country-based surveillance program on natalizumab therapy in multiple sclerosis was settled in Italy by a collaborative effort of the Italian Drug Agency (AIFA) and a group of experts and neurologists appointed by the National Society of Neurology (SIN). After 2 years, 1,818 patients are registered in the database. The majority of cases (88.6%) failed the therapy with beta interferon or glatiramer acetate and had relapses or accumulated disability during immunomodulating treatment, while 11.4% of patients enrolled in the surveillance study were not previously treated with immunomodulating therapies and had a rapidly evolving clinical course. Almost 10% of the patients treated with natalizumab interrupted, for various different reasons, the therapy. Treatment was well tolerated and side effects were similar to those reported in the registrative studies. The majority of treated cases are stable or ameliorated.

Is there a survival benefit within a German primary care-based disease management program?

PubMed

Miksch, Antje; Laux, Gunter; Ose, Dominik; Joos, Stefanie; Campbell, Stephen; Riens, Burgi; Szecsenyi, Joachim

2010-01-01

To compare the mortality rate of patients with type 2 diabetes who were enrolled in the German diabetes disease management program (DMP) with the mortality rate of those who were not enrolled. This observational study was part of the ELSID study (Evaluation of a Large Scale Implementation of disease management programs) in Germany. Participants had type 2 diabetes and were either enrolled or not enrolled in the DMP. The DMP provides systems-based, multifaceted, and patient-centered interventions. To reduce imbalances between the groups, a matched sample was created using sex, age, retirement status, federal state, pharmacy-based cost groups, and diagnostic-cost groups as matching criteria. Cox proportional hazards regression model and the Kaplan-Meier method were used to assess overall mortality. The observation period was 3 years beginning on January 1, 2006. A total of 11,079 patients were included in the analysis. As of January 1, 2006, 2300 patients were enrolled in the DMP and 8779 were receiving routine care. There were 1927 matched pairs of patients in the DMP group and the non-DMP group. The overall mortality rate was 11.3% in the DMP and 14.4% in the non-DMP group (log-rank test P <.01). We found an association between participation in the German diabetes DMP and reduced mortality. This reduced mortality cannot be attributed directly to the DMP. However, further research should evaluate whether a primary care-based DMP contributes to increased life expectancy in patients with diabetes.

Health-related quality of life, work productivity, and health care resource utilization of subjects with irritable bowel syndrome: baseline results from LOGIC (Longitudinal Outcomes Study of Gastrointestinal Symptoms in Canada), a naturalistic study.

PubMed

Paré, Pierre; Gray, James; Lam, Sy; Balshaw, Robert; Khorasheh, Shideh; Barbeau, Martin; Kelly, Suzanne; McBurney, Christopher R

2006-10-01

Abdominal pain/discomfort, bloating, and constipation are gastrointestinal dysmotility and sensory symptoms associated with irritable bowel syndrome (IBS). No studies have followed patients with IBS symptoms for 1 year under conditions of routine clinical practice to assess prospectively the impact of treatments on health outcomes. The objective of this ongoing, naturalistic study is to assess the long-term impact of IBS treatments on quality of life (QOL), work productivity, and resource utilization. This report describes the baseline characteristics and patterns of care of the patients enrolled in this study. Patients with physician-diagnosed IBS symptoms were enrolled from 147 physician sites across Canada between May 4, 2004, and March 31, 2005. Clinical data were collected at baseline and at the end of the 12-month follow-up (patients were followed for 1 year between May 4, 2005, and March 31, 2006). Patient-reported outcomes were collected at baseline and at months 1, 2, 6, 9, and 12. Health-related QOL, health status, and work productivity were assessed with the IBS-QOL, a 5-item EuroQol descriptive system, and Work Productivity and Activity Impairment questionnaires, respectively. A resource utilization questionnaire elicited information on physician; visits, treatments, and procedures. Baseline data are reported here. Data were obtained from 1555 patients; 85.1% (1320/1552) were women. Patients had a mean (SD) age of 45.8 (15.0) years and mean (SD) duration of IBS symptoms of 11.4 (11.5) years. Self-reported bowel patterns were predominantly constipation (41.0%, 587/1433) and constipation alternating with diarrhea (39.4%, 564/1433); 60.3% (938/1555) of subjects used > or =3 IBS treatments in the previous 4 weeks. Approximately 50% of all patients reported distress "quite a bit or "extremely" for abdominal pain, gas, bloating, and constipation. The mean overall IBS-QOL score (0-100 scale, with 0 indicating poor QOL) was 66.3; food avoidance (51.8) and health worry (59.3) were the most serious concerns. Patients reported 5.6% work absenteeism, 31.4% presenteeism, and 34.6% overall work productivity loss, equivalent to 13.8 hours lost productivity per 40-hour workweek. The baseline data from this ongoing, prospective, naturalistic study are consistent with previous findings that suggested significant use of health care resources with concomitant low QOL and decreased work productivity in patients with IBS symptoms.

Educators' expectations of roles, employability and career pathways of registered and enrolled nurses in Australia.

PubMed

Jacob, Elisabeth R; McKenna, Lisa; D'Amore, Angelo

2016-01-01

In Australia, like other countries, two levels of nurse are registered for entry to practice. Educational changes for second level nurses in Australia have led to questions regarding roles and career options. This paper reports on interviews with nursing course coordinators to examine educator expectations of roles and career pathways of registered and enrolled nurses. Coordinators of eight degree (registered) and diploma (enrolled) nursing programs were interviewed to determine their opinions on roles and careers that students were prepared for. Transcripts were thematically analysed. Educators reported similar graduate roles, although high acuity care was primarily the role of registered nurses. Career expectations differed with enrolled nurses having limited advancement opportunity, and registered nurses greater career options. Health organisations were unprepared to accommodate increased practice scope of enrolled nurses and limited work practice through policies stipulating who could perform procedures. Organisational health policies need to accommodate increased enrolled nurse skill base. Education of practising nurses is necessary regarding increased scope of enrolled nurse practice to ensure they are used to their full potential. Increasing patient acuity requires more registered nurses, as enrolled nurses are unprepared to care for complex or deteriorating patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Renal failure and concurrent RAAS blockade in older CKD patients with renal artery stenosis: an extended Mayo Clinic prospective 63-month experience.

PubMed

Onuigbo, Macaulay A C; Onuigbo, Nnonyelum T C

2008-01-01

Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.

Factors Influencing Enrollment in the Medication Therapy Management Clinic at an Academic Ambulatory Care Clinic.

PubMed

Shah, Mansi; Tilton, Jessica; Kim, Shiyun

2016-04-01

In 2001, the University of Illinois Hospital and Health Sciences System (UI Health) established a pharmacist-run, referral-based medication therapy management clinic (MTMC). Referrals are obtained from any UI Health provider or by self-referral. Although there is a high volume of referrals, a large percentage of patients do not enroll. This study was designed to determine the various factors that influence patient enrollment in the MTMC. This study was a retrospective chart review of demographic and patient variable data during years 2010 and 2011. Disabilities, distance from MTMC, mode of transportation, past medical history, and appointment dates were extracted from the medical records. Results were analyzed using descriptive statistics and logistic regression analysis. A total of 103 referrals were made; however, only 17% of patients remain enrolled in MTMC. The baseline demographics included a mean age of 63 years, 68% female, 70% African American, and 81% English speaking. Patients lived an average of 8 miles from MTMC; most utilized public or government-supplemented transport services; 24% of patients reported some type of disability, most commonly utilizing a walker or a wheelchair. On average, patients were prescribed 13 medications with hypertension (70%), diabetes (56%), and hyperlipidemia (48%) being the most common chronic disease states. The reason for referral included medication management, education, medication reconciliation, and disease state management. Five patients were unable to be contacted to schedule an initial appointment. Additionally, 18 patients failed their scheduled initial appointment and did not reschedule. Logistic regression analysis demonstrated distance traveled for clinic visit, age, and history of hypertension affected the probability of patients showing for their appointments (chi-square = 19.7, P < .001). This study demonstrated that distance from MTMC is the most common barrier in patient enrollment; therefore, strategies to improve patient access are necessary. © The Author(s) 2014.

Delirium after coronary bypass surgery evaluated by the organic brain syndrome protocol.

PubMed

Eriksson, Marléne; Samuelsson, Elsa; Gustafson, Yngve; Aberg, Torkel; Engström, Karl Gunnar

2002-08-01

The aim was to evaluate symptoms of delirium from a psychogeriatric perspective occurring postoperative to coronary bypass surgery. Patients, > or = 60 years, scheduled for coronary bypass surgery (n = 52) were enrolled in a prospective descriptive study. The patients were evaluated before and several times after surgery by the Organic Brain Syndrome scale, and delirium was diagnosed according to psychiatric codes. Of the 52 patients, 23% presented delirium. These patients were older than the control group, 73.5 +/- 4.2 and 69.3 +/- 5.9 years, respectively (mean +/- SD, p < 0.01), and had more frequently a history of previous stroke (p < 0.05). Emotional delirium was seen in 83%, hyperactive delirium in about 40%, and 25% were classified to have a psychotic delirium. A major finding was a 58% frequency of hallucinations and illusions among patients with delirium, and a similar rate among those without delirium. Delirium is common after cardiac surgery in particular in older patients, but is often under-diagnosed. Hallucinations were common in both delirious and non-delirious patients.

Anxiety Among Patients Undergoing Nail Surgery and Skin Punch Biopsy: Effects of Age, Gender, Educational Status, and Previous Experience.

PubMed

Göktay, Fatih; Altan, Zeynep Müzeyyen; Talas, Anıl; Akpınar, Esma; Özdemir, Ekin Özge; Aytekin, Sema

2016-01-01

Patient anxiety about nail surgery relates mainly to pain associated with needle puncture, anesthetic flow during the procedure, and postoperative care, as well as possible past traumatic experience. The aims of this study were to compare anxiety levels among patients undergoing nail surgery and skin punch biopsy and to assess the effects of demographic characteristics on anxiety. Forty-eight consecutive patients who were referred to a dermatological surgery unit for nail surgery intervention (group 1) and 50 age- and sex-matched patients referred to the same unit for skin punch biopsy (group 2) were enrolled in the study. Patients' anxiety levels were measured using Spielberger's State-Trait Anxiety Inventory. There was no significant difference in median anxiety level between group 1 (42.00; interquartile range, 6.50) and group 2 (41.00; interquartile range, 8.25) (P = .517). The demographic factors of patient sex, educational status, and prior surgery showed no significant effects on anxiety levels. Nail surgery does not seem to cause significantly greater anxiety than skin punch biopsy. © The Author(s) 2015.

Ambulatory Surgery Has Minimal Impact on Sleep Parameters: A Prospective Observational Trial.

PubMed

Hudson, Arlene J; Walter, Robert J; Flynn, John; Szpisjak, Dale F; Olsen, Cara; Rodgers, Matthew; Capaldi, Vincent F; McDuffie, Brent; Lettieri, Christopher J

2018-04-15

The presence of obstructive sleep apnea (OSA) in ambulatory surgical patients causes significant perioperative concern; however, few data exist to guide clinicians' management decisions. The objective of this study was to measure changes in perioperative sleep parameters among an ambulatory surgery population. This study is a prospective, observational study of ambulatory patients undergoing orthopedic surgery on an extremity. Study subjects completed three unattended home sleep apnea tests: baseline before surgery, the first night after surgery (N1), and third night after surgery (N3). Anesthesia and surgical teams were blinded to study participation and patients received routine perioperative care. Two hundred three subjects were enrolled and 166 completed the baseline home sleep test. Sixty-six (40.0%) had OSA at baseline, 35 patients received a new diagnosis, and 31 patients had a previous diagnosis of OSA. Of those with a previous diagnosis, 20 (64.5%) were compliant with continuous positive airway pressure therapy. Respiratory event index and SpO 2 nadir did not significantly change postoperatively from baseline. Cumulative percentage of time oxygen saturation < 90% significantly increased N1 as compared to baseline for all patients except for those with moderate to severe OSA. Ambulatory surgery had minimal effect on sleep parameters and there was no increase in adverse events among patients with either treated or untreated OSA. Registry: ClinicalTrials.gov; Title: Evaluation of Sleep Disordered Breathing Following Ambulatory Surgery; Identifier: NCT01851798; URL: https://clinicaltrials.gov/ct2/show/study/NCT01851798. © 2018 American Academy of Sleep Medicine.

A novel use of the Spine Tango registry to evaluate selection bias in patient recruitment into clinical studies: an analysis of patients participating in the Lumbar Spinal Stenosis Outcome Study (LSOS).

PubMed

Becker, H-J; Nauer, S; Porchet, F; Kleinstück, F S; Haschtmann, D; Fekete, T F; Steurer, J; Mannion, A F

2017-02-01

Patients enrolled in clinical studies typically represent a sub-set of all who are eligible, and selection bias may compromise the generalizability of the findings. Using Registry data, we evaluated whether surgical patients recruited by one of the referring centres into the Lumbar Spinal Stenosis Outcome Study (LSOS; a large-scale, multicentre prospective observational study to determine the probability of clinical benefit after surgery) differed in any significant way from those who were eligible but not enrolled. Data were extracted for all patients with lumbar spinal stenosis registered in our in-house database (interfaced to Eurospine's Spine Tango Registry) from 2011 to 2013. Patient records and imaging were evaluated in relation to the admission criteria for LSOS to identify those who would have been eligible for participation but were not enrolled (non-LSOS). The Tango surgery data and Core Outcome Measures Index (COMI) data at baseline and 3 and 12 months after surgery were analysed to evaluate the factors associated with LSOS enrolment or not. 514 potentially eligible patients were identified, of which 94 (18%) were enrolled into LSOS (range 2-48% for the 6 spine surgeons involved in recruiting patients) and 420 (82%) were not; the vast majority of the latter were due to non-referral to the study by the surgeon, with only 5% actually refusing participation. There was no significant difference in gender, age, BMI, smoking status, or ASA score between the two groups (p ≥ 0.18). Baseline COMI was significantly (p = 0.002) worse in the non-LSOS group (7.4 ± 1.9) than the LSOS group (6.7 ± 1.9). There were no significant group differences in any Tango surgery parameters (additional spine patholothegies, operation time, blood loss, complications, etc.) although significantly more patients in the non-LSOS group had a fusion procedure (38 vs 18% in LSOS; p = 0.0004). Postoperatively, neither the COMI nor its subdomain scores differed significantly between the groups (p > 0.05). Multiple logistic regression revealed that worse baseline COMI (p = 0.021), surgeon (p = 0.003), and having fusion (p = 0.014) predicted non-enrolment in LSOS. A high proportion of eligible patients were not enrolled in the study. Non-enrolment was explained in part by the specific surgeon, worse baseline COMI status, and having a fusion. The findings may reflect a tendency of the referring surgeon not to overburden more disabled patients and those undergoing more extensive surgery with the commitments of a study. Beyond these factors, non-enrolment appeared to be somewhat arbitrary, and was likely related to surgeon forgetfulness, time constraints, and administrative errors. Researchers should be aware of potential selection bias in their clinical studies, measure it (where possible) and discuss its implications for the interpretation of the study's findings.

Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis.

PubMed

Ruperto, Nicolino; Lovell, Daniel J; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhães, Claudia; Chavez-Corrales, J; Huemer, Christian; Kivitz, Alan; Blanco, Francisco J; Foeldvari, Ivan; Hofer, Michael; Horneff, Gerd; Huppertz, Hans-Iko; Job-Deslandre, Chantal; Loy, Anna; Minden, Kirsten; Punaro, Marilynn; Nunez, Alejandro Flores; Sigal, Leonard H; Block, Alan J; Nys, Marleen; Martini, Alberto; Giannini, Edward H

2010-06-01

We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >or=21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008. Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Outcomes of endodontic therapy in general practice

PubMed Central

Bernstein, Susan D.; Horowitz, Allan J.; Man, Martin; Wu, Hongyu; Foran, Denise; Vena, Donald A.; Collie, Damon; Matthews, Abigail G.; Curro, Frederick A.; Thompson, Van P.; Craig, Ronald G.

2014-01-01

Background The authors undertook a study involving members of a dental practice-based research network to determine the outcome and factors associated with success and failure of endodontic therapy. Methods Members in participating practices (practitioner-investigators [P-Is]) invited the enrollment of all patients seeking treatment in the practice who had undergone primary endodontic therapy and restoration in a permanent tooth three to five years previously. If a patient had more than one tooth so treated, the P-I selected as the index tooth the tooth treated earliest during the three- to five-year period. The authors excluded from the study any teeth that served as abutments for removable partial dentures or overdentures, third molars and teeth undergoing active orthodontic endodontic therapy. The primary outcome was retention of the index tooth. Secondary outcomes, in addition to extraction, that defined failure included clinical or radiographic evidence (or both) of periapical pathosis, endodontic retreatment or pain on percussion. Results P-Is in 64 network practices enrolled 1,312 patients with a mean (standard deviation) time to follow-up of 3.9 (0.6) years. During that period, 3.3 percent of the index teeth were extracted, 2.2 percent underwent retreatment, 3.6 percent had pain on percussion and 10.6 percent had periapical radiolucencies for a combined failure rate of 19.1 percent. The presence of preoperative periapical radiolucency with a diagnosis of either irreversible pulpitis or necrotic pulp was associated with failure after multivariate analysis, as were multiple canals, male sex and Hispanic/Latino ethnicity. Conclusions These results suggest that failure rates for endodontic therapy are higher than previously reported in general practices, according to results of studies based on dental insurance claims data. Clinical Implications The results of this study can help guide the practitioner in deciding the most appropriate course of therapy for teeth with irreversible pulpitis, necrotic pulp or periapical periodontitis. PMID:22547719

Outcomes of endodontic therapy in general practice: a study by the Practitioners Engaged in Applied Research and Learning Network.

PubMed

Bernstein, Susan D; Horowitz, Allan J; Man, Martin; Wu, Hongyu; Foran, Denise; Vena, Donald A; Collie, Damon; Matthews, Abigail G; Curro, Frederick A; Thompson, Van P; Craig, Ronald G

2012-05-01

The authors undertook a study involving members of a dental practice-based research network to determine the outcome and factors associated with success and failure of endodontic therapy. Members in participating practices (practitioner-investigators [P-Is]) invited the enrollment of all patients seeking treatment in the practice who had undergone primary endodontic therapy and restoration in a permanent tooth three to five years previously. If a patient had more than one tooth so treated, the P-I selected as the index tooth the tooth treated earliest during the three- to five-year period. The authors excluded from the study any teeth that served as abutments for removable partial dentures or overdentures, third molars and teeth undergoing active orthodontic endodontic therapy. The primary outcome was retention of the index tooth. Secondary outcomes, in addition to extraction, that defined failure included clinical or radiographic evidence (or both) of periapical pathosis, endodontic retreatment or pain on percussion. P-Is in 64 network practices enrolled 1,312 patients with a mean (standard deviation) time to follow-up of 3.9 (0.6) years. During that period, 3.3 percent of the index teeth were extracted, 2.2 percent underwent retreatment, 3.6 percent had pain on percussion and 10.6 percent had periapical radiolucencies for a combined failure rate of 19.1 percent. The presence of preoperative periapical radiolucency with a diagnosis of either irreversible pulpitis or necrotic pulp was associated with failure after multivariate analysis, as were multiple canals, male sex and Hispanic/Latino ethnicity. These results suggest that failure rates for endodontic therapy are higher than previously reported in general practices, according to results of studies based on dental insurance claims data. The results of this study can help guide the practitioner in deciding the most appropriate course of therapy for teeth with irreversible pulpitis, necrotic pulp or periapical periodontitis.

Low Serum Vitamin D Levels Are Associated With Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and LYSA Studies

PubMed Central

Kelly, Jennifer L.; Salles, Gilles; Goldman, Bryan; Fisher, Richard I.; Brice, Pauline; Press, Oliver; Casasnovas, Olivier; Maloney, David G.; Soubeyran, Pierre; Rimsza, Lisa; Haioun, Corinne; Xerri, Luc; LeBlanc, Michael; Tilly, Hervé; Friedberg, Jonathan W.

2015-01-01

Purpose Recent literature reports a potential association between high vitamin D and improved lymphoma prognosis. We evaluated the impact of pretreatment vitamin D on follicular lymphoma (FL) outcome. Patients and Methods SWOG participants were previously untreated patients with FL enrolled onto SWOG clinical trials (S9800, S9911, or S0016) involving CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab) between 1998 and 2008. Participants included in our second independent cohort were also previously untreated patients with FL enrolled onto the Lymphoma Study Association (LYSA) PRIMA trial of rituximab plus chemotherapy (randomly assigned to rituximab maintenance v observation) between 2004 and 2007. Using the gold-standard liquid chromatography–tandem mass spectrometry method, 25-hydroxyvitamin D was measured in stored baseline serum samples. The primary end point was progression-free survival (PFS). Results After a median follow-up of 5.4 years, the adjusted PFS and overall survival hazard ratios for the SWOG cohort were 1.97 (95% CI, 1.10 to 3.53) and 4.16 (95% CI, 1.66 to 10.44), respectively, for those who were vitamin D deficient (< 20 ng/mL; 15% of cohort). After a median follow-up of 6.6 years, the adjusted PFS and overall survival hazard ratios for the LYSA cohort were 1.50 (95% CI, 0.93 to 2.42) and 1.92 (95% CI, 0.72 to 5.13), respectively, for those who were vitamin D deficient (< 10 ng/mL; 25% of cohort). Conclusion Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and FL outcomes in two independent cohorts suggests that serum vitamin D might be the first potentially modifiable factor to be associated with FL survival. Further investigation is needed to determine the effects of vitamin D supplementation in this clinical setting. PMID:25823738

External prolonged electrocardiogram monitoring in unexplained syncope and palpitations: results of the SYNARR-Flash study.

PubMed

Locati, E T; Moya, A; Oliveira, M; Tanner, H; Willems, R; Lunati, M; Brignole, M

2016-08-01

SYNARR-Flash study (Monitoring of SYNcopes and/or sustained palpitations of suspected ARRhythmic origin) is an international, multicentre, observational, prospective trial designed to evaluate the role of external 4-week electrocardiogram (ECG) monitoring in clinical work-up of unexplained syncope and/or sustained palpitations of suspected arrhythmic origin. Consecutive patients were enrolled within 1 month after unexplained syncope or palpitations (index event) after being discharged from emergency room or hospitalization without a conclusive diagnosis. A 4-week ECG monitoring was obtained by external high-capacity loop recorder (SpiderFlash-T(®), Sorin) storing patient-activated and auto-triggered tracings. Diagnostic monitorings included (i) conclusive events with reoccurrence of syncope or palpitation with concomitant ECG recording (with/without arrhythmias) and (ii) events with asymptomatic predefined significant arrhythmias (sustained supraventricular or ventricular tachycardia, advanced atrio-ventricular block, sinus bradycardia <30 b.p.m., pauses >6 s). SYNARR-Flash study enrolled 395 patients (57.7% females, 56.9 ± 18.7 years, 28.1% with syncope, and 71.9% with palpitations) from 10 European centres. For syncope, the 4-week diagnostic yield was 24.5%, and predictors of diagnostic events were early start of recording (0-15 vs. >15 days after index event) (OR 6.2, 95% CI 1.3-29.6, P = 0.021) and previous history of supraventricular arrhythmias (OR 3.6, 95% CI 1.4-9.7, P = 0.018). For palpitations, the 4-week diagnostic yield was 71.6% and predictors of diagnostic events were history of recurrent palpitations (P < 0.001) and early start of recording (P = 0.001). The 4-week external ECG monitoring can be considered as first-line tool in the diagnostic work-up of syncope and palpitation. Early recorder use, history of supraventricular arrhythmia, and frequent previous events increased the likelihood of diagnostic events during the 4-week external ECG monitoring. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Prospective clinical observational study evaluating gender-associated differences of preoperative pain intensity.

PubMed

Tafelski, Sascha; Kerper, Léonie F; Salz, Anna-Lena; Spies, Claudia; Reuter, Eva; Nachtigall, Irit; Schäfer, Michael; Krannich, Alexander; Krampe, Henning

2016-07-01

Previous studies reported conflicting results concerning different pain perceptions of men and women. Recent research found higher pain levels in men after major surgery, contrasted by women after minor procedures. This trial investigates differences in self-reported preoperative pain intensity between genders before surgery.Patients were enrolled in 2011 and 2012 presenting for preoperative evaluation at the anesthesiological assessment clinic at Charité University hospital. Out of 5102 patients completing a computer-assisted self-assessment, 3042 surgical patients with any preoperative pain were included into this prospective observational clinical study. Preoperative pain intensity (0-100 VAS, visual analog scale) was evaluated integrating psychological cofactors into analysis.Women reported higher preoperative pain intensity than men with median VAS scores of 30 (25th-75th percentiles: 10-52) versus 21 (10-46) (P < 0.001). Adjusted multiple regression analysis showed that female gender remained statistically significantly associated with higher pain intensity (P < 0.001). Gender differences were consistent across several subgroups especially with varying patterns in elderly. Women scheduled for minor and moderate surgical procedures showed largest differences in overall pain compared to men.This large clinical study observed significantly higher preoperative pain intensity in female surgical patients. This gender difference was larger in the elderly potentially contradicting the current hypothesis of a primary sex-hormone derived effect. The observed variability in specific patient subgroups may help to explain heterogeneous findings of previous studies.

Anxiety and depression after failure of assisted reproductive treatment among patients experiencing infertility.

PubMed

Maroufizadeh, Saman; Karimi, Elaheh; Vesali, Samira; Omani Samani, Reza

2015-09-01

To investigate the impact of the number of previous infertility treatment failures on anxiety and depression. In a cross-sectional study, individuals (men and women, but not couples) aged at least 18 years who had a history of infertility and could read and write in Persian were enrolled at the Royan Institute, Tehran, Iran, between November 1, 2013, and February 28, 2014. Participants provided demographic and infertility information and completed the Persian version of the Hospital Anxiety and Depression Scale (HADS). Overall, 330 patients (122 men, 208 women) were included. Mean scores on the HADS anxiety and depression subscales (HADS-A and HADS-D) were 8.40±4.51 and 5.95±3.54, respectively. In multiple regression analysis, mean HADS-A scores were significantly higher for patients with one treatment failure (9.57±4.58) than for those without a history of treatment (7.79±4.13; P=0.003). HADS-D scores were significantly higher for patients with two failures (6.92±3.69) than for those with no previous treatment (5.59±3.79; P=0.019). Patients with infertility have increased depression and anxiety after infertility treatment failure. Counseling or treatment for these potential psychological effects should be considered after infertility treatment failure. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Child Care Enrollment Decisions Among Dual Language Learner Families: The Role of Spanish Language Instruction in the Child Care Setting

PubMed Central

Miller, Elizabeth B.

2016-01-01

Data from the Head Start Impact Study (N = 1,141) and the Head Start Family and Child Experiences Survey, 2009 Cohort (N = 825) were used to describe child care enrollment decisions among Spanish-speaking Dual Language Learner (DLL) families. In particular, logistic regression models tested which child, family, and institutional characteristics predicted enrollment in early care and education (ECE) settings that used Spanish for instruction versus enrollment in settings that did not use Spanish. Results showed that whether the child’s first language was exclusively Spanish and whether other DLL families previously attended the ECE arrangement strongly predicted whether that child enrolled. Policy implications for Head Start-eligible Spanish-speaking DLLs are discussed. PMID:26900255

Barriers to Clinical Trial Enrollment in Racial and Ethnic Minority Patients With Cancer

PubMed Central

Hamel, Lauren M.; Penner, Louis A.; Albrecht, Terrance L.; Heath, Elisabeth; Gwede, Clement K.; Eggly, Susan

2016-01-01

Background Clinical trials that study cancer are essential for testing the safety and effectiveness of promising treatments, but most people with cancer never enroll in a clinical trial — a challenge exemplified in racial and ethnic minorities. Underenrollment of racial and ethnic minorities reduces the generalizability of research findings and represents a disparity in access to high-quality health care. Methods Using a multilevel model as a framework, potential barriers to trial enrollment of racial and ethnic minorities were identified at system, individual, and interpersonal levels. Exactly how each level directly or indirectly contributes to doctor–patient communication was also reviewed. Selected examples of implemented interventions are included to help address these barriers. We then propose our own evidence-based intervention addressing barriers at the individual and interpersonal levels. Results Barriers to enrolling a diverse population of patients in clinical trials are complex and multilevel. Interventions focused at each level have been relatively successful, but multilevel interventions have the greatest potential for success. Conclusion To increase the enrollment of racial and ethnic minorities in clinical trials, future interventions should address barriers at multiple levels. PMID:27842322

Impact of PNPLA3 and IFNL3 polymorphisms on hepatic steatosis in Asian patients with chronic hepatitis C

PubMed Central

Huang, Chao-Min; Chang, Kuo-Chin; Hung, Chao-Hung; Chiu, King-Wah; Lu, Sheng-Nan; Wang, Jing-Houng; Chen, Chien-Hung; Kee, Kwong-Ming; Kuo, Yuan-Hung; Tsai, Ming-Chao; Tseng, Po-Lin; Lin, Ming-Tsung; Wu, Cheng-Kun; Hu, Tsung-Hui; Cho, Chung-Lung

2017-01-01

Background and aims A recent meta-analysis revealed that the genotype PNPLA3 rs738409 GG is associated with a higher risk of hepatic steatosis (HS) in Caucasian patients with chronic hepatitis C (CHC). However, controversial results were found regarding Asian populations. Furthermore, previous studies have shown a negative association between interferon lambda 3 (IFNL3) rs12979860 CC and HS in Caucasian CHC patients, but there have been no reports indicating any such association in Asian populations. In this study, then, we investigated the association of PNPLA3 and IFNL3 polymorphisms with HS in Asian CHC patients. Methods We enrolled consecutive CHC patients who underwent liver biopsy prior to antiviral therapy. We excluded those patients with decompensated liver disease, any co-existing chronic liver disease, or HIV or HBV co-infection. Results 1080 CHC patients were enrolled, and HS was found in 453 (41.9%) patients. The frequency distribution of the G allele was significantly associated with HS (P<0.001), and this conferred a higher risk to G allele homozygotes (OR: 2.06, 95% CI: 1.46–2.88, P <0.001) than to G allele carriers (OR: 1.98, 95% CI: 1.52–2.58, P<0.001). There was a borderline significant difference in the prevalence of HS in rs12979860 CC versus non-CC (40.8% versus 49.3%, P = 0.059). After adjustment for age, sex, body mass index, diabetes, and excessive alcohol intake, the rs738409 G allele homozygote carriers still carried a higher risk for HS (OR: 1.93, 95% CI: 1.35–2.77, P = 0.003). Conclusion The PNPLA3 rs738409 GG genotype is positively associated with HS, while the IFNL3 rs 12979860 CC genotype may be negatively associated with HS, in Asian CHC patients. PMID:28797039

Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer.

PubMed

Norton, Nadine; Fox, Nicholas; McCarl, Christie-Ann; Tenner, Kathleen S; Ballman, Karla; Erskine, Courtney L; Necela, Brian M; Northfelt, Donald; Tan, Winston W; Calfa, Carmen; Pegram, Mark; Colon-Otero, Gerardo; Perez, Edith A; Clynes, Raphael; Knutson, Keith L

2018-06-14

Resected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. Pre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival. Prior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p = 0.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR = 0.23; p = 0.04). These results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting. ClinicalTrials.gov, NCT00005970 . Registered on July 5, 2000.

Dual Therapy with Aspirin and Cilostazol May Improve Platelet Aggregation in Noncardioembolic Stroke Patients: A Pilot Study.

PubMed

Ohnuki, Yoichi; Ohnuki, Yuko; Kohara, Saori; Shimizu, Mie; Takizawa, Shunya

2017-01-01

Objective Some previous studies have found clinical benefit of dual antiplatelet therapy with aspirin and cilostazol for prevention of secondary stroke, but the physiological mechanism involved remains unknown. We aimed to clarify the effects of aspirin/cilostazol therapy on the platelet and endothelial functions of patients with acute noncardioembolic ischemic stroke, in comparison to patients who were treated with aspirin alone. Methods The present randomized prospective pilot study enrolled 24 patients within a week after the onset of noncardioembolic ischemic stroke. The patients were randomly allocated to receive aspirin (100 mg/day) (A group; 11 patients) or cilostazol (200 mg/day) plus aspirin (100 mg/day) (CA group; 13 patients). We measured platelet aggregation, platelet activation, and the thrombomodulin (TM), highly sensitive C-reactive protein (hs-CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand (vWF) antigen levels and vWF activity over a 4-week period after enrollment. Results There was no significant difference in the platelet functions of the A and CA groups. However, the platelet aggregation induced by adenosine diphosphate (ADP) was decreased at 2 and 4 weeks (p<0.05) after treatment in comparison to the pre-treatment values in the CA group, but not in the A group. Platelet activation, and the hs-CRP, TM, ICAM-1, VCAM-1 and vWF values did not significantly decrease after treatment in either group. Conclusion Although there were no significant differences in platelet aggregation, platelet activation or the endothelial biomarker levels of the A and CA groups, dual therapy with aspirin and cilostazol inhibited platelet aggregation in comparison to the pre-treatment values, similarly to patients who received aspirin alone. This may suggest the clinical usefulness of dual therapy with aspirin and cilostazol in the treatment of patients with noncardioembolic ischemic stroke.

An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010

PubMed Central

2011-01-01

Background In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak. Methods Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software. Results Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (p < 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008. Conclusions HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities. PMID:22168544

Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study.

PubMed

Jabbour, Elias; Kantarjian, Hagop; Ravandi, Farhad; Thomas, Deborah; Huang, Xuelin; Faderl, Stefan; Pemmaraju, Naveen; Daver, Naval; Garcia-Manero, Guillermo; Sasaki, Koji; Cortes, Jorge; Garris, Rebecca; Yin, C Cameron; Khoury, Joseph D; Jorgensen, Jeffrey; Estrov, Zeev; Bohannan, Zachary; Konopleva, Marina; Kadia, Tapan; Jain, Nitin; DiNardo, Courtney; Wierda, William; Jeanis, Vicky; O'Brien, Susan

2015-11-01

Combination of chemotherapy with a tyrosine-kinase inhibitor is effective in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia. Ponatinib is a more potent BCR-ABL1 inhibitor than all other tyrosine-kinase inhibitors and selectively suppresses the resistant T315I clones. We examined the activity and safety of combining chemotherapy with ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia in this continuing phase 2 trial. In this single-centre, phase 2, single-arm trial, adult patients with previously untreated Philadelphia chromosome-positive acute lymphoblastic leukaemia were sequentially enrolled. Patients who had received fewer than two courses of previous chemotherapy with or without tyrosine-kinase inhibitors were also eligible. Patients had to be aged 18 years or older, have an Eastern Cooperative Oncology Group performance status of 2 or less, have normal cardiac function (defined by ejection fraction above 50%), and have adequate organ function (serum bilirubin ≤3·0 mg/dL and serum creatinine ≤3·0 mg/dL, unless higher concentrations were believed to be due to a tumour). Patients received eight cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) alternating with high-dose methotrexate and cytarabine every 21 days. Ponatinib 45 mg was given daily for the first 14 days of cycle 1 then continuously for the subsequent cycles. Patients in complete remission received maintenance with ponatinib 45 mg daily with vincristine and prednisone monthly for 2 years followed by ponatinib indefinitely. The primary endpoint for this study was event-free survival. The trial is registered at ClinicalTrials.gov, number NCT01424982. 37 patients were enrolled and treated from Nov 1, 2011, to Sept 1, 2013. 2-year event-free survival rate was 81% (95% CI 64-90). Grade 3 or more toxic effects included infections during induction (20 [54%] patients), increased aspartate aminotransferase and alanine aminotransferase concentration (14 [38%] patients), thrombotic events (three [8%]), myocardial infarction (three [8%]), hypertension (six [16%]), skin rash (eight [22%]), and pancreatitis (six [16%] patients). Two patients died from from myocardial infarction potentially related to treatment; another patient also died from myocardial infarction related to sepsis. Two further patients died, one from bleeding and another from infection, both deemed unrelated to treatment. The first results of this ongoing trial indicate that the combination of chemotherapy with ponatinib is effective in achieving early sustained remissions in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukaemia. New strategies, including dosing titration of ponatinib and optimised control of vascular risk factors, might further improve outcomes. ARIAD Pharmaceuticals Inc. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inferior outcomes of stage III T lymphoblastic lymphoma relative to stage IV lymphoma and T-acute lymphoblastic leukemia: long-term comparison of outcomes in the JACLS NHL T-98 and ALL T-97 protocols.

PubMed

Kobayashi, Ryoji; Takimoto, Tetsuya; Nakazawa, Atsuko; Fujita, Naoto; Akazai, Ayumi; Yamato, Kazumi; Yazaki, Makoto; Deguchi, Takao; Hashii, Yoshiko; Kato, Koji; Hatakeyama, Naoki; Horibe, Keizo; Hori, Hiroki; Oda, Megumi

2014-06-01

T cell lymphoblastic lymphoma (T-LBL) accounts for 30 % of all childhood non-Hodgkin's lymphomas (NHL) in Japan. Twenty-nine patients with T-LBL in stages III and IV were eligible for and enrolled in the JACLS NHL-T98 trial (1998-2002), and 72 patients with T-ALL were enrolled in the JACLS ALL-T97 trial (1997-2001). The 10-year overall survival (OS) (61.1 ± 11.5 %) and the 10-year event-free survival (EFS) (44.4 ± 11.7 %) of stage III LBL were lower than those of other diseases, and the OS and EFS were nearly the same when comparing stage IV LBL and ALL (OS: stage IV LBL, 80.0 ± 12.7 % vs. ALL, 80.2 ± 4.9 %; EFS: stage IV, LBL 70.0 ± 14.5 % vs. ALL, 70.7 ± 5.5 %). Outcomes were worse for stage III LBL than for stage IV LBL or T-ALL. Given that the treatment results of T-ALL and LBL stage IV did not differ when compared with previous reports, LBL stage III in Japanese children may differ from LBL stage III in children in other countries.

Everolimus in Combination with Octreotide Long-Acting Repeatable in a First-Line Setting for Patients with Neuroendocrine Tumors: A 5-Year Update.

PubMed

Bajetta, Emilio; Catena, Laura; Pusceddu, Sara; Spada, Francesca; Iannacone, Claudio; Sarno, Italo; Di Menna, Giandomenico; Dottorini, Lorenzo; Marte, Anna Maria

2018-01-01

We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. Patients with advanced well-differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR). We performed an analysis of "long responder" patients and of time to progression (TTP) and overall survival (OS) at 5 years. Fifty patients were enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients). Seventeen (34%) of these patients have received treatment for more than 2 years. The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3 patients are still in treatment. The ORR (partial response + complete response) was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months (95% CI 49.8-not reached). In this update of clinical outcome at 5-year follow-up, everolimus plus octreotide has been shown to be active in advanced NENs. The current analysis showed a further prolongation of TTP and a long exposure to the study drug without major side effects in the long term. © 2017 S. Karger AG, Basel.

A Phase I Study of Triapine® in Combination with Doxorubicin in Patients with Advanced Solid Tumors

PubMed Central

Schelman, William R.; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M.; Ivy, Percy; Wilding, George; Traynor, Anne M.

2011-01-01

Purpose To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine® administered in combination with doxorubicin. Study Design Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine® IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m2 and Triapine® 25 mg/m2. PK analysis was performed at various time-points before and after treatment. Results Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m2, Triapine® 45 mg/m2), 2 patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional 3 patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m2) with Triapine® 45 mg/m2. The 2 patients enrolled on this level had 2 DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine® were reduced to 45 mg/m2 and 25 mg/m2, respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Conclusions Pretreated patients with advanced malignancies can tolerate the combination of Triapine® and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m2 on day 1 and Triapine® 25 mg/m2 on days 1-4 of a 21 day cycle. PMID:19082825

A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors.

PubMed

Schelman, William R; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M; Ivy, Percy; Wilding, George; Traynor, Anne M

2009-05-01

To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine administered in combination with doxorubicin. Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine 25 mg/m(2). PK analysis was performed at various time-points before and after treatment. Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Pretreated patients with advanced malignancies can tolerate the combination of Triapine and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine 25 mg/m(2) on days 1-4 of a 21-day cycle.

A qualitative analysis of patient-centered dentistry in consultations with dental phobic patients.

PubMed

Kulich, Károly R; Berggren, Ulf; Hallberg, Lillemor R-M

2003-01-01

Dental phobia is regarded as one of the greatest obstructions to adequate dental care. It has long been established that fearful dental patients are particularly sensitive to dentists' behavior and performance of dental care. There is a need for the establishment of a systematic theory of dentist-patient communication and new methods analyzing how dentists interact with their patients. In this qualitative study, thirty semi-structured interviews were conducted in 1998 and 1999 with five dentists (three male and two female). Dentists consulted on two occasions with 15 newly enrolled, consecutive dental phobic patients (2 male and 13 female) in a Swedish clinic specializing in the treatment of odontophobia. The time interval between consultation one and two was approximately 2-3 weeks. Analysis of the transcribed interviews was based by the principles of Grounded Theory. The study identified one core category, "Holistic perception and understanding of the patient", two categories, "The dentist's positive outlook on people" and "The dentist's positive view of patient contact", and six further subcategories. Findings support previous models of patient-centered medicine and contribute to a better understanding of how patient-centered dentists interact with dental phobic patients.

Impact of Smoke Evacuation on Patient Experience During Mohs Surgery.

PubMed

Yonan, Yousif; Ochoa, Shari

2017-11-01

There have been several investigations into possible health risks of surgical smoke exposure, and it has previously been associated with harboring pathogens and carcinogens. Patients in the authors' practice have expressed that the odor from the smoke created by electrosurgical equipment is unpleasant. The authors sought to determine if smoke evacuation decreases patient perception of smoke created by electrosurgery during Mohs surgery and if it subsequently improves patient satisfaction with their surgical experience by minimizing the associated odor. Thirty patients were enrolled in this comparative trial. Smoke evacuation was used during closure but not during Mohs stages. Patients were queried regarding their experience and preferences during and at the end of the procedure. 100% of patients reported the perception of a burning odor during removal of Mohs stages, compared with 40% reporting the perception of a burning odor during closure. During the Mohs stages, 66.6% of patients reported the odor as unpleasant compared with 16.6% of patients during closure. There were no statistically significant differences in patient perceptions when stratified by age, sex, or surgical site. The authors believe that using a wall suction smoke evacuation system is simple and can result in a more pleasant experience for patients undergoing Mohs surgery.

The Prevalence of Japanese Outpatients with Hypertension Who Meet the Definition of Treatment Resistant Hypertension and Are Eligible for Enrolment in Clinical Trials of Endovascular Ultrasound Renal Denervation.

PubMed

Okamura, Keisuke; Shirai, Kazuyuki; Okuda, Tetsu; Urata, Hidenori

2018-01-01

Objective A clinical trial (REQUIRE) was started to investigate the use of an ultrasound renal denervation system in the treatment of resistant hypertension (RHT). We analyzed the prevalence of patients who were eligible for inclusion in this cross-sectional study at the time of screening. Methods Nine-hundred ninety-nine consecutive hypertension (HT) patients who were treated in our hospital as outpatients were classified into the following categories: patients treated with at least 3 types of antihypertensive drugs including diuretic agents who were eligible for enrolment in SYMPLICITY HTN-Japan (SH-J) with an office systolic blood pressure (SBP) of ≥160 mmHg, who were ≤80 years of age, and an estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73 m 2 (RHT-S); and patients who were treated similar medications and who were eligible for enrolment in REQUIRE, with an SBP of ≥150 mmHg, ≤75 years of age, and an eGFR of ≥40 mL/min/1.73 m 2 (RHT-R). We investigated the proportion of patients in each category. We also investigated HT patients (1,423 cases) who were enrolled in the Chikushi Anti-Hypertension Trial (CHAT), a research network that includes general practitioners. Results Eleven patients (1.1%) with RHT-S and 18 patients (1.8%) with RHT-R were identified. After the exclusion of patients with secondary HT and a diastolic blood pressure (DBP) of <90 mmHg (applied in REQUIRE), 5 patients (0.5%) with RHT-S and 4 patients (0.4%) with RHT-R remained. In the analysis of the CHAT study, only 2 (0.1%) patients with RHT-R remained. Conclusion The number of eligible patients in the REQUIRE trial was decreased, largely due to the strict age restriction and the new DBP limitation. The prevalence of eligible patients in REQUIRE was estimated to be approximately 0.5 to 0.8 times that in SH-J. Since patient enrollment will be difficult, drastic measures may be required to recruit eligible patients.

Factors Influencing Depression Endpoints Research (FINDER): baseline results of Italian patients with depression

PubMed Central

Grassi, Luigi; Rossi, Andrea; Barraco, Alessandra

2009-01-01

Background Factors Influencing Depression Endpoints Research (FINDER) is a 6-month, prospective, observational study carried out in 12 European countries aimed at investigating health-related quality of life (HRQoL) in outpatients receiving pharmacological treatment for a first or new depressive episode. Baseline characteristics of patients enrolled in Italy are presented. Methods All treatment decisions were at the discretion of the investigator. Data were collected at baseline and after 3 and 6 months of treatment. Baseline evaluations included demographics, medical and psychiatric history, and medications used in the last 24 months and prescribed at enrolment. The Hospital Anxiety and Depression Scale (HADS), was adopted to evaluate depressive symptoms, while somatic and painful physical symptoms were assessed by using the Somatic Symptom Inventory (SSI) and a 0 to 100 mm visual analogue scale (VAS), HRQoL via 36-item Short Form Health Survey (SF-36), and the European Quality of Life 5-Dimensions (EQ-5D) instrument. Results A total of 513 patients were recruited across 38 sites. The mean ± standard deviation (SD) age at first depressive episode was 38.7 ± 15.9 years, the mean duration of depression 10.6 ± 12.3 years. The most common psychiatric comorbidities in the previous 24 months were anxiety/panic (72.6%) and obsessive/compulsive disorders (13.4%), while 35.9% had functional somatic syndromes. Most patients (65.1%) reported pain from any cause. Monotherapy with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) was prescribed at enrolment in 64.5% and 6.4% of the cases, respectively. The most commonly prescribed agents were sertraline (17.3%), escitalopram (16.2%), venlaflaxine (15.6%) and paroxetine (14.8%). The mean HADS subscores for depression and anxiety were 13.3 ± 4.2 and 12.2 ± 3.9, respectively; 76.4% of patients could be defined as being 'probable cases' for depression and 66.2% for anxiety. The mean total score of VAS-pain in the last week was 42.9 ± 27.1, with highest scores reported in the 'interference of pain with daily activities' and in 'amount of time patient was awake and had pain'. From SF-36, the worst health status was found for role limitations due to emotional problem, mental health and social functioning. A mean score < 50 (that is, below the standardised population norm) was also found in all remaining domains. The SF-36 summary scores and EQ-5D (health status and VAS) were lower in patients with moderate/severe pain than in those with no or mild pain. Conclusion The baseline results of patients enrolled in the FINDER study in Italy show clinical and functional impairments, and poor HRQoL. The results obtained after 6 months of therapy will permit better understanding the effects of different variables on clinical outcomes and HRQoL. PMID:19480684

Patient internet use surrounding cancer clinical trials: clinician perceptions and responses

PubMed Central

Simon, Christian; Schramm, Sarah; Hillis, Stephen

2010-01-01

Clinician perceptions of patient internet use related to clinical trials are not well documented. This exploratory study surveyed how cancer care providers at one NCI-designated cancer center viewed patient internet use surrounding cancer trials, including whether it affected patient decision making regarding trial enrollment. The sample included 20 oncologists (59%) and 14 (41%) nurses (n=34). Most clinicians (n=26; 76%) perceived the internet as having an effect on whether or not patients decided to enroll in a cancer trial. Two thirds (n=17; 65%) felt that this effect was positive, including in terms of enhancing patient knowledge of, access to, and enrollment in trials. Clinicians were asked if they ever discussed with their patients the topic of going online to find out more about cancer trials. Over half (n=18; 58%) who responded (n=31) to this item said yes; the rest (n=13; 42%) said no. The majority (n=10; 77%) in the “no” category were among those who reported that the internet had an effect on patient decision making. These data provisionally suggest that clinicians may see the internet as having mostly a positive effect on patient decision making about cancer trials, but that their communication efforts with patients do not always logically follow from this perception. Provider-patient discussion about internet use may be an opportunity for clinicians to contribute to improved patient knowledge of and enrollment in cancer trials. More research is needed to confirm and explain the gap between clinician perception and communication regarding trial-related internet use by cancer patients. PMID:20227523

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

PubMed

Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R; Andrews, Leslie; Rabkin, Judith G; McElhiney, Martin; Nieves, Jeri; Santella, Regina M; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S; Miller, Robert G; Katz, Jonathan S; Forshew, Dallas; Barohn, Richard J; Sorenson, Eric J; Oskarsson, Bjorn; Fernandes Filho, J Americo M; Kasarskis, Edward J; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D; Nations, Sharon P; Swenson, Andrea J; Shefner, Jeremy M; Andrews, Jinsy A; Koczon-Jaremko, Boguslawa A

2014-06-01

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

An educational video to increase clinical trials enrollment among breast cancer patients.

PubMed

Du, Wei; Mood, Darlene; Gadgeel, Shirish; Simon, Michael S

2009-09-01

Only 3% of women with breast cancer participate in cancer clinical trials nationwide. The lack of awareness about clinical trials is a significant barrier towards clinical trials participation. A study was conducted at a large urban Comprehensive Cancer Center to test (1) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute, and (2) to assess racial differences in attitudes regarding clinical trials. Participants were randomized to either the educational intervention prior to their first oncology clinic appointment or to standard care. A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants. Of 218 subjects recruited, 196 (55% white vs. 45% African American (AA)) eligible patients were included in the analysis. A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant (10.4% vs. 6.1%; P = 0.277). The intervention also did not result in a clear improvement in patients' attitudes toward clinical trials at posttest. However, a lower enrollment rate for the AA women was noted after adjusting for stage (OR = 0.282, P = 0.049). Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women. The educational video did not significantly increase enrollment in breast cancer clinical trials. The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment. An educational video remains a simple and cost-effective way to educate patients. Future studies should focus on designing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment.

Hemorrhoids and matrix metalloproteinases: A multicenter study on the predictive role of biomarkers.

PubMed

Serra, Raffaele; Gallelli, Luca; Grande, Raffaele; Amato, Bruno; De Caridi, Giovanni; Sammarco, Giuseppe; Ferrari, Francesco; Butrico, Lucia; Gallo, Gaetano; Rizzuto, Antonia; de Franciscis, Stefano; Sacco, Rosario

2016-02-01

An association between hemorrhoidal disease and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase-associated lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between tissue immunoreactive levels of MMPs and NGAL and different stages of hemorrhoids. In a multicenter, open-label, prospective study, the population under investigation consisted of 2 groups: group I (with symptomatic hemorrhoids; Goligher grade I-IV) and group II (healthy volunteers). We enrolled 97 patients with hemorrhoids: 21 with grade I hemorrhoids, 37 with grade II, 14 with grade III, and 25 with grade IV. Finally, 90 healthy volunteers (53 males and 37 females; age range, 19-70 years; median, 56) were enrolled in group II. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMPs and NGAL in all patients with hemorrhoids. We recorded significantly greater levels of MMP-1 and MMP-3 in grade I and II patients compared with control, and greater levels of MMP-3, MMP-7, MMP-8, and MMP-9 in grade III compared with grade II. MMP-9 and NGAL were particularly increased in patients with grade IV especially in case of thrombosed hemorrhoids. These results provide potentially important insights into the understanding of the natural history of hemorrhoids. MMPs and NGAL play a role in development of disease and may represent molecular markers for the complications such as hemorrhoidal thrombosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Parent's use of the Internet in the search for healthcare information and subsequent impact on the doctor-patient relationship.

PubMed

Harvey, S; Memon, A; Khan, R; Yasin, F

2017-11-01

The Internet is an unavoidable source of healthcare information. This information, both reliable and unreliable, has previously been shown to influence carer's decisions. Our aim was to evaluate this information seeking behavior among parents and its subsequent potential impact on the doctor-patient relationship. We undertook a cross-sectional questionnaire-based survey of paediatric outpatients. Enrollment took place over 4 weeks in March 2015. There were no inclusion or exclusion criteria and enrollment was voluntary. In total 100 questionnaires were completed. General Practitioners were the most common source of healthcare information. The Internet ranked third as a reliable source of healthcare information. The Internet was commonly used as an educational resource to learn about causes, treatment, and medications. A significant percentage of our population expressed concern regarding Internet information reliability. A small percentage of parents were concerned that disclosing Internet usage may worsen the relationship with their doctor. Parents showed a willingness to learn about diseases and treatments, and felt that the Internet was a good resource to do so. This study shows that open discussion about Internet usage between parents and doctors is not common and carers feel at risk of judgment should they admit to Internet usage. The Internet should be seen as a positive adjunct to patient education which can improve understanding, thus strengthening the doctor-patient relationship. The Internet will never replace the role of healthcare professionals but must be seen as an integral part of a multi-disciplinary approach.

Skills in Handling Turbuhaler, Diskus, and Pressurized Metered-Dose Inhaler in Korean Asthmatic Patients

PubMed Central

Lee, Sang Min; Chang, Yoon-Seok; Kim, Cheol-Woo; Kim, Tae-Bum; Kim, Sang-Heon; Kwon, Yong-Eun; Lee, Jong-Myung; Lee, Soo-Keol; Jeong, Jae-Won; Park, Jung-Won; Cho, Sang-Heon; Moon, Hee-Bom

2011-01-01

Purpose The objective of this study was to evaluate skills in handling inhalers and factors associated with these skills among patients with asthma who had undergone treatment at special asthma and allergy clinics in Korea. Methods We enrolled 78 subjects who used Turbuhaler and 145 who used Diskus for asthma control at special clinics in 10 university hospitals and visually assessed their skills in handling these inhalers. We also evaluated skills in 137 subjects who had used pressurized metered-dose inhalers (pMDIs) for symptom relief. Age, sex, duration of asthma and inhaler use, smoking status, monthly income, highest grade completed in school and previous instruction for handling inhalers were also measured to evaluate their association with overall inhaler skills. Results Performance grade was inadequate for 12.8% of participants using Turbuhaler, 6.2% for Diskus, and 23.4% for pMDIs. The success rates for each step in handling the inhalers were relatively high except for the "exhale slowly to residual volume" step, in which success rates ranged from 24.2% to 28.5%. Older age, male sex, lower educational grade, and absence of previous instruction for handling inhalers were associated with inadequate inhaler technique in univariate analysis; however, only older age and absence of previous instruction remained significant independent risk factors in multivariate analysis. Conclusions Among Korean asthmatic patients in special asthma and allergy clinics, skills in handling their inhalers were mostly excellent; meanwhile, older age and absence of previous instruction for handling inhalers were associated with inadequate techniques. PMID:21217925

Extending health maintenance organization insurance to the uninsured. A controlled measure of health care utilization.

PubMed

Bograd, H; Ritzwoller, D P; Calonge, N; Shields, K; Hanrahan, M

1997-04-02

To investigate the utilization of health care services of previously uninsured low-income patients after becoming insured by a health maintenance organization (HMO). Retrospective study of utilization in a previously uninsured study group compared with an age- and sex-matched randomly selected control group of commercial HMO enrollees. Group model HMO. A study group of 346 previously uninsured low-income patients and 382 controls. utpatient visits for primary and specialty care, outpatient pharmacy, laboratory, and radiology use, and inpatient admissions and hospital days over a 2-year period. Self-reported health status measures were obtained to control for differences in health status. There were no differences between the study and control groups in hospital admissions, hospital days, and measures of outpatient laboratory, pharmacy, and radiology use. The odds of having an outpatient visit per patient per month was 30% higher for the study group. Approximately half the increase in the odds ratio for outpatient visits was related to the worse self-perceived health status of the study group. While both groups utilized more services in the early phase of their enrollment, the intensity of this start-up effect was similar for both groups. Compared with a commercial group of the same age and sex, the patterns of utilization were similar and the financial costs of care were only moderately more for a previously uninsured group provided with comprehensive HMO insurance. With the growth of managed care, these data should be beneficial in the development of health care programs for the growing number of uninsured Americans.

Electrocardiographic abnormalities and relative bradycardia in patients with hantavirus-induced nephropathia epidemica.

PubMed

Kitterer, Daniel; Greulich, Simon; Grün, Stefan; Segerer, Stephan; Mustonen, Jukka; Alscher, M Dominik; Braun, Niko; Latus, Joerg

2016-09-01

Nephropathia epidemica (NE), caused by Puumala virus (PUUV), is characterized by acute kidney injury (AKI) and thrombocytopenia. Cardiac involvement with electrocardiographic (ECG) abnormalities has been previously reported in NE; however, its prognostic value is unknown. Relative bradycardia is an important clinical sign in various infectious diseases, and previous smaller studies have described pulse-temperature deficit in patients with PUUV infection. We performed a cross-sectional survey of 471 adult patients with serologically confirmed NE. Data were collected retrospectively from medical records and prospectively at follow-up visits. Patients for whom ECGs were recorded during the acute phase of disease were enrolled retrospectively (n=263). Three patients were excluded because of documented pre-existing ECG abnormalities prior to NE. All patients with ECG abnormalities during the acute phase underwent follow-up. A total of 46 patients had ECG abnormalities at the time of admission to hospital (18%). T-wave inversion was the most frequent ECG abnormality (n=31 patients), followed by ST segment changes (nine patients with elevation and six with depression). No major adverse cardiac events occurred during follow-up (median 37months; range 34-63months). Of note, ECG abnormalities reverted to normal in the majority of the patients during follow-up. During the acute phase of NE, 149 of 186 patients had relative bradycardia, without implications for disease course. Transient ECG abnormalities were detected in 18% of patients during acute NE but were not associated with negative cardiovascular outcome. Relative bradycardia was identified in 80% of the patients with acute NE. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Serum endocan levels in patients with chronic liver disease

PubMed Central

Tok, Duran; Ekiz, Fuat; Basar, Omer; Coban, Sahin; Ozturk, Gulfer

2014-01-01

Background and Aim: Early detection of fibrosis should be the main goal of treatment in liver cirrhosis. Endocan, previously called endothelial cell specific molecule-1, is expressed by endothelial cells, primarily in the lung, liver and kidney. In this study, we aimed to examine the correlation of liver fibrosis stage, histological activity and grade of steatosis between serum levels of endocan in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Patients and Methods: This cross-sectional study includes a total of 146 subjects. 55 CHB patients, 19 CHC patients, 38 NAFLD patients and 34 healthy controls were enrolled consecutively. Liver biopsies were performed in all patients with chronic viral hepatitis. NAFLD patients had either grade 2 or grade 3 steatosis on ultrasonography and elevated liver enzymes above the upper normal limits. Serum endocan levels were assessed from blood samples obtained at admission. Results: Gender distribution was similar among the groups (p=0.056). The mean age of the CHB patients was 45.8±12.1, CHC patients was 55.0±12.8 years, NAFLD patients was 42.8±10.8, while control group was 39.4±13.6 years old. Patients with CHC were older than all the others (p=0.001). Serum endocan levels were statistically significantly lower in CHB, CHC and NAFLD groups when compared with controls. Although levels of endocan were lower in CHB and CHC groups when compared with NAFLD group, the difference was not statistically significant. Conclusion: Serum endocan concentrations decrease in patients with liver disease. Unlike previous studies, we showed a negative correlation between endocan levels and inflammation stage of chronic hepatitis. However, further studies are needed to establish the association between endocan levels, liver fibrosis and hepatic inflammation. PMID:25126183

Associations between medical cannabis and prescription opioid use in chronic pain patients: A preliminary cohort study.

PubMed

Vigil, Jacob M; Stith, Sarah S; Adams, Ian M; Reeve, Anthony P

2017-01-01

Current levels and dangers of opioid use in the U.S. warrant the investigation of harm-reducing treatment alternatives. A preliminary, historical, cohort study was used to examine the association between enrollment in the New Mexico Medical Cannabis Program (MCP) and opioid prescription use. Thirty-seven habitual opioid using, chronic pain patients (mean age = 54 years; 54% male; 86% chronic back pain) enrolled in the MCP between 4/1/2010 and 10/3/2015 were compared to 29 non-enrolled patients (mean age = 60 years; 69% male; 100% chronic back pain). We used Prescription Monitoring Program opioid records over a 21 month period (first three months prior to enrollment for the MCP patients) to measure cessation (defined as the absence of opioid prescriptions activity during the last three months of observation) and reduction (calculated in average daily intravenous [IV] morphine dosages). MCP patient-reported benefits and side effects of using cannabis one year after enrollment were also collected. By the end of the 21 month observation period, MCP enrollment was associated with 17.27 higher age- and gender-adjusted odds of ceasing opioid prescriptions (CI 1.89 to 157.36, p = 0.012), 5.12 higher odds of reducing daily prescription opioid dosages (CI 1.56 to 16.88, p = 0.007), and a 47 percentage point reduction in daily opioid dosages relative to a mean change of positive 10.4 percentage points in the comparison group (CI -90.68 to -3.59, p = 0.034). The monthly trend in opioid prescriptions over time was negative among MCP patients (-0.64mg IV morphine, CI -1.10 to -0.18, p = 0.008), but not statistically different from zero in the comparison group (0.18mg IV morphine, CI -0.02 to 0.39, p = 0.081). Survey responses indicated improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few side effects from using cannabis one year after enrollment in the MCP (ps<0.001). The clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrants further investigations on cannabis as a potential alternative to prescription opioids for treating chronic pain.

High rates of ofloxacin resistance in Mycobacterium tuberculosis among both new and previously treated patients in Tamil Nadu, South India.

PubMed

Selvakumar, N; Kumar, Vanaja; Balaji, S; Prabuseenivasan, S; Radhakrishnan, R; Sekar, Gomathi; Chandrasekaran, V; Kannan, T; Thomas, Aleyamma; Arunagiri, S; Dewan, Puneet; Swaminathan, Soumya

2015-01-01

Periodic drug resistance surveillance provides useful information on trends of drug resistance and effectiveness of tuberculosis (TB) control measures. The present study determines the prevalence of drug resistance among new sputum smear positive (NSP) and previously treated (PT) pulmonary TB patients, diagnosed at public sector designated microscopy centers (DMCs) in the state of Tamil Nadu, India. In this single-stage cluster-sampling prevalence survey, 70 of 700 DMCs were randomly selected using a probability-proportional to size method. A cluster size of 24 for NSP and a varying size of 0 to 99 for PT cases were fixed for each selected DMC. Culture and drug susceptibility testing was done on Lowenstein-Jensen medium using the economic variant of proportion sensitivity test for isoniazid (INH), rifampicin (RMP), ofloxacin (OFX) and kanamycin (KAN). Human Immunodeficiency Virus (HIV) status was collected from patient records. From June 2011 to August 2012, 1524 NSP and 901 PT patients were enrolled. Any RMP resistance and any INH resistance were observed in 2.6% and 15.1%, and in 10.4% and 30% respectively in NSP and PT cases. Among PT patients, multi drug resistant TB (MDR-TB) was highest in the treatment failure (35%) group, followed by relapse (13%) and treatment after default (10%) groups. Extensively drug resistant TB (XDRTB) was seen in 4.3% of MDR-TB cases. Any OFX resistance was seen in 10.4% of NSP, 13.9% of PT and 29% of PT MDR-TB patients. The HIV status of the patient had no impact on drug resistance levels. RMP resistance was present in 2.6% of new and 15.1% of previously treated patients in Tamil Nadu. Rates of OFX resistance were high among NSP and PT patients, especially among those with MDR-TB, a matter of concern for development of new treatment regimens for TB.

High Rates of Ofloxacin Resistance in Mycobacterium tuberculosis among Both New and Previously Treated Patients in Tamil Nadu, South India

PubMed Central

Selvakumar, N.; Kumar, Vanaja; Balaji, S.; Prabuseenivasan, S.; Radhakrishnan, R.; Sekar, Gomathi; Chandrasekaran, V.; Kannan, T.; Thomas, Aleyamma; Arunagiri, S.; Dewan, Puneet; Swaminathan, Soumya

2015-01-01

Periodic drug resistance surveillance provides useful information on trends of drug resistance and effectiveness of tuberculosis (TB) control measures. The present study determines the prevalence of drug resistance among new sputum smear positive (NSP) and previously treated (PT) pulmonary TB patients, diagnosed at public sector designated microscopy centers (DMCs) in the state of Tamil Nadu, India. In this single-stage cluster-sampling prevalence survey, 70 of 700 DMCs were randomly selected using a probability-proportional to size method. A cluster size of 24 for NSP and a varying size of 0 to 99 for PT cases were fixed for each selected DMC. Culture and drug susceptibility testing was done on Lowenstein-Jensen medium using the economic variant of proportion sensitivity test for isoniazid (INH), rifampicin (RMP), ofloxacin (OFX) and kanamycin (KAN). Human Immunodeficiency Virus (HIV) status was collected from patient records. From June 2011 to August 2012, 1524 NSP and 901 PT patients were enrolled. Any RMP resistance and any INH resistance were observed in 2.6% and 15.1%, and in 10.4% and 30% respectively in NSP and PT cases. Among PT patients, multi drug resistant TB (MDR-TB) was highest in the treatment failure (35%) group, followed by relapse (13%) and treatment after default (10%) groups. Extensively drug resistant TB (XDRTB) was seen in 4.3% of MDR-TB cases. Any OFX resistance was seen in 10.4% of NSP, 13.9% of PT and 29% of PT MDR-TB patients. The HIV status of the patient had no impact on drug resistance levels. RMP resistance was present in 2.6% of new and 15.1% of previously treated patients in Tamil Nadu. Rates of OFX resistance were high among NSP and PT patients, especially among those with MDR-TB, a matter of concern for development of new treatment regimens for TB. PMID:25738956

The Geographical Distribution of Leadership in Globalized Clinical Trials

PubMed Central

Hoekman, Jarno; Frenken, Koen; de Zeeuw, Dick; Heerspink, Hiddo Lambers

2012-01-01

Background Pharmaceutical trials are mainly initiated by sponsors and investigators in the United States, Western Europe and Japan. However, more and more patients are enrolled in Central and Eastern Europe, Latin America and Asia. The involvement of patients in new geographical settings raises questions about scientific and ethical integrity, especially when experience with those settings is lacking at the level of trial management. We therefore studied to what extent the geographical shift in patient enrolment is anticipated in the composition of trial management teams using the author nationalities on the primary outcome publication as an indicator of leadership. Methods and Findings We conducted a cohort-study among 1,445 registered trials in www.clinicaltrials.gov that could be matched with a primary outcome publication using clinical trial registry numbers listed in publications. The name of the sponsor and the enrolment countries were extracted from all registrations. The author-addresses of all authors were extracted from the publications. We searched the author-address of all publications to determine whether enrolment countries and sponsors listed on registrations also appeared on a matched publication. Of all sponsors, 80.1% were listed with an author-address on the publication. Of all enrolment countries, 50.3% appeared with an author-address on the publication. The listing of enrolment countries was especially low for industry-funded trials (39.9%) as compared to government (90.4%) and not-for-profit funding (93.7%). We found that listing of enrolment countries in industry-funded trials was higher for traditional research locations such as the United States (98.2%) and Japan (72.0%) as compared to nontraditional research locations such as Poland (27.3%) and Mexico (14.1%). Conclusions Despite patient enrolment efforts, the involvement of researchers from nontraditional locations in trial management as measured by their contribution to manuscript writing is modest. This division of labor has significant implications for the scientific and ethical integrity of global clinical research. PMID:23071532

CT-Guided Percutaneous Step-by-Step Radiofrequency Ablation for the Treatment of Carcinoma in the Caudate Lobe

PubMed Central

Dong, Jun; Li, Wang; Zeng, Qi; Li, Sheng; Gong, Xiao; Shen, Lujun; Mao, Siyue; Dong, Annan; Wu, Peihong

2015-01-01

Abstract The location of the caudate lobe and its complex anatomy make caudate lobectomy and radiofrequency ablation (RFA) under ultrasound guidance technically challenging. The objective of the exploratory study was to introduce a novel modality of treatment of lesions in caudate lobe and discuss all details with our experiences to make this novel treatment modality repeatable and educational. The study enrolled 39 patients with liver caudate lobe tumor first diagnosed by computerized tomography (CT) or magnetic resonance imaging (MRI). After consultation of multi-disciplinary team, 7 patients with hepatic caudate lobe lesions were enrolled and accepted CT-guided percutaneous step-by-step RFA treatment. A total of 8 caudate lobe lesions of the 7 patients were treated by RFA in 6 cases and RFA combined with percutaneous ethanol injection (PEI) in 1 case. Median tumor diameter was 29 mm (range, 18–69 mm). A right approach was selected for 6 patients and a dorsal approach for 1 patient. Median operative time was 64 min (range, 59–102 min). Median blood loss was 10 mL (range, 8-16 mL) and mainly due to puncture injury. Median hospitalization time was 4 days (range, 2–5 days). All lesions were completely ablated (8/8; 100%) and no recurrence at the site of previous RFA was observed during median 8 months follow-up (range 3–11 months). No major or life-threatening complications or deaths occurred. In conclusion, percutaneous step-by-step RFA under CT guidance is a novel and effective minimally invasive therapy for hepatic caudate lobe lesions with well repeatability. PMID:26426638

Implementation of enhanced recovery programme for laparoscopic distal pancreatectomy: feasibility, safety and cost analysis.

PubMed

Richardson, John; Di Fabio, Francesco; Clarke, Hannah; Bajalan, Mohammed; Davids, Joe; Abu Hilal, Mohammed

2015-01-01

The adoption of laparoscopy for distal pancreatectomy has proven to substantially improve short-term outcomes. Stress response after major surgery can be further minimized within an enhanced recovery programme (ERP). However, data on the potential benefit of an ERP for laparoscopic distal pancreatectomy are still lacking. The aim was to assess the feasibility, safety and cost of ERP for patients undergoing laparoscopic distal pancreatectomy. This is a case-control study from a Tertiary University Hospital. Sixty-six consecutive patients who underwent laparoscopic distal pancreatectomy were analyzed. Twenty-two patients were enrolled for the ERP and compared with previous consecutive 44 patients managed traditionally (1:2 ratio). Operative details, post-operative outcome and cost analysis were compared in the two groups. Patients enrolled in the ERP had similar intraoperative blood loss (median 165 ml vs. 200 ml; p = 0.176), operation time (225 min vs. 210 min; p = 0.633), time to remove naso-gastric tube (1 vs. 1 day; p = 0.081) but significantly shorter time to mobilization (median 1 vs. 2 days; p = 0.0001), start solid diet (2 vs. 3 days; p = 0004), and pass stools (3 vs. 5 days; p = 0.002) compared to the control group. Median length of stay was significantly shorter in the ERP group (3 vs. 6 days; p < 0.0001). No significant difference in readmission or complication rate was observed. Cost analysis was significantly in favor of the ERP group (p = 0.0004). Implementation of ERP optimizes outcomes for laparoscopic distal pancreatectomy with significant earlier return to normal gut function, reduced length of stay and cost saving. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer: the ALCHEMIST trials.

PubMed

Alden, Ryan S; Mandrekar, Sumithra J; Oxnard, Geoffrey R

2015-09-01

Genotype-directed targeted therapies have revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC) but they have not yet been comprehensively studied in the adjuvant setting. Previous trials of adjuvant targeted therapy in unselected early stage NSCLC patients showed no benefit versus placebo, however retrospective data suggests improved disease free survival (DFS) with epidermal growth factor receptor (EGFR) inhibitors in patients with appropriate molecular alterations. A definitive prospective, randomized, placebo-controlled trial of targeted therapies for NSCLC is needed to determine the efficacy of targeted therapy following surgical resection and standard adjuvant therapy. The principal challenges facing such a trial are (I) identification of actionable alterations in early stage patients; and (II) realization of sufficient enrollment to power definitive analyses. The ALCHEMIST trial (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) was designed to overcome these challenges. Using the national clinical trials network (NCTN) of the National Cancer Institute (NCI), several thousand patients with operable NSCLC will undergo tumor genotyping for EGFR mutations or rearrangement of anaplastic lymphoma kinase (ALK). Following resection and completion of standard adjuvant therapy, patients with EGFR-mutant NSCLC will be randomized to erlotinib versus placebo (1:1), those with ALK-rearranged NSCLC will be randomized to crizotinib versus placebo (1:1), while those not enrolled onto the adjuvant trials will continue to be followed on the screening trial. ALCHEMIST also provides for the collection of tissue at baseline and at recurrence (if available) to characterize mechanisms of recurrence and of resistance to targeted therapy. Thus, ALCHEMIST is a platform for validation of targeted therapy as part of curative care in NSCLC and creates an opportunity to advance our understanding of disease biology.

Features and prognostic factors for elderly with acute poisoning in the emergency department.

PubMed

Hu, Yu-Hui; Chou, Hsiu-Ling; Lu, Wen-Hua; Huang, Hsien-Hao; Yang, Cheng-Chang; Yen, David H T; Kao, Wei-Fong; Deng, Jou-Fan; Huang, Chun-I

2010-02-01

Elderly persons with acute poisoning in the emergency department (ED) and prognostic factors of outcomes have not been well addressed in previous research. This study aimed to investigate the characteristics of elderly patients with acute poisoning visiting the ED, and to identify the possible predictive factors of mortality. Patients aged > or = 65 years with acute poisoning who visited the ED in Taipei Veterans General Hospital from January 1, 2006 through to September 30, 2008 were enrolled in the study. We collected demographic information on underlying diseases, initial presentations, causes and toxic substances, complications, dispositions, and outcomes. Analyses were conducted among different groups categorized according to age, suicide attempt, and outcome. Multiple logistic regression was applied to identify possible predictive clinical factors influencing mortality in the elderly with acute poisoning. A total of 250 patients were enrolled in the study, with a mean age of 77 years and male predominance. The most common cause of intoxication was unintentional poisoning. Medication accounted for 57.6% of poisonous substances, of which benzodiazepine was the most common drug, followed by warfarin. The overall mortality rate was 9.6%. The average length of stay in the ED increased significantly in the old (65-74 years), very old (75-84 years) and extremely old (> or = 85 years) groups. Suicide attempt patients experienced more complications including respiratory failure, aspiration pneumonia, hypotension and mortality. Three clinical predictive factors of mortality were identified: herbicide poisoning, hypotension and respiratory failure upon presentation. Our results demonstrated that elderly patients with acute poisoning had a mortality rate of 9.6%. Suicide attempts resulted in more serious complications. The risk factors for mortality were herbicide intoxication, hypotension and respiratory failure. Copyright 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG).

PubMed

Hishiki, Tomoro; Matsumoto, Kimikazu; Ohira, Miki; Kamijo, Takehiko; Shichino, Hiroyuki; Kuroda, Tatsuo; Yoneda, Akihiro; Soejima, Toshinori; Nakazawa, Atsuko; Takimoto, Tetsuya; Yokota, Isao; Teramukai, Satoshi; Takahashi, Hideto; Fukushima, Takashi; Kaneko, Takashi; Hara, Junichi; Kaneko, Michio; Ikeda, Hitoshi; Tajiri, Tatsuro; Nakagawara, Akira

2018-04-26

The Japanese Children's Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.

Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011.

PubMed

Izumi, Kiyohiko; Ohkado, Akihiro; Uchimura, Kazuhiro; Murase, Yoshiro; Tatsumi, Yuriko; Kayebeta, Aya; Watanabe, Yu; Ishikawa, Nobukatsu

2015-01-01

Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of "activity space", a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots. Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran's I and Getis-Ord Gi* statistics) identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients' characteristics in these hotspots were assessed. Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2%) were general inhabitants, 42 (6.5%) were foreign-born people, and 184 were homeless people (28.6%). The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households. Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further comprehension of TB transmission dynamics in an urban setting in Japan.

High- and low-dose oral delayed-release mesalamine in children with mild-to-moderately active ulcerative colitis.

PubMed

Winter, Harland S; Krzeski, Piotr; Heyman, Melvin B; Ibarguen-Secchia, Eduardo; Iwanczak, Barbara; Kaczmarski, Maciej; Kierkus, Jaroslaw; Kolaček, Sanja; Osuntokun, Bankole; Quiros, J Antonio; Shah, Manoj; Yacyshyn, Bruce; Dunnmon, Preston M

2014-12-01

The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis. Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥ 10 to ≤ 55 and a truncated Mayo Score of ≥ 1 for both rectal bleeding and stool frequency, were enrolled. They received body weight-dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27-71 mg · g(-1) · day(-1)) or high-dose group (53-118 mg · g(-1) · day(-1)). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥ 10 with a decrease from baseline by ≥ 20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity. The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups. Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose.