The Complete Automation of the Minnesota Multiphasic Personality Inventory and a Study of its Response Latency.

ERIC Educational Resources Information Center

Dunn, Thomas G.; And Others

The feasibility of completely automating the Minnesota Multiphasic Personality Inventory (MMPI) was tested, and item response latencies were compared with other MMPI item characteristics. A total of 26 scales were successfully scored automatically for 165 subjects. The program also typed a Mayo Clinic interpretive report on a computer terminal,…

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

PubMed

Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

2017-05-01

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUV max ). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Clinical comparison and complete cure rates of Terbinafine efficacy in affected onychomycotic toenails.

PubMed

Shemer, A; Sakka, N; Baran, R; Scher, R; Amichai, B; Norman, L; Farhi, R; Magun, R; Brazilai, A; Daniel, R

2015-03-01

Clinical studies regarding complete cure rate of onychomycosis using oral Terbinafine have a very broad range (14-90%) based solely on response to treatment on the big toenail. To evaluate the efficacy of Terbinafine in all affected onychomycotic toenails and, furthermore, to evaluate differences in mycological, clinical and complete cure rate between affected onychomycotic toenails. Inclusion criteria are as follows: distolateralsubungual onychomycotic involvement of the hallux and additional involvement of at least two more toenails of the same foot. Exclusion criteria are as follows: patients with nail traumata and hypersensitivity to Terbinafine. Patients were treated with oral Terbinafine 250 mg/day for 16 weeks. Mycological analysis was performed using direct microscopy and culture. Clinical improvement was assessed using digital photography. Statistically significant difference was found in clinical improvement between the great toenail and all other involved toenails. The rate of complete cure (100% clinical cure and mycological cure) of the big toenail was lower (23%) as compared to the second (65%), third (51%) and the fourth toenail (67%). This is a case series study that was based on a single-centre cohort. Our results support findings that efficacy of Terbinafine should be based on all involved onychomycotic toenails; the big toenail is not superior in response compared to other affected toenails. © 2014 European Academy of Dermatology and Venereology.

Clinical utility and validity of minoxidil response testing in androgenetic alopecia.

PubMed

Goren, Andy; Shapiro, Jerry; Roberts, Janet; McCoy, John; Desai, Nisha; Zarrab, Zoulikha; Pietrzak, Aldona; Lotti, Torello

2015-01-01

Clinical response to 5% topical minoxidil for the treatment of androgenetic alopecia (AGA) is typically observed after 3-6 months. Approximately 40% of patients will regrow hair. Given the prolonged treatment time required to elicit a response, a diagnostic test for ruling out nonresponders would have significant clinical utility. Two studies have previously reported that sulfotransferase enzyme activity in plucked hair follicles predicts a patient's response to topical minoxidil therapy. The aim of this study was to assess the clinical utility and validity of minoxidil response testing. In this communication, the present authors conducted an analysis of completed and ongoing studies of minoxidil response testing. The analysis confirmed the clinical utility of a sulfotransferase enzyme test in successfully ruling out 95.9% of nonresponders to topical minoxidil for the treatment of AGA. © 2014 Wiley Periodicals, Inc.

A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes.

PubMed

Serra-Guillén, Carlos; Nagore, Eduardo; Hueso, Luis; Traves, Victor; Messeguer, Francesc; Sanmartín, Onofre; Llombart, Beatriz; Requena, Celia; Botella-Estrada, Rafael; Guillén, Carlos

2012-04-01

Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious. We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately. Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen. In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment. Only one cycle of imiquimod was administered. The follow-up period was brief. Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Palliation of clinical signs in 48 dogs with nasal carcinomas treated with coarse-fraction radiation therapy.

PubMed

Gieger, Tracy; Rassnick, Kenneth; Siegel, Sheri; Proulx, David; Bergman, Philip; Anderson, Christine; LaDue, Tracy; Smith, Annette; Northrup, Nicole; Roberts, Royce

2008-01-01

Data from 48 dogs with nasal carcinomas treated with palliative radiation therapy (PRT) were retrospectively reviewed. Factors potentially influencing resolution of clinical signs and survival after PRT were evaluated. Clinical signs completely resolved in 66% of dogs for a median of 120 days. The overall median survival time was 146 days. Duration of response to PRT was shorter in dogs that had clinical signs for <90 days before PRT. Survival times were shorter in dogs that had partial or no resolution of clinical signs after PRT than in dogs that had complete resolution of clinical signs.

Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis.

PubMed

Renehan, Andrew G; Malcomson, Lee; Emsley, Richard; Gollins, Simon; Maw, Andrew; Myint, Arthur Sun; Rooney, Paul S; Susnerwala, Shabbir; Blower, Anthony; Saunders, Mark P; Wilson, Malcolm S; Scott, Nigel; O'Dwyer, Sarah T

2016-02-01

Induction of a clinical complete response with chemoradiotherapy, followed by observation via a watch-and-wait approach, has emerged as a management option for patients with rectal cancer. We aimed to address the shortage of evidence regarding the safety of the watch-and-wait approach by comparing oncological outcomes between patients managed by watch and wait who achieved a clinical complete response and those who had surgical resection (standard care). Oncological Outcomes after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) was a propensity-score matched cohort analysis study, that included patients of all ages diagnosed with rectal adenocarcinoma without distant metastases who had received preoperative chemoradiotherapy (45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy) at a tertiary cancer centre in Manchester, UK, between Jan 14, 2011, and April 15, 2013. Patients who had a clinical complete response were offered management with the watch-and-wait approach, and patients who did not have a complete clinical response were offered surgical resection if eligible. We also included patients with a clinical complete response managed by watch and wait between March 10, 2005, and Jan 21, 2015, across three neighbouring UK regional cancer centres, whose details were obtained through a registry. For comparative analyses, we derived one-to-one paired cohorts of watch and wait versus surgical resection using propensity-score matching (including T stage, age, and performance status). The primary endpoint was non-regrowth disease-free survival from the date that chemoradiotherapy was started, and secondary endpoints were overall survival, and colostomy-free survival. We used a conservative p value of less than 0·01 to indicate statistical significance in the comparative analyses. 259 patients were included in our Manchester tertiary cancer centre cohort, 228 of whom underwent surgical resection at referring hospitals and 31 of whom had a clinical complete response, managed by watch and wait. A further 98 patients were added to the watch-and-wait group via the registry. Of the 129 patients managed by watch and wait (median follow-up 33 months [IQR 19-43]), 44 (34%) had local regrowths (3-year actuarial rate 38% [95% CI 30-48]); 36 (88%) of 41 patients with non-metastatic local regrowths were salvaged. In the matched analyses (109 patients in each treatment group), no differences in 3-year non-regrowth disease-free survival were noted between watch and wait and surgical resection (88% [95% CI 75-94] with watch and wait vs 78% [63-87] with surgical resection; time-varying p=0·043). Similarly, no difference in 3-year overall survival was noted (96% [88-98] vs 87% [77-93]; time-varying p=0·024). By contrast, patients managed by watch and wait had significantly better 3-year colostomy-free survival than did those who had surgical resection (74% [95% CI 64-82] vs 47% [37-57]; hazard ratio 0·445 [95% CI 0·31-0·63; p<0·0001), with a 26% (95% CI 13-39) absolute difference in patients who avoided permanent colostomy at 3 years between treatment groups. A substantial proportion of patients with rectal cancer managed by watch and wait avoided major surgery and averted permanent colostomy without loss of oncological safety at 3 years. These findings should inform decision making at the outset of chemoradiotherapy. Bowel Disease Research Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Longitudinal Risk and Resilience Factors Predicting Psychiatric Disruption, Mental Health Service Utilization & Military Retention in OIF National Guard Troops

DTIC Science & Technology

2009-04-01

completing in-person clinical assessments that include structured clinical interviews and psychological testing . As an introduction to the three...coordinator to opt out of the project. 2.2.2. Analyses of Response Bias. To test for response bias, we compared responders and non-responders to the...used to include these subjects without Wave 2 data in the final analyses. 2.3.2. Analyses of Response Bias. To test for response bias at Wave 3

Continuous Low-Dose Oral Cyclophosphamide and Methotrexate as Maintenance Therapy in Patients With Advanced Ovarian Carcinoma After Complete Clinical Response to Platinum and Paclitaxel Chemotherapy.

PubMed

El-Husseiny, Khalid; Motawei, Helmy; Ali, Mohamad Sayed

2016-03-01

The aim of this study was to evaluate efficacy and safety of continuous, low dose of oral, metronomic chemotherapy as maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy. In this nonrandomized study, patients older than 18 years, with Eastern Cooperative Oncology Group performance status less than 2, with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy were enrolled in 2 arms--arm A (maintenance arm), treated with continuous low-dose oral cyclophosphamide 50 mg and methotrexate 2.5 mg, and arm B (observation arm). Both arms were followed up for progression-free survival and toxicity. Thirty patients were accrued in each arm from January 2009 to December 2010 in Ain Shams University Hospitals, where they received the treatment and followed up for disease progression and toxicity. Patients had a median age of 53 years in maintenance arm and 52.5 years in the observational arm, respectively. Over 80% had papillary serous adenocarcinoma, and over 40% of them had a stage IV disease in both arms. After median follow-up of 27 months, patients achieved median progression-free survival of 18 months in maintenance arm (A) and 15.5 months in observational arm (B), respectively. Toxicity profile was excellent with no grade 3 or 4 toxicity reported. Current study may provide an evidence of efficacy and tolerability of continuous low-dose oral cyclophosphamide and methotrexate as a maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy.

Minimal Residual Disease in Acute Myeloid Leukemia

PubMed Central

Hourigan, Christopher S.; Karp, Judith E.

2014-01-01

Technological advances in the laboratory have lead to substantial improvements in clinical decision-making by the use of pre-treatment prognostic risk stratification factors in acute myeloid leukemia (AML). Unfortunately similar progress has not been made in treatment response criteria, with the definition of “complete remission” in AML largely unchanged for over half a century. Several recent clinical trials have demonstrated that higher sensitivity measurements of residual disease burden during or after treatment can be performed, that results are predictive for clinical outcome and can be used to improve outcomes by guiding additional therapeutic intervention to patients in clinical complete remission but at increased relapse risk. We review here these recent trials, the characteristics and challenges of the modalities currently used to detect minimal residual disease (MRD), and outline opportunities to both refine detection and better clinically utilize MRD measurements. MRD measurement is already the standard of care in other myeloid malignancies such as chronic myelogenous leukemia (CML) and acute promyelocytic leukemia (APL). It is our belief that response criteria for non-APL AML should be updated to include assessment for molecular complete remission (mCR) and that recommendations for post-consolidation surveillance should include regular monitoring for molecular relapse as a standard of care. PMID:23799371

Phase I/II Clinical Trial of Hyaluronan-Cisplatin Nanoconjugate for the Treatment of Spontaneous Canine Cancers

PubMed Central

Cai, Shuang; Zhang, Ti; Forrest, W.C.; Yang, Qiuhong; Groer, Chad; Mohr, Eva; Aires, Daniel J.; Axiak-Bechtel, Sandra M.; Flesner, Brian K.; Henry, Carolyn J.; Selting, Kimberly A.; Tate, Deborah; Swarz, Jeffrey A.; Bryan, Jeffrey N.; Forrest, M. Laird

2015-01-01

Objective To conduct an open label, multi-dose Phase I/II clinical study in spontaneous canine cancers and evaluate the pharmacokinetics, safety, and efficacy of the hyaluronan-based cisplatin formulation (HA-Pt). Animals 13 dogs with heterogeneous, naturally occurring cancers. Procedures The dogs received up to four injections of 10-30 mg/m2 HA-Pt into the tumor or peritumoral sub-mucosa at three-week intervals. Blood sample (2 mL) was collected from the jugular catheter at 0.5, 1, 2, 4, and 24 hours following drug administration. A complete blood count and renal profile with urinalysis were conducted prior to and one week after each treatment. Tumor measurements were collected three weeks following each administration to assess response. Results Of the 13 dogs with heterogeneous, naturally occurring cancers, 23% had complete response and 15% had partial response or stable disease. Among the dogs that received drug with low diaquated content, the complete response rate for SCC was 3/7 (43%). Myelosuppression and cardiac toxicity were observed for 38% and 19% of the dogs, respectively. The formulation did not cause nephrotoxicity, the dose-limiting toxicity of standard cisplatin, in any dogs. Conclusions and Clinical Relevance The HA-Pt formulation demonstrated positive response in spontaneous canine squamous cell carcinomas. It did not cause nephrotoxicity in any patients. Canine oral SCC is very homogenous in progression and drug response to human HNSCC, and these results could be useful in developing human treatments. PMID:27580113

Response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol: 38 cases (1996-2003).

PubMed

Milner, Rowan J; Peyton, Jamie; Cooke, Kirsten; Fox, Leslie E; Gallagher, Alexander; Gordon, Patti; Hester, Juli

2005-10-01

To determine response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol. Retrospective study. 38 cats with lymphoma. Medical records were reviewed, and information on age, sex, breed, FeLV and FIV infection status, anatomic form, clinical stage, and survival time was obtained. Immunophenotyping was not performed. Mean +/- SD age of the cats was 10.9 +/- 4.4 years. Overall median survival time was 210 days (interquartile range, 90 to 657 days), and overall duration of first remission was 156 days (interquartile range, 87 to 316 days). Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first remission or survival time. Eighteen of the 38 (47%) cats had complete remission, 14 (37%) had partial remission, and 6 (16%) had no response. Duration of first remission was significantly longer for cats with complete remission (654 days) than for cats with partial remission (114 days). Median survival time for cats with complete remission (654 days) was significantly longer than median survival time for cats with partial remission (122 days) and for cats with no response (11 days). Results suggested that a high percentage of cats with lymphoma will respond to treatment with the University of Wisconsin-Madison chemotherapy protocol. Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first response or survival time, but initial response to treatment was.

Long-term complete remission of metastatic breast cancer, induced by a steroidal aromatase inhibitor after failure of a non-steroidal aromatase inhibitor

PubMed Central

Shioi, Yoshihiro; Kashiwaba, Masahiro; Inaba, Toru; Komatsu, Hideaki; Sugai, Tamotsu; Wakabayashi, Go

2014-01-01

Patient: Female, 56 Final Diagnosis: Breast cancer Symptoms: Solid mass in the right breast Medication: Exemestane Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: The efficacy of third-generation aromatase inhibitors for hormone receptor-positive postmenopausal metastatic breast cancer is well established. Although several clinical trials have reported incomplete cross-resistance between different aromatase inhibitors, few cases of complete responses of recurrent metastatic breast cancer occurring after substituting a second aromatase inhibitor have been reported. We here present a rare case of non-steroidal aromatase inhibitor-tolerant metastatic breast cancer with long-term complete remission following substitution of a steroidal aromatase inhibitor. Case Report: We present the case of a 56-year-old Japanese woman who underwent right breast-conserving surgery for breast cancer, TNM staging T1, N0, M0, Stage I. She received adjuvant chemotherapy with 6 cycles of FEC100 and radiation therapy, and then began hormonal therapy with anastrozole. Twelve months postoperatively, computed tomography (CT) revealed multiple lung metastases. Exemestane was substituted for anastrozole. After 3 months of exemestane, CT showed that all lung metastases had completely resolved. Her complete response was maintained for 5 years: she died during a tsunami 6 years after the initial surgery. Conclusions: Substitution of a steroidal for a non-steroidal aromatase inhibitor produced a sustained complete remission in a patient with hormonal receptor-positive postmenopausal recurrent breast cancer. Achieving complete response after switching from a non-steroidal to a steroidal aromatase inhibitor in a hormonal receptor-positive postmenopausal recurrent breast cancer contributed to a higher quality of life for the patient. Further investigation is needed to identify the predictors of long-term remission following such a switch. PMID:24587856

Gastric and colonic mantle cell lymphoma - incidental discovery.

PubMed

Pitigoi, Dan; Stoica, Victor; Stoia, Razvan; Dobrea, Camelia; Becheanu, Gabriel; Diculescu, Mircea

2009-03-01

A 65-year old patient, with no medical history, was admitted for lower gastrointestinal bleeding. On clinical examination the patient seemed to be in good health. However the examination was completed with a rectosigmoidoscopy revealing the presence of mucosal erosions, ulcerations, multiple papulae. The histopathological examination raised the suspicion of a colonic lymphoma. Gastric biopsies suggested a gastric MALT type lymphoma associated to the colonic lymphoma, but the immunohistochemical profile corresponded to a mantle cell lymphoma. In spite of the general poor prognosis of mantle cell lymphoma, our patient had a good clinical and endoscopic response to the standard cyclophosphamide, vincristine, prednisone (CVP) therapy. The cases of gastric and colonic mantle lymphoma are rare, the response to therapy is poor; fortunately, our patient had a complete resolution after completion of the six cycles of chemotherapy.

Clinical utility of pretreatment prediction of chemoradiotherapy response in rectal cancer: a review.

PubMed

Yoo, Byong Chul; Yeo, Seung-Gu

2017-03-01

Approximately 20% of all patients with locally advanced rectal cancer experience pathologically complete responses following neoadjuvant chemoradiotherapy (CRT) and standard surgery. The utility of radical surgery for patients exhibiting good CRT responses has been challenged. Organ-sparing strategies for selected patients exhibiting complete clinical responses include local excision or no immediate surgery. The subjects of this tailored management are patients whose presenting disease corresponds to current indications of neoadjuvant CRT, and their post-CRT tumor response is assessed by clinical and radiological examinations. However, a model predictive of the CRT response, applied before any treatment commenced, would be valuable to facilitate such a personalized approach. This would increase organ preservation, particularly in patients for whom upfront CRT is not generally prescribed. Molecular biomarkers hold the greatest promise for development of a pretreatment predictive model of CRT response. A combination of clinicopathological, radiological, and molecular markers will be necessary to render the model robust. Molecular research will also contribute to the development of drugs that can overcome the radioresistance of rectal tumors. Current treatments for rectal cancer are based on the expected prognosis given the presenting disease extent. In the future, treatment schemes may be modified by including the predicted CRT response evaluated at presentation.

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

Perez, Rodrigo O.; Angelita and Joaquim Gama Institute, Sao Paulo; Habr-Gama, Angelita, E-mail: gamange@uol.com.br

Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([{sup 18}FDG]PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied ( (ClinicalTrials.org) identifier (NCT00254683)). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks from CRT completion). Clinical assessment was at 12 weeks. Maximal standard uptake value (SUVmax) of the primary tumor was measured and recorded at each PET/CT study aftermore » 1 h (early) and 3 h (late) from {sup 18}FDG injection. Patients with an increase in early SUVmax between 6 and 12 weeks were considered 'bad' responders and the others as 'good' responders. Results: Ninety-one patients were included; 46 patients (51%) were 'bad' responders, whereas 45 (49%) patients were 'good' responders. 'Bad' responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; P=.001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; P=.008) and exhibited greater final tumor dimension (4.3 cm vs. 3.3 cm; P=.03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CT was a significant predictor of 'good' response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients.« less

Comparison of content of FDA letters not approving applications for new drugs and associated public announcements from sponsors: cross sectional study

PubMed Central

Chahal, Harinder S; Sigelman, Daniel W; Stacy, Sylvie; Sclar, Joshua; Ddamulira, Barbara

2015-01-01

Objectives To describe the content of non-public complete response letters issued by the US Food and Drug Administration (FDA) when they do not approve marketing applications from sponsors (drug companies) and to compare them with the content any subsequent press releases issued by those sponsors Design Cross sectional study. Data sources All applications for which FDA’s Center for Drug Evaluation and Research initially issued complete response letters (n=61) from 11 August 2008 to 27 June 2013. Complete response letters and press releases were divided into discrete statements related to seven domains and 64 subdomains and assessed to determine whether they matched. Results 48% (29) of complete response letters cited deficiencies in both the safety and efficacy domains, and only 13% cited neither safety nor efficacy deficiencies. No press release was issued for 18% (11) of complete response letters, and 21% (13) of press releases did not match any statements from the letters. Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements. Of 32 complete response letters that called for a new clinical trial for safety or efficacy, 59% (19) had matching press release statements. Seven complete response letters reported higher mortality rates in treated participants; only one associated press release mentioned this fact. Conclusions FDA generally issued complete response letters to sponsors for multiple substantive reasons, most commonly related to safety and/or efficacy deficiencies. In many cases, press releases were not issued in response to those letters and, when they were, omitted most of the statements in the complete response letters. Press releases are incomplete substitutes for the detailed information contained in complete response letters. PMID:26063327

Trough concentration and ABCG2 polymorphism are better to predict imatinib response in chronic myeloid leukemia: a meta-analysis.

PubMed

Jiang, Zhi-Ping; Zhao, Xie-Lan; Takahashi, Naoto; Angelini, Sabrina; Dubashi, Biswajit; Sun, Li; Xu, Ping

2017-01-01

The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C 0 ), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML). A literature search was conducted using the PubMed and Cochrane electronic databases to locate relevant papers from 2003 onward. Then, an initial meta-analysis of 14 studies involving 2184 patients was conducted to understand the effect of imatinib mesylate (IM) C 0 on clinical outcome in CML patients. Subsequently, a series of meta-analyses were performed, including up to 23 studies with 2577 patients, on the effect of genetic polymorphisms of ABCB1 and ABCG2 on the clinical response to IM. Meta-analysis revealed that patients who achieved a major molecular response (MMR) have a significantly higher IM C 0 than those who failed to achieve an MMR. We also found that the patients who achieved a complete cytogenic response (CCyR) have a significantly higher IM C 0 than those who did not achieve a CCyR. However, no significant difference in IM C 0 was found between the complete molecular response and non-complete molecular response groups. Additional analysis showed that ABCG2 421 variant A allele was significantly associated with a higher rate of MMR and overall response, especially in Asian patients. Meta-analysis did not reveal a correlation between ABCB1 C3435T and C1236T polymorphisms with any clinical response to IM. However, the G2677T/A polymorphism could play a role in IM response in the recessive model. This meta-analysis demonstrates that there was a significant correlation between the IM trough concentration and clinical responses, especially MMR and CCyR, in CML patients. Furthermore, we found that the probability of successful treatment was correlated with the ABCG2 C421A polymorphism, at least within the Asian population. We failed to determine an association between ABCB1 polymorphisms and IM response, although the G2677T/A polymorphism might be involved. However, further large-scale investigations using more sensitive genotyping methods would be required to confirm this.

Insights from clinical research completed during the west Africa Ebola virus disease epidemic

PubMed Central

Rojek, Amanda; Horby, Peter; Dunning, Jake

2018-01-01

The west Africa Ebola virus disease (EVD) epidemic was extraordinary in scale. Now that the epidemic has ended, it is a relevant time to examine published studies with direct relevance to clinical care and, more broadly, to examine the implications of the clinical research response mounted. Clinically relevant research includes literature detailing risk factors for and clinical manifestations of EVD, laboratory and other investigation findings in patients, experimental vaccine and therapeutic clinical trials, and analyses of survivor syndrome. In this Review, we discuss new insights from patient-oriented research completed during the west Africa epidemic, identify ongoing knowledge gaps, and suggest priorities for future research. PMID:28461209

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer.

PubMed

Beukinga, Roelof J; Hulshoff, Jan Binne; Mul, Véronique E M; Noordzij, Walter; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Plukker, John T M

2018-06-01

Purpose To assess the value of baseline and restaging fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18 F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18 F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

Sustainability of the prevention of passive infant smoking within well-baby clinics.

PubMed

Crone, M R; Verlaan, M; Willemsen, M C; van Soelen, P; Reijneveld, S A; Sing, R A Hira; Paulussen, T G W M

2006-04-01

This study assessed the antecedents of continued use of an education program to prevent passive smoking in infants. It consists of a booklet for parents and a manual for health professionals describing a five-step procedure for discussing passive smoking. A questionnaire was sent to 67 managers, 670 nurses, and 335 physicians working in well-baby clinics (response rate: 70%, 53%, 47% respectively). Questions concerned the completeness of use, level of institutionalization, and characteristics of the organization, the user, and the dissemination strategy. Seventy-one percent of nurses and 42% of physicians worked with the program. They foremost provided the first three steps of the five-step procedure. Physicians' completeness of use was related to their perceived responsibility in providing this education, and nurses' use was related to their perceived self-efficacy, responsibility, training attendance, participation in the adoption decision, and level of institutionalization. Diffusion efforts should focus on improving the completeness of use and level of institutionalization.

Construction of an efficient evaluative instrument for myasthenia gravis: the MG composite.

PubMed

Burns, Ted M; Conaway, Mark R; Cutter, Gary R; Sanders, Donald B

2008-12-01

We assessed the performance of items from the Quantitative Myasthenia Gravis (QMG), MMT (Manual Muscle Test), and MG-ADL (Myasthenia Gravis - Activities of Daily Living) scales, using data from two recently completed treatment trials of generalized MG. Items were selected that were relevant to manifestations of MG, meaningful to both the physician and the patient, and responsive to clinical change. After the 10 items were chosen, they were weighted based on input from MG experts from around the world, considering factors such as quality of life, disease severity, risk, prognosis, validity, and reliability. The MG Composite is easy to administer, takes less than 5 minutes to complete, and requires no equipment. Weighting of the response options of the 10 items should result in ordinal scores that better represent MG status and are more responsive to meaningful clinical change. To better determine its suitability for clinical use and for treatment trials, the MG Composite will be tested prospectively at several academic medical centers and will be used as a secondary measure of efficacy in pending clinical trials of MG.

Development of a Research Participants’ Perception Survey to Improve Clinical Research

PubMed Central

Yessis, Jennifer L.; Kost, Rhonda G.; Lee, Laura M.; Coller, Barry S.; Henderson, David K.

2012-01-01

Abstract Introduction: Clinical research participants’ perceptions regarding their experiences during research protocols provide outcome‐based insights into the effectiveness of efforts to protect rights and safety, and opportunities to enhance participants’ clinical research experiences. Use of validated surveys measuring patient‐centered outcomes is standard in hospitals, yet no instruments exist to assess outcomes of clinical research processes. Methods: We derived survey questions from data obtained from focus groups comprised of research participants and professionals. We assessed the survey for face/content validity, and privacy/confidentiality protections and fielded it to research participants at 15 centers. We conducted analyses of response rates, sample characteristics, and psychometrics, including survey and item completion and analysis, internal consistency, item internal consistency, criterion‐related validity, and item usefulness. Responses were tested for fit into existing patient‐centered dimensions of care and new clinical research dimensions using Cronbach's alpha coefficient. Results: Surveys were mailed to 18,890 individuals; 4,961 were returned (29%). Survey completion was 89% overall; completion rates exceeded 90% for 88 of 93 evaluable items. Questions fit into three dimensions of patient‐centered care and two novel clinical research dimensions (Cronbach's alpha for dimensions: 0.69–0.85). Conclusions: The validated survey offers a new method for assessing and improving outcomes of clinical research processes. Clin Trans Sci 2012; Volume 5: 452–460 PMID:23253666

Clinical responses to focused ultrasound applied to women with vulval intraepithelial neoplasia.

PubMed

Jia, Ying; Wu, Jin; Xu, Man; Tang, Liangdan; Li, Chengzhi; Luo, Ming; Lou, Meng

2014-11-01

Focused ultrasound waves penetrate superficial tissues and are aimed toward the target tissues at specific depths to exert their biological effects. Focused ultrasound has been applied for a number of clinical indications, including vulval dystrophies and low-grade vulval disease. This study aimed to assess the efficacy and safety of focused ultrasound treatment of high-grade vulval intraepithelial neoplasia (VIN). Eighteen women with high-grade VIN were recruited and treated with focused ultrasound. During each posttreatment follow-up, the safety of, side effects of, and clinical responses to focused ultrasound were evaluated by a standardized protocol, including symptoms, clinical appearance, and histologic findings. All patients completed the designed follow-ups. In most cases, superficial mild to moderate swelling and blisters were seen in the focused ultrasound-treated skin but not in adjacent normal skin. Of the 18 patients, 16 showed complete histologic regression and resolution of symptoms 6 months after treatment. Of the other 2 patients, 1 showed complete regression after a second focused ultrasound treatment. The other patient did not respond to the focused ultrasound treatment and underwent a partial vulvectomy 6 months after treatment. None of the patients developed invasive carcinoma of the vulva during the follow-up period. One patient had local pruritus that was not alleviated by anti-inflammatory medication and local care. The complete responses observed in women with high-grade VIN treated by focused ultrasound, together with the preservation of adjacent normal tissue, suggest that focused ultrasound may be considered for treatment of high-grade VIN. © 2014 by the American Institute of Ultrasound in Medicine.

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

The Effects of Focused Attention on Inhibition and State Regulation in Children with and without Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Ketch, Karen M.; Brodeur, Darlene A.; McGee, Robin

2009-01-01

This study investigated the effects of response rate and attention focusing on performance of ADHD, clinical-control (CRNA) and non-clinical control children in response inhibition tasks. All children completed the "Go-NoGo" task, a computer-based task of attention and impulsivity. Focused attention on this task was manipulated using a priming…

Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Heriot, A G

2015-10-01

Pathological complete response to neoadjuvant chemoradiotherapy is found in 20% of patients with rectal cancer undergoing long-course chemoradiotherapy. Some authors have suggested that these patients do not need to undergo surgery and can be managed with careful follow-up, with surgery only used in the event of clinical failure. Widespread adoption of this regimen is limited by the accuracy of methods to confirm a pathological complete response (pCR). A systematic search of PubMed, Medline and Cochrane databases was conducted to identify clinical, histological and radiological features in those patients with rectal cancer who achieved a pCR following chemoradiotherapy. Searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation' and 'tumour response'. After review of title and abstracts, 89 articles addressing the assessment of pCR were identified. Histology and clinical assessment are the most effective methods of assessment of pCR, with histology considered the gold standard. Clinical assessment is limited to low rectal tumours and is open to significant inter-rater variability, while histological examination requires a surgical specimen. Diffusion-weighted MRI and (18) F-fluorodeoxyglucose positron emission tomography/CT demonstrate the greatest potential for the assessment of pCR, but both modalities have limited accuracy. Determination of a pCR is crucial if a nonoperative approach is to be undertaken proactively. Various methods are available, but currently they lack sufficient sensitivity and specificity to define management. This is likely to be an area of further research in the future. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

PubMed

Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

2013-01-01

In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

Isolated Limb Perfusion for Malignant Melanoma: Systematic Review on Effectiveness and Safety

PubMed Central

de la Cruz-Merino, Luis; Ferrandiz, Lara; Villegas-Portero, Roman; Nieto-Garcia, Adoracion

2010-01-01

Background. Isolated limb perfusion (ILP) involves the administration of chemotherapy drugs directly into a limb involved by locoregional metastases. Unresectable locally advanced melanoma of the limbs represents one of the clinical settings in which ILP has demonstrated benefits. Methods. A systematic review of the literature on ILP for patients with unresectable locally advanced melanoma of the limbs was conducted. MEDLINE, EMBASE, and Cochrane database searches were conducted to identify studies fulfilling the following inclusion criteria: hyper- or normothermic ILP with melphalan with or without tumor necrosis factor (TNF) or other drugs providing valid data on clinical response, survival, or toxicity. To allocate levels of evidence and grades of recommendation the Scottish Intercollegiate Guidelines Network system was used. Results. Twenty-two studies including 2,018 ILPs were selected with a clear predominance of observational studies (90.90%) against experimental studies (9.10%). The median complete response rate to ILP was of 58.20%, with a median overall response rate of 90.35%. ILP with melphalan yielded a median complete response rate of 46.50%, against a 68.90% median complete response rate for melphalan plus TNF ILP. The median 5-year overall-survival rate was 36.50%, with a median overall survival interval of 36.70 months. The Wieberdink IV and V regional toxicity rates were 2.00% and 0.65%, respectively. Conclusions. ILP is effective in achieving clinical responses in patients with unresectable locally advanced melanoma of the limbs. The disease-free and overall survival rates provided by ILP are acceptable. ILP is safe, with a low incidence of severe regional and systemic toxicity. PMID:20348274

Collection of social determinants of health in the community clinic setting: a cross-sectional study.

PubMed

Kusnoor, Sheila V; Koonce, Taneya Y; Hurley, Suzanne T; McClellan, Kalonji M; Blasingame, Mallory N; Frakes, Elizabeth T; Huang, Li-Ching; Epelbaum, Marcia I; Giuse, Nunzia B

2018-04-24

Addressing social and behavioral determinants of health (SBDs) may help improve health outcomes of community clinic patients. This cross-sectional study explored how assessing SBDs can be used to complement health data collection strategies and provide clinicians with a more in-depth understanding of their patients. Adult patients, ages 18 and older, at an urban community health care clinic in Tennessee, U.S.A., were asked to complete a questionnaire regarding health status, health history and SBDs while waiting for their clinic appointment. The SBD component included items from the National Academy of Medicine, the Protocol for Responding to and Assessing Patient Assets, Risks, and Experiences instrument, and the Survey of Household Economics and Decisionmaking. Data collection and analysis occurred in 2017. One hundred participants completed the study. The questionnaire took approximately 11 min to complete, and the response rate was 90% or higher for all items except annual household income (unanswered by 40 participants). The median number of negative SBDs was 4 (IQR 2.75-7.0), 96 participants had at least one unmet need, and the most common negative SBD was physical activity (75%; 75/100). The hybrid questionnaire provided insight into a community clinic population's SBDs and allowed for a more complete understanding than a single questionnaire alone. The brief questionnaire administration time and low non-response rate support the questionnaire's feasibility in the community clinic setting, and results can be used by clinicians to further the personalization goals of precision medicine. Next steps include evaluating how to connect patients with appropriate resources for addressing their SBDs.

[Long term results of exclusive chemotherapy for glottic squamous cell carcinoma complete clinical responders after induction chemotherapy].

PubMed

Vachin, F; Hans, S; Atlan, D; Brasnu, D; Menard, M; Laccourreye, O

2004-06-01

To evaluate the long-term results of exclusive chemotherapy for T1-T3N0M0 glottic squamous cell carcinoma complete clinical responders after induction chemotherapy. Between 1985 and 2000, 69 patients with glottic squamous cell carcinoma complete clinical responders after induction chemotherapy were managed with exclusive chemotherapy at our department. Chemotherapy associated platinum and fluorouracil. This retrospective analysis evaluated actuarial survival, treatment morbidity, oncologic events and laryngeal preservation. Various independent factors were tested for potential correlation with survival and local recurrence. The 5-year Kaplan-Meier actuarial survival, local control, lymph node control estimate were 83,6%, 64,8%, 98,6% respectively. Chemotherapy never resulted in death. The 10-year actuarial metachronous second primary tumors estimate was 32%. The overall laryngeal preservation rate was 98,6%. Altogether our data and the review of the literature suggest that in patients achieving a complete clinical response after and induction based chemotherapy regimen, the completion of an exclusive chemotherapy regimen appears to be a valid alternative to the conventional use of radiotherapy or chemo-radiation protocols.

Peritoneal dialysis-related peritonitis caused by Pseudomonas species: Insight from a post-millennial case series.

PubMed

Lu, Wanhong; Kwan, Bonnie Ching-Ha; Chow, Kai Ming; Pang, Wing-Fai; Leung, Chi Bon; Li, Philip Kam-To; Szeto, Cheuk Chun

2018-01-01

Pseudomonas peritonitis is a serious complication of peritoneal dialysis (PD). However, the clinical course of Pseudomonas peritonitis following the adoption of international guidelines remains unclear. We reviewed the clinical course and treatment response of 153 consecutive episodes of PD peritonitis caused by Pseudomonas species from 2001 to 2015. Pseudomonas peritonitis accounted for 8.3% of all peritonitis episodes. The bacteria isolated were resistant to ceftazidime in 32 cases (20.9%), and to gentamycin in 18 cases (11.8%). In 20 episodes (13.1%), there was a concomitant exit site infection (ESI); in another 24 episodes (15.7%), there was a history of Pseudomonas ESI in the past. The overall primary response rate was 53.6%, and complete cure rate 42.4%. There was no significant difference in the complete cure rate between patients who treated with regimens of 3 and 2 antibiotics. Amongst 76 episodes (46.4%) that failed to respond to antibiotics by day 4, 37 had immediate catheter removal; the other 24 received salvage antibiotics, but only 6 achieved complete cure. Antibiotic resistance is common amongst Pseudomonas species causing peritonitis. Adoption of the treatment guideline leads to a reasonable complete cure rate of Pseudomonas peritonitis. Treatment with three antibiotics is not superior than the conventional two antibiotics regimen. When there is no clinical response after 4 days of antibiotic treatment, early catheter removal should be preferred over an attempt of salvage antibiotic therapy.

Phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate in dogs with naturally occurring malignant tumors.

PubMed

Cai, Shuang; Zhang, Ti; Forrest, W C; Yang, Qiuhong; Groer, Chad; Mohr, Eva; Aires, Daniel J; Axiak-Bechtel, Sandra M; Flesner, Brian K; Henry, Carolyn J; Selting, Kimberly A; Tate, Deborah; Swarz, Jeffrey A; Bryan, Jeffrey N; Forrest, M Laird

2016-09-01

OBJECTIVE To conduct a phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate (HA-Pt) in dogs with naturally occurring malignant tumors. ANIMALS 18 healthy rats, 9 healthy mice, and 16 dogs with cancer. PROCEDURES HA-Pt was prepared and tested by inductively coupled plasma mass spectrometry; DNA-platinum adduct formation and antiproliferation effects of cisplatin and HA-Pt were compared in vitro. Effects of cisplatin (IV) and HA-Pt (SC) in rodents were tested by clinicopathologic assays. In the clinical trial, dogs with cancer received 1 to 4 injections of HA-Pt (10 to 30 mg/m(2), intratumoral or peritumoral, q 3 wk). Blood samples were collected for pharmacokinetic analysis; CBC, serum BUN and creatinine concentration measurement, and urinalysis were conducted before and 1 week after each treatment. Some dogs underwent hepatic enzyme testing. Tumors were measured before the first treatment and 3 weeks after each treatment to assess response. RESULTS No adverse drug effects were detected in pretrial assessments in rodents. Seven of 16 dogs completed the study; 3 had complete tumor responses, 3 had stable disease, and 1 had progressive disease. Three of 7 dogs with oral and nasal squamous cell carcinoma (SCC) that completed the study had complete responses. Myelosuppression and cardiotoxicosis were identified in 6 and 2 dogs, respectively; none had nephrotoxicosis. Four of 5 dogs with hepatic enzymes assessed had increased ALT activities, attributed to diaquated cisplatin products in the HA-Pt. Pharmacokinetic data fit a 3-compartment model. CONCLUSIONS AND CLINICAL RELEVANCE HA-Pt treatment resulted in positive tumor responses in some dogs, primarily those with SCC. The adverse effect rate was high. IMPACT FOR HUMAN MEDICINE Oral SCC in dogs has characteristics similar to human head and neck SCC; these results could be useful in developing human treatments.

Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

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

Coen, John J., E-mail: jcoen@harthosp.org; Paly, Jonathan J.; Niemierko, Andrzej

2013-06-01

Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patientsmore » with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.« less

Responsiveness of clinical tests for people with neck pain.

PubMed

Jørgensen, René; Ris, Inge; Juhl, Carsten; Falla, Deborah; Juul-Kristensen, Birgit

2017-12-28

Responsiveness of a clinical test is highly relevant in order to evaluate the effect of a given intervention. However, the responsiveness of clinical tests for people with neck pain has not been adequately evaluated. The objective of the present study was to examine the responsiveness of four clinical tests which are low cost and easy to perform in a clinical setting, including the craniocervical flexion test, cervical active range of movement, test for the cervical extensors and pressure pain threshold testing. This study is a secondary analysis of data collected in a previously published randomised controlled trial. Participants were randomized to either physical training, exercises and pain education combined or pain education only. Participants were tested on the clinical tests at baseline and at 4-month follow-up. An anchor-based approach using Receiver Operator Characteristics (ROC) curves was used to evaluate responsiveness of the clinical tests. The Neck Disability Index was used to discriminate between those who had improved and those who were unchanged at the 4-month follow-up. Minimum Clinically Important Difference (MCID), together with sensitivity, specificity, positive and negative predictive values, in addition to positive and negative likelihood ratios were calculated. In total, 164 participants completed the 4 month follow up. One-hundred forty four participants were classified as unchanged whereas 20 patients were considered to be improved. Twenty-six participants didn't complete all of the clinical tests, leaving a total of 138 to be included for analyses. Area Under Curve (AUC) ranged from 0.50-0.62 for the clinical tests, and were all below an acceptable level. MCID was generally large, and the corresponding sensitivity and specificity was low with sensitivity ranging from 20 to 60%, and specificity from 54 to 86%. LR+ (0.8-2.07) and LR- (0.7-1.1) showed low diagnostic value for all variables, with PPV ranging from 12.1 to 26.1 and NPV ranging from 84.7 to 89.2. Responsiveness of the included clinical tests was generally low when using change in NDI score as the anchor from baseline to the 4-month follow up. Further investigations of responsiveness are warranted, possibly using other anchors, which to a higher degree resemble similar dimensions as the clinical tests.

Justify Your Answer: The Role of Written Think Aloud in Script Concordance Testing.

PubMed

Power, Alyssa; Lemay, Jean-Francois; Cooke, Suzette

2017-01-01

Construct: Clinical reasoning assessment is a growing area of interest in the medical education literature. Script concordance testing (SCT) evaluates clinical reasoning in conditions of uncertainty and has emerged as an innovative tool in the domain of clinical reasoning assessment. SCT quantifies the degree of concordance between a learner and an experienced clinician and attempts to capture the breadth of responses of expert clinicians, acknowledging the significant yet acceptable variation in practice under situations of uncertainty. SCT has been shown to be a valid and reliable clinical reasoning assessment tool. However, as SCT provides only quantitative information, it may not provide a complete assessment of clinical reasoning. Think aloud (TA) is a qualitative research tool used in clinical reasoning assessment in which learners verbalize their thought process around an assigned task. This study explores the use of TA, in the form of written reflection, in SCT to assess resident clinical reasoning, hypothesizing that the information obtained from the written TA would enrich the quantitative data obtained through SCT. Ninety-one pediatric postgraduate trainees and 21 pediatricians from 4 Canadian training centers completed an online test consisting of 24 SCT cases immediately followed by retrospective written TA. Six of 24 cases were selected to gather TA data. These cases were chosen to allow all phases of clinical decision making (diagnosis, investigation, and treatment) to be represented in the TA data. Inductive thematic analysis was employed when systematically reviewing TA responses. Three main benefits of adding written TA to SCT were identified: (a) uncovering instances of incorrect clinical reasoning despite a correct SCT response, (b) revealing sound clinical reasoning in the context of a suboptimal SCT response, and (c) detecting question misinterpretation. Written TA can optimize SCT by demonstrating when correct examinee responses are based on guessing or uncertainty rather than robust clinical rationale. TA can also enhance SCT by allowing examinees to provide justification for responses that otherwise would have been considered incorrect and by identifying questions that are frequently misinterpreted to avoid including them in future examinations. TA also has significant value in differentiating between acceptable variations in expert clinician responses and deviance associated with faulty rationale or question misinterpretation; this could improve SCT reliability. A written TA protocol appears to be a valuable tool to assess trainees' clinical reasoning and can strengthen the quantitative assessment provided by SCT.

Phase II Trial of Induction Chemotherapy Followed by Surgery for Squamous Cell Carcinoma of the Oral Tongue in Young Adults

PubMed Central

Kies, Merrill S.; Boatright, Dowin H.; Li, Guojun; Blumenschein, George; El-Naggar, Adel K.; Lewin, Jan S.; Steinhaus, Ganene; Sturgis, Erich M.

2013-01-01

Background We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. Methods From September 2001 to October 2004, 23 patients aged 18–49 years with clinical T2-3N0-2M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. Results On final surgical pathology, 9 (39%) patients had a complete/major (2 complete) histologic response at the primary tumor site; 8 (35%) had no response or progression. Similarly, 9 (39%) patients had a complete response in the neck or remained node negative; 6 (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 (43%) patients developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (P = .029), poor histologic differentiation (P = .012), and multiple adverse features on final surgical pathology (P = .040). Conclusions Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. PMID:22009800

Phase II trial of induction chemotherapy followed by surgery for squamous cell carcinoma of the oral tongue in young adults.

PubMed

Kies, Merrill S; Boatright, Dowin H; Li, Guojun; Blumenschein, George; El-Naggar, Adel K; Brandon Gunn, G; Lewin, Jan S; Steinhaus, Ganene D; Sturgis, Erich M

2012-09-01

We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2-3 N0-2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. Copyright © 2011 Wiley Periodicals, Inc.

Developing nursing and midwifery students' capacity for coping with bullying and aggression in clinical settings: Students' evaluation of a learning resource.

PubMed

Hogan, Rosemarie; Orr, Fiona; Fox, Deborah; Cummins, Allison; Foureur, Maralyn

2018-03-01

An innovative blended learning resource for undergraduate nursing and midwifery students was developed in a large urban Australian university, following a number of concerning reports by students on their experiences of bullying and aggression in clinical settings. The blended learning resource included interactive online learning modules, comprising film clips of realistic clinical scenarios, related readings, and reflective questions, followed by in-class role-play practice of effective responses to bullying and aggression. On completion of the blended learning resource 210 participants completed an anonymous survey (65.2% response rate). Qualitative data was collected and a thematic analysis of the participants' responses revealed the following themes: 'Engaging with the blended learning resource'; 'Responding to bullying' and 'Responding to aggression'. We assert that developing nursing and midwifery students' capacity to effectively respond to aggression and bullying, using a self-paced blended learning resource, provides a solution to managing some of the demands of the clinical setting. The blended learning resource, whereby nursing and midwifery students were introduced to realistic portrayals of bullying and aggression in clinical settings, developed their repertoire of effective responding and coping skills for use in their professional practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

A trial of e-simulation of sudden patient deterioration (FIRST2ACT WEB) on student learning.

PubMed

Bogossian, Fiona E; Cooper, Simon J; Cant, Robyn; Porter, Joanne; Forbes, Helen

2015-10-01

High-fidelity simulation pedagogy is of increasing importance in health professional education; however, face-to-face simulation programs are resource intensive and impractical to implement across large numbers of students. To investigate undergraduate nursing students' theoretical and applied learning in response to the e-simulation program-FIRST2ACT WEBTM, and explore predictors of virtual clinical performance. Multi-center trial of FIRST2ACT WEBTM accessible to students in five Australian universities and colleges, across 8 campuses. A population of 489 final-year nursing students in programs of study leading to license to practice. Participants proceeded through three phases: (i) pre-simulation-briefing and assessment of clinical knowledge and experience; (ii) e-simulation-three interactive e-simulation clinical scenarios which included video recordings of patients with deteriorating conditions, interactive clinical tasks, pop up responses to tasks, and timed performance; and (iii) post-simulation feedback and evaluation. Descriptive statistics were followed by bivariate analysis to detect any associations, which were further tested using standard regression analysis. Of 409 students who commenced the program (83% response rate), 367 undergraduate nursing students completed the web-based program in its entirety, yielding a completion rate of 89.7%; 38.1% of students achieved passing clinical performance across three scenarios, and the proportion achieving passing clinical knowledge increased from 78.15% pre-simulation to 91.6% post-simulation. Knowledge was the main independent predictor of clinical performance in responding to a virtual deteriorating patient R(2)=0.090, F(7, 352)=4.962, p<0.001. The use of web-based technology allows simulation activities to be accessible to a large number of participants and completion rates indicate that 'Net Generation' nursing students were highly engaged with this mode of learning. The web-based e-simulation program FIRST2ACTTM effectively enhanced knowledge, virtual clinical performance, and self-assessed knowledge, skills, confidence, and competence in final-year nursing students. Copyright © 2015 Elsevier Ltd. All rights reserved.

User compliance with documenting on a track and trigger-based observation and response chart: a two-phase multi-site audit study.

PubMed

Elliott, Doug; Allen, Emily; McKinley, Sharon; Perry, Lin; Duffield, Christine; Fry, Margaret; Gallagher, Robyn; Iedema, Rick; Roche, Michael

2017-12-01

To examine user compliance and completeness of documentation with a newly designed observation and response chart and whether a rapid response system call was triggered when clinically indicated. Timely recognition and responses to patient deterioration in hospital general wards remain a challenge for healthcare systems globally. Evaluating practice initiatives to improve recognition and response are required. Two-phase audit. Following introduction of the charts in ten health service sites in Australia, an audit of chart completion was conducted during a short trial for initial usability (Phase 1; 2011). After chart adoption as routine use in practice, retrospective and prospective chart audits were conducted (Phase 2; 2012). Overall, 818 and 1,058 charts were audited during the two phases respectively. Compliance was mixed but improved with the new chart (4%-14%). Contrary to chart guidelines, numbers rather than dots were written in the graphing section in 60% of cases. Rates of recognition of abnormal vital signs improved slightly with new charts in use, particularly for higher levels of surveillance and clinical review. Based on local calling criteria, an emergency call was initiated in 33% of cases during the retrospective audit and in 41% of cases with the new chart. User compliance was less than optimal, limiting full function of the chart sections and compliance with local calling criteria. Overcoming apparent behavioural and work culture barriers may improve chart completion, aiding identification of abnormal vital signs and triggering a rapid response system activation when clinical deterioration is detected. © 2017 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck.

PubMed

Weiss, Jared M; Grilley-Olson, Juneko E; Deal, Allison Mary; Zevallos, Jose P; Chera, Bhishamjit S; Paul, Jennifer; Knowles, Mary Fleming; Usenko, Dmitriy; Weissler, Mark C; Patel, Samip; Hayes, David N; Hackman, Trevor

2018-05-09

The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer. Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m 2 , and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility. Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow-up has recurred or died. Twenty-nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved. The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk-adapted adjuvant therapy resulted in high response rates and excellent long-term outcomes and should be further studied. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Imatinib adherence associated clinical outcomes of chronic myeloid leukaemia treatment in Taiwan.

PubMed

Chen, Teng-Chou; Chen, Li-Chia; Huang, Yaw-Bin; Chang, Chao-Sung

2014-02-01

Since the launch of imatinib, chronic myeloid leukaemia has become a chronic condition requiring costly long-term treatment. Emerging evidence from several short-term studies has raised concerns on the detrimental clinical outcomes and waste of resources associated with poor adherence to imatinib. This study aims to evaluate the effects of long-term imatinib adherence on clinical treatment responses and mortality. This retrospective cohort study was conducted in a medical centre in southern Taiwan. Chronic myeloid leukaemia patients who were prescribed for more than 1 month of imatinib were identified and their medical charts were reviewed from the first date of imatinib prescription to the last date of medical record or upon patients' death. Patients' basic characteristics, imatinib prescriptions, results of laboratory tests, episodes of imatinib-related side effects and mortality rate were recorded. Participants' basic characteristics, medication possession ratio and their mortality rate; the association between the medication possession ratio and treatment responses. Of the 119 included patients, the mean follow-up time was 3.9 ± 2.9 patient-years and the mean medication possession ratio was 89.7 %. At the 18th month of imatinib treatment, 67.2, 54.3 and 34.5 % patients achieved complete cytogenetic, major molecular and complete molecular responses, respectively. There was a significant difference in the 4-year survival rate between the adherence (n = 87) and non-adherence (n = 32) groups (91 vs. 72 %; p = 0.0076). Logistic regression analysis revealed that imatinib adherence was the only factor that significantly influenced the 18th month complete cytogenetic response [odds ratio (OR) 11.6; 95 % confidence interval (CI) 1.7, 114.7; p = 0.0131] and major molecular response (OR 5.1; 95 % CI 1.1, 26.8; p = 0.0351). Cox regression analysis demonstrated that a medication possession ratio greater than 90 % significantly reduced the mortality risk (hazard ratio 0.1; 95 % CI 0.01, 0.60; p = 0.0118). Chronic myeloid leukaemia patients' long-term adherence to imatinib is significantly associated with the 18th month treatment responses including the cytogenetic response, molecular response and the long-term survival rate in clinical practice.

A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

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

Hiniker, Susan M., E-mail: shiniker@stanford.edu; Reddy, Sunil A.; Maecker, Holden T.

Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasismore » measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.« less

An open, self-controlled study on the efficacy of topical indoxacarb for eliminating fleas and clinical signs of flea-allergy dermatitis in client-owned dogs in Queensland, Australia.

PubMed

Fisara, Petr; Sargent, Roger M; Shipstone, Michael; von Berky, Andrew; von Berky, Janet

2014-06-01

Canine flea-allergy dermatitis (FAD), a hypersensitivity response to antigenic material in the saliva of feeding fleas, occurs worldwide and remains a common presentation in companion animal veterinary practice despite widespread availability of effective systemic and topical flea-control products. To evaluate the clinical response in dogs with FAD treated topically with indoxacarb, a novel oxadiazine insecticide. Twenty-five client-owned dogs in Queensland, Australia diagnosed with pre-existing FAD on the basis of clinical signs, flea-antigen intradermal and serological tests. An open-label, noncontrolled study, in which all dogs were treated with topical indoxacarb at 4 week intervals, three times over 12 weeks. Twenty-four dogs completed the study. Complete resolution of clinical signs of FAD was observed in 21 cases (87.5%), with nearly complete resolution or marked improvement in the remaining three cases. Mean clinical scores (Canine Atopic Dermatitis Extent and Severity Index-03) were reduced by 93.3% at week 12. Mean owner-assessed pruritus scores were reduced by 88% by week 12. Mean flea counts reduced by 98.7 and 100% in weeks 8 and 12, respectively. Topical indoxacarb treatment applied every 4 weeks for 12 weeks, without concomitant antipruritic or ectoparasiticide therapy, completely alleviated flea infestations in all dogs and associated clinical signs of FAD in a high proportion of this population of dogs in a challenging flea-infestation environment. © 2014 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and the ACVD.

Understanding Clinic Practices for Human Papilloma Virus Vaccination Series Completion in Clinics That Provide Primary Care: Survey of Clinic Managers in Iowa.

PubMed

Askelson, Natoshia M; Edmonds, Stephanie W; Momany, Elizabeth T; Tegegne, Mesay A

2016-07-01

Rates for human papilloma virus (HPV) vaccination are low across the United States. Evidence-based-practices to increase immunization coverage have been recommended by public health organizations, yet many primary care clinics do not follow these practices. The purpose of this study was to examine if primary care clinics use these best practices to promote completion of the HPV vaccine series for their adolescent patients. Understanding the prevalence of evidence-based immunization strategies is key to increasing vaccination coverage. We mailed 914 surveys to clinic managers of clinics that provide primary care in Iowa. The survey content was based on immunization strategies related to clinic practice and policies that have been proven effective to promote the completion of the HPV vaccination series. Survey responses from 127 clinics were used in the final analysis. Most clinics always used the state's immunization information system to record HPV vaccinations (89.4%). Over a quarter of clinics (27.6%) did not use any type of reminder or recall system to alert parents or providers that an HPV vaccine was due, and 35.0% did not give the vaccine at sick visits. Clinics need to focus more on the recommended logistics and processes to ensure that patients receive the entire HPV vaccination series. Survey results indicate that clinics are not consistently implementing the recommended best practices to ensure that vaccination series are completed.

[Analysis of the impact of decitabine treatment cycles on efficacy and safety in patients of myelodysplastic syndrome-refractory anemia with excess blasts].

PubMed

Luo, X P; Xu, Z F; Qin, T J; Zhang, Y; Zhang, H L; Fang, L W; Pan, L J; Hu, N B; Qu, S Q; Li, B; Xiao, Z J

2016-10-14

Objective: To explore the impact of decitabine treatment cycles on efficacy and adverse events(AEs)in patients of myelodysplastic syndrome-refractory anemia with excess blasts(MDSRAEB). Methods: A total of fifty-six patients with MDS-RAEB who received decitabine 20 mg·m -2 ·d -1 by IV infusion daily for 5 consecutive days every 4 weeks at a single institute in China were enrolled from December 2008 to March 2016. Their clinical features, efficacy, predictors of efficacy and AEs were analyzed retrospectively. Results: Of the 56 patients enrolled, 25 cases were MDS- RAEB1, another 31 were MDS-RAEB2. A median of 3 cycles(range, 1-15 cycles)were delivered. The overall response rate was 67.9%(10 complete responses, 8 marrow complete responses without hematologic improvement, 17 marrow complete responses with hematologic improvements, and 3 hematologic improvements). With a median follow-up duration of 7.9(1.0-56.3)months, the median overall survival was 21.1(95% CI 16.0- 26.1)months. Compared with RAEB-2, RAEB-1 predicted higher overall response rates in a multivariate analysis. Of the 38 patients who experienced clinical responses, initial responses were detected by the end of two cycles in 37 patients. Twenty- five of the 38 patients who experienced clinical responses had their best response within the first two cycles, and 37 cases of the patients achieved best response by the end of fourth cycles. Grade 3 or 4 cytopenia and infection were the most prevalent AEs, which occurred frequently in the early courses and decreased later, and other non- hematologic AEs were rare. Conclusion: Decitabine treatment was favorable in patients with MDS- RAEB. In most of the cases, initial responses were observed within 2 cycles, and best response was achieved by the end of 4 th cycles. The most common AEs were grade 3 or 4 cytopenia and infection, which were observed frequently in first 2 cycles and decreased later as objective response were achieved.

PROMIS Fatigue Item Bank had Clinical Validity across Diverse Chronic Conditions.

PubMed

Cella, David; Lai, Jin-Shei; Jensen, Sally E; Christodoulou, Christopher; Junghaenel, Doerte U; Reeve, Bryce B; Stone, Arthur A

2016-05-01

To evaluate the comparability and responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue item bank across six chronic conditions. Individuals (n = 1,430) with chronic obstructive pulmonary disease (n = 125), chronic heart failure (n = 60), chronic back pain (n = 218), major depressive disorder (n = 196), rheumatoid arthritis (n = 521), and cancer (n = 310) completed assessments from the PROMIS fatigue item bank at baseline and a clinically relevant follow-up. The cancer and arthritis samples were followed in observational studies; the other four groups were enrolled immediately before a planned clinical intervention. All participants completed global ratings of change at follow-up. Linear mixed-effects models and standardized response means were estimated to examine clinical validity and responsiveness to change. All patient groups reported more fatigue than the general population (range = 0.2-1.29 standard deviation worse). The four clinical groups with pretreatment baseline data experienced significant improvement in fatigue at follow-up (effect size range = 0.25-0.91). Individuals reporting better overall health usually experienced larger fatigue changes than those reporting worse overall health. The results support the PROMIS fatigue measures's responsiveness to change in six different chronic conditions. In addition, these results support the ability of the PROMIS fatigue measures to compare differences in fatigue across a range of chronic conditions, thereby enabling comparative effectiveness research. Copyright © 2016 Elsevier Inc. All rights reserved.

Tumor infiltrating BRAFV600E-specific CD4 T cells correlated with complete clinical response in melanoma. | Office of Cancer Genomics

Cancer.gov

T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL).

Review of outcomes from a change in faculty clinic management in a U.S. dental school.

PubMed

Nadershahi, Nader A; Salmon, Eric S; Fathi, Nava; Schmedders, Karl; Hargis, Jace

2010-09-01

Dental schools use a variety of clinic management models with the goals of promoting patient care, student education, and fiscal responsibility. In 2004, the University of the Pacific Arthur A. Dugoni School of Dentistry transitioned to a more generalist model with these goals in mind. The purpose of this study was to evaluate the outcomes of this clinic model change relative to the quantity of specific procedures completed by students. The quantity of procedures completed by each student from the classes of 1995 through 2009 were compiled from our electronic clinic management system and analyzed. The post-transition group (2004-09) showed a greater number of completed oral diagnosis and treatment planning and root planing procedures per student compared to the pre-transition group (1995-2003), but fewer crowns, root canals, operative procedures, and dentures. Because the higher procedure numbers were for low-cost procedures, our transition to a generalist model did not necessarily enhance clinic income but may support student learning and enhanced patient care.

A randomized controlled trial comparing EMDR and CBT for obsessive-compulsive disorder.

PubMed

Marsden, Zoe; Lovell, Karina; Blore, David; Ali, Shehzad; Delgadillo, Jaime

2018-01-01

This study aimed to evaluate eye movement desensitization and reprocessing (EMDR) as a treatment for obsessive-compulsive disorder (OCD), by comparison to cognitive behavioural therapy (CBT) based on exposure and response prevention. This was a pragmatic, feasibility randomized controlled trial in which 55 participants with OCD were randomized to EMDR (n = 29) or CBT (n = 26). The Yale-Brown obsessive-compulsive scale was completed at baseline, after treatment and at 6 months follow-up. Treatment completion and response rates were compared using chi-square tests. Effect size was examined using Cohen's d and multilevel modelling. Overall, 61.8% completed treatment and 30.2% attained reliable and clinically significant improvement in OCD symptoms, with no significant differences between groups (p > .05). There were no significant differences between groups in Yale-Brown obsessive-compulsive scale severity post-treatment (d = -0.24, p = .38) or at 6 months follow-up (d = -0.03, p = .90). EMDR and CBT had comparable completion rates and clinical outcomes. Copyright © 2017 John Wiley & Sons, Ltd.

TRACO Course Registration Form | Center for Cancer Research

Cancer.gov

TRACO Translational Research in Clinical Oncology September 5 - December 4, 2017 For NIH Postdoctoral and Clinical Fellows Mandatory responses are marked by an asterisk (*). A confirmation e-mail will be sent to the address listed in the "E-mail Address" field upon completion and submission of the form.

Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura.

PubMed

Emilia, Giovanni; Morselli, Monica; Luppi, Mario; Longo, Giuseppe; Marasca, Roberto; Gandini, Giovanna; Ferrara, Leonardo; D'Apollo, Nicola; Potenza, Leonardo; Bertesi, Marcello; Torelli, Giuseppe

2002-02-15

Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory to most usual therapies is a difficult challenge. Little information exists on the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report describes long-term treatment with CyA (median, 40 months) and follow-up (median, 36.8 months) in 12 adult patients with resistant ITP. CyA used in relatively low doses (2.5-3 mg/kg of body weight per day) led to a clinical improvement in 10 patients (83.3%). Five had a complete response (41.1%), 4 a complete response to maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had no response. Most patients with a response (60%) had a long-term remission (mean, 28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4 years after CyA therapy was stopped. Side effects were moderate and transient, even in patients dependent on continued CyA treatment. CyA seems to represent reasonable salvage treatment in severe, potentially life-threatening, refractory ITP.

[Research advances of anti-tumor immune response induced by pulse electric field ablation].

PubMed

Cui, Guang-ying; Diao, Hong-yan

2015-11-01

As a novel tumor therapy, pulse electric field has shown a clinical perspective. This paper reviews the characteristics of tumor ablation by microsecond pulse and nanosecond pulse electric field, and the research advances of anti-tumor immune response induced by pulse electric field ablation. Recent researches indicate that the pulse electric field not only leads to a complete ablation of local tumor, but also stimulates a protective immune response, thereby inhibiting tumor recurrence and metastasis. These unique advantages will show an extensive clinical application in the future. However, the mechanism of anti-tumor immune response and the development of related tumor vaccine need further studies.

[Personal experience with VP-16 in the treatment of malignant lymphomas at the Chemotherapy Clinic of the Oncology Center--M. Skłodowskiej-Curie Institute in Warsaw].

PubMed

Pałucka, A; Walewski, J; Siedlecki, P; Zborzil, J

1990-01-01

Eighteen patients with advanced malignant lymphomas who had progressed with previous chemotherapy were treated with LEPP (chlorambucil, VP-16, procarbazine, prednisone). One complete response and 5 partial remissions were observed, yielding an overall response rate of 33%, with median response duration of about 2 months. Twenty three patients with advanced Hodgkin's disease all who had progressed with previous chemotherapy (MOPP and ABVD) and 19 of them also after radiation therapy were treated with third line salvage chemotherapy consisting of OPEC (VP- 16, chlorambucil, vincristine and prednisone). Two complete response and 3 partial remissions were obtained for overall response rate of 21% with median duration of about 9 months.

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

PubMed Central

Skroza, Nevena; Proietti, Ilaria; Bernardini, Nicoletta; Balduzzi, Veronica; Mambrin, Alessandra; Marchesiello, Anna; Tolino, Ersilia; Zuber, Sara; La Torre, Giuseppe; Potenza, Concetta

2017-01-01

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score. PMID:29067277

'Real-life' study of imatinib therapy in chronic phase-chronic myeloid leukemia: A novel retrospective observational longitudinal analysis.

PubMed

Merante, Serena; Ferretti, Virginia; Elena, Chiara; Calvello, Celeste; Rocca, Barbara; Zappatore, Rita; Cavigliano, Paola; Orlandi, Ester

2017-01-01

Imatinib is a cornerstone of treatment of chronic myeloid leukemia. It remains unclear whether transient treatment discontinuation or dose changes affect outcome and this approach has not yet been approved for use outside clinical trials. We conducted a retrospective single-institution observational study to evaluate factors affecting response in 'real-life' clinical practice in 138 chronic myeloid leukemia patients in chronic phase treated with imatinib. We used a novel longitudinal data analytical model, with a generalized estimating equation model, to study BCR-ABL variation according to continuous standard dose, change in dose or discontinuation; BCR-ABL transcript levels were recorded. Treatment history was subdivided into time periods for which treatment was given at constant dosage (total 483 time periods). Molecular and cytogenetic complete response was observed after 154 (32%) and 358 (74%) time periods, respectively. After adjusting for length of time period, no association between dose and cytogenetic complete response rate was observed. There was a significantly lower molecular complete response rate after time periods at a high imatinib dosage. This statistical approach can identify individual patient variation in longitudinal data collected over time and suggests that changes in dose or discontinuation of therapy could be considered in patients with appropriate biological characteristics.

Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

PubMed

Sada, Yvonne H; Tran Cao, Hop S; Chang, George J; Artinyan, Avo; Musher, Benjamin L; Smaglo, Brandon G; Massarweh, Nader N

2018-06-01

For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment. Published by Elsevier Inc.

Clinical significance of neonatal menstruation.

PubMed

Brosens, Ivo; Benagiano, Giuseppe

2016-01-01

Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely neglected and considered an uneventful episode of no clinical significance. Yet clinical studies have linked the risk of bleeding to a series of events indicating fetal distress. The potential link between the progesterone response and major adolescent disorders requires to be investigated by prospective studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients.

PubMed

Ellebaek, Eva; Iversen, Trine Zeeberg; Junker, Niels; Donia, Marco; Engell-Noerregaard, Lotte; Met, Özcan; Hölmich, Lisbet Rosenkrantz; Andersen, Rikke Sick; Hadrup, Sine Reker; Andersen, Mads Hald; thor Straten, Per; Svane, Inge Marie

2012-08-21

Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day. Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3-4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.

Responsible Translation of Stem Cell Research: An Assessment of Clinical Trial Registration and Publications.

PubMed

Fung, Moses; Yuan, Yan; Atkins, Harold; Shi, Qian; Bubela, Tania

2017-05-09

We assessed the extent to which the publication of clinical trial results of innovative cell-based interventions reflects International Society for Stem Cell Research best practice guidelines. We assessed: (1) characteristics and time to publication of completed trials; (2) quality of reported trials; and (3) results of published trials. We identified and analyzed publications from 1,052 novel stem cell clinical trials: 179 (45.4%) of 393 completed trials had published results; 48 trials were registered by known stem cell tourism clinics, none of which reported results. Completed non-industry-sponsored trials initially published more rapidly, but differences with industry-sponsored trials decreased over time. Most publications reported safety, and 67.3% (mainly early-stage trials) reported positive outcomes. A higher proportion of industry trials reported positive efficacy. Heightened patient expectations for stem cell therapies give rise to ethical obligations for the transparent conduct of clinical trials. Reporting guidelines need to be developed that are specific to early-phase clinical trials. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Identification of non-response to treatment using narrative data in an electronic health record inflammatory bowel disease cohort

PubMed Central

Ananthakrishnan, Ashwin N.; Cagan, Andrew; Cai, Tianxi; Gainer, Vivian S.; Shaw, Stanley Y; Savova, Guergana; Churchill, Susanne; Karlson, Elizabeth W.; Murphy, Shawn N.; Liao, Katherine P.; Kohane, Isaac

2016-01-01

Introduction Electronic health records (EHR), increasingly a part of healthcare, provide a wealth of untapped narrative free text data that has the potential to accurately inform clinical outcomes. Methods From a validated cohort of patients with Crohn’s disease (CD) or ulcerative colitis (UC), we identified patients with ≥ 1 coded or narrative mention of monoclonal antibodies to tumor necrosis factor α (anti-TNF). Chart review by ascertained true use of therapy, time of initiation and cessation of treatment, as well as clinical response stratified as non-response, partial, or complete response at one year. Internal consistency was assessed in an independent validation cohort. Results A total of 3,087 patients had a mention of an anti-TNF. Actual therapy initiation was within 60 days of the first coded mention in 74% of patients. In the derivation cohort, 18% of anti-TNF starts were classified as non-response at 1 year, 21% as partial, and 56% as complete response. On multivariate analysis, the number of narrative mentions of diarrhea (OR 1.08, 95% CI 1.02 – 1.14) and fatigue (OR 1.16, 95% CI 1.02 – 1.32) were independently associated with non-response at 1 year (AUC 0.82). A likelihood of non-response score comprising a weighted sum of both demonstrated a good dose response relationship across non-responders (2.18), partial (1.20), and complete (0.50) responders (p < 0.0001) and correlated well with need for surgery or hospitalizations. Conclusions Narrative data in an EHR offers considerable potential to define temporally evolving disease outcomes such as non-response to treatment. PMID:26332313

Prediction of Pathological Complete Response Using Endoscopic Findings and Outcomes of Patients Who Underwent Watchful Waiting After Chemoradiotherapy for Rectal Cancer.

PubMed

Kawai, Kazushige; Ishihara, Soichiro; Nozawa, Hiroaki; Hata, Keisuke; Kiyomatsu, Tomomichi; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

2017-04-01

Nonoperative management for patients with rectal cancer who have achieved a clinical complete response after chemoradiotherapy is becoming increasingly important in recent years. However, the definition of and modality used for patients with clinical complete response differ greatly between institutions, and the role of endoscopic assessment as a nonoperative approach has not been fully investigated. This study aimed to investigate the ability of endoscopic assessments to predict pathological regression of rectal cancer after chemoradiotherapy and the applicability of these assessments for the watchful waiting approach. This was a retrospective comparative study. This study was conducted at a single referral hospital. A total of 198 patients with rectal cancer underwent preoperative endoscopic assessments after chemoradiotherapy. Of them, 186 patients underwent radical surgery with lymph node dissection. The histopathological findings of resected tissues were compared with the preoperative endoscopic findings. Twelve patients refused radical surgery and chose watchful waiting; their outcomes were compared with the outcomes of patients who underwent radical surgery. The endoscopic criteria correlated well with tumor regression grading. The sensitivity and specificity for a pathological complete response were 65.0% to 87.1% and 39.1% to 78.3%. However, endoscopic assessment could not fully discriminate pathological complete responses, and the outcomes of patients who underwent watchful waiting were considerably poorer than the patients who underwent radical surgery. Eventually, 41.7% of the patients who underwent watchful waiting experienced uncontrollable local failure, and many of these occurrences were observed more than 3 years after chemoradiotherapy. The number of the patients treated with the watchful waiting strategy was limited, and the selection was not randomized. Although endoscopic assessment after chemoradiotherapy correlated with pathological response, it is unsuitable for surveillance of patients treated via a nonoperative approach. Incorporation of a "watchful waiting" strategy without establishing proper surveillance protocols and salvage strategies might result in poor local control.

Real-Time Data Collection Using Text Messaging in a Primary Care Clinic.

PubMed

Rai, Manisha; Moniz, Michelle H; Blaszczak, Julie; Richardson, Caroline R; Chang, Tammy

2017-12-01

The use of text messaging is nearly ubiquitous and represents a promising method of collecting data from diverse populations. The purpose of this study was to assess the feasibility and acceptability of text message surveys in a clinical setting and to describe key lessons to minimize attrition. We obtained a convenience sample of individuals who entered the waiting room of a low-income, primary care clinic. Participants were asked to answer between 17 and 30 survey questions on a variety of health-related topics, including both open- and closed-ended questions. Descriptive statistics were used to characterize the participants and determine the response rates. Bivariate analyses were used to identify predictors of incomplete surveys. Our convenience sample consisted of 461 individuals. Of those who attempted the survey, 80% (370/461) completed it in full. The mean age of respondents was 35.4 years (standard deviation = 12.4). Respondents were predominantly non-Hispanic black (42%) or non-Hispanic white (41%), female (75%), and with at least some college education (70%). Of those who completed the survey, 84% (312/370) reported willingness to do another text message survey. Those with incomplete surveys answered a median of nine questions before stopping. Smartphone users were less likely to leave the survey incomplete compared with non-smartphone users (p = 0.004). Text-message surveys are a feasible and acceptable method to collect real-time data among low-income, clinic-based populations. Offering participants a setting for immediate survey completion, minimizing survey length, simplifying questions, and allowing "free text" responses for all questions may optimize response rates.

Preliminary results of a phase I/II clinical trial using in situ photoimmunotherapy combined with imiquimod for metastatic melanoma patients

NASA Astrophysics Data System (ADS)

Li, Xiaosong; Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Howard, C. Anthony; Murray, Cynthia; Chen, Wei R.

2010-02-01

In Situ Photoimmunotherapy (ISPI), a newly developed modality for cancer therapy, has been shown to be able to modulate the body's own immune response. This clinical trial was designed to evaluate the safety and therapeutic effect of ISPI, using imiquimod as its immunoadjuvant for metastatic melanoma patients. ISPI consisted of three main components applied directly to the cutaneous metastases: 1) local application of topical imiquimod; 2) injection of indocyanine green; and 3) an 805 nm laser for local irradiation. All patients completed at least one cycle of treatment. All the patients completed at least one cycle of treatments; one patient received 6 cycles. The most common adverse effects were rash, pruritus, pain, fatigue and anorexia. Fever, chills, vomiting and cellulitis were relative rare. No grade 4 toxicity was observed. Complete Response (CR) was observed in 6 patients. Median overall survival of the 11 evaluated patients was 12.2 months. Six of the eleven patients were still alive at the time of this report. Treatment of ISPI using imiquimod is safe and well tolerant. Our preliminary clinical results suggest that this new method can be a promising modality for metastatic melanoma.

Towards socially inclusive research: an evaluation of telephone questionnaire administration in a multilingual population.

PubMed

Dormandy, Elizabeth; Brown, Katrina; Reid, Erin P; Marteau, Theresa M

2008-01-31

Missing data may bias the results of clinical trials and other studies. This study describes the response rate, questionnaire responses and financial costs associated with offering participants from a multilingual population the option to complete questionnaires over the telephone. Before and after study of two methods of questionnaire completion. Seven hundred and sixty five pregnant women from 25 general practices in two UK inner city Primary Care Trusts (PCTs) taking part in a cluster randomised controlled trial of offering antenatal sickle cell and thalassaemia screening in primary care. Two hundred and four participants did not speak English. Sixty one women were offered postal questionnaire completion only and 714 women were offered a choice of telephone or postal questionnaire completion. (i) Proportion of completed questionnaires, (ii) attitude and knowledge responses obtained from a questionnaire assessing informed choice. The response rate from women offered postal completion was 26% compared with 67% for women offered a choice of telephone or postal completion (41% difference 95% CI Diff 30 to 52). For non-English speakers offered a choice of completion methods the response rate was 56% compared with 71% for English speakers (95% CI Diff 7 to 23). No difference was found for knowledge by completion method, but telephone completion was associated with more positive attitude classifications than postal completion (87 vs 96%, 95% CI diff 0.006 to 15). Compared with postal administration the additional costs associated with telephone administration were pound3.90 per questionnaire for English speakers and pound71.60 per questionnaire for non English speakers. Studies requiring data to be collected by questionnaire may obtain higher response rates from both English and non-English speakers when a choice of telephone or postal administration (and where necessary, an interpreter)is offered compared to offering postal administration only. This approach will, however, incur additional research costs and uncertainty remains about the equivalence of responses obtained from the two methods.

Brentuximab vedotin in relapsed/refractory Hodgkin’s lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials

PubMed Central

Zinzani, Pier Luigi; Viviani, Simonetta; Anastasia, Antonella; Vitolo, Umberto; Luminari, Stefano; Zaja, Francesco; Corradini, Paolo; Spina, Michele; Brusamolino, Ercole; Gianni, Alessandro M.; Santoro, Armando; Botto, Barbara; Derenzini, Enrico; Pellegrini, Cinzia; Argnani, Lisa

2013-01-01

Clinical trial results indicate that brentuximab vedotin brings considerable promise for the treatment of patients with relapsed or refractory Hodgkin’s lymphoma. A retrospective multicenter study was conducted on 65 heavily pretreated patients who underwent therapy through a Named Patient Program in Italy (non trial-setting). The primary study endpoint was the objective response rate; secondary endpoints were safety, overall survival and progression-free survival. The best overall response rate (70.7%), including 21.5% complete responses, was observed at the first restaging after the third cycle of treatment. After a median follow up of 13.2 months, the overall survival rate at 20 months was 73.8% while the progression-free survival rate at 20 months was 24.2%. Globally nine patients are in continuous complete response with a median follow up of 14 months (range, 10–19 months). Four patients proceeded to autotransplantation and nine to allotransplantation. The most frequent extra-hematologic toxicity was peripheral neuropathy, observed in 21.5% of cases (9 patients with grade 1/2 and 5 patients with grade 3/4); neurological toxicity led to discontinuation of treatment in three patients and to dose reduction in four. In general the treatment was well tolerated and toxicities, both hematologic and extra-hematologic, were manageable. This report indicates and confirms that brentuximab vedotin as a single agent is effective and safe also when used in standard, everyday clinical practice outside a clinical trial. Best overall responses were recorded after three or four cycles and showed that brentuximab vedotin provides an effective bridge to further therapeutic interventions. PMID:23645687

Empowerment of physiotherapy students on placement: The interplay between autonomy, risk, and responsibility.

PubMed

Clouder, Lynn; Adefila, Arinola

2017-11-01

Knowledge of the effects on students of clinical educators' giving or withholding responsibility on placement is limited. The associated empowering, or disempowering impact indicates the need for research on what grounds such decisions are made. The study aimed to explore clinical educators' perspectives on the importance of giving student physiotherapists increasing levels of responsibility on clinical placement, and the factors considered when giving or withholding responsibility. A grounded theory methodology underpins this United Kingdom (UK) based study. The phase of the study reported in this article involved 26, semi-structured interviews with clinical educators, each followed by the completion of a diamond ranking exercise. Three themes emerged: 1) the ubiquity of risk; 2) the relationship between trust and trustworthiness; and 3) graduated supervision. The first theme, acknowledged that risk is ever-present and that clinical educators are used to managing it, balancing risk and responsibility given to students. The second theme highlighted the importance of developing trust/trustworthiness as a foundation for a sound working relationship between student and clinical educator. The third theme focusing on graduated supervision as a means of empowering students to take on increasingly demanding responsibilities on placement. The study illustrates the complex relationship between risk, trust, responsibility, and developing student autonomy. A strategy is proposed to provide an empowering alternative to the tendency to increase surveillance and/or limit the responsibility for students who lack confidence or capability in taking responsibility on clinical placement. Future research could aim to test the strategy more widely.

Methamphetamine dependence: a closer look at treatment response and clinical characteristics associated with route of administration in outpatient treatment.

PubMed

Rawson, Richard A; Gonzales, Rachel; Marinelli-Casey, Patricia; Ang, Alfonso

2007-01-01

Relatively little is known about the clinical treatment response characteristics associated with route of methamphetamine (MA) administration. We examined sociodemographic, drug use, treatment response, as well as psychiatric and medical characteristics associated with route of administration among 974 methamphetamine abusers in outpatient treatment during 1999-2001. Injectors had the poorest treatment prognosis: poorer treatment engagement, greater drug use during treatment, lower treatment completion rates, and more MA use at 12 months post-admission than did smokers and intranasal users. On many treatment response measures, MA smokers were almost as severely impaired as injectors, and in general, intranasal users were least impaired. Psychological and medical impairment, before and after treatment, was also highest among injectors. This study contributes new insights about clinical treatment response and outcomes associated with route of administration among MA-dependent users.

Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules

PubMed Central

Di Santo, Sara; Trignani, Marianna; Neri, Matteo; Milano, Angelo; Innocenti, Paolo; Taraborrelli, Maria; Augurio, Antonietta; Vinciguerra, Annamaria; Di Tommaso, Monica; Ursini, Lucia Anna; Di Pilla, Angelo; Di Nicola, Marta; Genovesi, Domenico

2014-01-01

Aim Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. Background Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. Methods Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan–Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. Results Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. Conclusion Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied. PMID:25859401

[An Investigation of the Role Responsibilities of Clinical Research Nurses in Conducting Clinical Trials].

PubMed

Kao, Chi-Yin; Huang, Guey-Shiun; Dai, Yu-Tzu; Pai, Ya-Ying; Hu, Wen-Yu

2015-06-01

Clinical research nurses (CRNs) play an important role in improving the quality of clinical trials. In Taiwan, the increasing number of clinical trials has increased the number of practicing CRNs. Understanding the role responsibilities of CRNs is necessary to promote professionalism in this nursing category. This study investigates the role responsibilities of CRNs in conducting clinical trials / research. A questionnaire survey was conducted in a medical center in Taipei City, Taiwan. Eighty CRNs that were registered to facilitate and conduct clinical trials at this research site completed the survey. "Subject protection" was the CRN role responsibility most recognized by participants, followed by "research coordination and management", "subject clinical care", and "advanced professional nursing". Higher recognition scores were associated with higher importance scores and lower difficulty scores. Participants with trial training had significantly higher difficulty scores for "subject clinical care" and "research coordination and management" than their peers without this training (p < .05). Participants who had participated in a long-term trial-training course earned higher importance scores for "CRN four-subthemes role responsibilities" (p <.05) and lower difficulty scores for "subject protection", "research coordination and management" (p <.005) than their short-term course peers. "Recognition of overall responsibilities" and "receiving trial training" were the significant predictors of difficulty in performing CRN role responsibilities, explaining 21.9% of the total variance. To further promote CRN as a professional career in Taiwan, the findings of this study recommend identifying the core competences of CRNs and adding CRN-related study materials into the advanced nursing curriculum. Long-term and systematic educational training may help CRNs understand the importance of their role responsibilities, better recognize their professional role, and reflect these responsibilities in clinical practice.

Biased Interpretation of Ambiguous Social Scenarios in Anorexia Nervosa.

PubMed

Cardi, Valentina; Turton, Robert; Schifano, Sylvia; Leppanen, Jenni; Hirsch, Colette R; Treasure, Janet

2017-01-01

Patients with anorexia nervosa experience increased sensitivity to the risk of social rejection. The aims of this study were to assess the interpretation of ambiguous social scenarios depicting the risk of rejection and to examine the relationship between interpretation biases and clinical symptoms. Thirty-five women with anorexia nervosa and 30 healthy eaters completed clinical questionnaires, alongside a sentence completion task. This task required participants to generate completions to ambiguous social scenarios and to endorse their best completion. Responses were rated as being negative, neutral or positive. Patients endorsed more negative interpretations and fewer neutral and positive interpretations compared with healthy eaters. The frequency of endorsed negative interpretations correlated with depression, anxiety and fear of weight gain and body disturbance. A negative interpretation bias towards social stimuli is present in women with anorexia nervosa and correlates with clinical symptoms. Interventions aimed at reducing this bias could improve illness prognosis. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Nomogram predicting response after chemoradiotherapy in rectal cancer using sequential PETCT imaging: a multicentric prospective study with external validation.

PubMed

van Stiphout, Ruud G P M; Valentini, Vincenzo; Buijsen, Jeroen; Lammering, Guido; Meldolesi, Elisa; van Soest, Johan; Leccisotti, Lucia; Giordano, Alessandro; Gambacorta, Maria A; Dekker, Andre; Lambin, Philippe

2014-11-01

To develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential (18)F-FDG PETCT imaging. Prospective data (i.a. THUNDER trial) were used to train (N=112, MAASTRO Clinic) and validate (N=78, Università Cattolica del S. Cuore) the model for pCR (ypT0N0). All patients received long-course chemoradiotherapy (CRT) and surgery. Clinical parameters were age, gender, clinical tumour (cT) stage and clinical nodal (cN) stage. PET parameters were SUVmax, SUVmean, metabolic tumour volume (MTV) and maximal tumour diameter, for which response indices between pre-treatment and intermediate scan were calculated. Using multivariate logistic regression, three probability groups for pCR were defined. The pCR rates were 21.4% (training) and 23.1% (validation). The selected predictive features for pCR were cT-stage, cN-stage, response index of SUVmean and maximal tumour diameter during treatment. The models' performances (AUC) were 0.78 (training) and 0.70 (validation). The high probability group for pCR resulted in 100% correct predictions for training and 67% for validation. The model is available on the website www.predictcancer.org. The developed predictive model for pCR is accurate and externally validated. This model may assist in treatment decisions during CRT to select complete responders for a wait-and-see policy, good responders for extra RT boost and bad responders for additional chemotherapy. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

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

Trentham, D.E.; Belli, J.A.; Anderson, R.J.

Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitutionmore » of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.« less

Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

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

Trentham, D.E.; Belli, J.A.Anderson, R.J.; Buckley, J.A.

Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly before a year after the completion of irradiation and was paralleled by a restitutionmore » of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.« less

Prognostic sub-grouping of diffuse large B-cell lymphomas into germinal centre and post germinal centre groups by immunohistochemistry after 6 cycles of chemotherapy.

PubMed

Hassan, Usman; Mushtaq, Sajid; Mamoon, Nadira; Asghar, Asghar Hussain; Ishtiaq, Sheeba

2012-01-01

Diffuse large B-cell lymphomas (DLBCL) can be divided into germinal centre (GC-DLBCL) and post germinal centre (post GC-DLBCL) groups by applying immunohistochemical antibodies. As these subgroups respond differently to chemotherapy, it is possible at diagnosis to select a poor prognostic subgroup for aggressive treatment. To determine the frequencies of GC-DLBCL and post GC-DLBCL in patients by immunohistochemistry (IHC) and the clinical response after six cycles of chemotherapy. In this descriptive study conducted in AFIP and CMH, Rawalpindi and NORI, Islamabad, from September 2010 to September 2011, a total of 75 pretreatment cases of DLBCL diagnosed during the study period were included. Cases were segregated in to GC-DLBCL and post GC-DLBCL groups according to results of immunohistochemistry markers CD10, BCL6 and MUM1. Immediate clinical response was assessed after 6 cycles of chemotherapy. Response was divided into complete response, partial response, stable disease or relapse or progression. The mean age was 54.2 ± 15. Males were 53 (70.7%). Forty (53.3%) cases comprised the GC-DLBCL group; 25(62.5%) of them showed a complete response. Most patients of the post GC-DLBCL 19(54%) showed relapse/progression. Results of immediate clinical response in both prognostic subgroups were significant (p<0.05). Results regarding positivity with immunohistochemical antibodies CD10 (p 0.011), BCL6 (p 0.013) and MUM1 (p 0.000) regarding immediate clinical response were also significant. GC-DLBCL group shows better response to CHOP chemotherapy regimen. Immunohistochemistry should be used to further classify DLBCL as this can enable us to select aggressive group for aggressive treatment. This manuscript is important because the study is the first to becarried out exclusively in Pakistan or our part of the world.

Computer-automated dementia screening using a touch-tone telephone.

PubMed

Mundt, J C; Ferber, K L; Rizzo, M; Greist, J H

2001-11-12

This study investigated the sensitivity and specificity of a computer-automated telephone system to evaluate cognitive impairment in elderly callers to identify signs of early dementia. The Clinical Dementia Rating Scale was used to assess 155 subjects aged 56 to 93 years (n = 74, 27, 42, and 12, with a Clinical Dementia Rating Scale score of 0, 0.5, 1, and 2, respectively). These subjects performed a battery of tests administered by an interactive voice response system using standard Touch-Tone telephones. Seventy-four collateral informants also completed an interactive voice response version of the Symptoms of Dementia Screener. Sixteen cognitively impaired subjects were unable to complete the telephone call. Performances on 6 of 8 tasks were significantly influenced by Clinical Dementia Rating Scale status. The mean (SD) call length was 12 minutes 27 seconds (2 minutes 32 seconds). A subsample (n = 116) was analyzed using machine-learning methods, producing a scoring algorithm that combined performances across 4 tasks. Results indicated a potential sensitivity of 82.0% and specificity of 85.5%. The scoring model generalized to a validation subsample (n = 39), producing 85.0% sensitivity and 78.9% specificity. The kappa agreement between predicted and actual group membership was 0.64 (P<.001). Of the 16 subjects unable to complete the call, 11 provided sufficient information to permit us to classify them as impaired. Standard scoring of the interactive voice response-administered Symptoms of Dementia Screener (completed by informants) produced a screening sensitivity of 63.5% and 100% specificity. A lower criterion found a 90.4% sensitivity, without lowering specificity. Computer-automated telephone screening for early dementia using either informant or direct assessment is feasible. Such systems could provide wide-scale, cost-effective screening, education, and referral services to patients and caregivers.

P-Glycoprotein Activity in Steroid-Responsive vs. Steroid-Resistant Nephrotic Syndrome.

PubMed

Badr, Hassan S; El-Hawy, Mahmoud A; Helwa, Mohammed A

2016-11-01

To explore the expression of P-glycoprotein (P-gp) in the peripheral blood nucleated cells (PBNCs) of children with nephrotic syndrome in relation to their clinical response to glucocorticoid treatment. Thirty-six children with nephrotic syndrome (20 cases of steroid-responsive and 16 cases of steroid-resistant) were examined. All the participants were subjected to complete history taking, thorough clinical examination, laboratory investigations (24-h urinary protein, serum albumin, complete blood count with differential white blood cell count, serum cholesterol, serum urea, serum creatinine) and functional assay of P-gp using FACS Calibur flowcytometry. P-gp assay was done in both groups during remission. P-gp activity was significantly higher in steroid-resistant than steroid-sensitive cases. P-gp can be used as a predictor of outcome, as a part of laboratory evaluation of the cases before starting steroid therapy, so as to determine whether to use alternative line of therapy or use one of the P-gp inhibitors with steroid therapy.

Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial.

PubMed

Huttner, Angela; Kowalczyk, Anna; Turjeman, Adi; Babich, Tanya; Brossier, Caroline; Eliakim-Raz, Noa; Kosiek, Katarzyna; Martinez de Tejada, Begoña; Roux, Xavier; Shiber, Shachaf; Theuretzbacher, Ursula; von Dach, Elodie; Yahav, Dafna; Leibovici, Leonard; Godycki-Cwirko, Maciek; Mouton, Johan W; Harbarth, Stephan

2018-05-01

The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI). To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis. Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel. Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection. The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events. Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively). Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion. ClinicalTrials.gov Identifier: NCT01966653.

Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

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

Unsal, Diclehan; Uner, Aytug; Akyurek, Nalan

2007-01-01

Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primarymore » endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.« less

Association between quality of response and outcomes in patients with newly diagnosed mantle cell lymphoma receiving VR-CAP versus R-CHOP in the phase 3 LYM-3002 study.

PubMed

Verhoef, Gregor; Robak, Tadeusz; Huang, Huiqiang; Pylypenko, Halyna; Siritanaratkul, Noppadol; Pereira, Juliana; Drach, Johannes; Mayer, Jiri; Okamoto, Rumiko; Pei, Lixia; Rooney, Brendan; Cakana, Andrew; van de Velde, Helgi; Cavalli, Franco

2017-05-01

In the phase 3 LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered or ineligible for transplant, the median progression-free survival was significantly improved with VR-CAP (24.7 versus 14.4 months with R-CHOP; P <0.001). This post-hoc analysis evaluated the association between the improved outcomes and quality of responses achieved with VR-CAP versus R-CHOP in LYM-3002. Patients were randomized to six to eight 21-day cycles of VR-CAP or R-CHOP. Outcomes included progression-free survival, duration of response (both assessed by an independent review committee), and time to next anti-lymphoma treatment, evaluated by response (complete response/unconfirmed complete response and partial response), MIPI risk status, and maximum reduction of lymph-node measurements expressed as the sum of the product of the diameters. Within each response category, the median progression-free survival was longer for patients given VR-CAP than for those given R-CHOP (complete response/unconfirmed complete response: 40.9 versus 19.8 months; partial response: 17.1 versus 11.7 months, respectively); similarly, the median time to next anti-lymphoma treatment was longer among the patients given VR-CAP than among those treated with R-CHOP (complete response/unconfirmed complete response: not evaluable versus 26.6 months; partial response: 35.3 versus 24.3 months). Within the complete/unconfirmed complete and partial response categories, improvements in progression-free survival, duration of response and time to next anti-lymphoma treatment were more pronounced in patients with low-and intermediate-risk MIPI treated with VR-CAP than with R-CHOP. In each response category, more VR-CAP than R-CHOP patients had a sum of the product of the diameters nadir of 0 during serial radiological assessments. Results of this post-hoc analysis suggest a greater duration and quality of response in patients treated with VR-CAP in comparison with those treated with R-CHOP, with the improvements being more evident in patients with low- and intermediate-risk MIPI. LYM-3002 ClinicalTrials.gov: NCT00722137 . Copyright© Ferrata Storti Foundation.

Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

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

Prabhu, Roshan S., E-mail: rprabhu@emory.edu; Kandula, Shravan; Liebman, Lang

2013-03-01

Purpose: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Methods and Materials: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without anmore » increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Results: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. Conclusions: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.« less

The impact of complete denture making instructional videos on self-directed learning of clinical skills.

PubMed

Kon, Haruka; Botelho, Michael George; Bridges, Susan; Leung, Katherine Chiu Man

2015-04-01

The aim of this research was to evaluate the effectiveness of a clinical instructional video with a structured worksheet for independent self-study in a complete denture program. 47 multilingual dental students completed a task by watching an instructional video with subtitles regarding clinical complete denture procedures. After completion, students evaluated their learning experience, and 11 students participated in focus group interviews to gain further insight. A mixed-methods approach to data collection and analysis provided descriptive statistical results and a grounded theory approach to coding identified key concepts and categories from the qualitative data. Over 70% of students had favorable opinions of the learning experience and indicated that the speed and length of the video were appropriate. Highly positive and conflicting negative comments regarding the use of subtitles showed both preferences for subtitles over audio and vice versa. The use of a video resource was considered valuable as the replay and review functions allowed better visualization of the procedures, which was considered a good recap tool for the clinical demonstration. It was also a better revision aid than textbooks. So, if the students were able to view these videos at will, they believed that videos supplemented their self-study. Despite the positive response, videos were not considered to replace live clinical demonstrations. While students preferred live demonstrations over the clinical videos they did express a realization of these as a supplemental learning material for self-study based on their ease of access, use for revision, and prior to clinical preparation. Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases.

PubMed

Lucidi, Valerio; Hendlisz, Alain; Van Laethem, Jean-Luc; Donckier, Vincent

2016-04-21

In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.

Changes in information behavior in clinical teams after introduction of a clinical librarian service

PubMed Central

Urquhart, Christine; Turner, Janet; Durbin, Jane; Ryan, Jean

2007-01-01

Objectives: The eighteen-month evaluation of a clinical librarian project (October 2003–March 2005) conducted in North Wales, United Kingdom (UK) assessed the benefits of clinical librarian support to clinical teams, the impact of mediated searching services, and the effectiveness of information skills training, including journal club support. Methods: The evaluation assessed changes in teams' information-seeking behavior and their willingness to delegate searching to a clinical librarian. Baseline (n = 69 responses, 73% response rate) and final questionnaire (n = 57, 77% response rate) surveys were complemented by telephone and face-to-face interviews (n = 33) among 3 sites served. Those attending information skills training sessions (n = 130) completed evaluations at the session and were surveyed 1 month after training (n = 24 questionnaire responses, n = 12 interviews). Results: Health professionals in clinical teams reported that they were more willing to undertake their own searching, but also more willing to delegate some literature searching, than at the start of the project. The extent of change depended on the team and the type of information required. Information skills training was particularly effective when organized around journal clubs. Conclusions: Collaboration with a clinical librarian increased clinician willingness to seek information. Clinical librarian services should leverage structured training opportunities such as journal clubs. PMID:17252062

Recent advances in T-cell immunotherapy for haematological malignancies.

PubMed

Rouce, Rayne H; Sharma, Sandhya; Huynh, Mai; Heslop, Helen E

2017-03-01

In vitro discoveries have paved the way for bench-to-bedside translation in adoptive T cell immunotherapy, resulting in remarkable clinical responses in a variety of haematological malignancies. Adoptively transferred T cells genetically modified to express CD19 CARs have shown great promise, although many unanswered questions regarding how to optimize T-cell therapies for both safety and efficacy remain. Similarly, T cells that recognize viral or tumour antigens though their native receptors have produced encouraging clinical responses. Honing manufacturing processes will increase the availability of T-cell products, while combining T-cell therapies has the ability to increase complete response rates. Lastly, innovative mechanisms to control these therapies may improve safety profiles while genome editing offers the prospect of modulating T-cell function. This review will focus on recent advances in T-cell immunotherapy, highlighting both clinical and pre-clinical advances, as well as exploring what the future holds. © 2016 John Wiley & Sons Ltd.

Physiotherapy Students' Attitudes toward Psychiatry and Mental Health: A Cross-Sectional Study.

PubMed

Connaughton, Joanne; Gibson, William

Purpose: A cross-sectional exploration of Notre Dame Australia physiotherapy students' attitudes toward psychiatry and mental illness, students' perceptions regarding preparation in this area for general clinical practice, and a cross-sectional investigation of current mental health-and psychiatry-related content in physiotherapy curricula across Australia and New Zealand. Methods: A questionnaire including demographic details, level of exposure to mental illness, and the Attitudes Toward Psychiatry-30 items (ATP-30) was completed by pre-clinical and clinically experienced physiotherapy students from the University of Notre Dame Australia. Students with clinical experience were asked additional questions about preparedness for practice. Staff of 10 of 17 physiotherapy programmes across Australia and New Zealand responded to an online questionnaire investigating relevant content and quantity of learning experiences in mental health. Results: Student response rate was 89%. Students generally had a positive attitude about psychiatry and mental health. Women were significantly more positive than men, and students who had completed clinical experience had a significantly more positive attitude. Physiotherapy program responses (response rate=59%) highlighted disparate approaches to psychiatry and mental health learning opportunities in terms of quantity and content. Conclusion: Entry-level physiotherapy students who have clinical experience generally have a more positive attitude toward psychiatry and people with mental illness. Given the prevalence of mental health problems and the increase in physical and mental health comorbidities, it is imperative that future clinicians have positive educational experiences in psychiatry. A coherent, integrated approach to mental illness and psychiatry is suggested for entry-level physiotherapy programmes in Australia and New Zealand.

Physiotherapy Students' Attitudes toward Psychiatry and Mental Health: A Cross-Sectional Study

PubMed Central

Gibson, William

2016-01-01

Purpose: A cross-sectional exploration of Notre Dame Australia physiotherapy students' attitudes toward psychiatry and mental illness, students' perceptions regarding preparation in this area for general clinical practice, and a cross-sectional investigation of current mental health—and psychiatry-related content in physiotherapy curricula across Australia and New Zealand. Methods: A questionnaire including demographic details, level of exposure to mental illness, and the Attitudes Toward Psychiatry–30 items (ATP-30) was completed by pre-clinical and clinically experienced physiotherapy students from the University of Notre Dame Australia. Students with clinical experience were asked additional questions about preparedness for practice. Staff of 10 of 17 physiotherapy programmes across Australia and New Zealand responded to an online questionnaire investigating relevant content and quantity of learning experiences in mental health. Results: Student response rate was 89%. Students generally had a positive attitude about psychiatry and mental health. Women were significantly more positive than men, and students who had completed clinical experience had a significantly more positive attitude. Physiotherapy program responses (response rate=59%) highlighted disparate approaches to psychiatry and mental health learning opportunities in terms of quantity and content. Conclusion: Entry-level physiotherapy students who have clinical experience generally have a more positive attitude toward psychiatry and people with mental illness. Given the prevalence of mental health problems and the increase in physical and mental health comorbidities, it is imperative that future clinicians have positive educational experiences in psychiatry. A coherent, integrated approach to mental illness and psychiatry is suggested for entry-level physiotherapy programmes in Australia and New Zealand. PMID:27909364

Combined mepacrine-hydroxychloroquine treatment in patients with systemic lupus erythematosus and refractory cutaneous and articular activity.

PubMed

Ugarte, A; Porta, S; Ríos, R; Martinez-Zapico, A; Ortego-Centeno, N; Agesta, N; Ruiz-Irastorza, G

2018-01-01

Aim The aim of this study was to evaluate the clinical response to combined therapy with hydroxychloroquine and mepacrine in patients with systemic lupus erythematosus and refractory joint and/or skin disease. Methods Mepacrine was added to 46 systemic lupus erythematosus patients unresponsive to treatment with the following drug combinations: hydroxychloroquine + prednisone + immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16), hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone ( n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1), hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1) or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was the clinical response, either complete or partial, based on clinical judgement. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were additionally used. Results A total of 91% patients showed complete/partial response, with similar rates among those with joint or skin disease. In patients with cutaneous activity, a statistically significant decrease in the CLASI was seen. There also was a statistically significant decrease in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone could be discontinued in 20% of patients. No serious adverse events were seen. Smoking was the only predictor of complete response. Conclusion In the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy including hydroxychloroquine was safe and effective in reducing disease activity and decreasing prednisone doses. The fact that smokers responded better opens the door to further studying the combination of mepacrine-hydroxychloroquine as a first-line therapy in such patients.

[Rituximab therapy for systemic manifestations and MALT lymphomas of the parotid gland in Sjögren's disease: preliminary data].

PubMed

Logvinenko, O A; Vasil'ev, V I; Sedyshev, S Kh; Safonova, T N; Rodionova, E B; Kokosadze, N V; Aleksandrova, E N; Cherkasova, M V; Radenska-Lopovok, S G; Nasonov, E L

2012-01-01

To evaluate the efficacy of rituximab (RT) in cryoglobulinemic vasculitis (CGV) and MALT lymphomas of the parotid gland (PG) in patients with Sjögren's disease (SD). RT therapy was performed in 13 patients with SD and CGV and in 17 with SD and PC MALT lymphoma. Eleven patients with SD received RT monotherapy and 19 with this disease had combined therapy with RT and cyclophosphan (CP). RT was used intravenously dropwise at a dose of 500 mg weekly or once every two weeks in combination with intravenous dropwise CP 1000 mg the next day with 4-6 per course. For the diagnosis of MALT lymphomas, all the patients with SD underwent incisional PG biopsy under local anesthesia at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. PG biopsy specimens were histologically and immunohistochemically studied at the Russian Cancer Research Center, Russian Academy of Medical Sciences. In 11 cases, B-cell clonality was identified from immunoglobulin (Ig) heavy chain genes rearrangements, by using polymerase chain reaction at the Hematology Research Center, Ministry of Health and Social Development of the Russian Federation. Cutaneous manifestations of vasculitis disappeared in 75% of cases after monotherapy with RT and in 100% of cases after combination therapy with RT and CP. At 6-month follow-up, a complete response to therapy remained in 25% of the patients after a course of monotherapy and in 83% after combined therapy. Serum monoclonal Ig cryoglobulins and their urinary light chains ceased to be detectable in 75% of the patients in both groups at 3 months. At 6 months, a recurrence of mixed monoclonal cryoglobulinemia was seen in 50 and 43% of cases after monotherapy and combined therapy, respectively. The clinical and laboratory response of cryoglobunemic glomerulonephritis to combined therapy with RT and CP was complete in 60% of cases at 6-month follow-up. After RT monotherapy, the patients with SD and PG MALT lymphoma achieved a complete clinical response in 88%, of whom histological and immunohistochemical reexaminations of PG biopsy specimens revealed no signs of MALT lymphoma in 71% of cases. B-cell clonality remained in the PG biopsy specimens following RT monotherapy. After the combination of RT and CP, a complete clinical response to therapy was observed in 100% of the patients, a complete histological response and a complete molecular one were seen in 83 and 60%, respectively. RT showed its efficacy in treating SD patients with CGV and PG MALT lymphomas.

Efficacy of TACE in TIPS Patients: Comparison of Treatment Response to Chemoembolization for Hepatocellular Carcinoma in Patients With and Without a Transjugular Intrahepatic Portosystemic Shunt

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

Kuo, Yuo-Chen, E-mail: yuo-chen.kuo@ucsf.edu; Kohi, Maureen P., E-mail: maureen.kohi@ucsf.edu; Naeger, David M., E-mail: david.naeger@ucsf.edu

Purpose: To compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods: A retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modifiedmore » response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented. Results: After TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation. Conclusion: TACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates.« less

Reporting Items for Updated Clinical Guidelines: Checklist for the Reporting of Updated Guidelines (CheckUp)

PubMed Central

Vernooij, Robin W. M.; Alonso-Coello, Pablo; Brouwers, Melissa

2017-01-01

Background Scientific knowledge is in constant development. Consequently, regular review to assure the trustworthiness of clinical guidelines is required. However, there is still a lack of preferred reporting items of the updating process in updated clinical guidelines. The present article describes the development process of the Checklist for the Reporting of Updated Guidelines (CheckUp). Methods and Findings We developed an initial list of items based on an overview of research evidence on clinical guideline updating, the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument, and the advice of the CheckUp panel (n = 33 professionals). A multistep process was used to refine this list, including an assessment of ten existing updated clinical guidelines, interviews with key informants (response rate: 54.2%; 13/24), a three-round Delphi consensus survey with the CheckUp panel (33 participants), and an external review with clinical guideline methodologists (response rate: 90%; 53/59) and users (response rate: 55.6%; 10/18). CheckUp includes 16 items that address (1) the presentation of an updated guideline, (2) editorial independence, and (3) the methodology of the updating process. In this article, we present the methodology to develop CheckUp and include as a supplementary file an explanation and elaboration document. Conclusions CheckUp can be used to evaluate the completeness of reporting in updated guidelines and as a tool to inform guideline developers about reporting requirements. Editors may request its completion from guideline authors when submitting updated guidelines for publication. Adherence to CheckUp will likely enhance the comprehensiveness and transparency of clinical guideline updating for the benefit of patients and the public, health care professionals, and other relevant stakeholders. PMID:28072838

Maternal care and paternal protection influence response to psychotherapy treatment for adult depression.

PubMed

Johnstone, Jeanette M; Carter, Janet D; Luty, Suzanne E; Mulder, Roger T; Frampton, Christopher M; Joyce, Peter R

2013-07-01

Adverse childhood experiences of neglect, overprotection and abuse, well-recognized risk factors for the development of adult psychopathology, were examined as predictors of response to psychotherapy treatment for adults with depression. Outpatients in a randomized clinical trial of interpersonal psychotherapy (IPT) or cognitive-behavioral therapy (CBT) completed the parental bonding instrument (PBI) at baseline to establish levels of care and protection. Childhood abuse was asked about using clinical interviews. The PBI variables were examined in tertiles while the abuse variables were categorized as "none," "some," and "severe." Associations between these childhood adversities and treatment response were examined in those who completed the trial. Of 177 outpatients with depression who were randomized, 159 completed an adequate trial of therapy. Within these 159 patients, 57% were categorized as responders to treatment. The mean percentage improvement on the MADRS was 57.7% (±31.4). Across both treatments, patients reporting intermediate levels of maternal care had the best response to treatment. Also across both treatments, the interaction effects of maternal care and paternal protection by treatment were statistically significant. Examining the two therapies independently, maternal care and paternal protection were associated with a differential response to IPT but not CBT. Reports of abuse, whether physical, emotional or sexual, did not impact treatment response. This study examined patients who completed treatment, which may have attenuated the findings. Two categories of childhood adversity were measured although a range of other adverse childhood experiences exist. The results were from exploratory analyses and require replication. Maternal care, demonstrating a robust main effect across treatments, appears to be the childhood variable most strongly associated with response to psychotherapy in this sample. In addition, maternal care and paternal protection were associated with a differential response to treatment. These results suggest that the quality of on-going intra-familial relationships has a greater impact on treatment response than experiences of abuse. The findings may aid clinicians in selecting which psychotherapy to use, depending on a patient's childhood history. Copyright © 2013 Elsevier B.V. All rights reserved.

CBT for depression: a pilot RCT comparing mobile phone vs. computer.

PubMed

Watts, Sarah; Mackenzie, Anna; Thomas, Cherian; Griskaitis, Al; Mewton, Louise; Williams, Alishia; Andrews, Gavin

2013-02-07

This paper reports the results of a pilot randomized controlled trial comparing the delivery modality (mobile phone/tablet or fixed computer) of a cognitive behavioural therapy intervention for the treatment of depression. The aim was to establish whether a previously validated computerized program (The Sadness Program) remained efficacious when delivered via a mobile application. 35 participants were recruited with Major Depression (80% female) and randomly allocated to access the program using a mobile app (on either a mobile phone or iPad) or a computer. Participants completed 6 lessons, weekly homework assignments, and received weekly email contact from a clinical psychologist or psychiatrist until completion of lesson 2. After lesson 2 email contact was only provided in response to participant request, or in response to a deterioration in psychological distress scores. The primary outcome measure was the Patient Health Questionnaire 9 (PHQ-9). Of the 35 participants recruited, 68.6% completed 6 lessons and 65.7% completed the 3-months follow up. Attrition was handled using mixed-model repeated-measures ANOVA. Both the Mobile and Computer Groups were associated with statistically significantly benefits in the PHQ-9 at post-test. At 3 months follow up, the reduction seen for both groups remained significant. These results provide evidence to indicate that delivering a CBT program using a mobile application, can result in clinically significant improvements in outcomes for patients with depression. Australian New Zealand Clinical Trials Registry ACTRN 12611001257954.

Clinical efficacy of second generation tyrosine kinase inhibitor and 5-azacytidine combination in chronic myelogenous leukaemia in myeloid blast crisis.

PubMed

Ghez, David; Micol, Jean-Baptiste; Pasquier, Florence; Auger, Nathalie; Saada, Véronique; Spentchian, Marc; Ianotto, Jean-Christophe; Bourhis, Jean-Henri; Bennaceur-Griscelli, Anelyse; Terré, Christine; Castaigne, Sylvie; Rigaudeau, Sophie; Rousselot, Philippe; de Botton, Stéphane

2013-11-01

Even in the tyrosine kinase inhibitors era, the prognosis of patients with chronic myeloid leukaemia in myeloid blast crisis remains dismal with few patients surviving longer than 6 months. Here we report the cases of 5 patients treated with the combination of 5-azacytidine and tyrosine kinase inhibitors for myeloid blast crisis CML. All patients achieved a complete haematological response including two with a complete cytogenetic and major molecular response. Two patients underwent an allogeneic stem cell transplantation. One died from relapse 34 months from diagnosis. The second is alive and free from disease at 11 months from diagnosis. The other 3 patients are still in complete haematological response after 15, 24 and 33 months of follow-up. These results suggest that the combination has a significant activity in myeloid blast crisis and may increase survival. Copyright © 2013 Elsevier Ltd. All rights reserved.

Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report.

PubMed

Sonntag, Katja; Hashimoto, Hisayoshi; Eyrich, Matthias; Menzel, Moritz; Schubach, Max; Döcker, Dennis; Battke, Florian; Courage, Carolina; Lambertz, Helmut; Handgretinger, Rupert; Biskup, Saskia; Schilbach, Karin

2018-02-06

Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. Vaccination started during chemotherapy in second complete remission and continued monthly thereafter. We tracked IFN-γ + T cell responses against vaccine peptides in peripheral blood after 12, 17 and 34 vaccinations by analyzing T-cell receptor (TCR) repertoire diversity and epitope-binding regions of peptide-reactive T-cell lines and clones. By restricting analysis to sorted IFN-γ-producing T cells we could assure epitope-specificity, functionality, and T H 1 polarization. A peptide-specific T-cell response against three of the four vaccine peptides could be detected sequentially. Molecular TCR analysis revealed a broad vaccine-reactive TCR repertoire with clones of discernible specificity. Four identical or convergent TCR sequences could be identified at more than one time-point, indicating timely persistence of vaccine-reactive T cells. One dominant TCR expressing a dual TCRVα chain could be found in three T-cell clones. The observed T-cell responses possibly contributed to clinical outcome: The patient is alive 6 years after initial diagnosis and in complete remission for 4 years now. Therapeutic vaccination with a neoantigen-derived four-peptide vaccine resulted in a diverse and long-lasting immune response against these targets which was associated with prolonged clinical remission. These data warrant confirmation in a larger proof-of concept clinical trial.

'BeAWARE': supporting non-clinical staff within general practice to promptly identify patients presenting with warning signs of heart attack or stroke.

PubMed

Poulter, Christopher; Stewart, Michelle; Fitzpatrick, Cliona; Keech, Wendy; Stavreski, Bill; Grenfell, Robert

2014-06-01

General practice requires systems to deal with patients presenting with urgent needs. BeAWARE was developed to support non-clinical staff to promptly identify patients with symptoms of heart attack or stroke. Data were collected from May 2012 to December 2012 on participants completing the BeAWARE learning module, including pre- and post-assessments on knowledge, confidence and intended action. From May 2012 to December 2012, 1865 participants completed the module. There were significant increases in recall of heart attack and stroke symptoms among non-clinical participants, including chest tightness (23.4-48.7%, P DISCUSSION: BeAWARE fulfils a practice gap in patient safety by improving non-clinical staff's knowledge, confidence and intended action in response to patients presenting with heart attack or stroke warning signs.

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.

Initial Assessments of E-Learning Modules in Cytotechnology Education.

PubMed

Mukherjee, Maheswari S; Donnelly, Amber D

2018-01-01

Nine E-learning modules (ELMs) were developed in our program using Articulate software. This study assessed our cytotechnology (CT) students' perceptions on the content of the ELMs, and the perceived influence of the ELMs on students' performance during clinical rotations. All CT students watched nine ELMs before the related classroom lecture and group discussion. Following that, students completed nine preclinical rotation surveys. After their clinical rotations, students completed nine postclinical rotation surveys. Statements on the content of the ELMs regarding the quality of the video and audio, duration, navigation, and the materials presented, received positive responses from the majority of the students. While there were a few disagreements and neutral responses, most of the students responded positively saying that the ELMs better prepared them for their role, as well as helped them to better perform their roles during the clinical rotation. The majority of the students recommended developing more EMLs for cytology courses in the future. This study has given hope that the ELMs have potential to enhance our online curriculum and benefit students, within the United States and internationally, who have no easy access to cytology clinical laboratories for hands-on training.

The role of interim 18F-FDG PET/CT in prediction of response to ipilimumab treatment in metastatic melanoma.

PubMed

Sachpekidis, Christos; Anwar, Hoda; Winkler, Julia; Kopp-Schneider, Annette; Larribere, Lionel; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

2018-07-01

The aim of the present study was to assess the value of interim 18 F-FDG PET/CT performed after the first two cycles of ipilimumab treatment in the prediction of the final clinical response to this type of immunotherapy. The study group comprised 41 patients with unresectable metastatic melanoma scheduled for ipilimumab therapy. Whole-body 18 F-FDG PET/CT was performed before the start of ipilimumab treatment (baseline PET/CT) and after the initial two cycles of ipilimumab treatment (interim PET/CT). Evaluation of patient response to treatment was based on the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria for PET as well as the recently proposed PET Response Evaluation Criteria for Immunotherapy (PERCIMT). The patients' best clinical response, assessed at a median of 21.4 months (range 6.3-41.9 months) was used as reference. According to their best clinical response, the patients were divided into two groups: those showing clinical benefit (CB) including stable disease, partial response and complete response (31 patients), and those showing no clinical benefit (no-CB including progressive disease (10 patients). According to the EORTC criteria, interim PET/CT demonstrated progressive metabolic disease (PMD) in 20 patients, stable metabolic disease (SMD) in 11 patients, partial metabolic response (PMR) in 8 patients, and complete metabolic response (CMR) in 2 patients. According to the PERCIMT, interim PET/CT demonstrated PMD in 9 patients, SMD in 24 patients, PMR in 6 patients and CMR in 2 patients. On the basis of the interim PET, the patients were divided in a similar manner to the division according to clinical response into those showing metabolic benefit (MB) including SMD, PMR and CMR, and those showing no metabolic benefit (no-MB) including PMD. According to this dichotomization, the EORTC criteria showed a sensitivity (correctly predicting CB) of 64.5%, a specificity (correctly predicting no-CB) of 90.0%, a positive predictive value (PPV) of 95.2%, a negative predictive value (NPV) of 45.0% and an accuracy of 70.7% in predicting best clinical response. The PERCIMT showed a sensitivity of 93.6%, a specificity of 70.0%, a PPV of 90.6%, a NPV of 77.8% and an accuracy of 87.8%. The McNemar test showed that the PERCIMT had a significantly higher sensitivity than EORTC criteria (p = 0.004), while there was no significant difference in specificity (p = 0.5). The agreement between the two sets of criteria was poor (McNemar test p = 0.001, and accordingly kappa = 0.46). The application of the recently proposed PERCIMT to interim 18 F-FDG PET/CT provides a more sensitive predictor of final clinical response to immunotherapy than the application of the EORTC criteria in patients with metastatic melanoma.

Influence of psychological factors on the acceptance of complete dentures.

PubMed

al Quran, F; Clifford, T; Cooper, C; Lamey, P J

2001-07-01

To assess the influence of psychological factors on the acceptance of complete dentures in a population wearing dentures judged to be clinically satisfactory. Subjects were asked to complete personality profiles and also to rate their dentures using a denture satisfaction questionnaire. The survey was conducted in the prosthetics clinic of a teaching hospital. Patients were selected from those who had new complete dentures constructed in the department within the previous two years. The personality inventory was a self-administered questionnaire comprising 240 items covering the five domains of personality. Denture satisfaction was scored on a nine item scale with four Likert type responses to each. A group of 16% consistently complained about their dentures. Statistical analysis showed that personality factors especially Neuroticism had a significant relationship with denture satisfaction. Psychological factors significantly influence denture satisfaction and profiles may provide useful in predicting potential difficult denture wearers.

Learning in clinical practice: Stimulating and discouraging response to social comparison.

PubMed

Raat, Janet; Kuks, Jan; Cohen-Schotanus, Janke

2010-01-01

Social comparison theory is relevant for learning in general. In a clinical context, we examined four hypotheses concerning: preferred other to compare with, preferred direction of comparison, response to social comparison and influence of personal social comparison orientation (SCO). To investigate the relevance of social comparison for clinical workplace learning. Students (n = 437) from nine different hospitals completed two questionnaires measuring their SCO and the direction of and response to their comparisons. t-tests were used to analyse the data. Students substantially did compare. They preferred to compare with peer students more than with residents or staff, and with peers doing better more than with peers doing worse. Their response to social comparison was more often stimulating for learning than discouraging. Students high in SCO reported a stronger stimulating and discouraging response to their comparisons than students low in SCO. Social comparison does play a role in clinical workplace learning. The mainly stimulating response to social comparison indicates a positive learning influence. The preferred comparison with peers emphasizes the role of peers in the learning process. Further research should focus on student comparison behaviour and on situations that strengthen the positive effects of social comparison and reduce the negative or obstructing ones.

A sentence completion procedure as an alternative to the Autobiographical Memory Test for assessing overgeneral memory in non-clinical populations

PubMed Central

Raes, Filip; Hermans, Dirk; Williams, J. Mark G.; Eelen, Paul

2007-01-01

Overgeneral memory (OGM) has been proposed as a vulnerability factor for depression (Williams et al., 2007) or depressive reactivity to stressful life-events (e.g., Gibbs & Rude, 2004). Traditionally, a cue word procedure known as the Autobiographical Memory Test (AMT; Williams & Broadbent, 1986) is used to assess OGM. Although frequently and validly used in clinical populations, there is evidence suggesting that the AMT is insufficiently sensitive to measure OGM in non-clinical groups. Study 1 evaluated the usefulness of a sentence completion method to assess OGM in non-clinical groups, as an alternative to the AMT. Participants were 197 students who completed the AMT, the Sentence Completion for Events from the Past Test (SCEPT), a depression measure, and visual analogue scales assessing ruminative thinking. Results showed that the mean proportion of overgeneral responses was markedly higher for the SCEPT than for the standard AMT. Also, overgeneral responding on the SCEPT was positively associated to depression scores and depressive rumination scores, whereas overgeneral responding on the AMT was not. Results suggest that the SCEPT, relative to the AMT, is a more sensitive instrument to measure OGM, at least in non-clinical populations. Study 2 further showed that this enhanced sensitivity is most likely due to the omission of the instruction to be specific rather than to the SCEPT's sentence completion format (as opposed to free recall to cue words). PMID:17613793

A sentence completion procedure as an alternative to the Autobiographical Memory Test for assessing overgeneral memory in non-clinical populations.

PubMed

Raes, Filip; Hermans, Dirk; Williams, J Mark G; Eelen, Paul

2007-07-01

Overgeneral memory (OGM) has been proposed as a vulnerability factor for depression (Williams et al., 2007) or depressive reactivity to stressful life-events (e.g., Gibbs & Rude, 2004). Traditionally, a cue word procedure known as the Autobiographical Memory Test (AMT; Williams & Broadbent, 1986) is used to assess OGM. Although frequently and validly used in clinical populations, there is evidence suggesting that the AMT is insufficiently sensitive to measure OGM in non-clinical groups. Study 1 evaluated the usefulness of a sentence completion method to assess OGM in non-clinical groups, as an alternative to the AMT. Participants were 197 students who completed the AMT, the Sentence Completion for Events from the Past Test (SCEPT), a depression measure, and visual analogue scales assessing ruminative thinking. Results showed that the mean proportion of overgeneral responses was markedly higher for the SCEPT than for the standard AMT. Also, overgeneral responding on the SCEPT was positively associated to depression scores and depressive rumination scores, whereas overgeneral responding on the AMT was not. Results suggest that the SCEPT, relative to the AMT, is a more sensitive instrument to measure OGM, at least in non-clinical populations. Study 2 further showed that this enhanced sensitivity is most likely due to the omission of the instruction to be specific rather than to the SCEPT's sentence completion format (as opposed to free recall to cue words).

Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer

PubMed Central

Wong, Claudia

2017-01-01

Neoadjuvant therapy before esophagectomy is evidence-based, and is a standard-of-care for locally advanced and operable esophageal cancer. However response to such treatment varies in individual patients, from no clinical response to pathological complete response. It has been consistently shown that a good pathological responses is of prognostic value, but perhaps in the expense of those who do not. It is important to identify suitable predictive factors for response, so that patients are not exposed to potentially harmful chemotherapy and/or radiotherapy without benefits. Alternative management strategies can be devised. Various clinical, radiological, serological and potential molecular markers have been studied. None has been shown to be sufficiently reliable to be used in daily practice. Certainly more understanding of the molecular basis for response to chemotherapy/radiotherapy is needed, so that patient treatment can be tailored and individualized. PMID:28815073

The effect of pneumatic dilation in management of postfundoplication dysphagia.

PubMed

Sunjaya, D; Podboy, A; Blackmon, S H; Katzka, D; Halland, M

2017-06-01

Fundoplication surgery is a commonly performed procedure for gastro-esophageal reflux disease or hiatal hernia repair. Up to 10% of patients develop persistent postoperative dysphagia after surgery. Data on the effectiveness of pneumatic dilation for treatment are limited. The aim of this study was to evaluate clinical outcomes and identify clinical factors associated with successful response to pneumatic dilation among patients with persistent postfundoplication dysphagia (PPFD). We retrospectively evaluated patients who had undergone pneumatic dilation for PPFD between 1999 and 2016. Patients with dysphagia or achalasia prior to fundoplication were excluded. Demographic information, surgical history, severity of dysphagia, and clinical outcomes were collected. Data pertaining to esophagram, manometry, endoscopy, and pneumatic dilation were also collected. We identified 38 patients (82% female, 95% Caucasian, and median age 59 years) with PPFD who completed pneumatic dilation. The median postfundoplication dysphagia score was 2. Eleven patients had abnormal peristalsis on manometry. Seventeen patients reported response (seven complete) with an average decrease of 1 in their dysphagia score. Fifteen patients underwent reoperation due to PPFD. Hiatal hernia repair was the only factor that predicts a higher response rate to pneumatic dilation. Only one patient in our study developed complication (pneumoperitoneum) from pneumatic dilation. We found that pneumatic dilation to be a safe treatment option for PPFD with moderate efficacy. Patients who developed PPFD after a hiatal hernia repair may gain the greatest benefit after pneumatic dilation. We were not able to identify additional clinical, radiological, endoscopic, or manometric parameters that were predictive of response. © 2017 John Wiley & Sons Ltd.

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program.

PubMed

González-Cao, M; Arance, A; Piulats, J M; Marquez-Rodas, I; Manzano, J L; Berrocal, A; Crespo, G; Rodriguez, D; Perez-Ruiz, E; Berciano, M; Soria, A; Castano, A G; Espinosa, E; Montagut, C; Alonso, L; Puertolas, T; Aguado, C; Royo, M A; Blanco, R; Rodríguez, J F; Muñoz, E; Mut, P; Barron, F; Martin-Algarra, S

2017-06-01

The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.

Effect of radiation therapy on bronchial obstruction due to bronchogenic carcinoma

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

Chetty, K.G.; Moran, E.M.; Sassoon, C.S.

1989-03-01

We evaluated the effect of radiation therapy in 57 patients with obstruction of a large bronchus with NSCC. Response with aeration of the atelectatic lung was seen in 12 patients (21 percent). Three patients (5 percent) showed partial response with persistent partial atelectasis, and nine patients (16 percent) showed good response with complete aeration of the atelectatic lung. In these patients the response appeared to be related to the dose of radiation. All of the patients who responded received more than 50 Gy. The difference in the response rate related to the dose of radiation was statistically significant (p lessmore » than 0.05). The rates were similar with all histologic types of NSCC. Regardless of the clinical response observed, bronchoscopy performed two to four months after completion of radiation therapy in 14 patients revealed persistent endobronchial tumor. There was no significant relationship between the persistence of endobronchial tumor, the dose of radiation therapy, and the tumor's histologic type. Of the 12 patients with radiographic improvement in atelectasis, fibrotic changes developed in four (33 percent) patients and pneumonitis in two (17 percent). Progression of disease with distant metastases occurred in 58 percent (seven) of the 12 patients who showed a clinical response of their bronchial obstruction. The median time to survival was nearly identical in responders and nonresponders.« less

Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study.

PubMed

Noordman, Bo Jan; Spaander, Manon C W; Valkema, Roelf; Wijnhoven, Bas P L; van Berge Henegouwen, Mark I; Shapiro, Joël; Biermann, Katharina; van der Gaast, Ate; van Hillegersberg, Richard; Hulshof, Maarten C C M; Krishnadath, Kausilia K; Lagarde, Sjoerd M; Nieuwenhuijzen, Grard A P; Oostenbrug, Liekele E; Siersema, Peter D; Schoon, Erik J; Sosef, Meindert N; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-05-31

After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m 2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET-CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12-14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed. Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17-50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4-23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17-44]). PET-CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7-28]). PET-CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas). After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET-CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Dutch Cancer Society. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparison of azelaic acid and anthralin for the therapy of patchy alopecia areata: a pilot study.

PubMed

Sasmaz, Sezai; Arican, Ozer

2005-01-01

Although topical azelaic acid has been previously used for the treatment of alopecia, no controlled trials of azelaic acid for this condition have been conducted to date. The goal of this study was to determine the efficacy, tolerability, and safety of azelaic acid treatment in patients with patchy alopecia areata (AA) in comparison with anthralin (dithranol) treatment. This study included 31 subjects with patchy AA who did not receive any treatment for at least 1 month prior to the study. Demographic and clinical characteristics of these subjects were recorded at baseline. Subjects were randomized to apply either 20% azelaic acid (15 subjects) or 0.5% anthralin (16 subjects) for 12 consecutive weeks. In a subsequent 8-week follow-up period no cream was applied. Two independent investigators performed an efficacy evaluation with clinical examination using a terminal hair regrowth score (RGS) with a scale ranging from 0 (inadequate response) to 2 (complete response) at week 20. Partial response was accepted as score 1. Both groups were well matched for the relevant demographic and clinical indicators affecting treatment response at baseline. All subjects completed the trial. At week 20 the RGS was 1.27 +/- 0.9 in the azelaic acid group versus 1.37 +/- 0.8 in the anthralin group (p > 0.05). A complete response was observed in 53.3% of cases in the azelaic acid group (8 of 15) compared with 56.2% (9 of 16) in the anthralin group (p > 0.05). No serious adverse events were observed in either group during the study. The present pilot study showed that the use of azelaic acid gave similar results to anthralin with regard to hair regrowth, and that it can be an effective topical therapy for patchy AA. More extensive trials are necessary, however, to reach a definitive conclusion.

Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

PubMed

2015-01-01

Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented. Vismodegib should only be proposed to patients in whom basal cell cancer markedly undermines quality of life, and only in the context of clinical research.

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.

PubMed

Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B; Galante, Pedro A F; Perez, Rodrigo O; Camargo, Anamaria A

2015-11-10

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.

Complete intracranial response to talimogene laherparepvec (T-Vec), pembrolizumab and whole brain radiotherapy in a patient with melanoma brain metastases refractory to dual checkpoint-inhibition.

PubMed

Blake, Zoë; Marks, Douglas K; Gartrell, Robyn D; Hart, Thomas; Horton, Patti; Cheng, Simon K; Taback, Bret; Horst, Basil A; Saenger, Yvonne M

2018-04-06

Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy. We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases. This patient achieved a complete CNS response and partial systemic response with standard whole brain radiation therapy (WBRT) combined with Talimogene laherparepvec (T-Vec) and pembrolizumab. Patients who do not respond to one immunotherapy combination may respond during treatment with an alternate combination, even in the presence of multiple brain metastases. Biomarkers are needed to assist clinicians in evidence based clinical decision making after progression on first line immunotherapy to determine whether response can be achieved with second line immunotherapy.

New Topical Treatment Options for Actinic Keratosis: A Systematic Review.

PubMed

Stockfleth, Eggert; Sibbring, Gillian C; Alarcon, Ivette

2016-01-01

This systematic review compared the relative efficacy of 5-fluorouracil 0.5% in salicylic acid 10% (5-FU/SA), ingenol mebutate (IMB) and imiquimod 2.5%/3.75% (IMI) for actinic keratosis on the face, forehead or scalp. Only 11 publications, relating to 7 randomised controlled trials, met inclusion criteria and it was only possible to compare the effect of all 3 treatments on complete clinical clearance, and the effect of 5-FU/SA and IMB on actinic keratosis recurrence rate. Despite a higher vehicle response rate for 5-FU/SA, complete clinical clearance was higher than IMB and IMI (55.4, 42.2, and 25.0-30.6/34.0-35.6%, [corrected] respectively). 5-FU/SA was also associated with lower actinic keratosis recurrence rate than IMB at 12 months post-treatment (32.7 vs. 53.9%). Although qualitative assessment suggested a numerical advantage of 5-FU/SA over IMB and IMI in terms of complete clinical clearance and sustained clearance, clinical data from longer term trials, with comparable outcome measures, are required to corroborate these findings.

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

PubMed Central

Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Shoji, Toshiharu; Miyasaka, Nobuyuki; Koike, Takao

2014-01-01

Abstract Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules. PMID:24593170

Experimental investigation on the vascular thermal response to near-infrared laser pulses.

PubMed

Li, Dong; Chen, Bin; Wu, Wenjuan; Ying, Zhaoxia

2017-12-01

Port wine stains (PWS) are congenital vascular malformations that progressively darken and thicken with age. To improve the effect of laser therapy in clinical practice, thermal response of blood vessel to a 1064 nm Nd:YAG laser with controlled energy doses and pulse durations was evaluated using the dorsal skin chamber model. A total of 137 vessels with 30-300 μm diameters were selected from the dorsal skin of the mouse to match those capillaries in port wine stains. Experimental results showed that the thermal response of blood vessels to 1064 nm laser irradiation can be classified as follows: vessel dilation, coagulation, constriction with decreased diameter, complete constriction, hemorrhage, and collagen damage with increasing laser radiant exposure. In most cases, that is, 83 of 137 blood vessels (60.6%), Nd:YAG laser irradiation was characterized by complete constriction (immediate blood vessel disappearance). To reveal the possible damage mechanisms and evaluate blood vessel photocoagulation patterns, theoretical investigation using bioheat transfer equation was conducted in mouse skin with a depth of 1000 μm. Complete constriction as the dominant thermal response as evidenced by uniform blood heating within the vessel lumen was noted in both experimental observation and theoretical investigation. To achieve the ideal clinical effect using the Nd:YAG laser treatment, the radiant exposure should not only be high enough to induce complete constriction of the blood vessels but also controlled carefully to avoid surrounding collagen damage. The short pulse duration of 1-3 ms is better than long pulse durations because hemorrhaging of small capillaries is occasionally observed postirradiation with pulse durations longer than 10 ms.

Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.

PubMed

Smith, Mark C; Zimmerman, M Bridget; Burke, Diane K; Bauman, Nancy M; Sato, Yutaka; Smith, Richard J H

2009-01-01

To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%). Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001). OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM. ClinicalTrials.gov Identifier: NCT00010452.

Surrogate marker analysis in cancer clinical trials through time-to-event mediation techniques.

PubMed

Vandenberghe, Sjouke; Duchateau, Luc; Slaets, Leen; Bogaerts, Jan; Vansteelandt, Stijn

2017-01-01

The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy. In the mediation analysis, the treatment effect is decomposed into an indirect effect via pathological complete response and the remaining direct effect. It shows that only 4.2% of the treatment effect on disease-free survival after five years is mediated by the treatment effect on pathological complete response. There is thus no evidence from our analysis that pathological complete response is a valuable surrogate marker to evaluate the effect of taxane versus anthracycline based chemotherapies on progression free survival of locally advanced breast cancer patients. The proposed analysis strategy is broadly applicable to mediation analyses of time-to-event endpoints, is easy to apply and outperforms existing strategies in terms of precision as well as robustness against model misspecification.

A 12-Day Course of Imiquimod 5% for the Treatment of Actinic Keratosis: Effectiveness and Local Reactions.

PubMed

Serra-Guillén, C; Nagore, E; Llombart, B; Sanmartín, O; Requena, C; Calomarde, L; Guillén, C

2018-04-01

Imiquimod is an excellent option for patients with actinic keratosis, although its use may be limited by the long course of treatment required (4 weeks) and the likelihood of local skin reactions. The objectives of the present study were to demonstrate the effectiveness of a 12-day course of imiquimod 5% for the treatment of actinic keratosis and to examine the association between treatment effectiveness and severity of local reactions. We included patients with at least 8 actinic keratoses treated with imiquimod 5% cream for 12 consecutive days. Local reactions were classified as mild, moderate, or severe. The statistical analysis of the association between local reactions and clinical response was based on the Pearson χ 2 test and the Spearman rank correlation test. Sixty-five patients completed the study. Complete response was recorded in 52.3% and partial response in 75.4%. We found a statistically significant association between severity of the local reaction and response to treatment in both the Pearson χ 2 test and the Spearman rank correlation test. A 12-day course of imiquimod 5% proved effective for the treatment of actinic keratosis. Severity of local reactions during treatment was correlated with clinical response. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Lymphatic Malformation Architecture: Implications for Treatment With OK-432.

PubMed

Malic, Claudia C; Guilfoyle, Regan; Courtemanche, Rebecca J M; Arneja, Jugpal S; Heran, Manraj K S; Courtemanche, Douglas J

2017-10-01

Herein, the authors aim to describe their findings of novel architectural types of lymphatic malformations (LM) and explain the relationship between these architectures and OK-432 treatment outcomes. A retrospective review was conducted of all patients diagnosed with a LM treated with OK-432 at the Vascular Anomalies Clinic at BC Children's Hospital from December 2002 to January 2012. Twenty-seven patients were included in the study. Sixty percent of lesions were present by 2 years of age with the majority located in the head and neck (59%). The average number of sclerotherapy procedures was 1.4 per patient. Treatment under fluoroscopic guidance revealed 3 new LM architectures: open-cell microcystic, closed-cell microcystic, and lymphatic channel. Response to treatment was complete or good for 14/19 macrocystic and for 1/2 mixed lesions. Open-cell microcystic LMs gave a complete or good response for 3/3, which was attributed to OK-432 freely communicating between cysts. Closed-cell microcystic LM had localized cysts that did not allow OK-432 to freely communicate and were associated with partial responses, 2/2. The lymphatic channel had a partial response. There were 2 minor complications and 1 instance of recurrence. The identification of 3 new LM architectures expands the current accepted classification to include: open-cell microcystic, closed-cell microcystic, and lymphatic channels. The majority of complete responses to OK-432 were found with macrocystic lesions. Open-cell microcystic lesions respond better to OK-432 than closed-cell microcystic lesions, and lymphatic channels may respond to OK-432. These key architecture-response relationships have direct clinical implications for treatment with OK-432 sclerotherapy.

Hoarding in Youth with Autism Spectrum Disorders and Anxiety: Incidence, Clinical Correlates, and Behavioral Treatment Response.

PubMed

Storch, Eric A; Nadeau, Joshua M; Johnco, Carly; Timpano, Kiara; McBride, Nicole; Jane Mutch, P; Lewin, Adam B; Murphy, Tanya K

2016-05-01

This study examined the nature and correlates of hoarding among youth with autism spectrum disorders (ASD). Forty children with ASD and a comorbid anxiety disorder were administered a battery of clinician-administered measures assessing presence of psychiatric disorders and anxiety severity. Parents completed questionnaires related to child hoarding behaviors, social responsiveness, internalizing and externalizing behaviors, and functional impairment. We examined the impact of hoarding behaviors on treatment response in a subsample of twenty-six youth who completed a course of personalized cognitive-behavioral therapy targeting anxiety symptoms. Hoarding symptoms were common and occurred in a clinically significant manner in approximately 25 % of cases. Overall hoarding severity was associated with increased internalizing and anxiety/depressive symptoms, externalizing behavior, and attention problems. Discarding items was associated with internalizing and anxious/depressive symptoms, but acquisition was not. Hoarding decreased following cognitive-behavioral therapy but did not differ between treatment responders and non-responders. These data are among the first to examine hoarding among youth with ASD; implications of study findings and future directions are highlighted.

Accelerated superfractionated radiotherapy for inflammatory breast carcinoma: complete response predicts outcome and allows for breast conservation.

PubMed

Arthur, D W; Schmidt-Ullrich, R K; Friedman, R B; Wazer, D E; Kachnic, L A; Amir, C; Bear, H D; Hackney, M H; Smith, T J; Lawrence, W

1999-05-01

Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed. Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy. Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for complete responders was 68%. This is in contrast to the 14% 5-year overall survival observed with incomplete responders. The 5-year actuarial disease-free survival and overall survival for the entire patient cohort was 11% and 33%, respectively. All patients tolerated irradiation with limited acute effects, of which all were managed conservatively. Our experience demonstrates that induction chemotherapy, accelerated superfractionated radiotherapy, and the selected use of mastectomy results in excellent locoregional control rates, is well tolerated, and optimizes breast preservation. Based on our present results, we recommend that a patient's response to induction chemotherapy guide the treatment approach used for locoregional disease, such that mastectomy be reserved for incomplete responders and avoided in those achieving a complete response.

Use of clinical placements as a means of recruiting health care students to underserviced areas in Southeastern Ontario: part 1 - student perspectives.

PubMed

MacRae, Michelle; van Diepen, Kelly; Paterson, Margo

2007-02-01

This two-part study examines the present gap between financial and educational incentives required and the recruitment strategies used to draw health science students to underserviced areas in Southeastern Ontario. Part 1 explores the impact of offering travel stipends, rent-free accommodation and interprofessional educational opportunities to health science students on their willingness to participate in clinical placements in underserviced areas. Mixed-method two-part study using a self-administered questionnaire. Canadian university campus. Four hundred and sixty-eight senior level medical, nursing, occupational therapy, physical therapy and X-ray technology students from a Canadian university and affiliated professional school. The influence of currently established incentives on student willingness to complete a clinical placement in designated underserviced communities in Southeastern Ontario. Based on a 75% response rate, the results demonstrate that, in general, students agree that they are more willing to complete a clinical placement in an underserviced community if provided travel stipends (75%), rent-free housing (92%) and interprofessional educational opportunities (65%). Students also identified 15 additional factors influencing willingness. Students are more willing to complete clinical placements in underserviced communities if provided incentives. The findings of this study support an interprofessional clinical education and recruitment enhancement program in Southeastern Ontario.

Use of anti-mullerian hormone for testing ovarian reserve: a survey of 796 infertility clinics worldwide.

PubMed

Tobler, Kyle J; Shoham, Gon; Christianson, Mindy S; Zhao, Yulian; Leong, Milton; Shoham, Zeev

2015-10-01

The aim of this study is to assess how anti-mullerian hormone (AMH) is used worldwide to test ovarian reserve and guide in vitro fertilization (IVF) cycle management. An internet-based survey was sent electronically to registered IVF providers within the IVF-Worldwide.com network. This survey consisted of nine questions which assessed the clinics' use of AMH. The questionnaire was completed online through the IVF-Worldwide.com website, and quality assurance tools were used to verify that only one survey was completed per clinical IVF center. Results are reported as the proportion of IVF cycles represented by a particular answer choice. Survey responses were completed from 796 globally distributed IVF clinics, representing 593,200 IVF cycles worldwide. Sixty percent of the respondent-IVF cycles reported to use AMH as a first line test, and 54 % reported it as the best test for evaluating ovarian reserve. Eighty-nine percent reported that AMH results were extremely relevant or relevant to clinical practice. However in contrast, for predicting live birth rate, 81 % reported age as the best predictor. AMH is currently considered a first line test for evaluating ovarian reserve and is considered relevant to clinical practice by the majority of IVF providers.

Professionalism--a required CLS/CLT curricular component.

PubMed

Latshaw, Sandra; Honeycutt, Karen

2010-01-01

Determine the impact of requiring Clinical Laboratory Science (CLS) students to participate in approved professionalism activities as part of a mandatory management course. Quasi-experimental, case study reporting qualitative results of 25 CLS students. During the admission interview, students complete a written response to questions about their perceptions related to professionalism. During the clinical educational year, students are required to complete approved professionalism activities as part of a management course. At the end of the course, students write a reflective paper focusing on their professional activities and how these experiences will influence their future professional practice. Overall themes of student reflections are provided. University of Nebraska Medical Center (UNMC) CLS Program in Omaha. After participating in a mandatory professionalism curricular component requiring active student participation in professional activities, student reflective writings provide evidence this is one successful approach to nurture professional identity within future Clinical Laboratory Science/Clinical Laboratory Technician (CLS/CLT) practitioners.

Information needs for the rapid response team electronic clinical tool.

PubMed

Barwise, Amelia; Caples, Sean; Jensen, Jeffrey; Pickering, Brian; Herasevich, Vitaly

2017-10-02

Information overload in healthcare is dangerous. It can lead to critical errors and delays. During Rapid Response Team (RRT) activations providers must make decisions quickly to rescue patients from physiological deterioration. In order to understand the clinical data required and how best to present that information in electronic systems we aimed to better assess the data needs of providers on the RRT when they respond to an event. A web based survey to evaluate clinical data requirements was created and distributed to all RRT providers at our institution. Participants were asked to rate the importance of each data item in guiding clinical decisions during a RRT event response. There were 96 surveys completed (24.5% response rate) with fairly even distribution throughout all clinical roles on the RRT. Physiological data including heart rate, respiratory rate, and blood pressure were ranked by more than 80% of responders as being critical information. Resuscitation status was also considered critically useful by more than 85% of providers. There is a limited dataset that is considered important during an RRT. The data is widely available in EMR. The findings from this study could be used to improve user-centered EMR interfaces.

Predictors of Clinical Response and Remission at One year among a Multicenter Cohort of Patients with Inflammatory Bowel Disease Treated with Vedolizumab

PubMed Central

Allegretti, Jessica R.; Barnes, Edward L.; Stevens, Betsey; Storm, Margaret; Ananthakrishnan, Ashwin; Yajnik, Vijay; Korzenik, Joshua

2017-01-01

Background Vedolizumab (VDZ) has demonstrated long term efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in phase III trials. Aims Our aim was to evaluate the efficacy of VDZ at week 54 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Adult patients completing induction therapy with VDZ were eligible for this study. Clinical response and remission was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment. Results Among 136 total patients (96 CD and 40 UC), 76 (56%) demonstrated clinical response or remission at week 54. In univariate analysis, for patients with CD concomitant initiation of immunomodulator therapy (2.71, 95% CI 1.11 – 6.57), the addition of an immunomodulator (OR 11.49, 3.16 – 41.75) and CRP <3 (4.92, 95% CI 1.99 – 12.15) were associated with increased odds of clinical response or remission at week 54. For UC patients hospitalization after VDZ induction was associated with decreased odds of response or remission at week 54 ( OR 0.22, 95%CI 0.05–0.88). On multivariate analysis in CD, addition of an immunomodulator (OR 8.33, 95% CI 2.15–32.26) remained significant predictors of clinical response or remission at week 54. Conclusions Among a multicenter cohort of patients with IBD demonstrating primary response to VDZ, the addition of combination therapy with an immunomodulator is a significant predictor of clinical response or remission at week 54 in patients with CD. PMID:28357697

TAKING THE PULSE OF PROLONGED EXPOSURE THERAPY: PHYSIOLOGICAL REACTIVITY TO TRAUMA IMAGERY AS AN OBJECTIVE MEASURE OF TREATMENT RESPONSE.

PubMed

Wangelin, Bethany C; Tuerk, Peter W

2015-12-01

Physiological reactivity to trauma-related cues is a primary symptom of PTSD and can be assessed objectively using script-driven imagery paradigms. However, subjective self-reported symptom measures are the most common outcome indices utilized in PTSD treatment trials and clinic settings. We examined physiological reactivity during a short trauma imagery task as an objective index of response to PTSD treatment, optimized for use in routine clinical care settings. Participants were 35 male combat veterans receiving prolonged exposure (PE) therapy in a Veterans Affairs outpatient clinic. In addition to traditional subjective self-reported and clinician-rated symptom measures, patients also completed a script-driven imagery task in which heart rate (HR) and skin conductance (SC) were recorded at three assessment points across treatment. We examined changes in subjective symptom measures and objective trauma-specific physiological reactivity over the course of PE, and investigated the association between pretreatment physiological reactivity and treatment response. Patients who completed PE showed significantly diminished HR and SC reactivity to trauma imagery across therapy. Additionally, individuals showing greater trauma-specific HR reactivity at pretreatment showed greater reductions in subjectively reported PTSD symptoms at posttreatment. Findings support the utility of physiological reactivity during trauma imagery as an objective outcome measure that has the potential to be incorporated into evidence-based PTSD treatment in routine clinical settings, or prospective studies related to the individualization of care at pretreatment. © 2015 Wiley Periodicals, Inc.

Japanese version of the Dermatology Life Quality Index: validity and reliability in patients with acne.

PubMed

Takahashi, Natsuko; Suzukamo, Yoshimi; Nakamura, Motonobu; Miyachi, Yoshiki; Green, Joseph; Ohya, Yukihiro; Finlay, Andrew Y; Fukuhara, Shunichi

2006-08-03

Patient-reported quality of life is strongly affected by some dermatologic conditions. We developed a Japanese version of the Dermatology Life Quality Index (DLQI-J) and used psychometric methods to examine its validity and reliability. The Japanese version of the DLQI was created from the original (English) version, using a standard method. The DLQI-J was then completed by 197 people, to examine its validity and reliability. Some participants completed the DLQI-J a second time, 3 days later, to examine the reproducibility of their responses. In addition to the DLQI-J, the participants completed parts of the SF-36 and gave data on their demographic and clinical characteristics. Their physicians provided information on the location and clinical severity of the skin disease. The participants reported no difficulties in answering the DLQI-J items. Their mean age was 24.8 years, 77.2% were female, and 78.7% had acne vulgaris. The mean score of DLQI was 3.99(SD: 3.99). The responses were found to be reproducible and stable. Results of principal-component and factor analysis suggested that this scale measured one construct. The correlations of DLQI-J scores with sex or age were very poor, but those with SF-36 scores and with clinical severity were high. The DLQI-J provides valid and reliable data despite having only a small number of items.

Medical student sexuality: how sexual experience and sexuality training impact U.S. and Canadian medical students' comfort in dealing with patients' sexuality in clinical practice.

PubMed

Shindel, Alan W; Ando, Kathryn A; Nelson, Christian J; Breyer, Benjamin N; Lue, Tom F; Smith, James F

2010-08-01

To determine factors associated with students' comfort in addressing patients' sexuality in the clinical context. The authors invited students enrolled in MD-degree-granting and osteopathic medical schools in the United States and Canada to participate in an anonymous Internet survey between February and July 2008. The survey assessed ethnodemographic factors and sexual history. Respondents also completed the Center for Epidemiologic Studies Depression Scale. Male respondents completed the International Index of Erectile Function and the Premature Ejaculation Diagnostic Tool. Female respondents completed the Female Sexual Function Index and the Index of Sex Life. The authors used descriptive statistics, ANOVA, and multivariable logistic regression to analyze responses. The authors' analyses included 2,261 completed survey responses: 910 from men, 1,343 from women, and 8 from individuals who self-identified as "other" gendered. Over 53% of respondents (n = 1,206) stated that they felt they had not received sufficient training in medical school to address sexual concerns clinically. Despite this, 81% of students (n = 1,827) reported feeling comfortable dealing with their patients' sexuality issues. Students with limited sexual experience, students at risk for sexual problems, and students who felt that they had not been trained adequately were less likely to report being comfortable talking to patients about sexual health issues. Perception of inadequate sexuality training in medical school and personal issues pertaining to sex may be associated with students' difficulty in addressing patients' sexuality. Adequate training is preeminently associated with feeling comfortable addressing patients' sexuality and should be a priority for medical education.

Delegation of clinical dietetic tasks in military and civilian hospitals: implications for practice.

PubMed

Myers, M E; Gregoire, M B; Spears, M C

1991-12-01

The purposes of our research were two-fold: to determine perceptions of the quality of task performance and to identify dietetic personnel currently performing clinical dietetic tasks in military and civilian hospitals. Questionnaires were returned from 309 dietitians and 208 dietetic support personnel at 151 military and civilian hospitals (73% response overall). For tasks completed by support personnel, no task was rated as having optimum quality, 1 was rated as highly acceptable, 6 as acceptable, 19 as somewhat unacceptable, and 4 as unacceptable. Current performance ratings indicated that 1 task was performed solely by dietitians, 21 were completed by dietitians with assistance, 6 were completed jointly by dietitians and support personnel, 2 were completed by support personnel with supervision by dietitians, and no task was completed independently by support personnel. Tasks were grouped into four categories: basic clinical dietetics (11 tasks), intermediate and in-depth clinical dietetics (12 tasks), outpatient nutrition clinic (5 tasks), and nutrition education (community) (4 tasks). Quality scores for the US Air Force (USAF) hospitals were higher for all task categories except intermediate and in-depth clinical dietetic tasks. The quality scores of support personnel were higher than those of dietitians for all task categories. The USAF performance scores indicated significantly more involvement of support personnel. Generally, the performance scores of dietitians increased with experience; the scores of support personnel decreased with experience. Correlations between quality and performance ratings for individual tasks revealed low to moderate relationships. Our results suggest that additional delegation of tasks to dietetic support personnel may be possible without negatively affecting perceptions of the quality of task outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

A deep learning classifier for prediction of pathological complete response to neoadjuvant chemotherapy from baseline breast DCE-MRI

NASA Astrophysics Data System (ADS)

Ravichandran, Kavya; Braman, Nathaniel; Janowczyk, Andrew; Madabhushi, Anant

2018-02-01

Neoadjuvant chemotherapy (NAC) is routinely used to treat breast tumors before surgery to reduce tumor size and improve outcome. However, no current clinical or imaging metrics can effectively predict before treatment which NAC recipients will achieve pathological complete response (pCR), the absence of residual invasive disease in the breast or lymph nodes following surgical resection. In this work, we developed and applied a convolu- tional neural network (CNN) to predict pCR from pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans on a per-voxel basis. In this study, DCE-MRI data for a total of 166 breast cancer pa- tients from the ISPY1 Clinical Trial were split into a training set of 133 patients and a testing set of 33 patients. A CNN consisting of 6 convolutional blocks was trained over 30 epochs. The pre-contrast and post-contrast DCE-MRI phases were considered in isolation and conjunction. A CNN utilizing a combination of both pre- and post-contrast images best distinguished responders, with an AUC of 0.77; 82% of the patients in the testing set were correctly classified based on their treatment response. Within the testing set, the CNN was able to produce probability heatmaps that visualized tumor regions that most strongly predicted therapeutic response. Multi- variate analysis with prognostic clinical variables (age, largest diameter, hormone receptor and HER2 status), revealed that the network was an independent predictor of response (p=0.05), and that the inclusion of HER2 status could further improve capability to predict response (AUC = 0.85, accuracy = 85%).

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

Igidbashian, Levon, E-mail: levonig@hotmail.co; Fortin, Bernard; Guertin, Louis

Purpose: To evaluate the role of neck dissection (ND) after chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC) with N3 disease. Methods and Materials: From March 1998 to September 2006, 70 patients with HNSCC and N3 neck disease were treated with concomitant CRT as primary therapy. Response to treatment was assessed using clinical examination and computed tomography 6 to 8 weeks posttreatment. Neck dissection was not routinely performed and considered for those with less than complete response. Of the patients, 26 (37.1%) achieved clinical complete response (cCR) after CRT. A total of 31 (44.3%) underwent ND aftermore » partial response (cPR-ND). Thirteen patients (29.5%) did not achieve cCR and did not undergo ND for the following reasons: incomplete response/progression at primary site, refusal/contraindication to surgery, metastatic progression, or death. These patients were excluded from the analysis. Outcomes were computed using Kaplan-Meier curves and were compared with log rank tests. Results: Comparing the cCR and cPR-ND groups at 2 years, the disease-free survival was respectively 62.7% and 84.9% (p = 0.048); overall survival was 63.0% and 79.4% (p = 0.26), regional relapse-free survival was 87.8% and 96.0% (p = 0.21); and distant disease-free survival was 67.1% and 92.6% (p = 0.059). In the cPR-ND group, 71.0% had no pathologic evidence of disease (PPV of 29.0%). Conclusions: Patients with N3 disease achieving regional cPR and primary cCR who underwent ND seemed to have better outcomes than patients achieving global cCR without ND. Clinical assessment with computed tomography is not adequate for evaluating response to treatment. Because of the inherent limitations of our study, further confirmatory studies are warranted.« less

Targeted Proteomics Predicts a Sustained Complete-Response after Transarterial Chemoembolization and Clinical Outcomes in Patients with Hepatocellular Carcinoma: A Prospective Cohort Study.

PubMed

Yu, Su Jong; Kim, Hyunsoo; Min, Hophil; Sohn, Areum; Cho, Young Youn; Yoo, Jeong-Ju; Lee, Dong Hyeon; Cho, Eun Ju; Lee, Jeong-Hoon; Gim, Jungsoo; Park, Taesung; Kim, Yoon Jun; Kim, Chung Yong; Yoon, Jung-Hwan; Kim, Youngsoo

2017-03-03

This study was aimed to identify blood-based biomarkers to predict a sustained complete response (CR) after transarterial chemoembolization (TACE) using targeted proteomics. Consecutive patients with HCC who had undergone TACE were prospectively enrolled (training (n = 100) and validation set (n = 80)). Serum samples were obtained before and 6 months after TACE. Treatment responses were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). In the training set, the MRM-MS assay identified five marker candidate proteins (LRG1, APCS, BCHE, C7, and FCN3). When this five-marker panel was combined with the best-performing clinical variables (tumor number, baseline PIVKA, and baseline AFP), the resulting ensemble model had the highest area under the receiver operating curve (AUROC) value in predicting a sustained CR after TACE in the training and validation sets (0.881 and 0.813, respectively). Furthermore, the ensemble model was an independent predictor of rapid progression (hazard ratio (HR), 2.889; 95% confidence interval (CI), 1.612-5.178; P value < 0.001) and overall an unfavorable survival rate (HR, 1.985; 95% CI, 1.024-3.848; P value = 0.042) in the entire population by multivariate analysis. Targeted proteomics-based ensemble model can predict clinical outcomes after TACE. Therefore, this model can aid in determining the best candidates for TACE and the need for adjuvant therapy.

Construct validation of an interactive digital algorithm for ostomy care.

PubMed

Beitz, Janice M; Gerlach, Mary A; Schafer, Vickie

2014-01-01

The purpose of this study was to evaluate construct validity for a previously face and content validated Ostomy Algorithm using digital real-life clinical scenarios. A cross-sectional, mixed-methods Web-based survey design study was conducted. Two hundred ninety-seven English-speaking RNs completed the study; participants practiced in both acute care and postacute settings, with 1 expert ostomy nurse (WOC nurse) and 2 nonexpert nurses. Following written consent, respondents answered demographic questions and completed a brief algorithm tutorial. Participants were then presented with 7 ostomy-related digital scenarios consisting of real-life photos and pertinent clinical information. Respondents used the 11 assessment components of the digital algorithm to choose management options. Participant written comments about the scenarios and the research process were collected. The mean overall percentage of correct responses was 84.23%. Mean percentage of correct responses for respondents with a self-reported basic ostomy knowledge was 87.7%; for those with a self-reported intermediate ostomy knowledge was 85.88% and those who were self-reported experts in ostomy care achieved 82.77% correct response rate. Five respondents reported having no prior ostomy care knowledge at screening and achieved an overall 45.71% correct response rate. No negative comments regarding the algorithm were recorded by participants. The new standardized Ostomy Algorithm remains the only face, content, and construct validated digital clinical decision instrument currently available. Further research on application at the bedside while tracking patient outcomes is warranted.

Medical student changes in self-regulated learning during the transition to the clinical environment.

PubMed

Cho, Kenneth K; Marjadi, Brahm; Langendyk, Vicki; Hu, Wendy

2017-03-21

Self-regulated learning (SRL), which is learners' ability to proactively select and use different strategies to reach learning goals, is associated with academic and clinical success and life-long learning. SRL does not develop automatically in the clinical environment and its development during the preclinical to clinical learning transition has not been quantitatively studied. Our study aims to fill this gap by measuring SRL in medical students during the transitional period and examining its contributing factors. Medical students were invited to complete a questionnaire at the commencement of their first clinical year (T0), and 10 weeks later (T1). The questionnaire included the Motivated Strategies for Learning Questionnaire (MSLQ) and asked about previous clinical experience. Information about the student's background, demographic characteristics and first clinical rotation were also gathered. Of 118 students invited to participate, complete paired responses were obtained from 72 medical students (response rate 61%). At T1, extrinsic goal orientation increased and was associated with gender (males were more likely to increase extrinsic goal orientation) and type of first attachment (critical care and community based attachments, compared to hospital ward based attachments). Metacognitive self-regulation decreased at T1 and was negatively associated with previous clinical experience. Measurable changes in self-regulated learning occur during the transition from preclinical learning to clinical immersion, particularly in the domains of extrinsic goal orientation and metacognitive self-regulation. Self-determination theory offers possible explanations for this finding which have practical implications and point the way to future research. In addition, interventions to promote metacognition before the clinical immersion may assist in preserving SRL during the transition and thus promote life-long learning skills in preparation for real-world practice.

A usability evaluation of four commercial dental computer-based patient record systems

PubMed Central

Thyvalikakath, Thankam P.; Monaco, Valerie; Thambuganipalle, Hima Bindu; Schleyer, Titus

2008-01-01

Background The usability of dental computer-based patient record (CPR) systems has not been studied, despite early evidence that poor usability is a problem for dental CPR system users at multiple levels. Methods The authors conducted formal usability tests of four dental CPR systems by using a purposive sample of four groups of five novice users. The authors measured task outcomes (correctly completed, incorrectly completed and incomplete) in each CPR system while the participants performed nine clinical documentation tasks, as well as the number of usability problems identified in each CPR system and their potential relationship to task outcomes. The authors reviewed the software application design aspects responsible for these usability problems. Results The range for correctly completed tasks was 16 to 64 percent, for incorrectly completed tasks 18 to 38 percent and for incomplete tasks 9 to 47 percent. The authors identified 286 usability problems. The main types were three unsuccessful attempts, negative affect and task incorrectly completed. They also identified six problematic interface and interaction designs that led to usability problems. Conclusion The four dental CPR systems studied have significant usability problems for novice users, resulting in a steep learning curve and potentially reduced system adoption. Clinical Implications The significant number of data entry errors raises concerns about the quality of documentation in clinical practice. PMID:19047669

Phase II trial of a syllable-timed speech treatment for school-age children who stutter.

PubMed

Andrews, Cheryl; O'Brian, Sue; Onslow, Mark; Packman, Ann; Menzies, Ross; Lowe, Robyn

2016-06-01

A recent clinical trial (Andrews et al., 2012) showed Syllable Timed Speech (STS) to be a potentially useful treatment agent for the reduction of stuttering for school-age children. The present trial investigated a modified version of this program that incorporated parent verbal contingencies. Participants were 22 stuttering children aged 6-11 years. Treatment involved training the children and their parents to use STS in conversation. Parents were also taught to use verbal contingencies in response to their child's stuttered and stutter-free speech and to praise their child's use of STS. Outcome assessments were conducted pre-treatment, at the completion of Stage 1 of the program and 6 months and 12 months after Stage 1 completion. Outcomes are reported for the 19 children who completed Stage 1 of the program. The group mean percent stuttering reduction was 77% from pre-treatment to 12 months post-treatment, and 82% with the two least responsive participants removed. There was considerable variation in response to the treatment. Eleven of the children showed reduced avoidance of speaking situations and 18 were more satisfied with their fluency post-treatment. However, there was some suggestion that stuttering control was not sufficient to fully eliminate situation avoidance for the children. The results of this trial are sufficiently encouraging to warrant further clinical trials of the method. Copyright © 2016 Elsevier Inc. All rights reserved.

Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

PubMed

Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas

2017-06-01

Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

Validating indicators of treatment response: application to trichotillomania.

PubMed

Nelson, Samuel O; Rogers, Kate; Rusch, Natalie; McDonough, Lauren; Malloy, Elizabeth J; Falkenstein, Martha J; Banis, Maria; Haaga, David A F

2014-09-01

Different studies of the treatment of trichotillomania (TTM) have used varying standards to determine the proportion of patients who obtain clinically meaningful benefits, but there is little information on the similarity of results yielded by these methods or on their comparative validity. Data from a stepped-care (Step 1: Web-based self-help; Step 2: Individual behavior therapy; N = 60) treatment study of TTM were used to evaluate 7 potential standards: complete abstinence, ≥ 25% symptom reduction, recovery of normal functioning, and clinical significance (recovery + statistically reliable change), each of the last 3 being measured by self-report (Massachusetts General Hospital Hairpulling Scale; MGH-HPS) or interview (Psychiatric Institute Trichotillomania Scale). Depending on the metric, response rates ranged from 25 to 68%. All standards were significantly associated with one another, though less strongly for the 25% symptom reduction metrics. Concurrent (with deciding to enter Step 2 treatment) and predictive (with 3-month follow-up treatment satisfaction, TTM-related impairment, quality of life, and diagnosis) validity results were variable but generally strongest for clinical significance as measured via self-report. Routine reporting of the proportion of patients who make clinically significant improvement on the MGH-HPS, supplemented by data on complete abstinence, would bolster the interpretability of TTM treatment outcome findings. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Radiopaque markers equal gastrografin in the study of small bowel obstructions (SBO): a preliminary study.

PubMed

Basile, Marco; Galica, Vikiela

2013-01-01

To compare the diagnostic accuracy of a consolidated method (i.e.gastrografin) and a new one (i.e.radiopaque markers) in detecting complete intestinal obstruction. Twenty-one patients with suspected small bowel obstruction were enrolled and received at admission orally 100 ml of Gastrografin and 10 radiopaque markers at the same time. A series of plain abdominal radiograms was taked and evaluated to decide whether the obstruction was complete or not. The results of radiological evaluations were not disclosed to the surgeons responsible for the patient's treatment, therefore clinical decisions were assumed on clinical grounds only. In 16 out of the 21 enrolled patients both methods demonstrated only a partial obstruction; clinically none of them required surgery. Five patients showed complete bowel obstruction by the radiopaque markers method; out of those the gastrografin study showed a complete obstruction in four of them. All of them were operated on. In the fifth case it was not clear if the gastrografin had passed through the ileum-cecal valve or not. The unclear clinical picture induced to perform a TC that revealed that a small quantity of gastrografin had passed the ileo-cecal valve but there was a complete small bowel occlusion due to an internal hernia requiring a surgical treatment (thus implying a false negative picture). This preliminary study showed that both methods are effective in the early diagnosis of complete SBO. The use of radiopaque markers could avoid some false negatives of the gastrografin method and is significantly less expensive.

Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data.

PubMed

Basra, M K A; Salek, M S; Camilleri, L; Sturkey, R; Finlay, A Y

2015-01-01

To determine the minimal clinically important difference (MCID) of the Dermatology Life Quality Index (DLQI) and its responsiveness to change in inflammatory skin diseases. A longitudinal study: at stage 1, patients completed the DLQI and a disease severity global question; at stage 2, a global rating of change in quality of life (QoL; Global Rating of Change Questionnaire, GRCQ) was added and used as an anchor to measure the MCID of the DLQI. 192 patients completed stage 1 and 107 completed stage 2. The mean DLQI score at stage 1 was 9.8 and 7.4 at stage 2 with a mean change of 2.4 (p < 0.0001). 31 patients experienced a 'small change' in their QoL (±3 and ±2) on the GRCQ. The mean corresponding change in DLQI scores was 3.3, which is regarded as the approximate MCID. Previous estimates of the MCID of the DLQI have varied from 3 to 5. Although this study demonstrated a MCID of 3.3, we recommend that the MCID in inflammatory skin diseases should be 4. © 2015 S. Karger AG, Basel.

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients

PubMed Central

Radvanyi, Laszlo G.; Bernatchez, Chantale; Zhang, Minying; Fox, Patricia S.; Miller, Priscilla; Chacon, Jessica; Wu, Richard; Lizee, Gregory; Mahoney, Sandy; Alvarado, Gladys; Glass, Michelle; Johnson, Valen E.; McMannis, John D.; Shpall, Elizabeth; Prieto, Victor; Papadopoulos, Nicholas; Kim, Kevin; Homsi, Jade; Bedikian, Agop; Hwu, Wen-Jen; Patel, Sapna; Ross, Merrick I.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Lucci, Anthony; Royal, Richard; Cormier, Janice N.; Davies, Michael A.; Mansaray, Rahmatu; Fulbright, Orenthial J.; Toth, Christopher; Ramachandran, Renjith; Wardell, Seth; Gonzalez, Audrey; Hwu, Patrick

2012-01-01

Purpose Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing Phase II clinical trial testing the efficacy of ACT using TIL in metastatic melanoma patients and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL followed by two cycles of high-dose (HD) IL-2 therapy. The effects of patient clinical features and the phenotypes of the T-cells infused on clinical response were determined. Results Overall, 15/31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC), with two patients (6.5%) having a complete response. Progression-free survival of >12 months was observed for 9/15 (60%) of the responding patients. Factors significantly associated with objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T-cells in the infusion product, a more differentiated effector phenotype of the CD8+ population and a higher frequency of CD8+ T-cells co-expressing the negative costimulation molecule “B- and T-lymphocyte attenuator” (BTLA). No significant difference in telomere lengths of TIL between responders and non-responders was identified. Conclusion These results indicate that immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in metastatic melanoma patients and that CD8+ T-cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression. PMID:23032743

A Single-Center Experience With Isolated Limb Infusion: An Interventional Oncology Opportunity.

PubMed

DeFoe, Adam; Heckman, Andrew; Slater, Dick; Silva-Lopez, Edibaldo; Foster, Jason; Bowden, Thom; Vargo, Christopher

2017-03-01

This retrospective review details our experience with isolated limb infusion for the treatment of melanoma, squamous cell carcinoma, and sarcoma in-transit metastases performed entirely in the interventional radiology suite. Eleven patients were treated over a 3-year period. Treatment response was assessed clinically and with PET/CT. Eight patients had either complete or partial response, giving an overall response rate of 72%. Isolated limb infusion can efficiently be performed entirely in the interventional radiology suite.

Cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) combination sequential chemotherapy for advanced diffuse histiocytic lymphoma

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

Sweet, D.L.; Golomb, H.M.; Ultmann, J.E.

A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference inmore » response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.« less

Evaluating the Psychometric Properties and Responsiveness to Change of 3 Depression Measures in a Sample of Persons With Traumatic Spinal Cord Injury and Major Depressive Disorder.

PubMed

Williams, Ryan T; Heinemann, Allen W; Neumann, Holly Demark; Fann, Jesse R; Forchheimer, Martin; Richardson, Elizabeth J; Bombardier, Charles H

2016-06-01

To compare the measurement properties and responsiveness to change of the Patient Health Questionnaire-9 (PHQ-9), the Hopkins Symptom Checklist-20 (HSCL-20), and the Hamilton Depression Rating Scale (HAM-D) in people with spinal cord injury (SCI) diagnosed with major depressive disorder (MDD). Secondary analysis of depression symptoms measured at 6 occasions over 12 weeks as part of a randomized controlled trial of venlafaxine XR for MDD in persons with SCI. Outpatient and community settings. Individuals (N=133) consented and completed the drug trial. Eligibility criteria were age at least 18 years, traumatic SCI, and diagnosis of MDD. Venlafaxine XR. Patients completed the PHQ-9 and the HSCL-20 depression scales; clinical investigators completed the HAM-D and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) Dissociative Disorders, which was used as a diagnostic criterion measure. All 3 instruments were improved with rating scale analysis. The HSCL-20 and the HAM-D contained items that misfit the underlying construct and that correlated weakly with the total scores. Removing these items improved the internal consistency, with floor effects increasing slightly. The HAM-D correlated most strongly with Structured Clinical Interview for DSM-IV Dissociative Disorders diagnoses. Improvement in depression was similar on all outcome measures in both treatment and control groups. The psychometric properties of the revised depression instruments are more than adequate for routine use in adults with SCI and are responsive to clinical improvement. The PHQ-9 is the simplest instrument with measurement properties as good as or better than those of the other instruments and required the fewest modifications. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Motivation for change as a predictor of treatment response for dysthymia.

PubMed

Frías Ibáñez, Álvaro; González Vallespí, Laura; Palma Sevillano, Carol; Farriols Hernando, Núria

2016-05-01

Dysthymia constitutes a chronic, mild affective disorder characterized by heterogeneous treatment effects. Several predictors of clinical response and attendance have been postulated, although research on the role of the psychological variables involved in this mental disorder is still scarce. Fifty-four adult patients, who met criteria for dysthymia completed an ongoing naturalistic treatment based on the brief interpersonal psychotherapy (IPT-B), which was delivered bimonthly over 16 months. As potential predictor variables, the therapeutic alliance, coping strategies, perceived self-efficacy, and motivation for change were measured at baseline. Outcome variables were response to treatment (Clinical Global Impression and Beck’s Depression Inventory) and treatment attendance. Stepwise multiple linear regression analyses revealed that higher motivation for change predicted better response to treatment. Moreover, higher motivation for change also predicted treatment attendance. Therapeutic alliance was not a predictor variable of neither clinical response nor treatment attendance. These preliminary findings support the adjunctive use of motivational interviewing (MI) techniques in the treatment of dysthymia. Further research with larger sample size and follow-up assessment is warranted.

Breast cancer: complete response with the combination of sunitinib and trastuzumab in a patient with grade III ductal carcinoma.

PubMed

Puente, Javier; Manzano, Aranzazu; Martin, Miguel; López-Tarruella, Sonia; Díaz-Rubio, Eduardo

2010-01-01

In August 2000, a previously healthy postmenopausal 52-year-old woman was diagnosed with grade III invasive ductal carcinoma. The tumor had an ER -, PR -, and HER2 + profile. Adjuvant treatment with FEC was initiated followed by radiotherapy. In October 2004, the patient presented a clinically asymptomatic supraclavicular and mediastinal lymph node recurrence and treatment with paclitaxel and trastuzumab was initiated. A complete response was achieved after 20 weeks of treatment, and in January 2006 treatment was interrupted due to toxicity. After a 34-month free-of-relapse period, a local recurrence was detected in the chest wall. In September 2007, the patient joined a phase II trial with sunitinib (37.5 mg once a day in 28 days cycles) and trastuzumab (6 mg/kg every 3 weeks), after having verified a normal cardiac function. After two courses, a partial cutaneous response and a complete radiological response were obtained. The most relevant toxicities included cutaneous hyperpigmentation, dysgeusia, mucositis, grade II diarrhea and hypertension. The development of grade III diarrhea led to sunitinib dose reduction (25mg/day). In January 2008, the patient developed hypothyroidism and a significant drop in the left ventricular ejection fraction that led to treatment interruption. In March 2008, once cardiac function was recovered, treatment at the same dose was reinitiated. After two months of treatment, a new descent in cardiac function was noted which led to the suspension of sunitinib, and the interruption of the trastuzumab treatment until recovery of normal cardiac function. In July 2008, trastuzumab monotherapy was resumed and since then no cardiac events have been reported, while maintaining a radiological and clinical response.

Clinical results of definitive-dose (50 Gy/25 fractions) preoperative chemoradiotherapy for unresectable esophageal cancer.

PubMed

Ishikawa, Kazuki; Nakamatsu, Kiyoshi; Shiraishi, Osamu; Yasuda, Takushi; Nishimura, Yasumasa

2015-06-01

The clinical results of definitive-dose preoperative chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal cancer were analyzed. Inclusion criteria were unresectable esophageal squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined concurrently with two courses of FP therapy (CDDP 70 mg/m(2) + 5-FU 700 mg/m(2)/d × 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were enrolled between 2008 and 2011. The clinical stages according to the 7th edition of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3, 3/25/1/1. All 30 patients completed RT of 50 Gy/25 fractions. Initial tumor responses were 21 patients with resectable disease, 7 with unresectable disease, and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60%) of the 30 patients. Pathological complete response was obtained in five (28%) patients. There were two patients with hospitalization death after surgery (11%). Six of the 7 patients who still had unresectable disease were treated with 1-3 courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery showed long-term survival. The 3-year loco-regional control rate and the 3-year overall survival rate for the 30 patients were 70 and 49%, respectively. Definitive-dose preoperative CRT was feasible, and is a promising treatment strategy for unresectable esophageal cancer.

Validation of Patient-Reported Outcomes Measurement Information System Short Forms for Use in Childhood-Onset Systemic Lupus Erythematosus.

PubMed

Jones, Jordan T; Carle, Adam C; Wootton, Janet; Liberio, Brianna; Lee, Jiha; Schanberg, Laura E; Ying, Jun; Morgan DeWitt, Esi; Brunner, Hermine I

2017-01-01

To validate the pediatric Patient-Reported Outcomes Measurement Information System short forms (PROMIS-SFs) in childhood-onset systemic lupus erythematosus (SLE) in a clinical setting. At 3 study visits, childhood-onset SLE patients completed the PROMIS-SFs (anger, anxiety, depressive symptoms, fatigue, physical function-mobility, physical function-upper extremity, pain interference, and peer relationships) using the PROMIS assessment center, and health-related quality of life (HRQoL) legacy measures (Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters [SMILEY], and visual analog scales [VAS] of pain and well-being). Physicians rated childhood-onset SLE activity on a VAS and completed the Systemic Lupus Erythematosus Disease Activity Index 2000. Using a global rating scale of change (GRC) between study visits, physicians rated change of childhood-onset SLE activity (GRC-MD1: better/same/worse) and change of patient overall health (GRC-MD2: better/same/worse). Questionnaire scores were compared in support of validity and responsiveness to change (external standards: GRC-MD1, GRC-MD2). In this population-based cohort (n = 100) with a mean age of 15.8 years (range 10-20 years), the PROMIS-SFs were completed in less than 5 minutes in a clinical setting. The PROMIS-SF scores correlated at least moderately (Pearson's r ≥ 0.5) with those of legacy HRQoL measures, except for the SMILEY. Measures of childhood-onset SLE activity did not correlate with the PROMIS-SFs. Responsiveness to change of the PROMIS-SFs was supported by path, mixed-model, and correlation analyses. To assess HRQoL in childhood-onset SLE, the PROMIS-SFs demonstrated feasibility, internal consistency, construct validity, and responsiveness to change in a clinical setting. © 2016, American College of Rheumatology.

A Mobile Health Platform for Clinical Monitoring in Early Psychosis: Implementation in Community-Based Outpatient Early Psychosis Care

PubMed Central

Iosif, Ana-Maria; Zakskorn, Lauren N; Nye, Kathleen E; Zia, Aqsa; Niendam, Tara Ann

2018-01-01

Background A growing body of literature indicates that smartphone technology is a feasible add-on tool in the treatment of individuals with early psychosis (EP) . However, most studies to date have been conducted independent of outpatient care or in a research clinic setting, often with financial incentives to maintain user adherence to the technology. Feasibility of dissemination and implementation of smartphone technology into community mental health centers (CMHCs) has yet to be tested, and whether young adults with EP will use this technology for long periods of time without incentive is unknown. Furthermore, although EP individuals willingly adopt smartphone technology as part of their treatment, it remains unclear whether providers are amenable to integrating smartphone technology into treatment protocols. Objective This study aimed to establish the feasibility of implementing a smartphone app and affiliated Web-based dashboard in 4 community outpatient EP clinics in Northern California. Methods EP individuals in 4 clinics downloaded an app on their smartphone and responded to daily surveys regarding mood and symptoms for up to 5 months. Treatment providers at the affiliated clinics viewed survey responses on a secure Web-based dashboard in sessions with their clients and between appointments. EP clients and treatment providers filled out satisfaction surveys at study end regarding usability of the app. Results Sixty-one EP clients and 20 treatment providers enrolled in the study for up to 5 months. Forty-one EP clients completed the study, and all treatment providers remained in the study for their duration in the clinic. Survey completion for all 61 EP clients was moderate: 40% and 39% for daily and weekly surveys, respectively. Completion rates were slightly higher in the participants who completed the study: 44% and 41% for daily and weekly surveys, respectively. Twenty-seven of 41 (66%) EP clients who completed the study and 11 of 13 (85%) treatment providers who responded to satisfaction surveys reported they would continue to use the app as part of treatment services. Six (15%; 6/41) clients and 3 providers (23%; 3/13) stated that technological glitches impeded their engagement with the platform. Conclusions EP clients and treatment providers in community-based outpatient clinics are responsive to integrating smartphone technology into treatment services. There were logistical and technical challenges associated with enrolling individuals in CMHCs. To be most effective, implementing smartphone technology in CMHC EP care necessitates adequate technical staff and support for utilization of the platform. PMID:29487044

Do parent protective responses mediate the relation between parent distress and child functional disability among children with chronic pain?

PubMed

Sieberg, Christine B; Williams, Sara; Simons, Laura E

2011-10-01

To examine whether protective parent responses mediate the relation between parent distress and child functioning. At a pain clinic evaluation, 157 families participated. Parents completed measures of global distress (BSI-18), distress in the context of their child's pain (BAP-PIQ), and protective responses to their child's pain. Children completed measures of functional disability and pain. BAP-PIQ subscales were significantly associated with child functional disability, whereas BSI subscales were unrelated. Protective parent responses partially mediated the relation between parent distress and child functional disability for depression, anxiety, and catastrophizing. However, parent protective behavior fully mediated the relationship between parent helplessness and child functional disability, indicating that feelings of parent helplessness did not uniquely contribute to child functional disability. Discussion Results suggest that when treating youth with chronic pain, parental distress in the context of children's pain needs to be addressed.

Key observations from the NHLBI Asthma Clinical Research Network.

PubMed

Szefler, Stanley J; Chinchilli, Vernon M; Israel, Elliot; Denlinger, Loren Clark; Lemanske, Robert F; Calhoun, William; Peters, Stephen P

2012-05-01

The National Heart, Lung and Blood Institute (NHLBI) Asthma Clinical Research Network (ACRN) recently completed its work after 20 years of collaboration as a multicentre clinical trial network. When formed, its stated mission was to perform multiple controlled clinical trials for treating patients with asthma by dispassionately examining new and existing therapies, and to rapidly communicate its findings to the medical community. The ACRN conducted 15 major clinical trials. In addition, clinical data, manual of operations, protocols and template informed consents from all ACRN trials are available via NHLBI BioLINCC (https://biolincc.nhlbi.nih.gov/studies/). This network contributed major insights into the use of inhaled corticosteroids, short-acting and long-acting ß-adrenergic agonists, leukotriene receptor antagonists, and novel agents (tiotropium, colchicine and macrolide antibiotics). They also pioneered studies of the variability in drug response, predictors of treatment response and pharmacogenetics. This review highlights the major research observations from the ACRN that have impacted the current management of asthma.

Clinical Validity of PROMIS® Depression, Anxiety, and Anger across Diverse Clinical Samples

PubMed Central

Schalet, Benjamin D.; Pilkonis, Paul A.; Yu, Lan; Dodds, Nathan; Johnston, Kelly L.; Yount, Susan; Riley, William; Cella, David

2016-01-01

Objective To evaluate the responsiveness to change of the PROMIS® negative affect measures (Depression, Anxiety, and Anger) using longitudinal data collected in six chronic health conditions. Study Design and Setting Individuals with major depressive disorder (MDD), back pain, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), and cancer completed PROMIS negative affect instruments as computerized adaptive test (CAT) or as fixed-length short form (SF) at baseline and a clinically-relevant follow-up interval. Participants also completed global ratings of health. Linear mixed effects models and standardized response means (SRM) were estimated at baseline and follow-up. Results 903 individuals participated (back pain, n = 218; cancer, n = 304; CHF, n = 60; COPD, n = 125; MDD, n = 196). All three negative affect instruments improved significantly for treatments of depression and pain. Depression improved for CHF patients (anxiety and anger not administered), while anxiety improved significantly in COPD groups (stable and exacerbation). Response to treatment was not assessed in cancer. Subgroups of patients reporting better or worse health showed a corresponding positive or negative average SRM for negative affect across samples. Conclusion This study provides evidence that the PROMIS negative affect scores are sensitive to change in intervention studies in which negative affect is expected to change. These results inform the estimation of meaningful change and enable comparative effectiveness research. PMID:26931289

Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma.

PubMed

Broccoli, Alessandro; Casadei, Beatrice; Morigi, Alice; Sottotetti, Federico; Gotti, Manuel; Spina, Michele; Volpetti, Stefano; Ferrero, Simone; Spina, Francesco; Pisani, Francesco; Merli, Michele; Visco, Carlo; Paolini, Rossella; Zilioli, Vittorio Ruggero; Baldini, Luca; Di Renzo, Nicola; Tosi, Patrizia; Cascavilla, Nicola; Molica, Stefano; Ilariucci, Fiorella; Rigolin, Gian Matteo; D'Alò, Francesco; Vanazzi, Anna; Santambrogio, Elisa; Marasca, Roberto; Mastrullo, Lucia; Castellino, Claudia; Desabbata, Giovanni; Scortechini, Ilaria; Trentin, Livio; Morello, Lucia; Argnani, Lisa; Zinzani, Pier Luigi

2018-05-04

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventy-seven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world.

Factor Structure, Factorial Invariance, and Validity of the Multidimensional Shame-Related Response Inventory-21 (MSRI-21)

PubMed Central

Garcia, Antonio F.; Acosta, Melina; Pirani, Saifa; Edwards, Daniel; Osman, Augustine

2017-01-01

We describe 2 studies designed to evaluate scores on the Multidimensional Shame-related Response Inventory-21 (MSRI-21), a recently developed instrument that measures affective and behavioral responses to shame. The inventory assesses shame-related responses in 3 categories: negative self-evaluation, fear of social consequences, and maladaptive behavior tendency. For Study 1, (N = 743) undergraduates completed the MSRI-21. Confirmatory factor analysis supported the validity of the MSRI-21 3-factor structure. Latent variable modeling of coefficient-α provided strong evidence for the internal consistency of scores on each scale. In Study 2, (N = 540) undergraduates completed the instrument along with 5 concurrent measures chosen for clinical significance. Achievement of factorial invariance supported the use of MSRI-21 scale scores to make valid mean comparisons across gender. In addition, MSRI-21 scale scores were associated as expected with scores on measures of self-harm, suicide, and other risk factors. Taken together, results of 2 studies support the internal consistency reliability, factorial validity, factorial invariance, and convergent validity of scores on the MSRI-21. Further work is needed to assess the temporal stability of the MSRI-21 scale scores, invariance across clinical status and other groupings, item-level measurement properties, and viability in highly symptomatic samples. PMID:28182490

Thoracic Epidural Anesthesia Can Be Effective for the Short-Term Management of Ventricular Tachycardia Storm.

PubMed

Do, Duc H; Bradfield, Jason; Ajijola, Olujimi A; Vaseghi, Marmar; Le, John; Rahman, Siamak; Mahajan, Aman; Nogami, Akihiko; Boyle, Noel G; Shivkumar, Kalyanam

2017-10-27

Novel therapies aimed at modulating the autonomic nervous system, including thoracic epidural anesthesia (TEA), have been shown in small case series to be beneficial in treating medically refractory ventricular tachycardia (VT) storm. However, it is not clear when these options should be considered. We reviewed a multicenter experience with TEA in the management of VT storm to determine its optimal therapeutic use. Data for 11 patients in whom TEA was instituted for VT storm between July 2005 and March 2016 were reviewed to determine the clinical characteristics, outcomes, and role in management. The clinical presentation was incessant VT in 7 (64%), with polymorphic VT in 3 (27%) and monomorphic VT in 8 (73%). The underlying conditions were nonischemic cardiomyopathy in 5 (45%), ischemic cardiomyopathy in 3 (27%), and hypertrophic cardiomyopathy, Brugada syndrome, and cardiac lipoma in 1 (9%) each. Five (45%) had a complete and 1 (9%) had a partial response to TEA; 4 of the complete responders had incessant VT. All 4 patients with a documented response to deep sedation demonstrated a complete response to TEA. More than half of the patients with VT storm in our series responded to TEA. TEA may be effective and should be considered as a therapeutic option in patients with VT storm, especially incessant VT, who are refractory to initial management. Improvement in VT burden with deep sedation may suggest that sympathoexcitation plays a key role in perpetuating VT and predict a positive response to TEA. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

PubMed

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-02-01

Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m 2 in month 1 and 500 mg/m 2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. AbbVie Inc and Genentech Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

PubMed Central

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-01-01

Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3–4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66–91) and 89% (95% CI 72–96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. Interpretation A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. PMID:28089635

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients

PubMed Central

2012-01-01

Background SBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients. Methods Between October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeamTM treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan. Results All dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded. Conclusions Data of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes. PMID:23216821

A Practicum for Oral Cancer Teaching.

ERIC Educational Resources Information Center

Barr, Charles E.; Goldberg, Marshal D.

1983-01-01

A hospital-based method for teaching general practice dental residents, involving patients for whom the residents are responsible, is described. Residents present prepared cases of dental patients according to a predetermined protocol: a talk, complete documentation of clinical history and laboratory findings, and discussion of therapy and…

PMS Awareness.

ERIC Educational Resources Information Center

Atwood, Joan D.

This study was conducted to examine the incidence of premenstrual mood changes in a non-clinical population and to explore how women report that these mood changes affect their interpersonal relationships. Women (N=101) completed a questionnaire about their background and their physical and psychological responses to the premenstrual experience.…

Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease

PubMed Central

De Cassan, Chiara; Savarino, Edoardo; Marson, Piero; Tison, Tiziana; Hatem, Giorgia; Sturniolo, Giacomo Carlo; D’Incà, Renata

2014-01-01

AIM: To evaluate whether the effectiveness of Granulo-monocyto apheresis (GMA), a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood, might vary according to the severity of ulcerative colitis (UC) in patients with mild to moderate-severe disease UC activity. METHODS: We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up. The demographics, clinical and laboratory data were extracted from the patients’ charts and electronic records. The severity of UC was scored according to the Modified Truelove Witts Severity Index (MTWSI). A clinical response was defined as a decrease from baseline of ≥ 2 points or a value of MTWSI ≤ 2 points. RESULTS: A total of 41 (24 males/17 females; mean age 47 years) patients were included in the study. After GMA cycle completion, 21/28 (75%) of mild UC patients showed a clinical response compared with 7/13 (54%) of patients with moderate to severe disease (P = 0.27). At 6-mo, 14/28 (50%) of the mild UC patients maintained a clinical response compared with 2/13 (15%) of the patients with moderate to severe disease (P = 0.04). After the GMA cycle completion and during the 6-mo follow up period, 13/16 (81%) and 9/16 (56%) of mild UC patients with intolerance, resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6 (33%) and 0/6 (0%) of patients with moderate to severe disease activity with these characteristics (P = 0.05 and P = 0.04, respectively). CONCLUSION: Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics. PMID:25493030

Predictive factors for the regression of canine transmissible venereal tumor during vincristine therapy.

PubMed

Scarpelli, Karime C; Valladão, Maria L; Metze, Konradin

2010-03-01

Canine transmissible venereal tumor (CTVT) is a neoplasm transmitted by transplantation. Monochemotherapy with vincristine is considered to be effective, but treatment time until complete clinical remission may vary. The aim of this study was to determine which clinical data at diagnosis could predict the responsiveness of CTVT to vincristine chemotherapy. One hundred dogs with CTVT entered this prospective study. The animals were treated with vincristine sulfate (0.025 mg/kg) at weekly intervals until the tumor had macroscopically disappeared. The time to complete remission was recorded. A multivariate Cox regression model indicated that larger tumor mass, increased age and therapy during hot and rainy months were independent significant unfavorable predictive factors retarding remission, whereas sex, weight, status as owned dog or breed were of no predictive relevance. Further studies are necessary to investigate whether these results are due to changes in immunological response mechanisms in animals with a diminished immune surveillance, resulting in delays in tumor regression. 2008 Elsevier Ltd. All rights reserved.

Sustained complete response of hepatocellular carcinoma with portal vein tumor thrombus following discontinuation of sorafenib: A case report

PubMed Central

SHIOZAWA, KAZUE; WATANABE, MANABU; IKEHARA, TAKASHI; MATSUKIYO, YASUSHI; KOGAME, MICHIO; KANAYAMA, MASAHIRO; MATSUI, TEPPEI; KIKUCHI, YOSHINORI; ISHII, KOJI; IGARASHI, YOSHINORI; SUMINO, YASUKIYO

2014-01-01

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated mortality worldwide. No effective treatment has been established for unresectable advanced HCC, and the prognosis is poor. Sorafenib is an oral multi-targeted tyrosine kinase inhibitor for unresectable advanced HCC that significantly improves progression-free and overall survival. However, in the two large phase III clinical trials (the SHARP and Asia-Pacific trials), no cases of complete response (CR) were reported. The present study reports the case of a 68-year-old male with hepatitis C virus-related cirrhosis and multiple recurrent HCCs, with a tumor thrombus of the third portal vein following resection. The patient received 400 mg once daily (half the standard dose) of sorafenib for two years and achieved a CR. At the most recent follow-up examination at one year after the cessation of treatment, the patient was observed to be in remission without clinical or imaging evidence of disease recurrence. PMID:24348819

Clinical and biological effects of demethylating agents on solid tumours - A systematic review.

PubMed

Linnekamp, J F; Butter, R; Spijker, R; Medema, J P; van Laarhoven, H W M

2017-03-01

It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the treatment of haematological malignancies. Based on encouraging preclinical results, demethylating agents may also be effective in solid tumours. This systematic review summarizes the evidence of the effect of demethylating agents on clinical response, methylation and the immune system in solid tumours. We conducted a systematic literature search from 1949 to December 2016, according to the PRISMA guidelines. Studies which evaluated treatment with azacitidine, decitabine, guadecitabine, hydralazine, procaine, MG98 and/or zebularine in patients with solid tumours were included. Data on clinical response, effects on methylation and immune response were extracted. Fifty-eight studies were included: in 13 studies complete responses (CR) were observed, 35 studies showed partial responses (PR), 47 studies stable disease (SD) and all studies except two showed progressive disease (PD). Effects on global methylation were observed in 11/15 studies and demethylation/re-expression of tumour specific genes was seen in 15/17 studies. No clear correlation between (de)methylation and clinical response was observed. In 14 studies immune-related responses were reported, such as re-expression of cancer-testis antigens and upregulation of interferon genes. Demethylating agents are able to improve clinical outcome and alter methylation status in patients with solid tumours. Although beneficial effect has been shown in individual patients, overall response is limited. Further research on biomarker predicting therapy efficacy is indicated, particularly in earlier stage and highly methylated tumours. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Using computer-assisted survey instruments instead of paper and pencil increased completeness of self-administered sexual behavior questionnaires.

PubMed

Spark, Simone; Lewis, Dyani; Vaisey, Alaina; Smyth, Eris; Wood, Anna; Temple-Smith, Meredith; Lorch, Rebecca; Guy, Rebecca; Hocking, Jane

2015-01-01

To compare the data quality, logistics, and cost of a self-administered sexual behavior questionnaire administered either using a computer-assisted survey instrument (CASI) or by paper and pencil in a primary care clinic. A self-administered sexual behavior questionnaire was administered to 16-29 year olds attending general practice. Questionnaires were administered by either paper and pencil (paper) or CASI. A personal digital assistant was used to self-administer the CASI. A total of 4,491 people completed the questionnaire, with 46.9% responses via CASI and 53.2% by paper. Completion of questions was greater for CASI than for paper for sexual behavior questions: number of sexual partners [odds ratio (OR), 6.85; 95% confidence interval (CI): 3.32, 14.11] and ever having had sex with a person of the same gender (OR, 2.89; 95% CI: 1.52, 5.49). The median number of questions answered was higher for CASI than for paper (17.6 vs. 17.2; P < 0.01). CASI was cheaper to run at $8.18 per questionnaire compared with $11.83 for paper. Electronic devices using CASI are a tool that can increase participants' questionnaire responses and deliver more complete data for a sexual behavior questionnaire in primary care clinics. Copyright © 2015 Elsevier Inc. All rights reserved.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers.

PubMed

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J; Brown, Powel H; Dannenberg, Andrew J; Szabo, Eva

2012-09-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. Published by Elsevier Inc.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers

PubMed Central

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J.; Brown, Powel H.; Dannenberg, Andrew J.; Szabo, Eva

2012-01-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. PMID:22771576

[Integration of the radiotherapy irradiation planning in the digital workflow].

PubMed

Röhner, F; Schmucker, M; Henne, K; Momm, F; Bruggmoser, G; Grosu, A-L; Frommhold, H; Heinemann, F E

2013-02-01

At the Clinic of Radiotherapy at the University Hospital Freiburg, all relevant workflow is paperless. After implementing the Operating Schedule System (OSS) as a framework, all processes are being implemented into the departmental system MOSAIQ. Designing a digital workflow for radiotherapy irradiation planning is a large challenge, it requires interdisciplinary expertise and therefore the interfaces between the professions also have to be interdisciplinary. For every single step of radiotherapy irradiation planning, distinct responsibilities have to be defined and documented. All aspects of digital storage, backup and long-term availability of data were considered and have already been realized during the OSS project. After an analysis of the complete workflow and the statutory requirements, a detailed project plan was designed. In an interdisciplinary workgroup, problems were discussed and a detailed flowchart was developed. The new functionalities were implemented in a testing environment by the Clinical and Administrative IT Department (CAI). After extensive tests they were integrated into the new modular department system. The Clinic of Radiotherapy succeeded in realizing a completely digital workflow for radiotherapy irradiation planning. During the testing phase, our digital workflow was examined and afterwards was approved by the responsible authority.

Response-adapted treatment with upfront high-dose chemotherapy followed by autologous stem-cell transplantation rescue or consolidation phase high-dose methotrexate for primary central nervous system lymphoma: a long-term mono-center study.

PubMed

Nakasu, Yoko; Mitsuya, Koichi; Hayashi, Nakamasa; Okamura, Ikue; Mori, Keita; Enami, Terukazu; Tatara, Raine; Nakasu, Satoshi; Ikeda, Takashi

2016-01-01

Treatment regimens for primary central nervous system lymphoma (PCNSL) include high-dose methotrexate (HD-MTX)-based chemotherapy, with or without radiotherapy and are based on studies of selected patient groups. This retrospective study assessed a consistent strategy of response-adapted protocol applied for patients including age >65 years in a cancer center for 10 years longitudinally. Case notes were studied of 61 consecutively treated patients with PCNSL histologically diagnosed between 2003 and 2013. Clinical follow-up during and after treatment included neurologic examination and magnetic resonance imaging. Of the patients studied, 14.8 % (9/61) were clinically unfit for chemotherapy; the remaining 85.2 % (52/61) of patients were treated with HD-MTX. Of these patients, 58 % (30/52) achieved an initial complete response, with a median survival of 100.1 months. Of these response-adapted patients, 33 % (10/30) were <65 years and were treated with upfront high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT). The remaining response-adapted patients included 53 % (16/30) who were ≥65 years underwent consolidation with HD-MTX, and 14 % (4/30) who chose radiotherapy. The median survival of patients with HDC-ASCT had not yet been reached compared with 67.6 months for patients with HD-MTX consolidation treatment (p = 0.26). At the end of the study, 75 % (39/52) of patients had died mainly owing to progression or relapse of PCNSL. Multivariate analysis showed that age younger than 65 years (p = 0.02) and complete response for up-front HD-MTX (p = 0.001) were independent prognostic indicators of overall survival. In conclusion, this single-center retrospective clinical study has shown that treatment of PCNSL with upfront HDC-ASCT and consolidation phase HD-MTX monotherapy may be feasible, even for elderly patients in a routine clinical setting, using the three-step selection by eligibility and response to initial HD-MTX, and age threshold of 65 years for ASCT.

Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine.

PubMed

Sobanski, E; Leppämäki, S; Bushe, C; Berggren, L; Casillas, M; Deberdt, W

2015-11-01

Atomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns. From 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n=1443) and/or short-term (12 weeks; n=2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling. Based on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e.≥30% reduction in CAARS-Inv:SV total score, and CGI-S score≤3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4. While many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Concordance between patient and clinician assessment of dry eye severity and treatment response in Taiwan.

PubMed

Yeh, Po-Ting; Chien, Hsu-Chih; Ng, Kwong; Tseng, Sung-Huei; Chen, Wei-Li; Hou, Yu-Chih; Wang, I-Jong; Chu, Hsiao-Sung; Kao Yang, Yea-Huei; Hu, Fung-Rong

2015-05-01

Accurate diagnosis and early recognition of dry eye symptoms are important in the management of dry eye disease (DED). This study aimed to evaluate concordance between patient and clinician assessment of DED severity and treatment response. This cross-sectional study was conducted in 2 ophthalmology clinics in Taiwan. Clinicians assessed severity based on the Dry Eye Workshop severity grading (levels 1-4; where 4 = most severe), whereas patients completed the Ocular Surface Disease Index questionnaire. To evaluate the treatment response, patients completed the Subject Global Assessment scale, and clinicians independently assessed patients using the Clinical Global Impression scale. A total of 466 patients were included. Clinicians graded 88.3% of patients as level 1/2, 9.0% as level 3, and 2.7% as level 4 Dry Eye Workshop severity, whereas 44.9% of patients reported normal/mild symptoms, 17.1% with moderate severity, and 38.0% with severe DED. Patients were primarily treated with artificial tears. The clinician assessed 10.3% of patients as unchanged on disease severity after treatment and 88.0% as improved, whereas 49.2% of patients reported dry eye symptoms being almost the same after treatment and 34.6% reported improved symptoms. There was low agreement between clinician and patient assessments in terms of disease severity (rho = 0.17, P < 0.001) and treatment response (rho = 0.22, P < 0.001). There were marked differences in the degree of DED severity and treatment response between patient and clinician assessment. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942226.

Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer

PubMed Central

Allevi, G; Strina, C; Andreis, D; Zanoni, V; Bazzola, L; Bonardi, S; Foroni, C; Milani, M; Cappelletti, M R; Gussago, F; Aguggini, S; Giardini, R; Martinotti, M; Fox, S B; Harris, A L; Bottini, A; Berruti, A; Generali, D

2013-01-01

Background: The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response (pathCR) and assess Ki-67 expression as an early predictor of response. Patients and methods: This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer (clinical stage ⩾T2, N0–1), from three sequential cohorts (cohort A of 40, cohort B of 40 and cohort C of 40 patients, respectively) based on different duration of the neoadjuvant letrozole. Biological markers such as ER, progesterone receptor, HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery. Results: A total of 89 patients (75.4%) achieved an objective response with 44 (37.3%) clinical CRs and 45 (38.1%) partial responses. The clinical CRs were significantly observed in cohort C (23 out of 40 patients, 57.5%) and B (16 out of 38 patients, 42.1%) compared with cohort A (5 out of 40 patients, 12.5%) (P-value for trend <0.001). Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts. The pathCR rate was significantly more frequent in cohort C (7 out of 40 patients, 17.5%) than in cohort A (1 out of 40 patients, 2.5%) and B (2 out of 40 patients, 5.0%) (P-value for trend <0.04). Conclusion: One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure. PMID:23579222

Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy.

PubMed

Rush, Gavin; O'Donovan, Aoife; Nagle, Laura; Conway, Catherine; McCrohan, AnnMaria; O'Farrelly, Cliona; Lucey, James V; Malone, Kevin M

2016-11-15

Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT. 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion. At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-β than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-β levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-β changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-α and CRP levels were found in relation to melancholia or response to ECT. As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use. Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-β, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotrophin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

Do attachment representations predict depression and anxiety in psychiatrically hospitalized prepubertal children?

PubMed

Goodman, Geoff; Stroh, Martha; Valdez, Adina

2012-01-01

Thirty-six prepubertal inpatients were videotaped completing five stories thematically related to attachment experiences and classified by their attachment representations. Children also completed the Children's Depression Inventory and Diagnostic Interview for Children and Adolescents-Revised. Mothers completed demographic questionnaires. Percentage of secure (B) attachment was only about one tenth of the normative percentage, anxious-ambivalent (C) attachment was between two and three times the normative percentage, and disorganized (D) attachment was almost twice the normative percentage. Both D attachment and the total number of disorganized story responses were associated with negative self-esteem and clinical-range depression. Anxious-avoidant (A) attachment decreased the likelihood, while C and D attachment increased the likelihood, of separation anxiety disorder. Clinical intervention needs to focus on the meaning of parental relationships represented in the child's mind, specifically the negative self-esteem and separation anxiety associated with the lack of felt security provided by the parents.

A framework for evaluating the appropriateness of clinical decision support alerts and responses

PubMed Central

Waitman, Lemuel R; Lewis, Julia B; Wright, Julie A; Choma, David P; Miller, Randolph A; Peterson, Josh F

2011-01-01

Objective Alerting systems, a type of clinical decision support, are increasingly prevalent in healthcare, yet few studies have concurrently measured the appropriateness of alerts with provider responses to alerts. Recent reports of suboptimal alert system design and implementation highlight the need for better evaluation to inform future designs. The authors present a comprehensive framework for evaluating the clinical appropriateness of synchronous, interruptive medication safety alerts. Methods Through literature review and iterative testing, metrics were developed that describe successes, justifiable overrides, provider non-adherence, and unintended adverse consequences of clinical decision support alerts. The framework was validated by applying it to a medication alerting system for patients with acute kidney injury (AKI). Results Through expert review, the framework assesses each alert episode for appropriateness of the alert display and the necessity and urgency of a clinical response. Primary outcomes of the framework include the false positive alert rate, alert override rate, provider non-adherence rate, and rate of provider response appropriateness. Application of the framework to evaluate an existing AKI medication alerting system provided a more complete understanding of the process outcomes measured in the AKI medication alerting system. The authors confirmed that previous alerts and provider responses were most often appropriate. Conclusion The new evaluation model offers a potentially effective method for assessing the clinical appropriateness of synchronous interruptive medication alerts prior to evaluating patient outcomes in a comparative trial. More work can determine the generalizability of the framework for use in other settings and other alert types. PMID:21849334

Autologous Mesenchymal Stem Cells, Applied in a Bioabsorbable Matrix, for Treatment of Perianal Fistulas in Patients With Crohn's Disease.

PubMed

Dietz, Allan B; Dozois, Eric J; Fletcher, Joel G; Butler, Greg W; Radel, Darcie; Lightner, Amy L; Dave, Maneesh; Friton, Jessica; Nair, Asha; Camilleri, Emily T; Dudakovic, Amel; van Wijnen, Andre J; Faubion, William A

2017-07-01

In patients with Crohn's disease, perianal fistulas recur frequently, causing substantial morbidity. We performed a 12-patient, 6-month, phase 1 trial to determine whether autologous mesenchymal stem cells, applied in a bioabsorbable matrix, can heal the fistula. Fistula repair was not associated with any serious adverse events related to mesenchymal stem cells or plug placement. At 6 months, 10 of 12 patients (83%) had complete clinical healing and radiographic markers of response. We found placement of mesenchymal stem cell-coated matrix fistula plugs in 12 patients with chronic perianal fistulas to be safe and lead to clinical healing and radiographic response in 10 patients. ClinicalTrials.gov Identifier: NCT01915927. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Long-Term Response and Remission with Pixantrone in Patients with Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma: Post-Hoc Analysis of the Multicenter, Open-Label, Randomized PIX301 Trial.

PubMed

Pettengell, Ruth; Coiffier, Bertrand; Egorov, Anton; Singer, Jack; Sivcheva, Lilia

2018-06-01

Pixantrone is recommended in relapsed and refractory non-Hodgkin lymphoma (NHL) or heavily pretreated NHL patients. Its conditional approval in Europe was based on results from the open-label, randomized, phase 3 PIX301 study, comparing pixantrone monotherapy with physician's choice of treatment in 140 patients with relapsed or refractory aggressive NHL. This post-hoc analysis of the PIX301 study investigated possible correlations between patient characteristics and clinical response in 17 patients (24%) treated with pixantrone who achieved a complete response (CR) or an unconfirmed complete response (CRu) at study end. These patients (10 male and 7 female) had a median age of 61 (range 41-75) years, and the most common diagnoses were diffuse large B-cell lymphoma (n = 10) and transformed indolent lymphoma (n = 4). Most had received two prior lines of therapy (n = 12). There was wide variation in the time from diagnosis to study entry (219-4777 days). Among the 17 patients who achieved a CR/CRu with pixantrone, 6 had stable or progressive disease as a response to their last regimen, 7 had a partial response, and 4 had a CR/CRu. Four patients from the pixantrone group survived without progression for more than 400 days. Prior response to previous therapies did not appear to affect long-term response to pixantrone. These observations suggest that pixantrone monotherapy in patients with multiply relapsed or refractory aggressive NHL who had received at least two prior therapies can be associated with durable responses and long-term remission, and this may be unrelated to the clinical response to the last therapy.

Practicum and clinical experiences: postpracticum students' views.

PubMed

Ralph, Edwin; Walker, Keith; Wimmer, Randolph

2009-08-01

The clinical or practicum component of preservice undergraduate education across all disciplines typically is rated by prebaccalaureate students as the most important phase of their entire professional preparation. This study collected e-mail survey responses from 63 post-practicum nursing students who had just completed their culminating fourth-year clinical course. Students identified the most positive and the most negative aspects of that final practicum experience. These responses were compared with those reported by postpracticum students from the disciplines of engineering and teacher education. The cross-disciplinary similarity of these data related to postpracticum students' perceptions of this experiential learning phase of their preservice professional training was noted. The student voice provides a critical dimension to the program-enhancement process for all professional disciplines, and practicum organizers across the disciplines should value such student input and collaborate to improve the clinical phase of preservice education for all professions. Copyright 2009, SLACK Incorporated.

Does a Therapist's World View Matter?

PubMed

Peteet, John R; Rodriguez, Vithya B; Herschkopf, Marta D; McCarthy, Alyssa; Betts, Jennifer; Romo, Stephanie; Michael Murphy, J

2016-06-01

While past research indicates that mental health professionals are less religious than the public they serve, little is known about the implications of therapists' world views for their practice. In this study, approximately 50 therapists completed surveys that assessed self-identification in relation to spirituality, religion, and/or world view; how relevant they considered their patients' and their own world views; and responses to clinical vignettes involving issues arising in treatment. While a minority considered themselves religious, a majority indicated that they considered themselves moderately or very spiritual. When asked how they would respond to a series of clinical vignettes involving topics such as assisted suicide and encouraging the use of spiritual resources, responses varied significantly by world view. Respondents endorsed several factors limiting the integration of religion/spiritualities/world views into their clinical work. These data raise questions about how to further explore the clinical relevance of the therapist's world view.

Medical Student Sexuality: How Sexual Experience and Sexuality Training Impact U.S. and Canadian Medical Students’ Comfort in Dealing with Patients’ Sexuality in Clinical Practice

PubMed Central

Shindel, Alan W.; Ando, Kathryn A.; Nelson, Christian J.; Breyer, Benjamin N.; Lue, Tom F.; Smith, James F.

2013-01-01

Purpose To determine factors associated with students’ comfort in addressing patients’ sexuality in the clinical context. Method The authors invited students enrolled in MD-degree-granting and osteopathic medical schools in the United States and Canada to participate in an anonymous Internet survey between February and July 2008. The survey assessed ethnodemographic factors and sexual history. Respondents also completed the Center for Epidemiologic Studies Depression Scale. Male respondents completed the International Index of Erectile Function and the Premature Ejaculation Diagnostic Tool. Female respondents completed the Female Sexual Function Index and the Index of Sex Life. The authors used descriptive statistics, ANOVA, and multivariable logistic regression to analyze responses. Results The authors’ analyses included 2,261 completed survey responses: 910 from men, 1,343 from women, and 8 from individuals who self-identified as “other” gendered. Over 53% of respondents (n = 1,206) stated that they felt they had not received sufficient training in medical school to address sexual concerns clinically. Despite this, 81% of students (n = 1,827) reported feeling comfortable dealing with their patients’ sexuality issues. Students with limited sexual experience, students at risk for sexual problems, and students who felt that they had not been trained adequately were less likely to report being comfortable talking to patients about sexual health issues. Conclusions Perception of inadequate sexuality training in medical school and personal issues pertaining to sex may be associated with students’ difficulty in addressing patients’ sexuality. Adequate training is preeminently associated with feeling comfortable addressing patients’ sexuality and should be a priority for medical education. PMID:20671459

The treatment of personality disorder in Jamaica with psychohistoriographic brief psychotherapy.

PubMed

Hickling, F W

2013-01-01

To assess the clinical outcome of patients with personality disorder, receiving treatment with psychohistoriographic brief psychotherapy (PBP). Patients seen in the author's private practice from 1974-2010 with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) personality disorder diagnosis were treated with PBP. Demographic, clinical responses and one-year clinical outcome measures were disaggregated and analysed, using SPSS, version 17. One hundred patients completed treatment with PBP, male:female 34:64; mean age of 35.86 ± 10.28 (range 16 - 66) years. Forty-five per cent were married, 73% were of predominantly African racial origin, with 59% from socio-economic class (SEC) I and 39% from SEC II and III. The presenting complaints were interpersonal conflict (35%), anxiety (21%) and depressed mood (20%). Major depression (30%), substance abuse disorder (18%) and generalized anxiety disorder (13%) were the most common Axis I diagnoses. Histrionic personality disorder (39%) and avoidant personality disorder (35%) were the main Axis II diagnoses. Psychohistoriography was completed with all patients, and charted by 96%. Transference variants were experienced by all patients and worked through with 87%. The quadranting process was completed by 42% with goal setting instituted by 96% and actualization scoring fully completed by 34%. A continuous exercise programme was instituted by all patients, and was maintained by 56% at one-year follow-up. Ninety-four per cent reported fair (10%), good (68%) to very good/excellent (16%) improvement on completion of PBP, with 72% assessed as maintaining fair to good clinical improvement by the therapist at one-year follow-up. Patients with personality disorders showed clinical improvement one year after being treated with psychohistoriographic brief psychotherapy.

225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer.

PubMed

Kratochwil, Clemens; Bruchertseifer, Frank; Giesel, Frederik L; Weis, Mirjam; Verburg, Frederik A; Mottaghy, Felix; Kopka, Klaus; Apostolidis, Christos; Haberkorn, Uwe; Morgenstern, Alfred

2016-12-01

Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to 225 Ac-PSMA-617 therapy. 68 Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of 225 Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with 68 Ga-PSMA-11 PET/CT. Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect. Targeted α-therapy with 225 Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A comparison of placebo response with major depressive disorder in patients recruited through newspaper advertising versus consultation referrals.

PubMed

Miller, C A; Hooper, C L; Bakish, D

1997-01-01

Recent evidence indicates few differences between patients recruited through advertising and by consultation referral, and there is some suggestion that those recruited through advertising are more representative of the target community population. However little has been reported on differences in placebo response and compliance in these two patient groups. We conducted a retrospective chart review of 49 patients with major depressive disorder (MDD), recruited through advertising or consultation, randomized to placebo in five clinical trials. Variables included demographics, clinical history, efficacy, compliance, and completion data. Homogeneity was demonstrated for most variables. Differences in placebo groups included significantly lower Hamilton Rating Scale for Depression (HAM-D) scores for the advertisement group throughout the trials. Advertisement patients were also more likely to be early placebo responders and in remission at Days 14 and 28. No differences were found in completion rates or reasons for early termination. Compliance was excellent for both groups. Early placebo response of the advertisement group reinforces the need for trials of at least 8 weeks. In addition, consultation patients may have a more severe illness and be treatment resistant, suggesting they are less generalizable to community practice populations.

Preliminary study of family accommodation in youth with autism spectrum disorders and anxiety: Incidence, clinical correlates, and behavioral treatment response.

PubMed

Storch, Eric A; Zavrou, Sophia; Collier, Amanda B; Ung, Danielle; Arnold, Elysse B; Mutch, P Jane; Lewin, Adam B; Murphy, Tanya K

2015-08-01

Anxiety symptoms are common in youth with autism spectrum disorders (ASD) and directly associated with symptom severity and functional impairment. Family accommodation occurs frequently among individuals with obsessive-compulsive and anxiety disorders; to date, no data exist on the nature and correlates of family accommodation in youth with ASD and anxiety, as well as its relationship to cognitive-behavioral therapy outcome. Forty children with ASD and a comorbid anxiety disorder participated. Clinicians administered measures of ASD and anxiety disorder caseness, anxiety symptom severity, and family accommodation; parents completed questionnaires assessing social responsiveness, internalizing and externalizing behaviors, and functional impairment. A subsample of youth (n = 24) completed a course of cognitive-behavioral therapy. Family accommodation was common and positively correlated with anxiety symptom severity, but not functional impairment, general internalizing symptoms, externalizing behavior, or social responsiveness. Family accommodation decreased following cognitive-behavioral therapy with decreases in family accommodation being associated with decreases in anxiety levels. Treatment responders reported lower family accommodation frequency and lower parent impact relative to non-responders. Clinical implications of this study in assessing and psychotherapeutically treating youth with ASD and comorbid anxiety are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

A longitudinal study of the Friedreich Ataxia Impact Scale.

PubMed

Tai, Geneieve; Yiu, Eppie M; Corben, Louise A; Delatycki, Martin B

2015-05-15

Quality of life in Friedreich ataxia (FRDA) has been explored using various generic health status measurement tools, most commonly the Short Form Health Survey Version 2 (SF-36v2). The tool did not address many specific issues related to disease impact in people with FRDA. The Friedreich Ataxia Impact Scale (FAIS) was developed to examine clinically relevant areas in FRDA. The aims of the current study were to assess the relationship between the FAIS and clinical characteristics of FRDA, as well as to determine the responsiveness of the FAIS to change over one and two years. One hundred and four individuals with FRDA, homozygous for the GAA expansion in intron 1 of FXN, completed the FAIS at baseline. Seventy individuals completed the FAIS again 12 months later and 49 completed the FAIS at 24 months. Clinical parameters and neurologic scales (Friedreich Ataxia Rating Scale (FARS)) were also recorded. The total FARS score, onset age and disease duration correlated significantly with FAIS subscales measuring symptoms and physical functioning. The physical and mental summary measures of the SF-36 V2 also correlated well with the FAIS subscales. Speech was the only subscale that demonstrated significant change over one and two years. The FAIS provides valuable insight into the perspective of individuals with FRDA on their health status, and is an important measure of morbidity. It has, however, limited responsiveness to change and its use in intervention studies is questionable. Copyright © 2015 Elsevier B.V. All rights reserved.

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma.

PubMed

Joseph, Jocelyn; Zobniw, Chrystia; Davis, Jennifer; Anderson, Jaime; Trinh, Van Anh

2018-04-01

To summarize the clinical development of avelumab and its clinical relevance in metastatic Merkel cell carcinoma (MCC). An English-language literature search using PubMed was performed using the terms avelumab, anti-PD-1, anti-PD-L1, and MCC from January of 1950 to March 2018. Data were also obtained from package inserts, meeting abstracts, and clinical registries. All relevant published articles of avelumab were reviewed. Clinical trial registries and meeting abstracts were used for information about ongoing trials. Avelumab is a fully human monoclonal antibody that inhibits programmed death ligand-1, which reverses T-cell exhaustion and induces antitumor responses. Avelumab is safe and effective in previously treated metastatic MCC based on a phase II trial of previously treated patients with objective response rates in 28 of 88 patients, including 10 complete responses and 19 partial responses. Median overall survival (OS) was 12.9 months, and 1-year progression-free survival and OS were 30% and 52%, respectively. Grade 3 treatment-related side effects included lymphopenia (2 patients), serum creatine phosphokinase increase (1 patient), aminotransferase elevation (1 patient), and serum cholesterol increase (1 patient). Relevance to Patient Care and Clinical Practice: This review outlines the pharmacology and clinical trial data for avelumab in metastatic MCC and guides clinicians on avelumab's place in therapy. Avelumab is the first Food and Drug Administration-approved medication for metastatic MCC and provides an advantage of durable responses and possibly improved tolerability compared with traditional platinum-based chemotherapy. Clinical trials are under way to expand its utility into the adjuvant and frontline settings.

Efficacy of skin-directed therapy for cutaneous metastases from advanced cancer: a meta-analysis.

PubMed

Spratt, Daniel E; Gordon Spratt, Elizabeth A; Wu, Shenhong; DeRosa, Antonio; Lee, Nancy Y; Lacouture, Mario E; Barker, Christopher A

2014-10-01

To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I(2) tests. After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed. © 2014 by American Society of Clinical Oncology.

Clinical responsiveness of self-report functional assessment measures for children with juvenile idiopathic arthritis undergoing intraarticular corticosteroid injections.

PubMed

Brown, G Ted; Wright, F Virginia; Lang, Bianca A; Birdi, Nina; Oen, Kim; Stephens, Derek; McComas, Joan; Feldman, Brian M

2005-12-15

The Childhood Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Functional Assessment Report (JAFAR), and Juvenile Arthritis Functional Status Index (JASI) are widely used functional measures for juvenile idiopathic arthritis (JIA) that differ in content, format, and completion time. We compared the responsiveness and child-parent agreement of the JAFAR, CHAQ, and JASI in a prospective, multicenter study. Children and adolescents from 5 rheumatology centers were enrolled. Subjects were about to undergo therapy (intraarticular corticosteroid injections [IAS] and methotrexate or hip surgery (MTX/hip]) expected to produce a functional improvement. All subjects were studied before the intervention and at 6 weeks and 6 months posttreatment. At each study visit, the 3 measures were administered in randomized, balanced order to both parents and children. A total of 92 subjects (mean age 12.8 years) were enrolled in the study, 74 of which were in the IAS group. The responsiveness of all 3 measures was moderate to strong. The standardized response mean at 6 weeks for the IAS group on the JAFAR, CHAQ, and JASI was 0.41 (95% confidence interval [95% CI] 0.18, 0.64), 0.70 (95% CI 0.47, 0.93), and 0.36 (95% CI 0.13, 0.59), respectively. The CHAQ was somewhat more responsive to change at 6 weeks (IAS group: relative efficiency 0.34 [JAFAR], 0.27 [JASI]), but less responsive at 6 months (MTX/hip group: relative efficiency 5.1 [JAFAR], 3.9 [JASI]). All 3 questionnaires showed acceptable parent-child agreement, and overall, there were few differences between the 3 questionnaires. The functional outcome measures currently used for JIA are all adequately responsive for use in trials or in the clinic setting. The choice of which measure to use should therefore be based on the time available for completion, the intended clinical/research use, and the depth of content required.

Absolute number of new lesions on 18F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab.

PubMed

Anwar, Hoda; Sachpekidis, Christos; Winkler, Julia; Kopp-Schneider, Annette; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

2018-03-01

Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of 18 F-FDG PET/CT, using the patients' clinical response as reference. The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent 18 F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged 18 F-FDG-avid lesions, as well as on the SUV changes after therapy. The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged 18 F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of 18 F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). Our results show that a cut-off of four newly emerged 18 F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical response. Validation of these results in larger cohorts of patients is warranted.

Simulation-Based Dysphagia Training: Teaching Interprofessional Clinical Reasoning in a Hospital Environment.

PubMed

Miles, Anna; Friary, Philippa; Jackson, Bianca; Sekula, Julia; Braakhuis, Andrea

2016-06-01

This study evaluated hospital readiness and interprofessional clinical reasoning in speech-language pathology and dietetics students following a simulation-based teaching package. Thirty-one students participated in two half-day simulation workshops. The training included orientation to the hospital setting, part-task skill learning and immersive simulated cases. Students completed workshop evaluation forms. They filled in a 10-question survey regarding confidence, knowledge and preparedness for working in a hospital environment before and immediately after the workshops. Students completed written 15-min clinical vignettes at 1 month prior to training, immediately prior to training and immediately after training. A marking rubric was devised to evaluate the responses to the clinical vignettes within a framework of interprofessional education. The simulation workshops were well received by all students. There was a significant increase in students' self-ratings of confidence, preparedness and knowledge following the study day (p < .001). There was a significant increase in student overall scores in clinical vignettes after training with the greatest increase in clinical reasoning (p < .001). Interprofessional simulation-based training has benefits in developing hospital readiness and clinical reasoning in allied health students.

The Patient Educator Presentation in Dental Education: Reinforcing the Importance of Learning About Rare Conditions.

PubMed

Edwards, Paul C; Graham, Jasmine; Oling, Rebecca; Frantz, Kate E

2016-05-01

The aim of this study was to determine whether a patient educator presentation (PEP) on pemphigus vulgaris would increase second-year dental students' awareness of the importance of learning about rare conditions and improve their retention of rare disease knowledge. The study involved students' subjective assessments of a PEP experience at two U.S. dental schools. In this mixed methods study, cross-sectional data were obtained by surveys and in-depth interviews. Questions focused on students' assessment of the messages acquired from the PEP and its likely impact on their future clinical care. At University 1, students completed paper surveys with open-ended questions and participated in a focus group. At University 2, students completed an online survey consisting of rating scale and open-ended questions. Responses to open-ended questions were categorized into themes. At University 1, 79 students (out of a possible 102; response rate 77.5%) completed the survey, and an additional ten students participated in a focus group. At University 2, 30 students (out of a possible 104; response rate 28.8%) completed the survey. At Universities 1 and 2, 88% and 100%, respectively, of respondents stated the PEP would influence their future clinical decision making. The vast majority of respondents (94% and 100% at University 1 and University 2, respectively) were of the opinion that the personal testimonial from a patient would help them recall information about pemphigus vulgaris in five years' time. Respondents from both universities commented that the PEP emphasized the importance of not dismissing a patient's concerns. These results suggest that a presentation by a patient with a rare condition can be an effective educational tool for preclinical dental students.

EXTRA-A Multicenter Phase II Study of Chemoradiation Using a 5 Day per Week Oral Regimen of Capecitabine and Intravenous Mitomycin C in Anal Cancer

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

Glynne-Jones, Rob; Meadows, Helen; UCL Cancer Trials Centre, London

Purpose: 5-Fluorouracil (5-FU) + mitomycin C (MMC)-based chemoradiotherapy is standard treatment for patients with epidermoid anal carcinoma. Clinical trials in other cancers have confirmed 5-FU can successfully be replaced by the oral fluoropyrimidine capecitabine. This phase II trial aimed to determine the feasibility, toxicity, and efficacy of capecitabine, MMC and radiotherapy (RT) in anal cancer patients. Methods and Materials: Radiotherapy comprised the schedule of the UK Anal Cancer Trial (ACT) II trial (50.4 Gy in 28 fractions of 1.8 Gy). With MMC (12 mg/m{sup 2}) on Day 1 and capecitabine on each RT treatment day in two divided doses (825more » mg/m{sup 2} b.i.d). The endpoints were complete response at 4 weeks, local control at 6 months and toxicity. Results: Thirty-one patients entered the trial. The median age was 61 years (range 45-86) with 14 males and 17 females. Compliance with chemotherapy with no dose interruptions or delays was 68%, and with RT was 81%. Eighteen (58%) patients completed both modalities of treatment as planned. Dose-limiting Grade 3 or 4 diarrhea was seen in 1 of 31 patients. Three patients experienced Grade 3 neutropenia. There were no treatment-related deaths. Four weeks following completion of chemoradiation, 24 patients (77%) had a complete clinical response, and 4 (16%) a partial response. With a median follow-up of 14 months, three locoregional relapses occurred. Conclusions: Capecitabine with MMC and RT in with patients anal carcinoma is well tolerated, with minimal toxicity and acceptable compliance. We recommend testing this schedule in future national Phase III studies in anal cancer.« less

Association between new-onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor therapy in phase I clinical trials.

PubMed

Bilen, Mehmet Asim; Patel, Amy; Hess, Kenneth R; Munoz, Javier; Busaidy, Naifa L; Wheler, Jennifer J; Janku, Filip; Falchook, Gerald S; Hong, David S; Meric-Bernstam, Funda; Habra, Mouhammed Amir; Naing, Aung

2016-07-01

Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction has been identified as an important but manageable adverse effect of targeted therapy. Several studies have suggested that patients who develop hypothyroidism respond better to TKIs, but this relationship is not well elucidated. We evaluated the relationship between new-onset hypothyroidism and clinical response in patients with advanced cancers treated with TKIs at our institution. We retrospectively reviewed records for patients from four clinical trials that included at least one TKI  therapy between January 2006 and December 2011. Patients with preexisting thyroid disease, including thyroid cancer, hypothyroidism, or hyperthyroidism, were excluded. Analysis of 197 patients was performed. Response was determined using RECIST 1.0. Clinical benefit was described as complete response, partial response, or stable disease greater than 4 months. Multivariable logistic regression analysis was performed to correlate patient characteristics with clinical response. The median age for the 197 patients was 58 years (range, 13-85 years), and 56 % were female. Of the 197 patients, 52 (26 %) developed hypothyroidism after therapy. Clinical benefit rates were 50 % in patients with new-onset hypothyroidism versus 34 % in patients without hypothyroidism. In the univariate model, the odds ratio (OR) for new-onset hypothyroidism was 1.9 [95 % confidence interval (CI) (1.0, 3.6) and p = 0.05]. We grouped tumor types into six categories (breast, colorectal carcinoma, melanoma, non-small cell lung cancer, pancreas, and other). When adjusted for tumor type, age (>50 years) and sex, the OR was 2.9 [95 % CI (1.3, 6.5) and p = 0.012] for new-onset hypothyroidism. New-onset hypothyroidism was associated with favorable clinical response in patients who received TKI treatment.

Short-Term Cognitive-Behavioural Group Treatment for Hoarding Disorder: A Naturalistic Treatment Outcome Study.

PubMed

Moulding, Richard; Nedeljkovic, Maja; Kyrios, Michael; Osborne, Debra; Mogan, Christopher

2017-01-01

The study aim was to test whether a 12-week publically rebated group programme, based upon Steketee and Frost's Cognitive Behavioural Therapy-based hoarding treatment, would be efficacious in a community-based setting. Over a 3-year period, 77 participants with clinically significant hoarding were recruited into 12 group programmes. All completed treatment; however, as this was a community-based naturalistic study, only 41 completed the post-treatment assessment. Treatment included psychoeducation about hoarding, skills training for organization and decision making, direct in-session exposure to sorting and discarding, and cognitive and behavioural techniques to support out-of-session sorting and discarding, and nonacquiring. Self-report measures used to assess treatment effect were the Savings Inventory-Revised (SI-R), Savings Cognition Inventory, and the Depression, Anxiety and Stress Scales. Pre-post analyses indicated that after 12 weeks of treatment, hoarding symptoms as measured on the SI-R had reduced significantly, with large effect sizes reported in total and across all subscales. Moderate effect sizes were also reported for hoarding-related beliefs (emotional attachment and responsibility) and depressive symptoms. Of the 41 participants who completed post-treatment questionnaires, 14 (34%) were conservatively calculated to have clinically significant change, which is considerable given the brevity of the programme judged against the typical length of the disorder. The main limitation of the study was the moderate assessment completion rate, given its naturalistic setting. This study demonstrated that a 12-week group treatment for hoarding disorders was effective in reducing hoarding and depressive symptoms in an Australian clinical cohort and provides evidence for use of this treatment approach in a community setting. Copyright © 2016 John Wiley & Sons, Ltd. A 12-week group programme delivered in a community setting was effective for helping with hoarding symptoms with a large effect size. Hoarding beliefs (emotional attachment and responsibility) and depression were reduced, with moderate effect sizes. A third of all participants who completed post-treatment questionnaires experienced clinically significant change. Suggests that hoarding CBT treatment can be effectively translated into real-world settings and into a brief 12-session format, albeit the study had a moderate assessment completion rate. Copyright © 2016 John Wiley & Sons, Ltd.

Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia.

PubMed

Konopleva, Marina; Pollyea, Daniel A; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L; Blum, William; DiNardo, Courtney D; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

2016-10-01

We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response or complete response with incomplete blood count recovery. Six (19%) patients had BCL2-sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. Venetoclax monotherapy demonstrated clinical activity in patients with AML (relapsed/refractory or unfit for intensive chemotherapy) with a tolerable safety profile in this phase II study. Predictive markers of response consistent with BCL2 dependence were identified. Clinical and preclinical findings provide a compelling rationale to evaluate venetoclax combined with other agents in AML. Cancer Discov; 6(10); 1106-17. ©2016 AACRSee related commentary by Pullarkat and Newman, p. 1082This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration

PubMed Central

Bossuyt, V.; Provenzano, E.; Symmans, W. F.; Boughey, J. C.; Coles, C.; Curigliano, G.; Dixon, J. M.; Esserman, L. J.; Fastner, G.; Kuehn, T.; Peintinger, F.; von Minckwitz, G.; White, J.; Yang, W.; Badve, S.; Denkert, C.; MacGrogan, G.; Penault-Llorca, F.; Viale, G.; Cameron, D.; Earl, Helena; Alba, Emilio; Lluch, Ana; Albanell, Joan; Amos, Keith; Biernat, Wojciech; Bonnefoi, Hervé; Buzdar, Aman; Cane, Paul; Pinder, Sarah; Carson, Lesley; Dickson-Witmer, Diana; Gong, Gyungyub; Green, Jimmy; Hsu, Chih-Yi; Tseng, Ling-Ming; Kroep, Judith; Leitch, A. Marilyn; Sarode, Venetia; Mamounas, Eleftherios; Marcom, Paul Kelly; Nuciforo, Paolo; Paik, Soonmyung; Peg, Vicente; Peston, David; Pierga, Jean-Yves; Quintela-Fandino, Miguel; Salgado, Roberto; Sikov, William; Thomas, Jeremy; Unzeitig, Gary; Wesseling, Jelle

2015-01-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. PMID:26019189

The Availability Heuristic: A Redux

ERIC Educational Resources Information Center

Rubel, Laurie H.

2007-01-01

This article reports on a subset of results from a larger study which examined middle and high school students' probabilistic reasoning. Students in grades 5, 7, 9, and 11 at a boys' school (n = 173) completed a Probability Inventory, which required students to answer and justify their responses to ten items. Supplemental clinical interviews…

Demodex Folliculitis of the Scalp: Clinicopathological Study of an Uncommon Entity.

PubMed

Helou, Wissam; Avitan-Hersh, Emily; Bergman, Reuven

2016-09-01

Demodex is a saprophytic mite in humans commonly present in the pilosebaceous units, which has been implicated as a pathogen in several skin conditions. The clinical presentation and histopathology of Demodex folliculitis of the scalp have been described in only a few case reports. This study was performed to further elucidate the clinicopathological features of this entity. We have studied 333 consecutively submitted scalp biopsies performed for hair loss and alopecia. All specimens were completely step-sectioned. Biopsies with Demodex mites were further studied histopathologically, and the patients' clinical files were reviewed. There were 17 biopsies (5.1%) with Demodex in at least 1 pilosebaceous unit. Based on the clinical presentation, histopathology, and response to therapy, Demodex was considered to be nonpathogenic in 13 cases. The remaining 4 cases were characterized by hair loss, scalp erythema, scales, and pustules. There were 2 or more pilosebaceous units with Demodex along mononuclear and/or neutrophilic infiltrates around and in the involved follicles and occasionally granulomas. All 4 cases responded completely to metronidazole therapy. In conclusion, Demodex is infrequently found in scalp biopsies for hair loss and alopecia, and, in most cases, it does not seem to be pathogenic. Occasionally, however, it is associated with folliculitis characterized by hair loss, erythema, scales, and pustules clinically; neutrophilic and/or mononuclear-cell folliculitis with occasional granulomas histopathologically; and a prompt response to anti-Demodex therapy.

Extrarenal perivascular epithelioid cell tumors (PEComas) respond to mTOR inhibition: Clinical and molecular correlates

PubMed Central

Dickson, Mark A.; Schwartz, Gary K.; Antonescu, Cristina R.; Kwiatkowski, David J.; Malinowska, Izabela A.

2012-01-01

Perivascular epithelioid cell tumors (PEComas) are a group of rare mesenchymal tumors that typically show both melanocytic and smooth muscle cell features. Some types of PEComa are seen at high frequency in tuberous sclerosis complex (TSC). The TSC1 and TSC2 genes are commonly mutated in both TSC-associated and sporadic PEComas, and mTOR signaling pathway activation is also common in these tumors. Preliminary reports have indicated that the mTOR inhibitors sirolimus and related drugs have activity in some patients with non-TSC-associated PEComa. Here we report on the use of these medications in the treatment of five consecutive patients with extrarenal non-pulmonary PEComas seen at one institution. Three complete responses, one partial response and one case of progression were seen. Molecular studies identified TSC2 aberrations in four of these patients, and TFE3 translocation was excluded in the resistant case. A review of all published cases as well as those reported here indicates that partial or complete response was seen in 6 of 11 PEComas, with 5 of the 6 having a complete response. These findings highlight the consistent though incomplete activity of mTOR inhibitors in the treatment of PEComas. PMID:22927055

Higher Dose Imatinib for Children With De Novo Chronic Phase Chronic Myelogenous Leukemia: A Report From the Children’s Oncology Group

PubMed Central

Champagne, Martin A.; Fu, Cecilia H.; Chang, Myron; Chen, Helen; Gerbing, Robert B.; Alonzo, Todd A.; Cooley, Linda D.; Heerema, Nyla A.; Oehler, Vivian; Wood, Charlotte; French, Mary Ellen; Arceci, Robert J.; Smith, Franklin O.; Bernstein, Mark L.

2016-01-01

Purpose To determine the efficacy of imatinib in children with newly diagnosed chronic phase (CP) chronic myelogenous leukemia (CML). Methods This was an open label, multi-center phase II clinical trial. Courses were defined as consecutive 28-day intervals. Oral imatinib was administered daily at 340 mg/m2 without interruption in the absence of toxicity. Results Fifty-one children received 978 28-day courses of imatinib. The most common toxicities encountered were hematologic. Forty-one patients (80%) achieved a complete hematologic response by the end of course 2. Nineteen children (38%) obtained a complete cytogenetic response (CCyR) at the end of course 3. Overall, 72% achieved CCyR at a median time of 5.6 months. The rate of complete molecular response (>3 log reduction) was 27%. Progression-free and overall survival at 3 years were 72% ± 6.4% and 92% ± 3.9%, respectively. Conclusions Daily oral imatinib at a dose of 340 mg/m2 is well tolerated in children. In addition, imatinib therapy is effective in inducing a high percent of hematologic, cytogenetic and molecular responses, comparable to adults with CML. PMID:21465636

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

PubMed

García, J R; Cozar, M; Soler, M; Bassa, P; Riera, E; Ferrer, J

2016-01-01

To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Text messaging to support off-campus clinical nursing facilitators: a descriptive survey.

PubMed

Howard, Christine; Fox, Amanda R; Coyer, Fiona

2014-06-01

Managing large student cohorts can be a challenge for university academics, coordinating these units. Bachelor of Nursing programmes have the added challenge of managing multiple groups of students and clinical facilitators whilst completing clinical placement. Clear, time efficient and effective communication between coordinating academics and clinical facilitators is needed to ensure consistency between student and teaching groups and prompt management of emerging issues. This study used a descriptive survey to explore the use of text messaging via a mobile phone, sent from coordinating academics to off-campus clinical facilitators, as an approach to providing direction and support. The response rate was 47.8% (n=22). Correlations were found between the approachability of the coordinating academic and clinical facilitator perception that, a) the coordinating academic understood issues on clinical placement (r=0.785, p<0.001), and b) being part of the teaching team (r=0.768, p<0.001). Analysis of responses to qualitative questions revealed three themes: connection, approachability and collaboration. This study demonstrates that use of regular text messages improves communication between coordinating academics and clinical facilitators. Findings suggest improved connection, approachability and collaboration between the coordinating academic and clinical facilitation staff. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adoptive Cell Therapy for the Treatment of Patients with Metastatic Melanoma

PubMed Central

Rosenberg, Steven A.; Dudley, Mark E.

2012-01-01

Adoptive cell therapy (ACT) is the best available treatment for patients with metastatic melanoma. In a recent series of three consecutive clinical trials using increasing lymphodepletion prior to infusion of autologous tumor infiltrating lymphocytes (TIL), objective response rates between 49% and 72% were seen. Persistence of infused cells in the circulation at one month was highly correlated with anti-tumor response as was the mean telomere length of the cells infused and the number of CD8+ CD27+ cells infused. Responses occur at all sites and appear to be durable with many patients in ongoing response beyond three years. In the most recent trial of 25 patients receiving maximum lymphodepletion, seven of the 25 patients (28%) achieved a complete response. Of the 12 patients in the three trials who achieved a complete response all but one are ongong between 18 and 75 months. We recently demonstrated that ACT using autologous lymphocytes genetically modified to express anti-tumor T cell receptors can mediate tumor regression and this approach is now being applied to patients with common epithelial cancers. PMID:19304471

Clinical effects of laser immunotherapy on metastatic cancer patients

NASA Astrophysics Data System (ADS)

Naylor, Mark F.; Lam, Anh K.; Bahavar, Cody F.; Nordquist, Robert E.; Chen, Wei R.

2016-03-01

Clinical trials of late-stage breast cancer patients and late-stage melanoma patients treated by laser immunotherapy (LIT) have shown promising results. In a 2010 study of Li et al, eleven late-stage melanoma patients received LIT in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. Long-term, positive response was observed in six patients. All lesions in the treatment area of the patients responded to LIT, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%.2 In 2011, Li et al, treated ten late stage breast cancer patients with LIT.1 In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%.1 This review demonstrates that LIT is safe and well tolerated, so it can be easily applied on an outpatient basis and can be combined with other pharmaceutical modalities to improve the therapeutic response of metastatic cancers.

IL-2 and Beyond in Cancer Immunotherapy.

PubMed

Wrangle, John M; Patterson, Alicia; Johnson, C Bryce; Neitzke, Daniel J; Mehrotra, Shikhar; Denlinger, Chadrick E; Paulos, Chrystal M; Li, Zihai; Cole, David J; Rubinstein, Mark P

2018-02-01

The development of the T- and natural killer (NK) cell growth factor IL-2 has been a sentinel force ushering in the era of immunotherapy in cancer. With the advent of clinical grade recombinant IL-2 in the mid-1980s, oncologists could for the first time directly manipulate lymphocyte populations with systemic therapy. By itself, recombinant IL-2 can induce clinical responses in up to 15% of patients with metastatic cancer or renal cell carcinoma. When administered with adoptively transferred tumor-reactive lymphocytes, IL-2 promotes T cell engraftment and response rates of up to 50% in metastatic melanoma patients. Importantly, these IL-2-driven responses can yield complete and durable responses in a subset of patients. However, the use of IL-2 is limited by toxicity and concern of the expansion of T regulatory cells. To overcome these limitations and improve response rates, other T cell growth factors, including IL-15 and modified forms of IL-2, are in clinical development. Administering T cell growth factors in combination with other agents, such as immune checkpoint pathway inhibitors, may also improve efficacy. In this study, we review the development of T- and NK cell growth factors and highlight current combinatorial approaches based on these reagents.

Experiences and perceptions of online continuing professional development among clinicians in sub-Saharan Africa.

PubMed

Feldacker, Caryl; Jacob, Sheena; Chung, Michael H; Nartker, Anya; Kim, H Nina

2017-12-29

Limitations in healthcare worker (HCW) capacity compound the burden of dual TB and HIV epidemics in sub-Saharan Africa. To fill gaps in knowledge and skills, effective continuing profession development (CPD) initiatives are needed to support practicing HCWs reach high standards of care. e-learning opportunities can bring expert knowledge to HCWs in the field and provide a flexible learning option adaptable to local settings. Few studies provide insight into HCW experiences with online CPD in the developing country context. An online survey using both close-ended and free response was conducted to HCWs in sub-Saharan Africa who completed the University of Washington (UW) School of Medicine online graduate course, "Clinical Management of HIV." Associations between respondent characteristics (age, gender, rural/urban, job title) and learning preferences, course barriers, and facilitators with an emphasis on online courses were examined using chi-square. Covariates significant at the p < 0.05 were analyzed using multivariable logistic regression. Responses to open-ended comments were analyzed using simplified grounded theory. Of 2,299 former students, 464 (20%) HCWs completed surveys from 13 countries: about half were women. Physicians (33%), nurses (27%), and clinical officers (30%) responded mostly from urban areas (67%) and public institutions (69%). Sixty-two percent accessed the online course from work, noting that slow (55%) or limited (41%) internet as well as lack of time (53%) were barriers to course completion. Women (p < 0.001) and HCWs under age 40 (p = 0.007) were more likely to prefer learning through mentorship than men or older HCWs. Respondents favored group discussion (46%), case studies (42%), and self-paced Internet/computer-based learning (39%) and clinical mentorship (37%) when asked to choose 3 preferred learning modalities. Free-response comments offered additional positive insights into the appeal of online courses by noting the knowledge gains, the flexibility of format, a desire for recognition of course completion, and a request for additional online coursework. Online CPD opportunities were accepted across a diverse group of HCWs from sub-Saharan Africa and should be expanded to provide more flexible opportunities for self-initiated learning; however, these need to be responsive to the limited resources of those who seek these courses.

Use of a Self-Instructional Radiographic Anatomy Module for Dental Hygiene Faculty Calibration.

PubMed

Brame, Jennifer L; AlGheithy, Demah Salem; Platin, Enrique; Mitchell, Shannon H

2017-06-01

Purpose: Dental hygiene educators often provide inconsistent instruction in clinical settings and various attempts to address the lack of consistency have been reported in the literature. The purpose of this pilot study was to determine if the use of a use of a self-instructional, radiographic anatomy (SIRA) module improved DH faculty calibration regarding the identifica-tion of normal intraoral and extraoral radiographic anatomy and whether its effect could be sustained over a period of four months. Methods: A convenience sample consisting of all dental hygiene faculty members involved in clinical instruction (N=23) at the University of North Carolina (UNC) was invited to complete the four parts of this online pilot study: a pre-test, review of the SIRA module, an immediate post-test, and a four-month follow-up post-test. Descriptive analyses, the Friedman's ANOVA, and the exact form of the Wilcoxon-Signed-Rank test were used to an-alyze the data. Level of significance was set at 0.05. Participants who did not complete all parts of the study were omitted from data analysis comparing the pre to post-test performance. Results: The pre-test response rate was 73.9% (N=17), and 88.2% (N=15) of those initial participants completed both the immediate and follow-up post-tests. Faculty completing all parts of the study consisted of: 5 full-time faculty, 5 part-time faculty, and 5 graduate teaching assistants. The Friedman's ANOVA revealed no statistically significant difference (P=0.179) in percentages of correct responses between the three tests (pre, post and follow-up). The exact form of the Wilcoxon-Signed-Rank test revealed marginal significance when comparing percent of correct responses at pre-test and immediate post-test (P=0.054), and no statistically significant difference when comparing percent of correct responses at immediate post-test and the follow-up post-test four months later (P=0.106). Conclusions: Use of a SIRA module did not significantly affect DH faculty test performance. Lack of statistical significance in the percentages of correct responses between the three tests may have been affected by the small number of participants completing all four parts of the study (N=15). Additional research is needed to identify and improve methods for faculty calibration. Copyright © 2017 The American Dental Hygienists’ Association.

Effects of diabetes mellitus on the clinical presentation and treatment response in tuberculosis.

PubMed

Leung, Chi C; Yew, Wing W; Mok, Thomas Y W; Lau, Kam S; Wong, Chi F; Chau, Chi H; Chan, Chi K; Chang, Kwok C; Tam, Greta; Tam, Cheuk M

2017-08-01

With the colliding global epidemics of diabetes mellitus (DM) and tuberculosis (TB), we studied the effects of DM on the presentation of TB and its response to treatment. Consecutive TB patients from 2006 to 2010 in a territory-wide treatment programme offering 9-month extended treatment for TB patients with DM were examined and followed up prospectively to assess their treatment response. Successful treatment completers were tracked through the TB registry and death registry for relapse, death or till 31 December 2014, whichever was the earliest. DM was independently associated with more chest symptoms (adjusted OR (AOR): 1.13) and systemic symptoms (AOR: 1.30) but less with other site-specific symptoms (AOR: 0.58) at TB presentation. There was more frequent pulmonary involvement (AOR: 1.69), with more extensive lung lesion (AOR: 1.25), lung cavity (AOR: 2.00) and positive sputum smear (AOR: 1.83) and culture (AOR: 1.38), but no difference in the proportion of retreatment cases or isoniazid and/or rifampicin resistance. After treatment initiation, there was higher overall incidence (AOR: 1.38) of adverse effects (mainly gastrointestinal symptoms, renal impairment and peripheral neuropathy but less fever and skin hypersensitivity reactions), more smear non-conversion (AOR: 1.59) and culture non-conversion (AOR: 1.40) at 2 months, and lower combined cure/treatment completion rate at 12 months (AOR: 0.79), but no difference in the relapse rate after having successfully completed treatment. DM adversely affected the clinical presentation and treatment response of TB, but there was no difference in the drug resistance and relapse rates. © 2017 Asian Pacific Society of Respirology.

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial.

PubMed

Gleeson, Mary; Peckitt, Clare; To, Ye Mong; Edwards, Laurice; Oates, Jacqueline; Wotherspoon, Andrew; Attygalle, Ayoma D; Zerizer, Imene; Sharma, Bhupinder; Chua, Sue; Begum, Ruwaida; Chau, Ian; Johnson, Peter; Ardeshna, Kirit M; Hawkes, Eliza A; Macheta, Marian P; Collins, Graham P; Radford, John; Forbes, Adam; Hart, Alistair; Montoto, Silvia; McKay, Pamela; Benstead, Kim; Morley, Nicholas; Kalakonda, Nagesh; Hasan, Yasmin; Turner, Deborah; Cunningham, David

2018-05-01

Outcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients. We did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0-3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1-5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m 2 on days 1, 8, and 15, cisplatin 100 mg/m 2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1-5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18). Between June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6-38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21-1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections. The number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma. Bloodwise and the UK National Institute of Health Research. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Clinical validity of PROMIS Depression, Anxiety, and Anger across diverse clinical samples.

PubMed

Schalet, Benjamin D; Pilkonis, Paul A; Yu, Lan; Dodds, Nathan; Johnston, Kelly L; Yount, Susan; Riley, William; Cella, David

2016-05-01

The purpose of this study was to evaluate the responsiveness to change of the PROMIS negative affect measures (depression, anxiety, and anger) using longitudinal data collected in six chronic health conditions. Individuals with major depressive disorder (MDD), back pain, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), and cancer completed PROMIS negative affect instruments as computerized adaptive test or as fixed-length short form at baseline and a clinically relevant follow-up interval. Participants also completed global ratings of health. Linear mixed effects models and standardized response means (SRM) were estimated at baseline and follow-up. A total of 903 individuals participated (back pain, n = 218; cancer, n = 304; CHF, n = 60; COPD, n = 125; MDD, n = 196). All three negative affect instruments improved significantly for treatments of depression and pain. Depression improved for CHF patients (anxiety and anger not administered), whereas anxiety improved significantly in COPD groups (stable and exacerbation). Response to treatment was not assessed in cancer. Subgroups of patients reporting better or worse health showed a corresponding positive or negative average SRM for negative affect across samples. This study provides evidence that the PROMIS negative affect scores are sensitive to change in intervention studies in which negative affect is expected to change. These results inform the estimation of meaningful change and enable comparative effectiveness research. Copyright © 2016 Elsevier Inc. All rights reserved.

A PILOT STUDY OF TOPICAL IMIQUIMOD THERAPY FOR THE TREATMENT OF RECURRENT EXTRAMAMMARY PAGET'S DISEASE

PubMed Central

Cowan, Renee A.; Black, Destin R.; Hoang, Lien N.; Park, Kay J.; Soslow, Robert A.; Backes, Floor J.; Gardner, Ginger J.; Abu-Rustum, Nadeen R.; Leitao, Mario M.; Eisenhauer, Eric L.; Chi, Dennis S.

2016-01-01

Objective The objective of this prospective pilot study was to assess the clinical and histologic effects of topical imiquimod therapy on recurrent extramammary Paget's disease of the vulva. Methods Patients with biopsy-proven recurrent extramammary Paget's disease presenting to the gynecology outpatient services at two participating institutions were recruited for conservative treatment with 5% imiquimod cream from 2007 to 2011. The topical cream was to be applied 3 times per week for 12 weeks. Punch biopsy and photography were performed at baseline and at the 12-week time point. Results Eight patients from two institutions were enrolled. Complete clinical and histologic response was achieved in 6 (75%) patients by the 12-week follow-up appointment. Of the two remaining patients, one had a complete clinical response but no significant histologic response; the other patient was removed from the study protocol secondary to intolerable local irritation. Two patients continue to have no evidence of disease after a median follow-up of 35 months. Five are alive with disease. No patients progressed to invasive cancer while receiving therapy. Conclusion Topical 5% imiquimod cream is a safe and feasible option for women suffering from recurrent extramammary Paget's disease of the vulva, and should be considered as a viable alternative to surgical management. Given the rare nature of this disease, additional multi-institutional prospective studies should be conducted to explore the efficacy of this treatment regime. PMID:27112632

Photodynamic therapy in the management of actinic keratosis: Retrospective evaluation of outcome.

PubMed

Jerjes, Waseem; Hamdoon, Zaid; Abdulkareem, Ali A; Hopper, Colin

2017-03-01

Photodynamic therapy (PDT) is a minimally invasive intervention used in the management of tissue disorders. In this retrospective study, a total of 62 patients with actinic keratosis (AKs) were treated with surface illumination PDT. Comparisons with the clinical features, rate of recurrence as well as malignant transformation and overall outcome were made. The medical records of 62 consecutive patients who presented with suspicious skin lesions and diagnosed with AKs were examined. These patients with 178 AKs lesions were treated with surface illumination methyl aminolevulinate-photodynamic therapy (MAL-PDT). The 16% strength cream (MAL) was applied topically 3h prior to tissue illumination. A single-channel 628nm diode laser was used for illumination and light was delivered at 100J/cm 2 per site. These patients were followed-up for a mean of 7.4 years. Eight recurrences were reported after the first round of MAL-PDT, and two recurrences after the second round. Malignant transformation to squamous cell carcinoma (SCC) was noted in 2 patients only. The 3-year outcome resulted in 60 patients with complete response (CR), and this was maintained at the final outcome (last clinic review). Assessment of lesional outcome vs. response showed that 175/178 treated lesions had complete response (CR) at 3-year follow-up, which increased to 176/178 lesions at the last clinic follow-up. MAL-PDT offers an effective treatment for AKs lesions with excellent cosmetic outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptive Randomization of Neratinib in Early Breast Cancer.

PubMed

Park, John W; Liu, Minetta C; Yee, Douglas; Yau, Christina; van 't Veer, Laura J; Symmans, W Fraser; Paoloni, Melissa; Perlmutter, Jane; Hylton, Nola M; Hogarth, Michael; DeMichele, Angela; Buxton, Meredith B; Chien, A Jo; Wallace, Anne M; Boughey, Judy C; Haddad, Tufia C; Chui, Stephen Y; Kemmer, Kathleen A; Kaplan, Henry G; Isaacs, Claudine; Nanda, Rita; Tripathy, Debasish; Albain, Kathy S; Edmiston, Kirsten K; Elias, Anthony D; Northfelt, Donald W; Pusztai, Lajos; Moulder, Stacy L; Lang, Julie E; Viscusi, Rebecca K; Euhus, David M; Haley, Barbara B; Khan, Qamar J; Wood, William C; Melisko, Michelle; Schwab, Richard; Helsten, Teresa; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Esserman, Laura J; Berry, Donald A

2016-07-07

The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery). We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature. Neratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone-receptor-negative signature. Among patients with HER2-positive, hormone-receptor-negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54%). The final predictive probability of success in phase 3 testing was 79%. Neratinib added to standard therapy was highly likely to result in higher rates of pathological complete response than standard chemotherapy with trastuzumab among patients with HER2-positive, hormone-receptor-negative breast cancer. (Funded by QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

Comparison of self-administered survey questionnaire responses collected using mobile apps versus other methods.

PubMed

Marcano Belisario, José S; Jamsek, Jan; Huckvale, Kit; O'Donoghue, John; Morrison, Cecily P; Car, Josip

2015-07-27

Self-administered survey questionnaires are an important data collection tool in clinical practice, public health research and epidemiology. They are ideal for achieving a wide geographic coverage of the target population, dealing with sensitive topics and are less resource-intensive than other data collection methods. These survey questionnaires can be delivered electronically, which can maximise the scalability and speed of data collection while reducing cost. In recent years, the use of apps running on consumer smart devices (i.e., smartphones and tablets) for this purpose has received considerable attention. However, variation in the mode of delivering a survey questionnaire could affect the quality of the responses collected. To assess the impact that smartphone and tablet apps as a delivery mode have on the quality of survey questionnaire responses compared to any other alternative delivery mode: paper, laptop computer, tablet computer (manufactured before 2007), short message service (SMS) and plastic objects. We searched MEDLINE, EMBASE, PsycINFO, IEEEXplore, Web of Science, CABI: CAB Abstracts, Current Contents Connect, ACM Digital, ERIC, Sociological Abstracts, Health Management Information Consortium, the Campbell Library and CENTRAL. We also searched registers of current and ongoing clinical trials such as ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform. We also searched the grey literature in OpenGrey, Mobile Active and ProQuest Dissertation & Theses. Lastly, we searched Google Scholar and the reference lists of included studies and relevant systematic reviews. We performed all searches up to 12 and 13 April 2015. We included parallel randomised controlled trials (RCTs), crossover trials and paired repeated measures studies that compared the electronic delivery of self-administered survey questionnaires via a smartphone or tablet app with any other delivery mode. We included data obtained from participants completing health-related self-administered survey questionnaire, both validated and non-validated. We also included data offered by both healthy volunteers and by those with any clinical diagnosis. We included studies that reported any of the following outcomes: data equivalence; data accuracy; data completeness; response rates; differences in the time taken to complete a survey questionnaire; differences in respondent's adherence to the original sampling protocol; and acceptability to respondents of the delivery mode. We included studies that were published in 2007 or after, as devices that became available during this time are compatible with the mobile operating system (OS) framework that focuses on apps. Two review authors independently extracted data from the included studies using a standardised form created for this systematic review in REDCap. They then compared their forms to reach consensus. Through an initial systematic mapping on the included studies, we identified two settings in which survey completion took place: controlled and uncontrolled. These settings differed in terms of (i) the location where surveys were completed, (ii) the frequency and intensity of sampling protocols, and (iii) the level of control over potential confounders (e.g., type of technology, level of help offered to respondents). We conducted a narrative synthesis of the evidence because a meta-analysis was not appropriate due to high levels of clinical and methodological diversity. We reported our findings for each outcome according to the setting in which the studies were conducted. We included 14 studies (15 records) with a total of 2275 participants; although we included only 2272 participants in the final analyses as there were missing data for three participants from one included study.Regarding data equivalence, in both controlled and uncontrolled settings, the included studies found no significant differences in the mean overall scores between apps and other delivery modes, and that all correlation coefficients exceeded the recommended thresholds for data equivalence. Concerning the time taken to complete a survey questionnaire in a controlled setting, one study found that an app was faster than paper, whereas the other study did not find a significant difference between the two delivery modes. In an uncontrolled setting, one study found that an app was faster than SMS. Data completeness and adherence to sampling protocols were only reported in uncontrolled settings. Regarding the former, an app was found to result in more complete records than paper, and in significantly more data entries than an SMS-based survey questionnaire. Regarding adherence to the sampling protocol, apps may be better than paper but no different from SMS. We identified multiple definitions of acceptability to respondents, with inconclusive results: preference; ease of use; willingness to use a delivery mode; satisfaction; effectiveness of the system informativeness; perceived time taken to complete the survey questionnaire; perceived benefit of a delivery mode; perceived usefulness of a delivery mode; perceived ability to complete a survey questionnaire; maximum length of time that participants would be willing to use a delivery mode; and reactivity to the delivery mode and its successful integration into respondents' daily routine. Finally, regardless of the study setting, none of the included studies reported data accuracy or response rates. Our results, based on a narrative synthesis of the evidence, suggest that apps might not affect data equivalence as long as the intended clinical application of the survey questionnaire, its intended frequency of administration and the setting in which it was validated remain unchanged. There were no data on data accuracy or response rates, and findings on the time taken to complete a self-administered survey questionnaire were contradictory. Furthermore, although apps might improve data completeness, there is not enough evidence to assess their impact on adherence to sampling protocols. None of the included studies assessed how elements of user interaction design, survey questionnaire design and intervention design might influence mode effects. Those conducting research in public health and epidemiology should not assume that mode effects relevant to other delivery modes apply to apps running on consumer smart devices. Those conducting methodological research might wish to explore the issues highlighted by this systematic review.

Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy.

PubMed

Miyamura, Koichi; Miyamoto, Toshihiro; Tanimoto, Mitsune; Yamamoto, Kazuhito; Kimura, Shinya; Kawaguchi, Tatsuya; Matsumura, Itaru; Hata, Tomoko; Tsurumi, Hisashi; Saito, Shigeki; Hino, Masayuki; Tadokoro, Seiji; Meguro, Kuniaki; Hyodo, Hideo; Yamamoto, Masahide; Kubo, Kohmei; Tsukada, Junichi; Kondo, Midori; Aoki, Makoto; Okada, Hikaru; Yanada, Masamitsu; Ohyashiki, Kazuma; Taniwaki, Masafumi

2016-12-01

Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874. Copyright © 2016 Elsevier Ltd. All rights reserved.

Treatment with DAV for advanced-stage hemangiosarcoma in dogs.

PubMed

Dervisis, Nikolaos G; Dominguez, Pedro A; Newman, Rebecca G; Cadile, Casey D; Kitchell, Barbara E

2011-01-01

Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P=0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P=0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P=0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.

Interprofessional teamwork skills as predictors of clinical outcomes in a simulated healthcare setting.

PubMed

Shrader, Sarah; Kern, Donna; Zoller, James; Blue, Amy

2013-01-01

Teaching interprofessional (IP) teamwork skills is a goal of interprofessional education. The purpose of this study was to examine the relationship between IP teamwork skills, attitudes and clinical outcomes in a simulated clinical setting. One hundred-twenty health professions students (medicine, pharmacy, physician assistant) worked in interprofessional teams to manage a "patient" in a health care simulation setting. Students completed the Interdisciplinary Education Perception Scale (IEPS) attitudinal survey instrument. Students' responses were averaged by team to create an IEPS attitudes score. Teamwork skills for each team were rated by trained observers using a checklist to calculate a teamwork score (TWS). Clinical outcome scores (COS) were determined by summation of completed clinical tasks performed by the team based on an expert developed checklist. Regression analyses were conducted to determine the relationship of IEPS and TWS with COS. IEPS score was not a significant predictor of COS (p=0.054), but TWS was a significant predictor (p<0.001) of COS. Results suggest that in a simulated clinical setting, students' interprofessional teamwork skills are significant predictors of positive clinical outcomes. Interprofessional curricular models that produce effective teamwork skills can improve student performance in clinical environments and likely improve teamwork practice to positively affect patient care outcomes.

A double-blind randomized placebo-controlled clinical trial of squalamine ointment for tinea capitis treatment.

PubMed

Coulibaly, Oumar; Thera, Mahamadou A; Koné, Abdoulaye K; Siaka, Goïta; Traoré, Pierre; Djimdé, Abdoulaye A; Brunel, Jean-Michel; Gaudart, Jean; Piarroux, Renaud; Doumbo, Ogobara K; Ranque, Stéphane

2015-04-01

Novel treatments against for tinea capitis are needed, and the natural aminosterol squalamine is a potential topical antidermatophyte drug candidate. This phase II randomized double-blind placebo-controlled clinical trial aimed at testing the efficacy and safety of a three-week squalamine ointment regimen for the treatment of tinea capitis. Males aged 6-15 years presenting with tinea capitis were treated with either topical squalamine ointment or placebo for 3 weeks. The primary endpoint was complete clinical cure. The secondary endpoints were the occurrence of local and/or systemic adverse events, mycological cure, and partial clinical response. Prospective follow-up of clinical adverse events was performed daily. Five patients were treated with 1% squalamine ointment and 15 with placebo. No complete cure was observed. No clinical or biological adverse event was recorded. A significantly (p = 0.03) better hair-growth score, indicating a partial clinical improvement of the tinea capitis lesion, was observed in the patients treated with squalamine compared to those treated with placebo. This three-week squalamine ointment regimen was well tolerated and showed an encouraging partial clinical activity for the treatment of tinea capitis. Further studies are needed to evaluate the efficacy of topical squalamine alone against tinea corporis or in combination with a systemic antidermatophyte drug against tinea capitis.

Computer-generated reminders and quality of pediatric HIV care in a resource-limited setting.

PubMed

Were, Martin C; Nyandiko, Winstone M; Huang, Kristin T L; Slaven, James E; Shen, Changyu; Tierney, William M; Vreeman, Rachel C

2013-03-01

To evaluate the impact of clinician-targeted computer-generated reminders on compliance with HIV care guidelines in a resource-limited setting. We conducted this randomized, controlled trial in an HIV referral clinic in Kenya caring for HIV-infected and HIV-exposed children (<14 years of age). For children randomly assigned to the intervention group, printed patient summaries containing computer-generated patient-specific reminders for overdue care recommendations were provided to the clinician at the time of the child's clinic visit. For children in the control group, clinicians received the summaries, but no computer-generated reminders. We compared differences between the intervention and control groups in completion of overdue tasks, including HIV testing, laboratory monitoring, initiating antiretroviral therapy, and making referrals. During the 5-month study period, 1611 patients (49% female, 70% HIV-infected) were eligible to receive at least 1 computer-generated reminder (ie, had an overdue clinical task). We observed a fourfold increase in the completion of overdue clinical tasks when reminders were availed to providers over the course of the study (68% intervention vs 18% control, P < .001). Orders also occurred earlier for the intervention group (77 days, SD 2.4 days) compared with the control group (104 days, SD 1.2 days) (P < .001). Response rates to reminders varied significantly by type of reminder and between clinicians. Clinician-targeted, computer-generated clinical reminders are associated with a significant increase in completion of overdue clinical tasks for HIV-infected and exposed children in a resource-limited setting.

Extensive disease small cell carcinoma of the lung; trial of non-cross resistant chemotherapy and consolidation radiotherapy. [X ray

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

Dillman, R.O., Taelle, R., Segren, S.; Royston, I.; Koziol, J.

1982-05-15

Twenty-nine patients with extensive disease, small-cell carcinoma of the lung, were treated with two cycles of intensive combination chemotherapy: HexaVAC (hexamethylmelamine, vincristine, Adriamycin, cyclophosphamide). Responders received prophylactic cranial radiation (2000 rad/10 fractions) and non cross resistant chemotherapy via a schedule of alternating cycles of CMV (cyclophosphamide, methotrexate, VP-16-213) and AMV (Adriamycin, methotrexate, VP-16-213). Whenever a complete response was achieved, consolidation radiotherapy was given to the lung primary (4000 rad/20 fractions, split dose) and abdominal metastases (2000 rad/10 fractions) synchronous with CMV therapy. The complete response rate was 14% with HexaVAC, but increased to 38% during CMV/AMV. Total response rate (completemore » and partial) was 59% and median survival was 42 weeks. Prophylactic brain radiation prevented clinical relapse in the brain in all 14 patients who received it. However, consolidation radiotherapy failed to prevent clinical relapse in the lung and/or liver, and therapeutic brain radiation (3000 rad) failed to prevent relapse in that site. The simultaneous administration of radiotherapy and chemotherapy was well-tolerated although two patients with poor performance status died of infectious complications while leukopenic. In spite of the high response rate, durable remissions with prolonged disease free survival were rare. Further evaluation of induction, consolidation, and maintenance modes of therapy are indicated.« less

Tracking medication changes to assess outcomes in comparative effectiveness research: A bipolar CHOICE study.

PubMed

Reilly-Harrington, Noreen A; Sylvia, Louisa G; Rabideau, Dustin J; Gold, Alexandra K; Deckersbach, Thilo; Bowden, Charles L; Bobo, William V; Singh, Vivek; Calabrese, Joseph R; Shelton, Richard C; Friedman, Edward S; Thase, Michael E; Kamali, Masoud; Tohen, Mauricio; McInnis, Melvin G; McElroy, Susan L; Ketter, Terence A; Kocsis, James H; Kinrys, Gustavo; Nierenberg, Andrew A

2016-11-15

Comparative effectiveness research uses multiple tools, but lacks outcome measures to assess large electronic medical records and claims data. Aggregate changes in medications in response to clinical need may serve as a surrogate outcome measure. We developed the Medication Recommendation Tracking Form (MRTF) to record the frequency, types, and reasons for medication adjustments in order to calculate Necessary Clinical Adjustments (NCAs), medication adjustments to reduce symptoms, maximize treatment response, or address problematic side effects. The MRTF was completed at every visit for 482 adult patients in Bipolar CHOICE, a 6-month randomized comparative effectiveness trial. Responders had significantly fewer NCAs compared to non-responders. NCAs predicted subsequent response status such that every additional NCA during the previous visit decreased a patient's odds of response by approximately 30%. Patients with more severe symptoms had a greater number of NCAs at the subsequent visit. Patients with a comorbid anxiety disorder demonstrated a significantly higher rate of NCAs per month than those without a comorbid anxiety disorder. Patients with greater frequency, intensity, and interference of side effects had higher rates of NCAs. Participants with fewer NCAs reported a higher quality of life and decreased functional impairment. The MRTF has not been examined in community clinic settings and did not predict response more efficiently than the Clinical Global Impression-Bipolar Version (CGI-BP). The MRTF is a feasible proxy of clinical outcome, with implications for clinical training and decision-making. Analyses of big data could use changes in medications as a surrogate outcome measure. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation study of a web-based assessment of functional recovery after radical prostatectomy.

PubMed

Vickers, Andrew J; Savage, Caroline J; Shouery, Marwan; Eastham, James A; Scardino, Peter T; Basch, Ethan M

2010-08-05

Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy. We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities. Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction. We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice.

Validation study of a web-based assessment of functional recovery after radical prostatectomy

PubMed Central

2010-01-01

Background Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy. Methods We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities. Results Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction. Conclusions We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice. PMID:20687938

Genetic Susceptibility to Chagas Disease: An Overview about the Infection and about the Association between Disease and the Immune Response Genes

PubMed Central

Ayo, Christiane Maria; Dalalio, Márcia Machado de Oliveira; Visentainer, Jeane Eliete Laguila; Reis, Pâmela Guimarães; Jarduli, Luciana Ribeiro; Alves, Hugo Vicentin; Sell, Ana Maria

2013-01-01

Chagas disease, which is caused by the flagellate parasite Trypanosoma cruzi, affects 8–10 million people in Latin America. The disease is endemic and is characterised by acute and chronic phases that develop in the indeterminate, cardiac, and/or gastrointestinal forms. The immune response during human T. cruzi infection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Polymorphisms in genes involved in the innate and specific immune response are being widely studied in order to clarify their possible role in the occurrence or severity of disease. Here we review the role of classic and nonclassic MHC, KIR, and cytokine host genetic factors on the infection by T. cruzi and the clinical course of Chagas disease. PMID:24069594

A Cross-Sectional Study of Barriers to Personal Health Record Use among Patients Attending a Safety-Net Clinic

PubMed Central

Hilton, Joan F.; Barkoff, Lynsey; Chang, Olivia; Halperin, Lindsay; Ratanawongsa, Neda; Sarkar, Urmimala; Leykin, Yan; Muñoz, Ricardo F.; Thom, David H.; Kahn, James S.

2012-01-01

Background Personal health records (PHR) may improve patients' health by providing access to and context for health information. Among patients receiving care at a safety-net HIV/AIDS clinic, we examined the hypothesis that a mental health (MH) or substance use (SU) condition represents a barrier to engagement with web-based health information, as measured by consent to participate in a trial that provided access to personal (PHR) or general (non-PHR) health information portals and by completion of baseline study surveys posted there. Methods Participants were individually trained to access and navigate individualized online accounts and to complete study surveys. In response to need, during accrual months 4 to 12 we enhanced participant training to encourage survey completion with the help of staff. Using logistic regression models, we estimated odds ratios for study participation and for survey completion by combined MH/SU status, adjusted for levels of computer competency, on-study training, and demographics. Results Among 2,871 clinic patients, 70% had MH/SU conditions, with depression (38%) and methamphetamine use (17%) most commonly documented. Middle-aged patients and those with a MH/SU condition were over-represented among study participants (N = 338). Survey completion was statistically independent of MH/SU status (OR, 1.85 [95% CI, 0.93–3.66]) but tended to be higher among those with MH/SU conditions. Completion rates were low among beginner computer users, regardless of training level (<50%), but adequate among advanced users (>70%). Conclusions Among patients attending a safety-net clinic, MH/SU conditions were not barriers to engagement with web-based health information. Instead, level of computer competency was useful for identifying individuals requiring substantial computer training in order to fully participate in the study. Intensive on-study training was insufficient to enable beginner computer users to complete study surveys. PMID:22363761

Evaluation of Complete Blood Count Indices (NLR, PLR, MPV/PLT, and PLCRi) in Healthy Dogs, Dogs With Periodontitis, and Dogs With Oropharyngeal Tumors as Potential Biomarkers of Systemic Inflammatory Response.

PubMed

Rejec, Ana; Butinar, Janos; Gawor, Jerzy; Petelin, Milan

2017-12-01

The aim of the study was to retrospectively assess complete blood count (CBC) indices of dogs with periodontitis (PD; n = 73) and dogs with oropharyngeal tumors (OT; n = 92) in comparison to CBC indices of healthy dogs (HD; n = 71). Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, mean platelet volume to platelet ratio, and platelet large cell ratio index (PLCRi) were evaluated as biomarkers of systemic inflammatory response provoked by PD and OT. Results of multivariable polytomous logistic regression analysis indicated no significant associations between CBC indices and PD. Both NLR and PLCRi were significantly higher in dogs with OT when compared to HD and dogs with PD and could, therefore, indicate a tumor-associated systemic inflammatory response. Additional studies of CBC indices, along with other biomarkers of systemic inflammatory response, are recommended to validate them as reliable indicators of clinical disease activity.

Illustrative cases for monitoring by quantitative analysis of BRAF/NRAS ctDNA mutations in liquid biopsies of metastatic melanoma patients who gained clinical benefits from anti-PD1 antibody therapy.

PubMed

Seremet, Teofila; Planken, Simon; Schreuer, Max; Jansen, Yanina; Delaunoy, Mélanie; El Housni, Hakim; Lienard, Danielle; Del Marmol, Véronique; Heimann, Pierre; Neyns, Bart

2018-02-01

Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma. The cases described exemplify four distinct clinical benefit patterns: rapid and durable complete response (CR), early progression, followed by CR, CR followed by early progression after interrupting treatment and long-term disease stabilization. These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring during anti-PD1 therapy is informative and can be of added value for the monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment. An important advantage of our approach is that using the cartridge system on the Idylla platform for mutation analysis, the results become available the same day 2 h after plasma collection. Therefore, in the future, the ctDNA level can be an element in the clinical management of the patients.

The combination of trimethoprim and sulfamethoxazole in the treatment of urinary tract infection

PubMed Central

Crichton, Erica P.; McDonnell, C. E.

1972-01-01

In a series of 52 patients the combination of trimethoprim and sulfamethoxazole was used for the treatment of urinary tract infection and the results are analyzed with respect to the clinical diagnosis and bacterial etiology. There was complete agreement between in vitro sensitivity and clinical response except in the case of one strain of Streptococcus fecalis. The combination of drugs was effective against some bacterial strains which were resistant to the commonly used antimicrobial agents. PMID:4626767

Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study.

PubMed

Dannon, Pinhas N; Lowengrub, Katherine; Musin, Ernest; Gonopolski, Yehudit; Kotler, Moshe

2005-12-01

Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the bupropion group were rated as partial responders. In the naltrexone group, 3 (23%) of 13 completers were rated as partial responders. Full response was defined as the absence of gambling for a 2-week duration together with improvement on the Clinical Global Impression-Improvement Scale. Partial response was defined as a decrease in the frequency of gambling behavior and a decrease in the amount of money spent on gambling. This preliminary study shows that sustained-release bupropion may be effective as naltrexone in the treatment of PG. Further studies are needed to confirm our findings.

Acetyl-L-Carnitine Augmentation of Clozapine in Partial-Responder Schizophrenia: A 12-Week, Open-Label Uncontrolled Preliminary Study.

PubMed

Bruno, Antonio; Pandolfo, Gianluca; Crucitti, Manuela; Lorusso, Simona; Zoccali, Rocco Antonio; Muscatello, Maria Rosaria Anna

This was the first 12-week, open-label, uncontrolled trial aimed at exploring the efficacy of acetyl-L-carnitine (ALC) add-on pharmacotherapy on clinical symptoms and cognitive functioning in 15 schizophrenia patients with suboptimal clinical response despite receiving clozapine (CLZ) monotherapy at the highest tolerated dosage. After clinical (Positive and Negative Symptoms Scale [PANSS]) and neuropsychological (Wisconsin Card Sorting Test, Stroop Color-Word Test, Verbal Fluency Test) assessments, patients received 1 g/d of ALC for 12 weeks. A final sample of 9 subjects completed the study. Acetyl-L-carnitine augmentation of CLZ significantly reduced only PANSS domains "positive" (P = 0.049); at end point, only 2 subjects (22.2% of the completers) reached a minimal improvement (25% reduction in PANSS total score). No significant differences emerged in cognitive performances at the end of the study; effect sizes were small in each explored cognitive dimension. The findings provide preliminary evidence that ALC added to ongoing CLZ treatment appeared to be ineffective to improve symptoms in schizophrenia patients who have failed to respond sufficiently to CLZ. Further trials with adequately powered methodology are needed to identify which augmentation strategies are more effective in schizophrenia patients showing a suboptimal response to CLZ.

Treatment of refractory sino-nasal aspergillosis with posaconazole and terbinafine in 10 dogs.

PubMed

Stewart, J; Bianco, D

2017-09-01

To determine the safety and efficacy of posaconazole and terbinafine for the treatment of naturally occurring sino-nasal aspergillosis in dogs refractory to conventional topical and systemic treatment. Ten client-owned dogs with sino-nasal aspergillosis and not responsive to conventional treatments were prospectively enrolled to receive a dose of 5 mg/kg posaconazole orally every 12 hours for six months. All dogs were concurrently treated with doses of 30 mg/kg terbinafine orally every 12 hours and 5 mg/kg doxycycline orally every 12 hours for 6 to 18 months. All 10 enrolled dogs completed the study. The treatment response was defined as complete clinical remission (n=7) or partial clinical remission (n=3). Two dogs relapsed after cessation of combination therapy. All dogs lived more than one year after starting combination therapy and eight dogs are alive at the time of writing. No clinically relevant adverse reactions or increases in hepatic enzyme activity occurred during the combination therapy. The results of this study suggest that this combination therapy appears safe and well-tolerated for the treatment of refractory sino-nasal aspergillosis in dogs. Long-term survival is possible with prolonged treatment, but relapse is possible. Larger prospective studies are warranted to further evaluate these preliminary findings. © 2017 British Small Animal Veterinary Association.

A Phase II Trial of Neoadjuvant Preoperative Chemoradiotherapy With S-1 Plus Irinotecan and Radiation in Patients With Locally Advanced Rectal Cancer: Clinical Feasibility and Response Rate

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

Sato, Takeo; Ozawa, Heita; Hatate, Kazuhiko

Purpose: We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting. Methods and Materials: Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80mg/m{sup 2} on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80mg/m{sup 2}) was infused on Days 1, 8, 22, and 29. Four or more weeksmore » after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety. Results: We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea. Conclusions: A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.« less

Perceived comfort level of medical students and residents in handling clinical ethics issues.

PubMed

Silverman, Henry J; Dagenais, Julien; Gordon-Lipkin, Eliza; Caputo, Laura; Christian, Matthew W; Maidment, Bert W; Binstock, Anna; Oyalowo, Akinbowale; Moni, Malini

2013-01-01

Studies have shown that medical students and residents believe that their ethics preparation has been inadequate for handling ethical conflicts. The objective of this study was to determine the self-perceived comfort level of medical students and residents in confronting clinical ethics issues. Clinical medical students and residents at the University of Maryland School of Medicine completed a web-based survey between September 2009 and February 2010. The survey consisted of a demographic section, questions regarding the respondents' sense of comfort in handling a variety of clinical ethics issues, and a set of knowledge-type questions in ethics. Survey respondents included 129 medical students (response rate of 40.7%) and 207 residents (response rate of 52.7%). There were only a few clinical ethics issues with which more than 70% of the respondents felt comfortable in addressing. Only a slight majority (60.8%) felt prepared, in general, to handle clinical situations involving ethics issues, and only 44.1% and 53.2% agreed that medical school and residency training, respectively, helped prepare them to handle such issues. Prior ethics training was not associated with these responses, but there was an association between the level of training (medical students vs residents) and the comfort level with many of the clinical ethics issues. Medical educators should include ethics educational methods within the context of real-time exposure to medical ethics dilemmas experienced by physicians-in-training.

Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

PubMed

Rafii, Saeed; Gourley, Charlie; Kumar, Rajiv; Geuna, Elena; Ern Ang, Joo; Rye, Tzyvia; Chen, Lee-May; Shapira-Frommer, Ronnie; Friedlander, Michael; Matulonis, Ursula; De Greve, Jacques; Oza, Amit M; Banerjee, Susana; Molife, L Rhoda; Gore, Martin E; Kaye, Stan B; Yap, Timothy A

2017-07-18

The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients

PubMed Central

Levandovsky, Mark; Harvey, Danielle; Lara, Primo; Wun, Ted

2008-01-01

Background Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for important short- and long-term outcome measures. Results Overall 30-day mortality was 16% (n = 27). 171 patients (96%) received plasma exchange as the principal treatment, with a mean of 8 exchanges and a mean cumulative infused volume of 42 ± 71 L of fresh frozen plasma. The rate of complete response was 65% or 55% depending on whether this was defined by a platelet count of 100,000/μl or 150,000/μl, respectively. The rate of relapse was 18%. The Clinical Severity Score did not predict for 30-day mortality or relapse. The time to complete response did not predict for relapse. Renal insufficiency at presentation was associated with a decreased risk of relapse, with each unit increase in serum creatinine associated with a 40% decreased odds of relapse. 72% of our cohort had an idiopathic TTP-sporadic HUS, while 17% had an underlying cancer, received a solid organ transplant or were treated with a mitomycin-based therapy. The estimated overall 5-year survival was 55% and was significantly better in those without serious underlying conditions. Conclusion Plasma exchange therapy produced both high response and survival rates in this large cohort of patients with TTP-HUS. The Clinical Severity Score did not predict for 30-day mortality or relapse, contrary to our previous findings. Interestingly, the presence of renal insufficiency was associated with a decreased risk of relapse. The most important predictor of mortality was the presence or absence of a serious underlying disorder. PMID:19046460

Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation

PubMed Central

Lee, Seung-Shin; Jung, Sung-Hoon; Ahn, Seo-Yeon; Kim, Jae-Yong; Jang, Hee-Chang; Kang, Seung-Ji; Jang, Mi-Ok; Yang, Deok-Hwan; Kim, Yeo-Kyeoung; Lee, Je-Jung; Kim, Hyeoung-Joon

2015-01-01

Background/Aims BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. Methods Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. Results Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. Conclusions Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC. PMID:25750563

Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation.

PubMed

Lee, Seung-Shin; Ahn, Jae-Sook; Jung, Sung-Hoon; Ahn, Seo-Yeon; Kim, Jae-Yong; Jang, Hee-Chang; Kang, Seung-Ji; Jang, Mi-Ok; Yang, Deok-Hwan; Kim, Yeo-Kyeoung; Lee, Je-Jung; Kim, Hyeoung-Joon

2015-03-01

BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.

Impact of Evidence-Based Dentistry Workshops on Educators' Use of Evidence in Teaching and Practice: A Pilot Study.

PubMed

Moreira, Narjara C F; Leonardi-Dutra, Kamile; Feres, Murilo F N; Colangelo, Erica A M; Balevi, Ben; Matthews, Debora; Flores-Mir, Carlos

2018-06-01

The aims of this pilot study were to evaluate the short-term impact of evidence-based dentistry (EBD) workshops on educators' use of clinical evidence in their clinical practice and educational activities and to identify barriers they encountered in implementing evidence in their teaching and clinical practice. Between April 2012 and January 2014, a series of EBD workshops was delivered to 31 dental faculty members and postdoctoral students at three Canadian dental schools. Survey I, assessing participants' perceptions of various aspects of the workshops, was administered immediately following the workshops. Survey II, evaluating the impact of the workshops on participants' EBD implementation, was conducted 10 to 31 months after their completion. Survey I was completed by all 31 participants (100% response rate); their mean scores ranged from 3.94 to 4.65 on a five-point scale. Survey II was completed by 20 participants (64.5% response rate; five postdoctoral students and 15 faculty members), using an online 20-item questionnaire. Of the respondents, 19 (95%) reported implementing EBD in their professional activities at that time, and 14 (70%) stated that the workshops had positively helped with EBD implementation. Eight respondents (40%) reported having experienced barriers to EBD implementation, while 15 (75%) reported that their patients/students welcomed use of EBD. The respondents reported believing that strategies such as increasing EBD education and dissemination and improving quality and accessibility of evidence would facilitate the transition to EBD practice. Reported barriers to EBD implementation included resistance and criticism from colleagues, difficulty in changing current practice model, and lack of time.

Sodium Thiosulfate Therapy for Calcific Uremic Arteriolopathy

PubMed Central

Brunelli, Steven M.; Meade, Debra; Wang, Weiling; Hymes, Jeffrey; Lacson, Eduardo

2013-01-01

Summary Background and objective Calcific uremic arteriolopathy (CUA) is an often fatal condition with no effective treatment. Multiple case reports and case series have described intravenous sodium thiosulfate (STS) administration in CUA, but no studies have systematically evaluated this treatment. Design, setting, participants, & measurements This study included 172 patients undergoing maintenance hemodialysis who had CUA and were treated with STS between August 2006 and June 2009 at Fresenius Medical Care North America. Of these, 85% completed STS therapy. Clinical, laboratory, and mortality data were abstracted from clinical information systems. Responses to survey questionnaires sent to treating physicians regarding patient-level outcomes were available for 53 patients. Effect on CUA lesions and mortality were summarized as CUA outcomes. Relevant laboratory measures, weight (using pairwise comparisons of values before, during, and after STS), and adverse events were summarized as safety parameters. Results Mean age of the cohort was 55 years, and 74% of patients were women. Median STS dose was 25 g, and median number of doses was 38. Among surveyed patients, CUA completely resolved in 26.4%, markedly improved in 18.9%, improved in 28.3%, and did not improve in 5.7%; in the remaining patients (20.8%), the response was unknown. One-year mortality in patients treated with STS was 35%. Adverse events, laboratory abnormalities, and weight-related changes were mild. Significant reductions in serum phosphorous (P=0.02) and parathyroid hormone (P=0.01) were noted during STS treatment in patients who completed the therapy. Conclusions Although conclusive evidence regarding its efficacy is lacking, a majority of patients who received STS demonstrated clinical improvement in this study. PMID:23520041

Hoarding in Youth with Autism Spectrum Disorders and Anxiety: Incidence, Clinical Correlates, and Behavioral Treatment Response

ERIC Educational Resources Information Center

Storch, Eric A.; Nadeau, Joshua M.; Johnco, Carly; Timpano, Kiara; McBride, Nicole; Mutch, P. Jane; Lewin, Adam B.; Murphy, Tanya K.

2016-01-01

This study examined the nature and correlates of hoarding among youth with autism spectrum disorders (ASD). Forty children with ASD and a comorbid anxiety disorder were administered a battery of clinician-administered measures assessing presence of psychiatric disorders and anxiety severity. Parents completed questionnaires related to child…

Expressive and Receptive Language Effects of African American English on a Sentence Imitation Task

ERIC Educational Resources Information Center

Terry, J. Michael; Jackson, Sandra C.; Evangelou, Evangelos; Smith, Richard L.

2010-01-01

This study tests the extent to which giving credit for African American English (AAE) responses on a General American English sentence imitation test mitigates dialect effects. Forty-eight AAE-speaking second graders completed the Recalling Sentences subtest of the Clinical Evaluation of Language Fundamentals-Third Edition (1995). A Bayesian…

Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy.

PubMed

Schaeffer, Edward M; Guzzo, Thomas J; Furge, Kyle A; Netto, George; Westphal, Michael; Dykema, Karl; Yang, Ximing; Zhou, Ming; Teh, Bin Tean; Pavlovich, Christian P

2010-07-01

Aetiology (case series) Level of Evidence 4. To present the molecular rationale and potential clinical benefit of topoisomerase II (TopoII)-inhibiting therapy for renal medullary carcinoma (RMC), a rare but extremely lethal form of kidney cancer that classically afflicts young men with sickle-cell trait. The current therapeutic approach with these aggressive tumours is radical nephrectomy followed by systemic chemotherapy, but the prognosis remains dismal. The whole-genome expression was analysed in four RMC tumours. We also report a case of metastatic RMC in which a complete response was achieved for 9 months using a TopoII-inhibiting therapy. Expanded whole-genome expression analysis showed increases of TopoII in all cases. There was also overall deregulation of DNA remodelling and repair, and an ontological association between RMC and urothelial carcinoma. Using a TopoII-inhibiting agent, there was a complete response for 9 months in a patient with metastatic RMC. This report provides molecular evidence for the rational use of TopoII inhibitors in the treatment of RMC.

Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01).

PubMed

Charehbili, A; van de Ven, S; Smit, V T H B M; Meershoek-Klein Kranenbarg, E; Hamdy, N A T; Putter, H; Heijns, J B; van Warmerdam, L J C; Kessels, L; Dercksen, M; Pepels, M J; Maartense, E; van Laarhoven, H W M; Vriens, B; Wasser, M N; van Leeuwen-Stok, A E; Liefers, G J; van de Velde, C J H; Nortier, J W R; Kroep, J R

2014-05-01

The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.

Efficacy of Skin-Directed Therapy for Cutaneous Metastases From Advanced Cancer: A Meta-Analysis

PubMed Central

Spratt, Daniel E.; Gordon Spratt, Elizabeth A.; Wu, Shenhong; DeRosa, Antonio; Lee, Nancy Y.; Lacouture, Mario E.; Barker, Christopher A.

2014-01-01

Purpose To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. Methods MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I2 tests. Results After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Conclusion Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed. PMID:25154827

The Script Concordance Test: a new tool assessing clinical judgement in neurology.

PubMed

Lubarsky, Stuart; Chalk, Colin; Kazitani, Driss; Gagnon, Robert; Charlin, Bernard

2009-05-01

Clinical judgment, the ability to make appropriate decisions in uncertain situations, is central to neurological practice, but objective measures of clinical judgment in neurology trainees are lacking. The Script Concordance Test (SCT), based on script theory from cognitive psychology, uses authentic clinical scenarios to compare a trainee's judgment skills with those of experts. The SCT has been validated in several medical disciplines, but has not been investigated in neurology. We developed an Internet-based neurology SCT (NSCT) comprising 24 clinical scenarios with three to four questions each. The scenarios were designed to reflect the uncertainty of real-life clinical encounters in adult neurology. The questions explored aspects of the scenario in which several responses might be acceptable; trainees were asked to judge which response they considered to be best. Forty-one PGY1-PGY5 neurology residents and eight medical students from three North American neurology programs (McGill, Calgary, and Mayo Clinic) completed the NSCT. The responses of trainees to each question were compared with the aggregate responses of an expert panel of 16 attending neurologists. The NSCT demonstrated good reliability (Cronbach alpha = 0.79). Neurology residents scored higher than medical students and lower than attending neurologists, supporting the test's construct validity. Furthermore, NSCT scores discriminated between senior (PGY3-5) and junior residents (PGY1-2). Our NSCT is a practical and reliable instrument, and our findings support its construct validity for assessing judgment in neurology trainees. The NSCT has potentially widespread applications as an evaluation tool, both in neurology training and for licensing examinations.

[Adriamycin, cyclophosphamide, ftorafur and tamoxifen (ACFT) in patients with advanced breast cancer].

PubMed

Imajo, K; Ogawa, M; Horikoshi, N; Inoue, K; Mukaiyama, T; Ozeki, H; Nagamine, D; Shinagawa, K; Fukutani, H

1988-01-01

One hundred and six patients with advanced breast cancer were treated with chemoendocrine therapy consisting of adriamycin (40 mg/m2) i.v. on day 1 and cyclophosphamide (130 mg/m2) i.v. daily for 5 days every 3 weeks, ftorafur (500 mg/m2) and tamoxifen (40 mg) orally daily. Of 82 evaluable patients, 16 showed complete response (20%), 32 partial response (39%), 32 no change (39%), and two progressive disease (2%). The overall response rate was 59%, and the median duration of response was 16.3 (3.5-67+) months with a median survival time from the start of chemoendocrine therapy of 25.5 (3.5-67+) months. The median survival time of responders (32.5 months) was significantly longer than that of non-responders (15.3 months). The major toxicities were hair loss, G1 symptoms, and hematological toxicity, but these were clinically well tolerated. No serious cardiac, renal or liver damage was seen. These results indicated that the addition of tamoxifen to the ACF regimen increased the number of complete responses and prolonged the survival time of responders.

First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases.

PubMed

Sharma, Mayur; Jia, Xuefei; Ahluwalia, Manmeet; Barnett, Gene H; Vogelbaum, Michael A; Chao, Samuel T; Suh, John H; Murphy, Erin S; Yu, Jennifer S; Angelov, Lilyana; Mohammadi, Alireza M

2017-09-01

Local progression (LP) and radiation necrosis (RN) occur in >20% of cases following stereotactic radiosurgery (SRS) for brain metastases (BM). Expected outcomes following SRS for BM include tumor control/shrinkage, local progression and radiation necrosis. 1427 patients with 4283 BM lesions were treated using SRS at Cleveland Clinic from 2000 to 2012. Clinical, imaging and radiosurgery data were collected from the database. Local tumor progression and RN were the primary end points and correlated with patient and tumor-related variables. 5.7% of lesions developed radiographic RN and 3.6% showed local progression at 6 months. Absence of new extracranial metastasis (P < 0.001), response to SRS at first follow-up scan (local progression versus stable size (P < 0.001), partial resolution versus complete resolution at first follow up [P = 0.009]), prior SRS to the same lesion (P < 0.001), IDL% (≤55; P < 0.001), maximum tumor diameter (>0.9 cm; P < 0.001) and MD/PD gradient index (≤1.8, P < 0.001) were independent predictors of high risk of local tumor progression. Absence of systemic metastases (P = 0.029), good neurological function at 1st follow-up (P ≤ 0.001), no prior SRS to other lesion (P = 0.024), low conformity index (≤1.9) (P = 0.009), large maximum target diameter (>0.9 cm) (P = 0.003) and response to SRS (tumor progression vs. stable size following SRS [P < 0.001]) were independent predictors of high risk of radiographic RN. Complete tumor response at first follow-up, maximum tumor diameter <0.9 cm, tumor volume <2.4 cc and no prior SRS to the index lesion are good prognostic factors with reduced risk of LP following SRS. Complete tumor response to SRS, poor neurological function at first follow-up, prior SRS to other lesions and high conformity index are favorable factors for not developing RN. Stable or partial response at first follow-up after SRS have same impact on local progression and RN compared to those with complete resolution or progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Midwifery students׳ experiences of an innovative clinical placement model embedded within midwifery continuity of care in Australia.

PubMed

Carter, Amanda G; Wilkes, Elizabeth; Gamble, Jenny; Sidebotham, Mary; Creedy, Debra K

2015-08-01

midwifery continuity of care experiences can provide high quality clinical learning for students but can be challenging to implement. The Rural and Private Midwifery Education Project (RPMEP) is a strategic government funded initiative to (1) grow the midwifery workforce within private midwifery practice and rural midwifery, by (2) better preparing new graduates to work in private midwifery and rural continuity of care models. this study evaluated midwifery students׳ experience of an innovative continuity of care clinical placement model in partnership with private midwifery practice and rural midwifery group practices. a descriptive cohort design was used. All students in the RPMEP were invited to complete an online survey about their experiences of clinical placement within midwifery continuity models of care. Responses were analysed using descriptive statistics. Correlations between total scale scores were examined. Open-ended responses were analysed using content analysis. Internal reliability of the scales was assessed using Cronbach׳s alpha. sixteen out of 17 completed surveys were received (94% response rate). Scales included in the survey demonstrated good internal reliability. The majority of students felt inspired by caseload approaches to care, expressed overall satisfaction with the mentoring received and reported a positive learning environment at their placement site. Some students reported stress related to course expectations and demands in the clinical environment (e.g. skill acquisition and hours required for continuity of care). There were significant correlations between scales on perceptions of caseload care and learning culture (r=.87 p<.001) and assessment (r=.87 p<.001). Scores on the clinical learning environment scale were significantly correlated with perceptions of the caseload model (rho=.86 p<.001), learning culture (rho=.94 p<.001) and assessment (rho=.65 p<.01) scales. embedding students within midwifery continuity of care models was perceived to be highly beneficial to learning, developed partnerships with women, and provided appropriate clinical skills development required for registration, while promoting students׳ confidence and competence. The flexible academic programme enabled students to access learning at any time and prioritise continuity of care experiences. Strategies are needed to better support students achieve a satisfactory work-life balance. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Sentinel Lymph Node Biopsy in Breast Cancer: A Clinical Review and Update

PubMed Central

Haji, Altaf; Battoo, Azhar; Qurieshi, Mariya; Mir, Wahid; Shah, Mudasir

2017-01-01

Sentinel lymph node biopsy has become a standard staging tool in the surgical management of breast cancer. The positive impact of sentinel lymph node biopsy on postoperative negative outcomes in breast cancer patients, without compromising the oncological outcomes, is its major advantage. It has evolved over the last few decades and has proven its utility beyond early breast cancer. Its applicability and efficacy in patients with clinically positive axilla who have had a complete clinical response after neoadjuvant chemotherapy is being aggressively evaluated at present. This article discusses how sentinel lymph node biopsy has evolved and is becoming a useful tool in new clinical scenarios of breast cancer management. PMID:28970846

Sentinel Lymph Node Biopsy in Breast Cancer: A Clinical Review and Update.

PubMed

Zahoor, Sheikh; Haji, Altaf; Battoo, Azhar; Qurieshi, Mariya; Mir, Wahid; Shah, Mudasir

2017-09-01

Sentinel lymph node biopsy has become a standard staging tool in the surgical management of breast cancer. The positive impact of sentinel lymph node biopsy on postoperative negative outcomes in breast cancer patients, without compromising the oncological outcomes, is its major advantage. It has evolved over the last few decades and has proven its utility beyond early breast cancer. Its applicability and efficacy in patients with clinically positive axilla who have had a complete clinical response after neoadjuvant chemotherapy is being aggressively evaluated at present. This article discusses how sentinel lymph node biopsy has evolved and is becoming a useful tool in new clinical scenarios of breast cancer management.

Reirradiation of canine nasal carcinomas treated with coarsely fractionated radiation protocols: 37 cases.

PubMed

Gieger, Tracy; Siegel, Sheri; Rosen, Kari; Jackson, Dorothy; Ware, Kevin; Kiselow, Michael; Shiomitsu, Keijiro

2013-01-01

Data from 37 dogs with nasal carcinomas treated with two or more coarsely fractionated courses of radiation therapy (RT) were retrospectively reviewed. The median radiation dose for the first course of RT was 24 Gray (Gy). All dogs clinically responded, and 11 had complete resolution of signs for a median of 114 days. Dogs were retreated at relapse, with a median dose of 20 Gy, and 26 of 37 dogs (70%) had clinical responses. The second course of RT was initiated at a median of 150 days following completion of the first course. Side effects were mild: four dogs had chronic ocular conditions necessitating medication, one of which required enucleation. Median survival time (ST) from the first dose of RT was 453 days and 180 days from the first dose of the second course of RT. The following factors were examined but were not significant for survival: total RT dose, dose of the first course of RT, complete resolution of clinical signs, use of either chemotherapy or nonsteroidal anti-inflammatory drugs (NSAIDs), and stage (T1/T2 versus T3/T4). Dogs responded well to reirradiation with a subset experiencing chronic ocular side effects.

Using simulation to prepare for clinical practice.

PubMed

Morgan, James; Green, Victoria; Blair, John

2018-02-01

A significant proportion of medical students feel underprepared for clinical practice, especially in skills such as decision making, prioritisation and prescribing. Changes to medical curricula, including assistantships and shadowing, provide supervised practise, but students remain unable to fully take responsibility for patient care. Simulation may assist in addressing this deficit. A simulation course entitled 'Simulated ward round and professional skills' (SWAPS) was developed to improve student preparation for clinical practice. Preliminary work surveyed 22 foundation doctors to identify perceived areas of weakness and to guide the learning outcomes of the course. Following the design and development of the course, 133 final-year medical students were observed completing a 60-minute simulation scenario aimed at providing experiential learning in a ward environment, reflecting professional practice. Students received structured feedback and completed pre- and post-course questionnaires to evaluate changes in confidence over the learning domains. Qualitative feedback was also collected. A significant proportion of medical students feel underprepared for clinical practice RESULTS: The p values were significant in all assessed domains, indicating a perceived improvement in confidence following the SWAPS course. Qualitative feedback highlighted the perceived utility of the course in exposing students to clinical ward-based scenarios infrequently encountered in their medical curriculum. Students praised the personal feedback received and realism of the simulation. This paper contributes to the growing body of literature supporting the use of simulation to replicate a ward round and the daily roles of a junior doctor. The SWAPS course seems to empower students to take responsibility for clinical decision making and experience some of the realities of foundation training in a simulated setting. © 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Impact of supervised student optometry consultations on the patient experience.

PubMed

Bentley, Sharon A; Trevaskis, Jane E; Woods, Craig A; Guest, Daryl; Watt, Kathleen G

2018-03-01

Understanding patient perceptions of having students involved in their clinical care is important as we strive to develop optimal models of care that integrate teaching with the best possible experience for the patient. The aim was to ascertain the impact of supervised optometry student consultations on the patient experience. A survey comprising 45 questions was mailed to consecutive adult patients who had undergone a comprehensive eye examination at the Australian College of Optometry over a four-week period. Responses were received from 193 patients who had a student involved in their care (44 per cent response rate; 156 completed correctly) and 177 who did not have a student involved (32 per cent response rate; 105 completed correctly). There was no significant difference in overall patient satisfaction between the teaching and non-teaching clinics (p = 0.18). Over 87 per cent of patients in the teaching clinic felt completely comfortable with a student examining them, 44 per cent felt their care was better because a student was involved and 97 per cent rated the overall performance of the student as very good or good. Although 12 per cent would rather have seen only the optometrist and three per cent would not be happy to have a student involved in their eye care again, 100 per cent believed it is important for students to work with patients. The most common reason for student acceptance was the importance of students needing opportunities to learn. The main reasons for unwillingness to have a student involved in future were the additional time taken and prolonged testing. The findings of this study suggest that most patients view supervised student involvement in their optometric care as an important and highly positive experience. However, efforts should be made to avoid excessively long consultations and prolonged testing. Concerns about patient satisfaction and acceptance are largely unwarranted and should not prevent optometry students being involved in patient care. © 2017 Optometry Australia.

A retrospective review of pain control by a two-step irradiance schedule during topical ALA-photodynamic therapy of non-melanoma skin cancer.

PubMed

Zeitouni, Nathalie C; Paquette, Anne D; Housel, Joseph P; Shi, Yi; Wilding, Gregory E; Foster, Thomas H; Henderson, Barbara W

2013-02-01

Photodynamic therapy (PDT) with topical δ-aminolevulinic acid (ALA) of non-melanoma skin cancers is often associated with treatment-limiting pain. A previous study on basal cell carcinomas (BCCs) at Roswell Park Cancer Institute evaluated a two-step irradiance scheme as a means of minimizing pain, preserving outcomes, and limiting treatment time. We used an initial low irradiance until 90% of the protoporphyrin IX was photobleached, followed by a high irradiance interval until the prescribed fluence was delivered. Success of this pilot investigation motivated integration of the protocol into routine practice. Here, we present a retrospective review of recent clinical experience in a broad patient population. This was a retrospective review of an existing dermatology database. Fourteen caucasion patients-nine men and five women, ages 18-80, with a total of 51 superficial and 73 nodular BCCs, and three Bowen's disease lesions-were included. ALA was applied to each lesion for approximately 4 hours. Lesions received an initial irradiance of 30-50 mW/cm(2) for 20 J/cm(2) , followed by 150 mW/cm(2) for a total fluence of 200-300 J/cm(2) . Pain was assessed using a visual analog scale (VAS). Clinical outcome was determined at 6-12 months. Median VAS scores were 1.0 for both irradiances. Five of 127 lesions required pain control with 1% xylocaine. Pain was strongly influenced by lesion location but not by lesion type, number, or size. Complete responses were achieved in 84.1% of BCCs, which compares favorably with reported results for single ALA-PDT treatments. Two of three Bowen's disease lesions showed a complete response. Complete responses for nodular BCCs were 37%, which are also within the range of reported outcomes. A two-step irradiance protocol in ALA-PDT effectively minimizes pain, maintains excellent clinical outcomes in superficial lesions, and adds minimal treatment time. Copyright © 2013 Wiley Periodicals, Inc.

Does clinical presentation predict response to a nonsurgical chronic disease management program for endstage hip and knee osteoarthritis?

PubMed

Eyles, Jillian P; Lucas, Barbara R; Patterson, Jillian A; Williams, Matthew J; Weeks, Kate; Fransen, Marlene; Hunter, David J

2014-11-01

To identify baseline characteristics of participants who will respond favorably following 6 months of participation in a chronic disease management program for hip and knee osteoarthritis (OA). This prospective cohort study assessed 559 participants at baseline and following 6 months of participation in the Osteoarthritis Chronic Care Program. Response was defined as the minimal clinically important difference of an 18% and 9-point absolute improvement in the Western Ontario and McMaster Universities Arthritis Index global score. Multivariate logistic regression modeling was used to identify predictors of response. Complete data were available for 308 participants. Those who withdrew within the study period were imputed as nonresponders. Three variables were independently associated with response: signal joint (knee vs hip), sex, and high level of comorbidity. Index joint and sex were significant in the multivariate model, but the model was not a sensitive predictor of response. Strong predictors of response to a chronic disease management program for hip and knee OA were not identified. The significant predictors that were found should be considered in future studies.

Access to abortion: what women want from abortion services.

PubMed

Wiebe, Ellen R; Sandhu, Supna

2008-04-01

Whether Canadian physicians can refuse to refer women for abortion and whether private clinics can charge for abortions are matters of controversy. We sought to identify barriers to access for women seeking therapeutic abortion and to have them identify what they considered to be most important about access to abortion services. Women presenting for abortion over a two-month period at two free-standing abortion clinics, one publicly funded and the other private, were invited to participate in the study. Phase I of the study involved administration of a questionnaire seeking information about demographics, perceived barriers to access to abortion, and what the women wanted from abortion services. Phase II involved semi-structured interviews of a convenience sample of women to record their responses to questions about access. Responses from Phase I questionnaires were compared between the two clinics, and qualitative analysis was performed on the interview responses. Of 423 eligible women, 402 completed questionnaires, and of 45 women approached, 39 completed interviews satisfactorily. Women received information about abortion services from their physicians (60.0%), the Internet (14.8%), a telephone directory (7.8%), friends or family (5.3%), or other sources (12.3%). Many had negative experiences in gaining access. The most important issue regarding access was the long wait time; the second most important issue was difficulty in making appointments. In the private clinic, 85% of the women said they were willing to pay for shorter wait times, compared with 43.5% in the public clinic. Physicians who failed to refer patients for abortion or provide information about obtaining an abortion caused distress and impeded access for a significant minority of women requesting an abortion. Management of abortion services should be prioritized to reflect what women want: particularly decreased wait times for abortion and greater ease and convenience in booking appointments. Since many women are willing to pay for services in order to have an abortion within one week, this option should be considered by policy makers.

Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist

PubMed Central

Levine, Bruce L.

2016-01-01

The field of cancer immunotherapy has rapidly progressed in the past decade as several therapeutic modalities have entered into the clinic. One such immunotherapy that has shown promise in the treatment of cancer is the use of chimeric antigen receptor (CAR)-modified T lymphocytes. CARs are engineered receptors constructed from antigen recognition regions of antibodies fused to T-cell signaling and costimulatory domains that can be used to reprogram a patient’s T cells to specifically target tumor cells. CAR T-cell therapy has demonstrated sustained complete responses for some patients with advanced leukemia, and a number of CAR therapies are being evaluated in clinical studies. CAR T-cell therapy-associated toxicities, including cytokine release syndrome, macrophage activation syndrome, and tumor lysis syndrome, have been observed and effectively managed in the clinic. In patients with significant clinical responses, sustained B-cell aplasia has also been observed and is a marker of CAR T-cell persistence that might provide long-term disease control. Education on CAR T-cell therapy efficacy and safety management is critical for clinicians and patients who are considering this novel type of treatment. In the present report, the current landscape of CAR T-cell therapy, the effective management of patients undergoing treatment, and which patients are the most suitable candidates for current trials are discussed. Implications for Practice: The present report describes the current status of chimeric antigen receptor (CAR) T lymphocytes as an immunotherapy for patients with relapsed or refractory B-cell malignancies. CAR T cells targeting CD19, a protein expressed on many B-cell malignancies, typically induce high complete response rates in patients with B-cell leukemia or lymphoma who have very limited therapeutic options. Recent clinical trial results of CD19 CAR T-cell therapies and the management of CAR T-cell-associated adverse events are discussed. The present report will therefore inform physicians regarding the efficacy and safety of CAR T cells as a therapy for B-cell malignancies. PMID:27009942

Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract.

PubMed

Horvath, Dennis J; Patel, Ashay S; Mohamed, Ahmad; Storm, Douglas W; Singh, Chandra; Li, Birong; Zhang, Jingwen; Koff, Stephen A; Jayanthi, Venkata R; Mason, Kevin M; Justice, Sheryl S

2016-01-11

Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract

PubMed Central

Horvath, Dennis J.; Patel, Ashay S.; Mohamed, Ahmad; Storm, Douglas W.; Singh, Chandra; Li, Birong; Zhang, Jingwen; Koff, Stephen A.; Jayanthi, Venkata R.; Mason, Kevin M.

2016-01-01

ABSTRACT Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. IMPORTANCE The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production. PMID:26755631

[Evaluation of the radiofrequency ablation effectiveness in patients with the Wolff-Parkinson-White syndrome].

PubMed

Ushakov, I B; Ardashev, A V; Ardashev, V N; Voronkov, Iu I; Sharoĭko, M V; Akimova, O S

2012-01-01

A one-year prospective study involved 22 patients with the Wolff-Parkinson-White syndrome (WPW) and 20 healthy people. Means age of patients was 34.3 +/- 16.3 years. All 22 patients were successfully treated with radiofrequency ablation (RFA) of additional pathways. RFA effectiveness was evaluated with the help of clinical questionnaire, data of ECG, EchoCG, heart rate variability (HRV), frequency response and nonlinear dynamics. Cardiac rhythm disturbances were verified using Holter monitoring applied to all patients. Positive clinical effect was achieved in all the WPW patients, as RFA arrested cardiac arrhythmias completely. Holter monitoring did not register cardiac disturbances which points to high RFA effectiveness in WPW patients. HRV, frequency response and nonlinear dynamics reassumed their normal patterns.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

PubMed

Bossuyt, V; Provenzano, E; Symmans, W F; Boughey, J C; Coles, C; Curigliano, G; Dixon, J M; Esserman, L J; Fastner, G; Kuehn, T; Peintinger, F; von Minckwitz, G; White, J; Yang, W; Badve, S; Denkert, C; MacGrogan, G; Penault-Llorca, F; Viale, G; Cameron, D

2015-07-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[What role for paraclinical investigations within clinical trials conducted in psychiatric patients?

PubMed

Kaladjian, A; Adida, M; Simon, N; Belzeaux, R; Blin, O; Fakra, E; Azorin, J-M

2016-12-01

As in the usual care of patients, paraclinical investigations have today only a very modest role in clinical trials in psychiatry, mainly to complete the pre-therapeutical assessments prior to inclusion of subjects or to monitor treatment tolerance. Yet, the accumulation of data in neurosciences suggests the next emergence of biomarkers, whose interest is that they are closely associated to the biological disturbances underlying psychiatric illnesses, and that they are accessible by means of technological tools such as imaging devices. These tools allow to explore the effects on brain of psychotropic medications, such as antidepressants, antipsychotics, or mood stabilizers, in relation to their therapeutic action. The obtained results allow to consider the use of such biomarkers in clinical trials in addition to more conventional approaches. In particular, they could be used as targets to measure brain response to treatment in association with clinical response, to predict a therapeutic response from the neurofunctional characteristics of patients, or to establish the safety profile of drugs on the nervous system. The use of such biomarkers in clinical trials would help to better define the explored populations and their characteristics, as well as the variables to assess, and to better measure the impact of the treatments and their potential harmful effects on the nervous system. © L’Encéphale, Paris, 2016.

A call for more transparency of registered clinical trials on endometriosis

PubMed Central

Guo, Sun-Wei; Hummelshoj, Lone; Olive, David L.; Bulun, Serdar E.; D'Hooghe, Thomas M.; Evers, Johannes L.H.

2009-01-01

In response to the pressing need for more efficacious and safer therapeutics for endometriosis, there have been numerous reports in the last decade of positive results from animal and in vitro studies of various compounds as potential therapeutics for endometriosis. A handful of these have undergone phase II/III clinical trials. Since the announcement of the International Committee of Medical Journal Editors that mandated registration as a prerequisite for publication, 57 endometriosis-related clinical trials have been registered at ClinicalTrials.gov, an Internet-based public depository for information on drug studies. Among them, 25 are listed as completed, and 2 as suspended. There are 15 completed phase II/III trials, which evaluated the efficacy of various promising compounds. Yet only three of the 15 trials (20%) have published their results. The remaining 12 (80%) studies so far have not published their findings. We argue that this apparent lack of transparency will actually not benefit the trial sponsors or the public, and will ultimately prove detrimental to research efforts attempting to develop more efficacious and safer therapeutics for endometriosis. Thus we call for more transparency of clinical trials on endometriosis. PMID:19264712

Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

PubMed

Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

1995-07-01

In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.

Maintenance therapy in colon cancer.

PubMed

Giuliani, F; De Vita, F; Colucci, G; Pisconti, S

2010-11-01

In the last decade dramatic improvements have been obtained in the treatment of metastatic colorectal cancer. Thanks to the introduction in the clinical practice of new drugs such as Irinotecan and Oxaliplatin, and modern biological drugs such as Bevacizumab and Cetuximab, the response rate, progression-free and overall survival are about 50-60%, 9-11 and 20-24 months respectively. Despite this progress, many questions remain unsolved especially those related to the optimal duration of treatment and the role of maintenance therapy. To treat until progression (or unacceptable toxicity) is the classical way but in the common clinical practice is frequent to perform an induction therapy (until the maximum response is obtained) followed by a complete stop and restart on progression, or by a maintenance without the drug/s responsible of the major cumulative toxicities. The following report focus on the role of different strategies respect to the classic "treatment until progression". Copyright © 2010 Elsevier Ltd. All rights reserved.

Doctor-office collaborative care for pediatric behavioral problems: a preliminary clinical trial.

PubMed

Kolko, David J; Campo, John V; Kilbourne, Amy M; Kelleher, Kelly

2012-03-01

To evaluate the feasibility and clinical benefits of an integrated mental health intervention (doctor-office collaborative care [DOCC]) vs enhanced usual care (EUC) for children with behavioral problems. Cases were assigned to DOCC and EUC using a 2:1 randomization schedule that resulted in 55 DOCC and 23 EUC cases. Preassessment was conducted in 4 pediatric primary care practices. Postassessment was conducted in the pediatric or research office. Doctor-office collaborative care was provided in the practice; EUC was initiated in the office but involved a facilitated referral to a local mental health specialist. Of 125 referrals (age range, 5-12 years), 78 children participated. Children and their parents were assigned to receive DOCC or EUC. Preassessment diagnostic status was evaluated using the Schedule for Affective Disorders and Schizophrenia for School-aged Children. Preassessment and 6-month postassessment ratings of behavioral and emotional problems were collected from parents using the Vanderbilt Attention-Deficit/Hyperactivity Disorder Diagnostic Parent Rating Scale, as well as individualized goal achievement ratings forms. At discharge, care managers and a diagnostic evaluator completed the Clinical Global Impression Scale, and pediatricians and parents completed satisfaction and study feedback measures. Group comparisons found significant improvements for DOCC over EUC in service use and completion, behavioral and emotional problems, individualized behavioral goals, and overall clinical response. Pediatricians and parents were highly satisfied with DOCC. The feasibility and clinical benefits of DOCC for behavioral problems support the integration of collaborative mental health services for common mental disorders in primary care.

Responsiveness of pain and disability measures for chronic whiplash.

PubMed

Stewart, Mark; Maher, Christopher G; Refshauge, Kathryn M; Bogduk, Nikolai; Nicholas, Michael

2007-03-01

Cohort study. To evaluate the responsiveness of common pain and disability measures in a cohort of patients with chronic whiplash. Pain and disability are routinely measured in clinical practice and clinical research. However, to date, a head-to-head comparison of competing measures for whiplash patients has not been performed. Pain (pain intensity, bothersomeness, and SF-36 bodily pain score) and disability (Patient Specific Functional Scale, Neck Disability Index, Functional Rating Index, Copenhagen Scale, and SF-36 physical summary) measures were completed by 132 patients with chronic whiplash at baseline and then again after 6 weeks together with an 11-point global perceived effect scale. Internal responsiveness was evaluated by calculating effect sizes and standardized response means, and external responsiveness by correlating change scores with global perceived effect scores and by ROC curves. The ranking of responsiveness was consistent across the different analyses. Pain bothersomeness was more responsive than pain intensity, which was more responsive than the SF-36 pain measure. The Patient Specific Functional Scale was the most responsive disability measure, followed by the spine-specific measures, with the SF-36 physical summary measure the least responsive. Pain bothersomeness and the Patient Specific Functional Scale provide the most responsive measures of pain and disability, respectively, in patients with chronic whiplash.

Radiosensitivity of cancer-initiating cells and normal stem cells (or what the Heisenberg uncertainly principle has to do with biology).

PubMed

Woodward, Wendy Ann; Bristow, Robert Glen

2009-04-01

Mounting evidence suggests that parallels between normal stem cell biology and cancer biology may provide new targets for cancer therapy. Prospective identification and isolation of cancer-initiating cells from solid tumors has promoted the descriptive and functional identification of these cells allowing for characterization of their response to contemporary cancer therapies, including chemotherapy and radiation. In clinical radiation therapy, the failure to clinically eradicate all tumor cells (eg, a lack of response, partial response, or nonpermanent complete response by imaging) is considered a treatment failure. As such, biologists have explored the characteristics of the small population of clonogenic cancer cells that can survive and are capable of repopulating the tumor after subcurative therapy. Herein, we discuss the convergence of these clonogenic studies with contemporary radiosensitivity studies that use cell surface markers to identify cancer-initiating cells. Implications for and uncertainties regarding incorporation of these concepts into the practice of modern radiation oncology are discussed.

A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma

PubMed Central

Deniger, Drew C.; Kwong, Mei Li M.; Pasetto, Anna; Dudley, Mark E.; Wunderlich, John R.; Langhan, Michelle M.; Lee, Chyi-Chia Richard; Rosenberg, Steven A.

2016-01-01

Purpose This pilot feasibility clinical trial evaluated the co-administration of vemurafenib, a small molecule antagonist of BRAFV600 mutations, and tumor infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. Experimental Design A metastatic tumor was resected for growth of TIL and patients were treated with vemurafenib for 2 weeks followed by resection of a second lesion. Patients then received a non-myeloablative pre-conditioning regimen, infusion of autologous TIL and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by RECIST 1.0. Metastases resected prior to and after two weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation and recognition of autologous tumor. Results The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TIL and peripheral blood T cells were inhibited in vitro by vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TIL grown from pre- and post-vemurafenib metastases. Conclusions Co-administration of vemurafenib and TIL was safe, feasible and generated objective clinical responses in this small pilot clinical trial. PMID:28093487

Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes

NASA Astrophysics Data System (ADS)

Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Kumar, Sameera; Shang, Yu; Huang, Chong; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

2016-08-01

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs‧) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96.

Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes

PubMed Central

Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Kumar, Sameera; Shang, Yu; Huang, Chong; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

2016-01-01

Abstract. This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs′) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96. PMID:27564315

Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study)

PubMed Central

García-Cabeza, Ignacio; Gómez, Juan-Carlos; Sacristán, Jose A; Edgell, Eric; González de Chavez, Manuel

2001-01-01

Background In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. Method Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. Results A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. Conclusion Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS. PMID:11835695

A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma.

PubMed

Deniger, Drew C; Kwong, Mei Li M; Pasetto, Anna; Dudley, Mark E; Wunderlich, John R; Langhan, Michelle M; Lee, Chyi-Chia Richard; Rosenberg, Steven A

2017-01-15

This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF V600 mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Metastases resected prior to and after 2 weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation, and recognition of autologous tumor. The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response, and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TILs and peripheral blood T cells were inhibited in vitro by research-grade vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality, and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TILs grown from pre- and post-vemurafenib metastases. Coadministration of vemurafenib and TILs was safe and feasible and generated objective clinical responses in this small pilot clinical trial. Clin Cancer Res; 23(2); 351-62. ©2016 AACRSee related commentary by Cogdill et al., p. 327. ©2016 American Association for Cancer Research.

Hematoporphyrin-mediated photodynamic therapy for treatment of head and neck cancer: clinical update 1996

NASA Astrophysics Data System (ADS)

Schweitzer, Vanessa G.

1996-04-01

From 1983 to 1996 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 55 of 56 patients treated with hematoporphyrin-derivative or PHOTOFRIN-mediated photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial 'condemned mucosa' or 'field cancerization' of the oral cavity and larynx (7 cases); (2) Stage III/IV head and neck cancer (25 cases); (3) mucocutaneous AIDS-associated Kaposi's sarcoma of the upper aerodigestive tract and non AIDS-related Kaposi's sarcoma of the lower extremity (15 cases); (4) recurrent laryngotracheal papillomatosis (3 cases); (5) severe dysplasia/adenocarcinoma or squamous cell carcinoma in situ in Barrett's esophagus (4 cases); (6) partial or completely obstructing terminal esophageal cancer (9 cases). At the time of this report, HPD-PDT produced complete responses in 24 patients (follow up 6 months to 9 years) with 'field cancerization' (CIS, T1N0M0) of the oral cavity and larynx (6 cases), adenocarcinoma in situ in Barrett's esophagus (3 cases), mucocutaneous Kaposi's sarcoma (12 cases), obstructing esophageal carcinoma (1 case), and stage IV squamous cell carcinoma of the nasopharynx (1 case), and radiation therapy or solar-induced basal cell/squamous cell carcinomas (2 cases). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck cancer are reviewed in this article.

Photodynamic therapy--1994: treatment of benign and malignant upper aerodigestive tract disease

NASA Astrophysics Data System (ADS)

Schweitzer, Vanessa G.

1995-03-01

From 1983 to 1994 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 46 of 47 patients treated with hematoporphyrin-derivative photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial `condemned mucosa' or `field cancerization' of the oral cavity; (2) stage III/IV head and neck cancer; (3) mucocutaneous AIDS-related Kaposi's sarcoma of the upper aerodigestive tract; (4) recurrent laryngotracheal papillomatosis; (5) severe dysplasia/adenocarcinoma in situ in Barrett's esophagus; (6) partial or completely obstructing terminal esophageal cancer. HPD-PDT produced complete responses in 19 patients (follow up 6 months to 8 years) with `field cancerization' (CIS, T1) of the oral cavity and larynx (6), adenocarcinoma in situ in Barrett's esophagus (2), mucocutaneous Kaposi's sarcoma (9), obstructing esophageal carcinoma (1), and stage IV squamous cell carcinoma of the nasopharynx (1). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck disease are reviewed.

Cumulative recruitment experience in two large single-center randomized, controlled clinical trials.

PubMed

Galbreath, Autumn Dawn; Smith, Brad; Wood, Pamela; Forkner, Emma; Peters, Jay I

2008-05-01

Trial recruitment is challenging for researchers, who frequently overestimate the pool of qualified, willing participants. Little has been written about recruitment and the comparative success of recruitment strategies. We describe one center's experience with recruitment in two regional single-center clinical trials with a combined total of 1971 participants. The heart failure trial was conducted between 1999 and 2003. The asthma trial was performed between 2003 and 2006. Trial databases were queried for referral source of each individual. Data were analyzed for effectiveness of referral source using three measures: percentage of enrollment due to that source, subject commitment to the trial (retention rate), and economics (cost per enrollee). 47.8% of CHF enrollees came from computer-generated lists or from healthcare provider referrals. Average marketing cost for enrollees and completers was $29.20 and $41.96 respectively. The most economical marketing strategy was self-referral in response to flyers. Most asthma participants (53.5%) were referred from healthcare providers, mailings to lists from local healthcare institutions, or self-referred in response to flyers. Average marketing cost for enrollees and completers was $20.44 and $38.10 respectively. The most economical marketing strategy was patient mailings. Retention rates were not markedly different among referral sources in either trial. In order to be considered effective, a recruitment strategy must demonstrate a balance between response to recruitment, retention rates, and economics. Despite the differences between these two clinical trials, the most effective recruitment strategies in both trials were mailings to locally-generated, targeted lists, and referrals from healthcare providers.

Development of a Questionnaire to Investigate Study Design Factors Influencing Participation in Gait Rehabilitation Research by People with Stroke: A Brief Report.

PubMed

Patterson, Kara K; Gallant, Nicole; Ormiston, Tracey; Patience, Chad; Whitechurch, Mandy; Mansfield, Avril; Brown, Janet

2015-08-01

The main objective of this study was to evaluate the feasibility of a newly developed questionnaire to assess the influence of study design on participation in gait rehabilitation research in a pilot test with individuals with stroke. A secondary objective was to investigate the relationship between participation in gait rehabilitation research and social and clinical factors of interest after stroke. A questionnaire was developed with expert opinion and guidance from related previous research. The questionnaire was pilot tested in a group of 21 people with stroke, and social and clinical factors (including gait function) were collected. Gait function was assessed using a pressure-sensitive mat; social and clinical characteristics were extracted from patient charts. Correlations were performed to investigate relationships between questionnaire responses and gait function, motor impairment, and chronicity; t-tests were used to examine response differences between people with a caregiver at home and those without. A total of 21 people with stroke completed the questionnaire without difficulty; mean completion time was 7.2 (SD 3.5) minutes, with a range of responses across participants. Borderline significant associations were found between gait function and the number of studies in which a person would participate and between stroke chronicity and the location of studies in which a person would participate. A questionnaire to investigate the influence of study design factors on participation in rehabilitation research is feasible for administration in the post-stroke population and has potential to inform the design of future studies.

Mother-Child Agreement on the Child's Past Food Exposure

ERIC Educational Resources Information Center

Thongudomporn, Udom; Chongsuvivatwong, Virasakdi; Geater, Alan F.

2010-01-01

Objective: To assess mother-child agreement on the child's past food exposure, and factors affecting response discrepancy. Methods: Twelve- to 14-year-old children and their mothers (n = 78) in an urban community, a rural community, and 2 orthodontic clinics completed a 69-item food questionnaire to determine mother-child level of agreement on the…

[Diagnosis and evolution of scabies].

PubMed

Piérard-Franchimont, C; Hermanns-Lê, T; Piérard, G E

2014-01-01

Human scabies is an ectoparasitosis affecting any individual at any age. The level of infestation by Sarcoptes scabiei var. hominis is influenced by any defect in immune response. Several clinical types of scabies are described including baby scabies, profuse scabies of immunodepression, norvegian scabies and sarcoptic mange. Onchocerciasis dermatitis is a tropical microfilariosis completely distinct by its parasitic nature.

Revisions to the International Neuroblastoma Response Criteria: A Consensus Statement From the National Cancer Institute Clinical Trials Planning Meeting

PubMed Central

Bagatell, Rochelle; Cohn, Susan L.; Pearson, Andrew D.; Villablanca, Judith G.; Berthold, Frank; Burchill, Susan; Boubaker, Ariane; McHugh, Kieran; Nuchtern, Jed G.; London, Wendy B.; Seibel, Nita L.; Lindwasser, O. Wolf; Maris, John M.; Brock, Penelope; Schleiermacher, Gudrun; Ladenstein, Ruth; Matthay, Katherine K.; Valteau-Couanet, Dominique

2017-01-01

Purpose More than two decades ago, an international working group established the International Neuroblastoma Response Criteria (INRC) to assess treatment response in children with neuroblastoma. However, this system requires modification to incorporate modern imaging techniques and new methods for quantifying bone marrow disease that were not previously widely available. The National Cancer Institute sponsored a clinical trials planning meeting in 2012 to update and refine response criteria for patients with neuroblastoma. Methods Multidisciplinary investigators from 13 countries reviewed data from published trials performed through cooperative groups, consortia, and single institutions. Data from both prospective and retrospective trials were used to refine the INRC. Monthly international conference calls were held from 2011 to 2015, and consensus was reached through review by working group leadership and the National Cancer Institute Clinical Trials Planning Meeting leadership council. Results Overall response in the revised INRC will integrate tumor response in the primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and iodine-123 (123I) –metaiodobenzylguanidine (MIBG) scans or [18F]fluorodeoxyglucose–positron emission tomography scans if the tumor is MIBG nonavid. 123I-MIBG scans, or [18F]fluorodeoxyglucose–positron emission tomography scans for MIBG-nonavid disease, replace technetium-99m diphosphonate bone scintigraphy for osteomedullary metastasis assessment. Bone marrow will be assessed by histology or immunohistochemistry and cytology or immunocytology. Bone marrow with ≤ 5% tumor involvement will be classified as minimal disease. Urinary catecholamine levels will not be included in response assessment. Overall response will be defined as complete response, partial response, minor response, stable disease, or progressive disease. Conclusion These revised criteria will provide a uniform assessment of disease response, improve the interpretability of clinical trial results, and facilitate collaborative trial designs. PMID:28471719

Idiopathic hypersomnia: clinical features and response to treatment.

PubMed

Ali, Mohsin; Auger, R Robert; Slocumb, Nancy L; Morgenthaler, Timothy I

2009-12-15

A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. A retrospective review of our database initially identified 997 patients, utilizing "idiopathic hypersomnia", "hypersomnia NOS", and "primary hypersomnia" as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a "complete response" to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of "complete" or "partial" responses than modafinil, although statistical significance was not reached (38/40 [95%] vs. 22/25 [88%], respectively, p = 0.291). The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored.

Predictors of outcome in patients with advanced nonseminomatous germ cell testicular tumors.

PubMed

Yetisyigit, Tarkan; Babacan, Nalan; Urun, Yuksel; Seber, Erdogan Selcuk; Cihan, Sener; Arpaci, Erkan; Yildirim, Nuriye; Aksoy, Sercan; Budakoglu, Burcin; Zengin, Nurullah; Oksuzoglu, Berna; Yalcin, Banu Cicek; Alkis, Necati

2014-01-01

Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

Exploring Carers' Judgements of Responsibility and Control in Response to the Challenging Behaviour of People with Intellectual Disabilities.

PubMed

Williams, Sophie; Dagnan, Dave; Rodgers, Jacqui; Freeston, Mark

2015-11-01

This study examines Weiner's recent cognitive emotional model which makes a distinction between judgements of control and responsibility and emphasizes the moderation of control by 'mitigating' factors. In response to four vignettes describing two conditions of control (high or low) and mitigating factors (present or absent), questionnaires rating judgements of responsibility and emotional responses (anger and sympathy) were completed by 52 care staff. Analysis of the data for sympathy demonstrated that attributions of control were moderated by communication ability and that the effect of control upon sympathy was mediated by the judgement of responsibility. The data offer tentative support Weiner's account of the mitigation of control attributions in making responsibility judgements and their subsequent effects on emotional responses. Implications for research and clinical work are discussed. © 2015 John Wiley & Sons Ltd.

The Analysis of Constitutions of Traditional Chinese Medicine in Relation to Cerebral Infarction in a Chinese Sample.

PubMed

Liu, Jiaqi; Xu, Fei; Mohammadtursun, Nabijan; Lv, Yubao; Tang, Zihui; Dong, Jingcheng

2018-05-01

To investigate the relationships between the constitutions of Traditional Chinese Medicine (TCM) and patients with cerebral infarction (CI) in a Chinese sample. A total of 3748 participants with complete data were available for data analysis. All study subjects underwent complete clinical baseline characteristics' evaluation, including a physical examination and response to a structured, nurse-assisted, self-administrated questionnaire. A population of 2010 neutral participants were used as the control group. Multiple variable regression (MLR) were employed to estimate the relationship between constitutions of TCM and the outcome. A cross-sectional study was conducted to evaluate the association of body constitution of TCM and CI. Communications and healthcare centers in Shanghai. A total of 3748 participants with complete data were available for data analysis. All study subjects underwent complete clinical baseline characteristics' evaluation, including a physical examination and response to a structured, nurse-assisted, self-administrated questionnaire. A population of 2010 neutral participants were used as the control group. MLR were employed to estimate the relationship between constitutions of TCM and the outcome. The prevalence of CI was 2.84% and 4.66% in neutral participants and yang-deficient participants (p = 0.012), respectively. Univariate analysis demonstrated a positive correlation between yang deficiency and CI. After adjustment for relevant potential confounding factors, the MLR detected significant associations between yang deficiency and CI (odds ratio = 1.44, p = 0.093). A yang-deficient constitution was significantly and independently associated with CI. A higher prevalence of CI was found in yang-deficient participants as compared with neutral participants.

Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma.

PubMed

Crago, Aimee M; Singer, Samuel

2011-07-01

Liposarcoma, a rare disease, is classified into five histologic subtypes. These include well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS), both characterized by chromosome 12q13-15 amplification. This review will focus on the clinical management of WDLS and DDLS and examine recent molecular studies that have the potential to affect clinical management. Outcome of patients with WDLS and DDLS depends on completeness of surgical resection as well as tumor location and histologic subtype. Risk of recurrence is high for patients with dedifferentiated histology or retroperitoneal location. We now understand that surgical outcomes are poor for patients with rapidly growing or incompletely resectable tumors, so these patients should be managed nonoperatively. Radiation and chemotherapy have low response rates in WDLS and DDLS, but novel agents targeted at chromosome 12 gene products MDM2 and CDK4 have shown promise in preclinical studies and are being tested in clinical trials. Cell line, tissue microarray, and genomic analyses have identified additional targets including ZIC1, TOP2A, AURKA, and IGF-1R, which could form the basis of future therapies. Although complete surgical resection is currently the most effective treatment for WDLS and DDLS, the majority of patients with retroperitoneal liposarcoma will eventually have recurrence and die of disease. It is hoped that a multimodality approach, which incorporates targeted therapies and complete surgical resection, will significantly improve patient outcomes.

Phase II study of neoadjuvant treatment with doxorubicin, docetaxel, and capecitabine (ATX) in locally advanced or inflammatory breast cancer.

PubMed

Manga, Gumersindo Pérez; Shahi, Parham Khosravi; Ureña, Miguel Méndez; Pereira, Rosa Quiben; Plaza, María Isabel Palomero; Peron, Yann Izarzugaza; Val, Ricardo González Del; Carrión, Joaquín Belón; Cañón, Esperanza Pérez; Alfonso, Pilar García

2010-07-01

Pathologic complete response (pCR) after preoperative systemic chemotherapy (PSCh) is associated with better outcome in locally advanced breast cancer (LABC). PSCh included: doxorubicin (A) 50 mg/m(2) i.v. on day 1; docetaxel (T) 30 mg/m(2) i.v. on days 1, 8 and 15; and capecitabine (X) 1,500 mg/m(2)/day p.o. on days 1-14, in a 4-week course repeated for up to four cycles (ATX), followed by surgery. The primary end point of this study was to evaluate the pCR rate. Secondary endpoints included clinical response rate, disease-free survival (DFS), overall survival (OS), and the toxicity profile. A total of 60 patients were included in the analysis. Median age was 49 years, and 63.3% of patients were hormone receptor positive. The median number of cycles of PSCh was four (95% CI: 3-4). Five patients (8.3%) achieved pCR in both breast and nodes, and 16.7% reached pCR only in nodes. The clinical response rate was 77% (27% complete response), but only 18% of the patients underwent conservative surgery. With a median follow-up of 20 months, 3-year DFS and OS were 76 and 90%, respectively. Grade III/IV toxicity included neutropenia (74%), febrile neutropenia (9%), mucositis (12%), and diarrhea (12%). ATX every 28 days for four cycles is associated with a modest activity (low pCR rate) in the neoadjuvant setting of LABC.

Comparison of cyclophosphamide-thalidomide-dexamethasone to bortezomib-cyclophosphamide-dexamethasone as induction therapy for multiple myeloma patients in Brazil.

PubMed

Vigolo, Suelen; Zuckermann, Joice; Bittencourt, Rosane Isabel; Silla, Lúcia; Pilger, Diogo André

2017-09-01

Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency. Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progression-free survival, and overall survival of patients. Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p=0.023). Disease progression after autologous HSCT did not differ between the two groups. VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Vancomycin Ophthalmic Ointment 1% for methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis infections: a case series

PubMed Central

Sotozono, Chie; Fukuda, Masahiko; Ohishi, Masao; Yano, Keiko; Origasa, Hideki; Saiki, Yoshinori; Shimomura, Yoshikazu; Kinoshita, Shigeru

2013-01-01

Objectives To investigate the efficacy and safety of Vancomycin Ophthalmic Ointment 1% (Toa Pharmaceutical Co., Ltd, Toyama, Japan) in patients with external ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). Design A case series. Setting This study was a multicentre, open-label, uncontrolled study in Japan approved as orphan drug status. Participants Patients with MRSA or MRSE external ocular infections unresponsive to the treatment of fluoroquinolone eye drops. Interventions Vancomycin Ophthalmic Ointment 1% was administered four times daily. Primary and secondary outcome measures The subjective and objective clinical scores and bacterial cultures were collected at days 0 (baseline), 3, 7 and 14. The primary outcome was clinical response evaluation (efficacy rate) determined as complete response, partial response, no response and worsening. Secondary outcome was the eradication of the bacteria. Safety was assessed by adverse events including cases in which neither MRSA nor MRSE was detected. Results Twenty-five cases with MRSA (20) or MRSE (5) infections were enrolled. Of these 25 cases, 4 discontinued the treatment due to the negative results for bacterial culture during screening or at baseline. Of the 21 cases with conjunctivitis (14), blepharitis (3), meibomitis (1), dacryocystitis (2) or keratitis (1), 14 (66.7%) cases were evaluated as being excellently (complete response, 2 cases) or well (partial response, 12 cases) treated. The eradication rates were 68.4% in MRSA (13 of 19 cases) and 100% in MRSE (2 of 2 cases). Ten adverse events occurred in 7 (28.0%) of 25 cases at the local administration site. Conclusions Vancomycin Ophthalmic Ointment 1% was considered to be useful for the treatment of intractable ocular MRSA/MRSE infections. PMID:23364319

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

PubMed

Rugo, Hope S; Olopade, Olufunmilayo I; DeMichele, Angela; Yau, Christina; van 't Veer, Laura J; Buxton, Meredith B; Hogarth, Michael; Hylton, Nola M; Paoloni, Melissa; Perlmutter, Jane; Symmans, W Fraser; Yee, Douglas; Chien, A Jo; Wallace, Anne M; Kaplan, Henry G; Boughey, Judy C; Haddad, Tufia C; Albain, Kathy S; Liu, Minetta C; Isaacs, Claudine; Khan, Qamar J; Lang, Julie E; Viscusi, Rebecca K; Pusztai, Lajos; Moulder, Stacy L; Chui, Stephen Y; Kemmer, Kathleen A; Elias, Anthony D; Edmiston, Kirsten K; Euhus, David M; Haley, Barbara B; Nanda, Rita; Northfelt, Donald W; Tripathy, Debasish; Wood, William C; Ewing, Cheryl; Schwab, Richard; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Berry, Donald A; Esserman, Laura J

2016-07-07

The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

PubMed

Katroditou, Eirini; Kyrtsonis, Marie-Christine; Delimpasi, Sosana; Kyriakou, Despoina; Symeonidis, Argiris; Spanoudakis, Emmanouil; Vasilopoulos, Georgios; Anagnostopoulos, Achilles; Kioumi, Anna; Zikos, Panagiotis; Aktypi, Anthi; Briasoulis, Evangelos; Megalakaki, Aikaterini; Repousis, Panayiotis; Adamopoulos, Ioannis; Gogos, Dimitrios; Kotsopoulou, Maria; Pappa, Vassiliki; Papadaki, Eleni; Fotiou, Despoina; Nikolaou, Eftychia; Giannopoulou, Evlambia; Hatzimichael, Eleftheria; Giannakoulas, Nikolaos; Douka, Vassiliki; Kokoviadou, Kyriaki; Timotheatou, Despoina; Terpos, Evangelos

2018-05-13

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

Evaluation of pharmacy students' knowledge and perceptions of pharmacogenetics before and after a simulation activity.

PubMed

Patel, Radha V; Chudow, Melissa; Vo, Teresa T; Serag-Bolos, Erini S

The purpose of this study was to evaluate students' knowledge and perceptions of the clinical application of pharmacogenetics through a simulation activity and to assess communication of pharmacogenetic-guided treatment recommendations utilizing standardized patients. Third-year students in the four-year doctor of pharmacy (PharmD) program at University of South Florida College of Pharmacy completed a pharmacogenetics simulation involving a patient case review, interpretation of pharmacogenetic test results, completion of a situation, background, assessment, recommendation (SBAR) note with drug therapy recommendations, and patient counseling. Voluntary assessments were completed before and after the simulation, which included demographics, knowledge, and perceptions of students' ability to interpret and communicate pharmacogenetic results. Response rates for the pre- and post-simulation assessments were 109 (98%) and 104 (94%), respectively. Correct responses in application-type questions improved after the simulation (74%) compared to before the simulation (44%, p < 0.01). Responses to perception questions shifted towards "strongly agree" or "agree" after the simulation (p < 0.01). The simulation gave students an opportunity to apply pharmacogenetics knowledge and allowed them to gain an appreciation of pharmacists' roles within the pharmacogenetics field. Copyright © 2017 Elsevier Inc. All rights reserved.

Epithelial membrane protein-1 is a biomarker of gefitinib resistance.

PubMed

Jain, Anjali; Tindell, Charles A; Laux, Isett; Hunter, Jacob B; Curran, John; Galkin, Anna; Afar, Daniel E; Aronson, Nina; Shak, Steven; Natale, Ronald B; Agus, David B

2005-08-16

We describe a molecular resistance biomarker to gefitinib, epithelial membrane protein-1 (EMP-1). Gefitinib is a small-molecule inhibitor that competes for the ATP-binding site on EGF receptor (EGFR) and has been approved for patients with advanced lung cancers. Treatment with gefitinib has resulted in clinical benefit in patients, and, recently, heterozygous somatic mutations within the EGFR catalytic domain have been identified as a clinical correlate to objective response to gefitinib. However, clinical resistance to gefitinib limits the utility of this therapeutic to a fraction of patients, and objective clinical responses are rare. We aimed to assess the molecular phenotype and mechanism of in vivo gefitinib resistance in xenograft models and in patient samples. We generated in vivo gefitinib-resistance models in an adenocarcinoma xenograft model by serially passaging tumors in nude mice in presence of gefitinib until resistance was acquired. EMP-1 was identified as a surface biomarker whose expression correlated with acquisition of gefitinib resistance. EMP-1 expression was further correlated with lack of complete or partial response to gefitinib in lung cancer patient samples as well as clinical progression to secondary gefitinib resistance. EMP-1 expression and acquisition of gefitinib clinical resistance was independent of gefitinib-sensitizing EGFR somatic mutations. This report suggests the role of the adhesion molecule, EMP-1, as a biomarker of gefitinib clinical resistance, and further suggests a probable cross-talk between this molecule and the EGFR signaling pathway.

Epithelial membrane protein-1 is a biomarker of gefitinib resistance

PubMed Central

Jain, Anjali; Tindell, Charles A.; Laux, Isett; Hunter, Jacob B.; Curran, John; Galkin, Anna; Afar, Daniel E.; Aronson, Nina; Shak, Steven; Natale, Ronald B.; Agus, David B.

2005-01-01

We describe a molecular resistance biomarker to gefitinib, epithelial membrane protein-1 (EMP-1). Gefitinib is a small-molecule inhibitor that competes for the ATP-binding site on EGF receptor (EGFR) and has been approved for patients with advanced lung cancers. Treatment with gefitinib has resulted in clinical benefit in patients, and, recently, heterozygous somatic mutations within the EGFR catalytic domain have been identified as a clinical correlate to objective response to gefitinib. However, clinical resistance to gefitinib limits the utility of this therapeutic to a fraction of patients, and objective clinical responses are rare. We aimed to assess the molecular phenotype and mechanism of in vivo gefitinib resistance in xenograft models and in patient samples. We generated in vivo gefitinib-resistance models in an adenocarcinoma xenograft model by serially passaging tumors in nude mice in presence of gefitinib until resistance was acquired. EMP-1 was identified as a surface biomarker whose expression correlated with acquisition of gefitinib resistance. EMP-1 expression was further correlated with lack of complete or partial response to gefitinib in lung cancer patient samples as well as clinical progression to secondary gefitinib resistance. EMP-1 expression and acquisition of gefitinib clinical resistance was independent of gefitinib-sensitizing EGFR somatic mutations. This report suggests the role of the adhesion molecule, EMP-1, as a biomarker of gefitinib clinical resistance, and further suggests a probable cross-talk between this molecule and the EGFR signaling pathway. PMID:16087880

Tumor shrinkage and objective response rates: gold standard for oncology efficacy screening trials, or an outdated end point?

PubMed

Bradbury, Penelope; Seymour, Lesley

2009-01-01

Phase II clinical trials have long been used to screen new cancer therapeutics for antitumor activity ("efficacy") worthy of further evaluation. Traditionally, the primary end point used in these screening trials has been objective response rate (RR), with the desired rate being arbitrarily set by the researchers before initiation of the trial. For cytotoxic agents, especially in common tumor types, response has been a reasonably robust and validated surrogate of benefit. Phase II trials with response as an end point have a modest sample size (15-40 patients) and are completed rapidly allowing early decisions regarding future development of a given agent. More recently, a number of new agents have proven successful in pivotal phase III studies, despite a low or very modest RR demonstrated in early clinical trials. Researchers have postulated that these novel agents, as a class, may not induce significant regression of tumors, and that the use of RR as an end point for phase II studies will result in false negative results, and point out that not all available data is used in making the decision. Others have pointed out that even novel agents have proven unsuccessful in pivotal trials if objective responses are not demonstrated in early clinical trials. We review here the historical and current information regarding objective tumor response.

Experiences and Perceptions of Pharmacy Students on Practical Skills and Education During Clinical Rotations in India.

PubMed

Bhagavathula, Akshaya Srikanth; Bandari, Deepak Kumar; Gogikar, Sudhir Kumar; Elnour, Asim Ahmed; Shehab, Abdulla

2017-08-01

Objective. To investigate the overall experience of pharmacy students in India during their clinical rotations and their assessment of primary mentors in imparting the intended clinical skills. Methods. A prospective cross-sectional study using a self-administered survey instrument containing 34 items to obtain feedback from senior PharmD students in the latter three years of their six-year program from November 2014 to February 2015. Results. Of the 415 PharmD students invited for this survey, 261(63% response rate) completed the survey (54% males and 46% females). Of the surveyed participants, 74% were fifth- and final-year interns undertaking clinical training in private hospitals (60.9%). Interestingly, 37.9% of the students ranked their clinical training as "least satisfactory" and remarked that their clinical pharmacy services were not recognized or appreciated in their respective hospitals (42.9%). However, 20% of the students expressed that their site "definitely" provided them with the opportunity to hone clinical pharmacy skills. Only 10% of the students strongly agreed that their mentors encouraged them to use resource materials and learn on their own, met with them regularly to review their work and to provide feedback, and encouraged them to express their opinion in patient-care issues. Conclusion. Majority of PharmD students who completed the survey were "least satisfied" with their clinical training program. Mentors should take more effort to demonstrate practice-based clinical training and provide patient-centered education to PharmD students at their clinical sites.

Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis.

PubMed

Lanternier, F; Poiree, S; Elie, C; Garcia-Hermoso, D; Bakouboula, P; Sitbon, K; Herbrecht, R; Wolff, M; Ribaud, P; Lortholary, O

2015-11-01

Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haematological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). High-dose L-AMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Acute stress responses: A review and synthesis of ASD, ASR, and CSR.

PubMed

Isserlin, Leanna; Zerach, Gadi; Solomon, Zahava

2008-10-01

Toward the development of a unifying diagnosis for acute stress responses this article attempts to find a place for combat stress reaction (CSR) within the spectrum of other defined acute stress responses. This article critically compares the diagnostic criteria of acute stress disorder (ASD), acute stress reaction (ASR), and CSR. Prospective studies concerning the predictive value of ASD, ASR, and CSR are reviewed. Questions, recommendations, and implications for clinical practice are raised concerning the completeness of the current acute stress response diagnoses, the heterogeneity of different stressors, the scope of expected outcomes, and the importance of decline in function as an indicator of future psychological, psychiatric, and somatic distress. PsycINFO Database Record 2009 APA.

A national radiation oncology medical student clerkship survey: didactic curricular components increase confidence in clinical competency.

PubMed

Jagadeesan, Vikrant S; Raleigh, David R; Koshy, Matthew; Howard, Andrew R; Chmura, Steven J; Golden, Daniel W

2014-01-01

Students applying to radiation oncology residency programs complete 1 or more radiation oncology clerkships. This study assesses student experiences and perspectives during radiation oncology clerkships. The impact of didactic components and number of clerkship experiences in relation to confidence in clinical competency and preparation to function as a first-year radiation oncology resident are evaluated. An anonymous, Internet-based survey was sent via direct e-mail to all applicants to a single radiation oncology residency program during the 2012-2013 academic year. The survey was composed of 3 main sections including questions regarding baseline demographic information and prior radiation oncology experience, rotation experiences, and ideal clerkship curriculum content. The survey response rate was 37% (70 of 188). Respondents reported 191 unique clerkship experiences. Of the respondents, 27% (19 of 70) completed at least 1 clerkship with a didactic component geared towards their level of training. Completing a clerkship with a didactic component was significantly associated with a respondent's confidence to function as a first-year radiation oncology resident (Wilcoxon rank-sum P=.03). However, the total number of clerkships completed did not correlate with confidence to pursue radiation oncology as a specialty (Spearman ρ P=.48) or confidence to function as a first year resident (Spearman ρ P=.43). Based on responses to this survey, rotating students perceive that the majority of radiation oncology clerkships do not have formal didactic curricula. Survey respondents who completed a clerkship with a didactic curriculum reported feeling more prepared to function as a radiation oncology resident. However, completing an increasing number of clerkships does not appear to improve confidence in the decision to pursue radiation oncology as a career or to function as a radiation oncology resident. These results support further development of structured didactic curricula for the radiation oncology clerkship. Copyright © 2014 Elsevier Inc. All rights reserved.

A National Radiation Oncology Medical Student Clerkship Survey: Didactic Curricular Components Increase Confidence in Clinical Competency

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

Jagadeesan, Vikrant S.; Raleigh, David R.; Koshy, Matthew

Purpose: Students applying to radiation oncology residency programs complete 1 or more radiation oncology clerkships. This study assesses student experiences and perspectives during radiation oncology clerkships. The impact of didactic components and number of clerkship experiences in relation to confidence in clinical competency and preparation to function as a first-year radiation oncology resident are evaluated. Methods and Materials: An anonymous, Internet-based survey was sent via direct e-mail to all applicants to a single radiation oncology residency program during the 2012-2013 academic year. The survey was composed of 3 main sections including questions regarding baseline demographic information and prior radiation oncologymore » experience, rotation experiences, and ideal clerkship curriculum content. Results: The survey response rate was 37% (70 of 188). Respondents reported 191 unique clerkship experiences. Of the respondents, 27% (19 of 70) completed at least 1 clerkship with a didactic component geared towards their level of training. Completing a clerkship with a didactic component was significantly associated with a respondent's confidence to function as a first-year radiation oncology resident (Wilcoxon rank–sum P=.03). However, the total number of clerkships completed did not correlate with confidence to pursue radiation oncology as a specialty (Spearman ρ P=.48) or confidence to function as a first year resident (Spearman ρ P=.43). Conclusions: Based on responses to this survey, rotating students perceive that the majority of radiation oncology clerkships do not have formal didactic curricula. Survey respondents who completed a clerkship with a didactic curriculum reported feeling more prepared to function as a radiation oncology resident. However, completing an increasing number of clerkships does not appear to improve confidence in the decision to pursue radiation oncology as a career or to function as a radiation oncology resident. These results support further development of structured didactic curricula for the radiation oncology clerkship.« less

RESPONSIVENESS OF THE ACTIVITIES OF DAILY LIVING SCALE OF THE KNEE OUTCOME SURVEY AND NUMERIC PAIN RATING SCALE IN PATIENTS WITH PATELLOFEMORAL PAIN

PubMed Central

Piva, Sara R.; Gil, Alexandra B.; Moore, Charity G.; Fitzgerald, G. Kelley

2016-01-01

Objective To assess internal and external responsiveness of the Activity of Daily Living Scale of the Knee Outcome Survey and Numeric Pain Rating Scale on patients with patellofemoral pain. Design One group pre-post design. Subjects A total of 60 individuals with patellofemoral pain (33 women; mean age 29.9 (standard deviation 9.6) years). Methods The Activity of Daily Living Scale and the Numeric Pain Rating Scale were assessed before and after 8 weeks of physical therapy program. Patients completed a global rating of change scale at the end of therapy. The standardized effect size, Guyatt responsiveness index, and the minimum clinical important difference were calculated. Results Standardized effect size of the Activity of Daily Living Scale was 0.63, Guyatt responsiveness index was 1.4, area under the curve was 0.83 (95% confidence interval: 0.72, 0.94), and the minimum clinical important difference corresponded to an increase of 7.1 percentile points. Standardized effect size of the Numeric Pain Rating Scale was 0.72, Guyatt responsiveness index was 2.2, area under the curve was 0.80 (95% confidence interval: 0.70, 0.92), and the minimum clinical important difference corresponded to a decrease of 1.16 points. Conclusion Information from this study may be helpful to therapists when evaluating the effectiveness of rehabilitation intervention on physical function and pain, and to power future clinical trials on patients with patellofemoral pain. PMID:19229444

Responsiveness of the activities of daily living scale of the knee outcome survey and numeric pain rating scale in patients with patellofemoral pain.

PubMed

Piva, Sara R; Gil, Alexandra B; Moore, Charity G; Fitzgerald, G Kelley

2009-02-01

To assess internal and external responsiveness of the Activity of Daily Living Scale of the Knee Outcome Survey and Numeric Pain Rating Scale on patients with patellofemoral pain. One group pre-post design. A total of 60 individuals with patellofemoral pain (33 women; mean age 29.9 (standard deviation 9.6) years). The Activity of Daily Living Scale and the Numeric Pain Rating Scale were assessed before and after 8 weeks of physical therapy program. Patients completed a global rating of change scale at the end of therapy. The standardized effect size, Guyatt responsiveness index, and the minimum clinical important difference were calculated. Standardized effect size of the Activity of Daily Living Scale was 0.63, Guyatt responsiveness index was 1.4, area under the curve was 0.83 (95% confidence interval: 0.72, 0.94), and the minimum clinical important difference corresponded to an increase of 7.1 percentile points. Standardized effect size of the Numeric Pain Rating Scale was 0.72, Guyatt responsiveness index was 2.2, area under the curve was 0.80 (95% confidence interval: 0.70, 0.92), and the minimum clinical important difference corresponded to a decrease of 1.16 points. Information from this study may be helpful to therapists when evaluating the effectiveness of rehabilitation intervention on physical function and pain, and to power future clinical trials on patients with patellofemoral pain.

Unilateral Laryngoscopic Findings Associated With Response to Gabapentin in Patients With Chronic Cough.

PubMed

Giliberto, John Paul; Dibildox, Daniel; Merati, Albert

2017-11-01

Chronic cough is a debilitating, often multifactorial problem. Vagal neuropathy has been proposed as a cause for a fraction of these cases. There are certain features that support the clinical diagnosis of vagal neuropathy. It is hypothesized that patients with neurogenic cough who have vocal fold motion asymmetry (VFMA) on laryngoscopy will be more likely to respond to gabapentin. To evaluate the association between the history, physical and videostroboscopic examinations, and clinical response to gabapentin. In a retrospective cohort study, patients with chronic cough visiting an academic tertiary laryngology clinic from January 1, 2013, to September 1, 2015, were identified through International Classification of Diseases, Ninth Revision. Of those who had a chronic cough (>8 weeks), 27 patients who received a prescription for gabapentin were included. Patients without videostroboscopy, who did not complete voice therapy, or those without a follow-up examination more than 1 month from the initial evaluation were excluded. Initial history, physical and videostroboscopic examinations, and follow-up evaluations, were performed in a multidisciplinary laryngology clinic including a speech-language pathologist. Documented VFMA by a multidisciplinary team was decided by consensus after review of videostroboscopy recording at the time of the visit. Response to gabapentin was defined by physician-documented subjective patient report of improvement in cough symptoms. Follow-up data were available on 25 of the 27 patients (15 [60%] women; mean [SD] age, 57 [11.8] years). Therapy was initiated in patients with chronic cough with gabapentin, 100 mg twice daily, which was titrated to response or adverse effects. The maximum daily dose was 1800 mg. Partial or complete response to gabapentin was noted in 16 (64%) patients. Vocal fold motion asymmetry was noted in 20 (80%) patients. Fifteen of 16 (94%) responders had VFMA compared with 5 of 9 (56%) nonresponders. The difference in the frequency of VFMA between responders and nonresponders was 38% (95% CI, 18%-58%). Adverse effects limited the gabapentin dose in 4 of 9 (44%) nonresponders and 4 of 16 (25%) responders (odds ratio, 2.5; 95% CI, 0.42-13.6). In patients with chronic cough suspected to be related to vagal neuropathy, the odds of response to gabapentin are higher with the presence of VFMA noted on videostroboscopy.

Low-dose Photofrin-induced PDT offers excellent clinical response with minimal morbidity in chest wall recurrence of breast cancer

NASA Astrophysics Data System (ADS)

Allison, Ron; Mang, Thomas S.

2000-03-01

Limited therapeutic options exist when chest wall recurrence form breast cancer progresses despite standard salvage treatment. As photodynamic therapy offers excellent response for cutaneous lesions this may be a possible indication for PDT. A total of 102 treatment fields were illuminated on 9 women with biopsy proven chest wall recurrence of breast cancer which was progressing despite salvage surgery, radiation, and chemi-hormonal therapy. PDT consisted of outpatient IV infusion of Photofrin at 0.8 mg/kg followed 48 hours laser by illumination at 140-170 J/cm2 via a KTP Yag laser coupled to a dye unit. No patient was lost to follow up. At 6 months post PDT; complete response, defined as total lesion elimination was 89 percent, partial response 8 percent, and no response 3 percent. No photosensitivity was seen and no patient developed scarring, fibrosis, or healing difficulties. Low dose Photofrin induced PDT is very active against chest wall lesions. Despite fragile and heavily pre-treated tissues, excellent clinical and cosmetic outcome was obtained. PDT is an underutilized modality for this indication.

Six months versus nine months anti-tuberculous therapy for female genital tuberculosis: a randomized controlled trial.

PubMed

Sharma, Jai B; Singh, Neeta; Dharmendra, Sona; Singh, Urvashi B; P, Vanamail; Kumar, Sunesh; Roy, K K; Hari, Smriti; Iyer, V; Sharma, S K

2016-08-01

To compare six months versus nine months anti-tuberculous therapy in patients of female genital tuberculosis. It was a randomized controlled trial in a tertiary referral center teaching institute on 175 women presenting with infertility and found to have female genital tuberculosis on clinical examination and investigations. Group I women (86 women) were given 9 months of intermitted anti-tuberculous therapy under directly observed treatment short course (DOTS) strategy while Group II (89 women) were given 6 months of anti-tuberculous therapy under DOTS. Patients were evaluated for primary end points (complete cure, partial response, no response) and secondary end points (recurrence rate, pregnancy rate) during treatment. All patients were followed up further for one year after completion of therapy to assess recurrence of disease and further pregnancies. Baseline characteristics were similar between two randomized groups. There was no difference in the complete clinical response rate (95.3% vs 97.7%, p=0.441) between 9-months and 6-months groups. Four patients in 9-months group and two patients in 6-months group had recurrence of disease and required category II anti tuberculous therapy (p=0.441). Pregnancy rate during treatment and up to one year follow up was also similar in the two groups (23.2% vs 21.3%, p=0.762). Side effects occurred in 27(31.4%) and 29(32.6%) in 9-months and 6-months of therapy and were similar (p=0.866). There was no difference in complete cure rate, recurrent rate and pregnancy rate for either 6-months or 9-months of intermittent directly observed treatment short course anti-tuberculous therapy in female genital tuberculosis. The trial was registered in clinicaltrials.gov with registration no: CTRI/2009/091/001088. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Internet-based data inclusion in a population-based European collaborative follow-up study of inflammatory bowel disease patients: Description of methods used and analysis of factors influencing response rates

PubMed Central

Wolters, Frank L; van Zeijl, Gilbert; Sijbrandij, Jildou; Wessels, Frederik; O’Morain, Colm; Limonard, Charles; Russel, Maurice G; Stockbrügger, Reinhold W

2005-01-01

AIM: To describe an Internet-based data acquisition facility for a European 10-year clinical follow-up study project of a population-based cohort of inflammatory bowel disease (IBD) patients and to investigate the influence of demographic and disease related patient characteristics on response rates. METHODS: Thirteen years ago, the European Collaborative study group of IBD (EC-IBD) initiated a population-based prospective inception cohort of 2 201 uniformly diagnosed IBD patients within 20 well-described geographical areas in 11 European countries and Israel. For the 10-year follow-up of this cohort, an electronic patient questionnaire (ePQ) and electronic physician per patient follow-up form (ePpPFU) were designed as two separate data collecting instruments and made available through an Internet-based website. Independent demographic and clinical determinants of ePQ participation were analyzed using multivariate logistic regression. RESULTS: In 958 (316 CD and 642 UC) out of a total number of 1 505 (64%) available IBD patients, originating from 13 participating centers from nine different countries, both ePQ and ePpPFU were completed. Patients older than 40 years at ePQ completion (OR: 1.53 (95%CI: 1.14-2.05)) and those with active disease during the 3 mo previous to ePQ completion (OR: 3.32 (95%CI: 1.57-7.03)) were significantly more likely to respond. CONCLUSION: An Internet-based data acquisition tool appeared successful in sustaining a unique Western-European and Israelian multi-center 10-year clinical follow-up study project in patients afflicted with IBD. PMID:16437663

Internet-based data inclusion in a population-based European collaborative follow-up study of inflammatory bowel disease patients: description of methods used and analysis of factors influencing response rates.

PubMed

Wolters, Frank L; van Zeijl, Gilbert; Sijbrandij, Jildou; Wessels, Frederik; O'Morain, Colm; Limonard, Charles; Russel, Maurice G; Stockbrugger, Reinhold W

2005-12-07

To describe an Internet-based data acquisition facility for a European 10-year clinical follow-up study project of a population-based cohort of inflammatory bowel disease (IBD) patients and to investigate the influence of demographic and disease related patient characteristics on response rates. Thirteen years ago, the European Collaborative study group of IBD (EC-IBD) initiated a population-based prospective inception cohort of 2 201 uniformly diagnosed IBD patients within 20 well-described geographical areas in 11 European countries and Israel. For the 10-year follow-up of this cohort, an electronic patient questionnaire (ePQ) and electronic physician per patient follow-up form (ePpPFU) were designed as two separate data collecting instruments and made available through an Internet-based website. Independent demographic and clinical determinants of ePQ participation were analyzed using multivariate logistic regression. In 958 (316 CD and 642 UC) out of a total number of 1 505 (64%) available IBD patients, originating from 13 participating centers from nine different countries, both ePQ and ePpPFU were completed. Patients older than 40 years at ePQ completion (OR: 1.53 (95%CI: 1.14-2.05)) and those with active disease during the 3 mo previous to ePQ completion (OR: 3.32 (95%CI: 1.57-7.03)) were significantly more likely to respond. An Internet-based data acquisition tool appeared successful in sustaining a unique Western-European and Israelian multi-center 10-year clinical follow-up study project in patients afflicted with IBD.

Validation of a modified FRAX® tool for improving outpatient efficiency--part of the "Catch Before a Fall" initiative.

PubMed

Parker, Simon; Ciaccio, Maria; Cook, Erica; Davenport, Graham; Cooper, Alun; Grange, Simon; Smitham, Peter

2015-01-01

We have validated our touch-screen-modified FRAX® tool against the traditional healthcare professional-led questionnaire, demonstrating strong concordance between doctor- and patient-derived results. We will use this in outpatient clinics and general practice to increase our capture rate of at-risk patients, making valuable use of otherwise wasted patient waiting times. Outpatient clinics offer an opportunity to collect valuable health information from a captive population. We have previously developed a modified fracture risk assessment (FRAX®) tool, enabling patients to self-assess their osteoporotic fracture risk in a touch-screen computer format and demonstrated its acceptability with patients. We aim to validate the accuracy of our tool against the traditional questionnaire. Fifty patients over 50 years of age within the fracture clinic independently completed a paper equivalent of our touch-screen-modified FRAX® questionnaire. Responses were analysed against the traditional healthcare professional (HCP)-led questionnaire which was carried out afterwards. Correlation was assessed by sensitivity, specificity, Cohen's kappa statistic and Fisher's exact test for each potential FRAX® outcome of "treat", "measure BMD" and "lifestyle advice". Age range was 51-98 years. The FRAX® tool was completed by 88 % of patients; six patients lacked confidence in estimating either their height or weight. Following question adjustment according to patient response and feedback, our tool achieved >95 % sensitivity and specificity for the "treat" and "lifestyle advice" groups, and 79 % sensitivity and 100 % specificity in the "measure BMD" group. Cohen's kappa value ranged from 0.823 to 0.995 across all groups, demonstrating "very good" agreement for all. Fisher's exact test demonstrated significant concordance between doctor and patient decisions. Our modified tool provides a simple, accurate and reliable method for patients to self-report their own FRAX® score outside the clinical contact period, thus releasing the HCP from the time required to complete the questionnaire and potentially increasing our capture rate of at-risk patients.

Relationships between thermal dose parameters and the efficacy of definitive chemoradiotherapy plus regional hyperthermia in the treatment of locally advanced cervical cancer: data from a multicentre randomised clinical trial.

PubMed

Ohguri, Takayuki; Harima, Yoko; Imada, Hajime; Sakurai, Hideyuki; Ohno, Tatsuya; Hiraki, Yoshiyuki; Tuji, Koh; Tanaka, Masahiro; Terashima, Hiromi

2018-06-01

To evaluate the contribution of the thermal dose parameters during regional hyperthermia (HT) treatment to the clinical outcomes in patients with cervical carcinoma (CC) who received chemoradiotherapy (CRT) plus HT. Data from a multicentre randomised clinical trial of concurrent CRT + HT vs. CRT alone were used to evaluate the efficacy and safety of this combination therapy in the CC patients. The intrarectal temperatures of patients undergoing HT were recorded. The complete thermal data of 47 (92%) of the 51 patients in the CRT + HT group were available for the thermal analysis. Thus, 47 patients who received CRT + HT were included in the present study. Among the patients who received CRT + HT, a higher CEM43T90 (≥1 min) value (a thermal dose parameter) was significantly associated with better local relapse-free survival in both univariate (p = 0.024) and multivariate (p = 0.0097) analyses. The disease-free survival of the patients with higher CEM43T90 (≥1 min) values tended to be better in comparison to patients with lower CEM43T90 (<1 min) value (p = 0.071). A complete response tended to be associated with the CEM43T90 (p = 0.056). Disease-free survival, local relapse-free survival and complete response rate for patients with higher CEM43T90 (≥1) were significantly better than those for patients with CRT alone (p = 0.036, p = 0.036 and p = 0.048). Dose-effect relationships between thermal dose parameters and clinical outcomes were confirmed in the CC patients treated with a combination of CRT + HT. This study also confirmed that HT with lower CEM43T90 is insufficient to achieve a significant hyperthermic sensitisation to CRT.

An assessment of burnout in graduate assistant certified athletic trainers.

PubMed

Mazerolle, Stephanie M; Monsma, Eva; Dixon, Colin; Mensch, James

2012-01-01

Graduate assistant athletic trainers (GAATs) must balance the demands of clinical care and the academic load of graduate-level students. To examine burnout among GAATs with clinical assistantships at National Collegiate Athletic Association (NCAA) Division I institutions and to identify the personal and situational variables that are related to burnout. Cross-sectional study. Division I universities offering graduate assistantship programs. Two hundred one GAATs enrolled at NCAA Division I universities with graduate assistantship positions. The Athletic Training Burnout Inventory, which assesses stress and burnout among ATs through 4 constructs: emotional exhaustion and depersonalization, administrative responsibility, time commitment, and organizational support. The 6-point Likert scale is anchored by 1 (never true) and 6 (always true). The GAATs who traveled with athletic teams (4.051 ± 0.895) and those who provided classroom instruction (4.333 ± 1.16) reported higher levels of stress due to time commitment than those who did not travel (3.713 ± 1.22) or teach (3.923 ± 0.929). We also found a difference in administrative responsibility across clinical settings (F(6,194) = 3.507, P = .003). The results showed that GAATs in NCAA Division I clinical settings (44.55 ± 13.17 hours) worked more hours than those in NCAA Division III clinical settings (33.69 ± 12.07 hours) and those in high school settings (30.51 ± 9.934 hours). Graduate assistant ATs are at risk for burnout because of the time necessary to complete their clinical and academic responsibilities and their additional administrative responsibilities. Graduate assistants who work in the Division I clinical setting are at greater risk for burnout than those in the secondary school setting because of the large number of hours required.

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

PubMed

Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

2015-08-01

In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

Novel assessment tools to evaluate clinical and laboratory responses in a subset of patients enrolled in the Rituximab in Myositis trial.

PubMed

Rider, Lisa G; Yip, Adrienne L; Horkayne-Szakaly, Iren; Volochayev, Rita; Shrader, Joseph A; Turner, Maria L; Kong, Heidi H; Jain, Minal S; Jansen, Anna V; Oddis, Chester V; Fleisher, Thomas A; Miller, Frederick W

2014-01-01

We aimed to assess changes in myositis core set measures and ancillary clinical and laboratory data from the National Institutes of Health's subset of patients enrolled in the Rituximab in Myositis trial. Eighteen patients (5 dermatomyositis, 8 polymyositis, 5 juvenile dermatomyositis) completed more in-depth testing of muscle strength and cutaneous assessments, patient-reported outcomes, and laboratory tests before and after administration of rituximab. Percentage change in individual measures and in the definitions of improvement (DOIs) and standardized response means were examined over 44 weeks. Core set activity measures improved by 18-70% from weeks 0-44 and were sensitive to change. Fifteen patients met the DOI at week 44, 9 patients met a DOI 50% response, and 4 met a DOI 70% response. Muscle strength and function measures were more sensitive to change than cutaneous assessments. Constitutional, gastrointestinal, and pulmonary systems improved 44-70%. Patient-reported outcomes improved up to 28%. CD20+ B cells were depleted in the periphery, but B cell depletion was not associated with clinical improvement at week 16. This subset of patients had high rates of clinical response to rituximab, similar to patients in the overall trial. Most measures were responsive, and muscle strength had a greater degree of change than cutaneous assessments. Several novel assessment tools, including measures of strength and function, extra-muscular organ activity, fatigue, and health-related quality of life, are promising for use in future myositis trials. Further study of B cell-depleting therapies in myositis, particularly in treatment-naïve patients, is warranted.

Recruitment methods for survey research: Findings from the Mid-South Clinical Data Research Network.

PubMed

Heerman, William J; Jackson, Natalie; Roumie, Christianne L; Harris, Paul A; Rosenbloom, S Trent; Pulley, Jill; Wilkins, Consuelo H; Williams, Neely A; Crenshaw, David; Leak, Cardella; Scherdin, Jon; Muñoz, Daniel; Bachmann, Justin; Rothman, Russell L; Kripalani, Sunil

2017-11-01

The objective of this study was to report survey response rates and demographic characteristics of eight recruitment approaches to determine acceptability and effectiveness of large-scale patient recruitment among various populations. We conducted a cross sectional analysis of survey data from two large cohorts. Patients were recruited from the Mid-South Clinical Data Research Network using clinic-based recruitment, research registries, and mail, phone, and email approaches. Response rates are reported as patients who consented for the survey divided by the number of eligible patients approached. We contacted more than 90,000 patients and 13,197 patients completed surveys. Median age was 56.3years (IQR 40.9, 67.4). Racial/ethnic distribution was 84.1% White, non-Hispanic; 9.9% Black, non-Hispanic; 1.8% Hispanic; and 4.0% other, non-Hispanic. Face-to-face recruitment had the highest response rate of 94.3%, followed by participants who "opted-in" to a registry (76%). The lowest response rate was for unsolicited emails from the clinic (6.1%). Face-to-face recruitment enrolled a higher percentage of participants who self-identified as Black, non-Hispanic compared to other approaches (18.6% face-to-face vs. 8.4% for email). Technology-enabled recruitment approaches such as registries and emails are effective for recruiting but may yield less racial/ethnic diversity compared to traditional, more time-intensive approaches. Copyright © 2017. Published by Elsevier Inc.

First BNCT treatment of a skin melanoma in Argentina: dosimetric analysis and clinical outcome.

PubMed

González, S J; Bonomi, M R; Santa Cruz, G A; Blaumann, H R; Calzetta Larrieu, O A; Menéndez, P; Jiménez Rebagliati, R; Longhino, J; Feld, D B; Dagrosa, M A; Argerich, C; Castiglia, S G; Batistoni, D A; Liberman, S J; Roth, B M C

2004-11-01

A Phase I/II protocol for treating cutaneuos melanomas with BNCT was designed in Argentina by the Comisión Nacional de Energía Atómica and the medical center Instituto Roffo. The first of a cohort of thirty planned patients was treated on October 9, 2003. This article depicts the protocol-based procedure and describes the first clinical case, treatment regime and planning, patient irradiation, retrospective dosimetric analysis and clinical outcome. Considering the low acute skin toxicity and the complete response in 21 of the 25 subcutaneous melanoma nodules treated, a second irradiation was performed in a different location of the extremity of the same patient. The corresponding clinical outcome is still under evaluation.

The Incremental Value of Subjective and Quantitative Assessment of 18F-FDG PET for the Prediction of Pathologic Complete Response to Preoperative Chemoradiotherapy in Esophageal Cancer.

PubMed

van Rossum, Peter S N; Fried, David V; Zhang, Lifei; Hofstetter, Wayne L; van Vulpen, Marco; Meijer, Gert J; Court, Laurence E; Lin, Steven H

2016-05-01

A reliable prediction of a pathologic complete response (pathCR) to chemoradiotherapy before surgery for esophageal cancer would enable investigators to study the feasibility and outcome of an organ-preserving strategy after chemoradiotherapy. So far no clinical parameters or diagnostic studies are able to accurately predict which patients will achieve a pathCR. The aim of this study was to determine whether subjective and quantitative assessment of baseline and postchemoradiation (18)F-FDG PET can improve the accuracy of predicting pathCR to preoperative chemoradiotherapy in esophageal cancer beyond clinical predictors. This retrospective study was approved by the institutional review board, and the need for written informed consent was waived. Clinical parameters along with subjective and quantitative parameters from baseline and postchemoradiation (18)F-FDG PET were derived from 217 esophageal adenocarcinoma patients who underwent chemoradiotherapy followed by surgery. The associations between these parameters and pathCR were studied in univariable and multivariable logistic regression analysis. Four prediction models were constructed and internally validated using bootstrapping to study the incremental predictive values of subjective assessment of (18)F-FDG PET, conventional quantitative metabolic features, and comprehensive (18)F-FDG PET texture/geometry features, respectively. The clinical benefit of (18)F-FDG PET was determined using decision-curve analysis. A pathCR was found in 59 (27%) patients. A clinical prediction model (corrected c-index, 0.67) was improved by adding (18)F-FDG PET-based subjective assessment of response (corrected c-index, 0.72). This latter model was slightly improved by the addition of 1 conventional quantitative metabolic feature only (i.e., postchemoradiation total lesion glycolysis; corrected c-index, 0.73), and even more by subsequently adding 4 comprehensive (18)F-FDG PET texture/geometry features (corrected c-index, 0.77). However, at a decision threshold of 0.9 or higher, representing a clinically relevant predictive value for pathCR at which one may be willing to omit surgery, there was no clear incremental value. Subjective and quantitative assessment of (18)F-FDG PET provides statistical incremental value for predicting pathCR after preoperative chemoradiotherapy in esophageal cancer. However, the discriminatory improvement beyond clinical predictors does not translate into a clinically relevant benefit that could change decision making. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Implementation of a fall screening program in a high risk of fracture population.

PubMed

Ritchey, Katherine; Olney, Amanda; Shofer, Jane; Phelan, Elizabeth A; Matsumoto, Alvin M

2017-10-31

Fall prevention is an important way to prevent fractures in person with osteoporosis. We developed and implemented a fall screening program in the context of routine osteoporosis care. This program was found to be feasible and showed that a significant proportion of persons with osteoporosis are at risk of falling. Falls are the most common cause of fracture in persons with osteoporosis. However, osteoporosis care rarely includes assessment and prevention of falling. We thus sought to assess the feasibility of a fall screening and management program integrated into routine osteoporosis care. The program was developed and offered to patients with osteoporosis or osteopenia seen at an outpatient clinic between May 2015 and May 2016. Feasibility was measured by physical therapist time required to conduct screening and ease of integrating the screening program into the usual clinic workflow. Self-report responses and mobility testing were conducted to describe the fall and fracture risk profile of osteoporosis patients screened. Effects on fall-related care processes were assessed via chart abstraction of patient participation in fall prevention exercise. Of the 154 clinic patients who presented for a clinic visit, 68% met screening criteria and completed in two thirds of persons. Screening was completed in a third of the time typically allotted for traditional PT evaluations and did not interfere with clinic workflow. Forty percent of those screened reported falling in the last year, and over half had two or more falls in the past year. Over half reported a balance or lower extremity impairment, and over 40% were below norms on one or more performance tests. Most patients who selected a group exercise fall prevention program completed all sessions while only a quarter completed either supervised or independent home-based programs. Implementation of a fall risk screening program in an outpatient osteoporosis clinic appears feasible. A substantial proportion of people with osteoporosis screened positive for being at risk of falling, justifying integration of fall prevention into routine osteoporosis care.

Use of a reduced-carbohydrate, modified-fat enteral formula for improving metabolic control and clinical outcomes in long-term care residents with type 2 diabetes: results of a pilot trial.

PubMed

Craig, L D; Nicholson, S; SilVerstone, F A; Kennedy, R D

1998-06-01

Physiologic responses of 30 enterally-fed long-term care residents with type 2 diabetes receiving total nutrition support via either a disease-specific (reduced-carbohydrate, modified-fat) formula or a standard high-carbohydrate formula for 3 mo were compared. Objectives of the study included evaluating metabolic response (glycemic control and lipids) and clinical outcomes. Thirty-four subjects requiring total enteral nutrition support by tube were enrolled in this prospectively randomized, double-blind, controlled, parallel group 3-mo pilot trial. Thirty were evaluable in that they completed 4 wk. Twenty-seven completed all 12 wk. The groups were well-matched for physiologic and demographic parameters at baseline. Fasting serum glucose and capillary (fingerstick) glucose values demonstrated better control in the disease-specific formula-fed group. Serum lipid profiles of this group were similar to or better than those of the standard formula-fed group. The amount of insulin administered to insulin-using subjects in the disease-specific formula-fed group was consistently less than before initiation of the formula, whereas the amount administered was consistently higher in the group fed the standard formula. Overall, subjects randomized to the disease-specific formula experienced better numerical biochemical control and better clinical outcomes when expressed on a numerical and percentage basis. These included surrogate markers of diabetes control such as serum glucose and glycohemoglobin, as well as clinical outcomes such as incidence of infections and pressure ulcers. These findings confirm that the disease-specific formula provides better glycemic control, poses no risk to lipoprotein metabolism, and provides for better clinical outcomes.

Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials.

PubMed

Arias, Ana; Aguilera, Antonio; Soriano, Vicente; Benítez-Gutiérrez, Laura; Lledó, Gemma; Navarro, Daniel; Treviño, Ana; Otero, Esteban; Peña, José M; Cuervas-Mons, Valentín; de Mendoza, Carmen

2017-01-01

Cure rates above 90% have been reported in most Phase III clinical trials using distinct all-oral direct-acting antivirals (DAAs) in chronic hepatitis C patients. Preliminary results in real-world patients have confirmed this, although efficacy tends to be lower. All consecutive chronic hepatitis C patients treated with all-oral DAA regimens at three hepatitis clinics in Spain were retrospectively examined. Host and viral factors were tested as predictors of treatment failure. A total of 363 chronic hepatitis C patients had completed a course of all-oral DAA therapy outside clinical trials up to the end of 2015. All but 14 (4%) patients achieved sustained virological response. There were 10 failures that occurred after 12 weeks of sofosbuvir-ledipasvir, despite 5 of them being on ribavirin. All failures but one were relapses. The only patient with viral breakthrough selected NS5B L159F and NS5A Y93H. In multivariate analyses, only advanced liver fibrosis (Metavir F3-F4) and HIV coinfection were significantly associated with treatment failure. A trend towards lower response was seen for HCV genotype 4. Treatment failures outside clinical trials are roughly seen in 4% of chronic hepatitis C patients who complete a course of all-oral DAA therapy, resembling what is seen in registration trials. In our series, outcomes were not significantly influenced by ribavirin addition, IL28B polymorphisms, HCV genotype, high baseline HCV RNA or prior interferon failure. However, advanced liver fibrosis and HIV coinfection were significantly associated with treatment failure. Our findings support that there is still room for individualization of current DAA therapy.

Clinical evaluation incorporating a personal genome

PubMed Central

Ashley, Euan A.; Butte, Atul J.; Wheeler, Matthew T.; Chen, Rong; Klein, Teri E.; Dewey, Frederick E.; Dudley, Joel T.; Ormond, Kelly E.; Pavlovic, Aleksandra; Hudgins, Louanne; Gong, Li; Hodges, Laura M.; Berlin, Dorit S.; Thorn, Caroline F.; Sangkuhl, Katrin; Hebert, Joan M.; Woon, Mark; Sagreiya, Hersh; Whaley, Ryan; Morgan, Alexander A.; Pushkarev, Dmitry; Neff, Norma F; Knowles, Joshua W.; Chou, Mike; Thakuria, Joseph; Rosenbaum, Abraham; Zaranek, Alexander Wait; Church, George; Greely, Henry T.; Quake, Stephen R.; Altman, Russ B.

2010-01-01

Background The cost of genomic information has fallen steeply but the path to clinical translation of risk estimates for common variants found in genome wide association studies remains unclear. Since the speed and cost of sequencing complete genomes is rapidly declining, more comprehensive means of analyzing these data in concert with rare variants for genetic risk assessment and individualisation of therapy are required. Here, we present the first integrated analysis of a complete human genome in a clinical context. Methods An individual with a family history of vascular disease and early sudden death was evaluated. Clinical assessment included risk prediction for coronary artery disease, screening for causes of sudden cardiac death, and genetic counselling. Genetic analysis included the development of novel methods for the integration of whole genome sequence data including 2.6 million single nucleotide polymorphisms and 752 copy number variations. The algorithm focused on predicting genetic risk of genes associated with known Mendelian disease, recognised drug responses, and pathogenicity for novel variants. In addition, since integration of risk ratios derived from case control studies is challenging, we estimated posterior probabilities from age and sex appropriate prior probability and likelihood ratios derived for each genotype. In addition, we developed a visualisation approach to account for gene-environment interactions and conditionally dependent risks. Findings We found increased genetic risk for myocardial infarction, type II diabetes and certain cancers. Rare variants in LPA are consistent with the family history of coronary artery disease. Pharmacogenomic analysis suggested a positive response to lipid lowering therapy, likely clopidogrel resistance, and a low initial dosing requirement for warfarin. Many variants of uncertain significance were reported. Interpretation Although challenges remain, our results suggest that whole genome sequencing can yield useful and clinically relevant information for individual patients, especially for those with a strong family history of significant disease. PMID:20435227

Use and Perceived Benefits of Handheld Computer-based Clinical References

PubMed Central

Rothschild, Jeffrey M.; Fang, Edward; Liu, Vincent; Litvak, Irina; Yoon, Cathy; Bates, David W.

2006-01-01

Objective Clinicians are increasingly using handheld computers (HC) during patient care. We sought to assess the role of HC-based clinical reference software in medical practice by conducting a survey and assessing actual usage behavior. Design During a 2-week period in February 2005, 3600 users of a HC-based clinical reference application were asked by e-mail to complete a survey and permit analysis of their usage patterns. The software includes a pharmacopeia, an infectious disease reference, a medical diagnostic and therapeutic reference and transmits medical alerts and other notifications during HC synchronizations. Software usage data were captured during HC synchronization for the 4 weeks prior to survey completion. Measurements Survey responses and software usage data. Results The survey response rate was 42% (n = 1501). Physicians reported using the clinical reference software for a mean of 4 years and 39% reported using the software during more than half of patient encounters. Physicians who synchronized their HC during the data collection period (n = 1249; 83%) used the pharmacopeia for unique drug lookups a mean of 6.3 times per day (SD 12.4). The majority of users (61%) believed that in the prior 4 weeks, use of the clinical reference prevented adverse drug events or medication errors 3 or more times. Physicians also believed that alerts and other notifications improved patient care if they were public health warnings (e.g. about influenza), new immunization guidelines or drug alert warnings (e.g. rofecoxib withdrawal). Conclusion Current adopters of HC-based medical references use these tools frequently, and found them to improve patient care and be valuable in learning of recent alerts and warnings. PMID:16929041

Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

PubMed

Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

2010-09-01

This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

Blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: a pilot study.

PubMed

Jiang, Lan; Weatherall, Paul T; McColl, Roderick W; Tripathy, Debu; Mason, Ralph P

2013-05-01

To determine whether a simple noninvasive method of assessing tumor oxygenation is feasible in the clinical setting and can provide useful, potentially predictive information. Tumor microcirculation and oxygenation play critical roles in tumor growth and responsiveness to cytotoxic treatment and may provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic and can serve as an endogenous contrast agent causing signal loss in echo planar magnetic resonance imaging (MRI) (blood oxygenation level-dependent [BOLD]-MRI). We used BOLD-MRI to provide early evaluation of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MRI was performed on 11 patients with biopsy-proven malignancy. MRI exams were scheduled before, during, and after chemotherapy. The BOLD study applied a 6-minute oxygen breathing challenge. Seven patients successfully completed the exams. Before chemotherapy, BOLD contrast enhancement was observed in all tumors, but the patients, who ultimately had complete pathological response, exhibited a significantly higher BOLD response to oxygen breathing. We have successfully implemented an oxygen-breathing challenge BOLD contrast technique as part of the standard breast MRI exam in patients with locally advanced breast cancer. The preliminary observation that a large BOLD response correlated with better treatment response suggests a predictive capability for BOLD MRI. Copyright © 2012 Wiley Periodicals, Inc.

High-intensity focused ultrasound (HIFU) in patients with solid malignancies: evaluation of feasibility, local tumour response and clinical results.

PubMed

Orgera, G; Monfardini, L; Della Vigna, P; Zhang, L; Bonomo, G; Arnone, P; Padrenostro, M; Orsi, F

2011-08-01

The purpose of this study was to evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of solid tumours without damaging the surrounding structures. A specific written informed consent was obtained from every patient before treatment. From September 2008 to April 2009, 22 patients with 29 lesions were treated: nine patients with liver and/or soft-tissue metastases from colorectal carcinoma (CRC), six with pancreatic solid lesions, three with liver and/or bone metastases from breast cancer, one with osteosarcoma, one with muscle metastasis from lung cancer, one with iliac metastasis from multiple myeloma and one with abdominal liposarcoma. The mean diameter of tumours was 4.2 cm. All patients were evaluated 1 day, 1 month and 3 months after HIFU treatment by multidetector computed tomography (MDCT), positron-emission tomography (PET)-CT and clinical evaluation. The treatment time and adverse events were recorded. All patients had one treatment. Average treatment and sonication times were, respectively, 162.7 and 37.4 min. PET-CT or/and MDCT showed complete response in 11/13 liver metastases; all bone, soft-tissue and pancreatic lesions were palliated in symptoms, with complete response to PET-CT, MDCT or magnetic resonance imaging (MRI); the liposarcoma was almost completely ablated at MRI. Local oedema was observed in three patients. No other side effects were observed. All patients were discharged 1-3 days after treatment. According to our preliminary experience in a small number of patients, we conclude that HIFU ablation is a safe and feasible technique for locoregional treatment and is effective in pain control.

Is It Important to Adapt Neoadjuvant Chemotherapy to the Visible Clinical Response? An Open Randomized Phase II Study Comparing Response-Guided and Standard Treatments in HER2-Negative Operable Breast Cancer

PubMed Central

Mouret-Reynier, Marie-Ange; Savoye, Aude-Marie; Abrial, Catherine; Kwiatkowski, Fabrice; Garbar, Christian; DuBray-Longeras, Pascale; Eymard, Jean-Christophe; Lebouedec, Guillaume; Vanpraagh, Isabelle; Penault-Llorca, Frederique; Chollet, Philippe; Cure, Hervé

2015-01-01

Background. Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment. Methods. Overall, 264 previously untreated stage II–III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m2, respectively, for 3 cycles) followed by docetaxel (100 mg/m2 for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by <30% after 2 cycles or <50% after 4 cycles of FEC100 (ultrasound assessments according to World Health Organization criteria). Otherwise, FEC100 was given for six cycles before surgery. Intent-to-treat analysis was performed. Results. Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses. Conclusion. Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected. PMID:25637380

Association between dynamic features of breast DCE-MR imaging and clinical response of neoadjuvant chemotherapy: a preliminary analysis

NASA Astrophysics Data System (ADS)

Huang, Lijuan; Fan, Ming; Li, Lihua; Zhang, Juan; Shao, Guoliang; Zheng, Bin

2016-03-01

Neoadjuvant chemotherapy (NACT) is being used increasingly in the management of patients with breast cancer for systemically reducing the size of primary tumor before surgery in order to improve survival. The clinical response of patients to NACT is correlated with reduced or abolished of their primary tumor, which is important for treatment in the next stage. Recently, the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used for evaluation of the response of patients to NACT. To measure this correlation, we extracted the dynamic features from the DCE- MRI and performed association analysis between these features and the clinical response to NACT. In this study, 59 patients are screened before NATC, of which 47 are complete or partial response, and 12 are no response. We segmented the breast areas depicted on each MR image by a computer-aided diagnosis (CAD) scheme, registered images acquired from the sequential MR image scan series, and calculated eighteen features extracted from DCE-MRI. We performed SVM with the 18 features for classification between patients of response and no response. Furthermore, 6 of the 18 features are selected to refine the classification by using Genetic Algorithm. The accuracy, sensitivity and specificity are 87%, 95.74% and 50%, respectively. The calculated area under a receiver operating characteristic (ROC) curve is 0.79+/-0.04. This study indicates that the features of DCE-MRI of breast cancer are associated with the response of NACT. Therefore, our method could be helpful for evaluation of NACT in treatment of breast cancer.

Clinical COPD Questionnaire in patients with chronic respiratory disease.

PubMed

Canavan, Jane L; Dilaver, Deniz; Clark, Amy L; Jones, Sarah E; Nolan, Claire M; Kon, Samantha S C; Man, William D-C

2014-10-01

The Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (CCQ) is an easy to complete, health-related quality of life questionnaire which has been well-validated in COPD. The responsiveness of the CCQ in chronic respiratory disease patients other than COPD has not been previously described. The study aims were to determine if the CCQ in chronic respiratory disease correlates with other health related quality of life questionnaires, to assess the responsiveness of the CCQ to pulmonary rehabilitation and to determine the minimum important difference. The CCQ, COPD Assessment Test (CAT), the Chronic Respiratory Questionnaire (CRQ) and St George's Respiratory Questionnaire (SGRQ) were measured in 138 chronic respiratory disease patients completing pulmonary rehabilitation. Change in CCQ with pulmonary rehabilitation was correlated with change in the other questionnaires. The minimum important difference of the CCQ was calculated using distribution and anchor-based approaches. The CCQ, CAT, CRQ and SGRQ improved significantly with rehabilitation with effect sizes of -0.43, -0.26, 0.62, -0.37. Change in CCQ correlated significantly with CAT, CRQ and SGRQ (r = 0.53, -0.64, 0.30, all P < 0.0001). The minimum important difference was -0.42 at the population level and -0.4 at the individual level. The CCQ is responsive to pulmonary rehabilitation in chronic respiratory disease patients, with an MID estimated at -0.4 at the individual level. © 2014 Asian Pacific Society of Respirology.

The molecular aspects of personalized anticancer treatment

NASA Astrophysics Data System (ADS)

Cherdyntseva, N.; Litviakov, N.; Ivanova, F.; Denisov, E.; Gervas, P.; Cherdyntsev, E.

2016-08-01

Only 25% of cancer patients, on average, benefit from therapy. Even in the cases of complete clinical response the tumor progression is an event of high level expectation. The main reasons for tumor progression are: intratumor heterogeneity resulted from clonal evolution, drug resistance, and tumor-promoting microenvironment. The reprogramming of microenvironmental stromal-inflammatory components is expected to allow tumor phenotype reversion. So, to find the new effective markers of tumor progression, drug response and targets for therapy, it could be promising to take into account the tumor-microenvironment heterogeneity and tumor clonal evolution.

Experience of Comamonas acidovorans keratitis with delayed onset and treatment response in immunocompromised cornea.

PubMed

Lee, Sang Mok; Kim, Mee Kum; Lee, Jae Lim; Wee, Won Ryang; Lee, Jin Hak

2008-03-01

To report 2 cases of Comamonas acidovorans keratitis in immunocompromised cornea. A complete review of the medical records of the two cases of Comamonas acidovorans keratitis. We found some similarities in clinical courses of two cases. Both of them showed development of keratitis during the management with corticosteroids, delayed onset, slow response to antibiotics, and relatively less affected corneal epithelium. Comamonas acidovorans is known as a less virulent organism. However it can cause an indolent infection that responds slowly even to adequate antibiotics therapy in immunocompromised corneas.

Rumination as a Vulnerability Factor to Depression in Adolescents in Mainland China: Lifetime History of Clinically Significant Depressive Episodes

ERIC Educational Resources Information Center

Hong, Wei; Abela, John R. Z.; Cohen, Joseph R.; Sheshko, Dana M.; Shi, Xiao Ting; Hamel, Anton Van; Starrs, Claire

2010-01-01

The current study tested the vulnerability and sex differences hypotheses of the response styles theory of depression (Nolen-Hoeksema, 1991). Participants included 494 tenth-grade students (M = 15.25 years, SD = 0.47) recruited from two secondary schools in Beijing, China. Participants completed self-report measures assessing rumination and…

Assessing the oral health of an ageing population: methods, challenges and predictors of survey participation.

PubMed

Matthews, Debora C; Brillant, Martha G S; Clovis, Joanne B; McNally, Mary E; Filiaggi, Mark J; Kotzer, Robert D; Lawrence, Herenia P

2012-06-01

To examine predictors of participation and to describe the methodological considerations of conducting a two-stage population-based oral health survey. An observational, cross-sectional survey (telephone interview and clinical oral examination) of community-dwelling adults aged 45-64 and ≥65 living in Nova Scotia, Canada was conducted. The survey response rate was 21% for the interview and 13.5% for the examination. A total of 1141 participants completed one or both components of the survey. Both age groups had higher levels of education than the target population; the age 45-64 sample also had a higher proportion of females and lower levels of employment than the target population. Completers (participants who completed interview and examination) were compared with partial completers (who completed only the interview), and stepwise logistic regression was performed to examine predictors of completion. Identified predictors were as follows: not working, post-secondary education and frequent dental visits. Recruitment, communications and logistics present challenges in conducting a province-wide survey. Identification of employment, education and dental visit frequency as predictors of survey participation provide insight into possible non-response bias and suggest potential for underestimation of oral disease prevalence in this and similar surveys. This potential must be considered in analysis and in future recruitment strategies. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

Live and Web-based orientations are comparable for a required rotation.

PubMed

Prunuske, Jacob

2010-03-01

Studies show equivalency in knowledge when measured following Web-based learning and live lecture. However, the effectiveness of a Web-based orientation for a required clinical rotation is unknown. Medical students viewed a Web-based orientation and completed a 13-item evaluation before beginning a required 6-week community medicine rotation. Evaluation data from 2007-2008 live orientation sessions were compared to responses from 2008-2009 Web-based orientation sessions. Data were analyzed by two-sample tests of proportion. A total of 169 students completed surveys during the study period--78 following the live and 91 following the Web-based orientation. Response rates were equal in the two groups. The survey tool had a high level of reliability (Cronbach's alpha=0.96). There was no statistical difference in student evaluations for 12 of 13 orientation evaluation items. Live and Web-based formats are comparable for presenting orientation materials to a required clinical rotation. Students felt the purpose of the rotation, educational goals, course structure, and requirements were clearly presented regardless of format. Transition from a live to Web-based format reduced faculty time required to present at rotation orientations.

Photodynamic therapy for actinic cheilitis: a systematic review.

PubMed

Yazdani Abyaneh, Mohammad-Ali; Falto-Aizpurua, Leyre; Griffith, Robert D; Nouri, Keyvan

2015-02-01

Actinic cheilitis (AC) is a premalignant lesion of the lips that can progress to squamous cell carcinoma and metastasize. Actinic cheilitis is difficult to treat because surgical treatments have significant adverse effects whereas less invasive procedures have uncertain efficacy. Photodynamic therapy (PDT) may offer a noninvasive yet effective treatment option for AC. To systematically review the safety and efficacy of PDT for AC. The terms "photodynamic," "actinic," "solar," "cheilitis," and "cheilosis" were used in combinations to search the PubMed database. Studies were considered for inclusion based on eligibility criteria, and specific data were extracted from all studies. The authors identified 15 eligible case series encompassing a total of 242 treated subjects. Among studies that evaluated subjects for complete clinical response, 139 of 223 subjects (62%) showed complete response at final follow-ups ranging from 3 to 30 months. Among studies that evaluated subjects for histological outcome, 57 of 121 subjects (47%) demonstrated histological cure at final follow-ups ranging from 1.5 to 18 months. Cosmetic outcomes were good to excellent in the majority of subjects, and adverse events were well tolerated. Photodynamic therapy is safe and has the potential to clinically and histologically treat AC, with a need for future randomized controlled trials.

Considerations on bringing warehoused HCV patients into active care following interferon-free, direct-acting antiviral drug approval.

PubMed

Palak, Aleksandra; Livoti, Christine; Audibert, Céline

2017-05-01

Until recently, lack of efficacious and tolerable hepatitis C virus (HCV) treatments prompted patient warehousing until better treatment options became available. We investigated whether the introduction of ledipasvir/sofosbuvir precipitated patient return to clinics, thereby changing HCV clinic dynamics. Online questionnaire responses indicated the volume of HCV patients followed, the proportion of warehoused patients and those who were proactively offered new options, methods for identifying and contacting patients, and insurance authorization/reimbursement-related information. Of 168 practices surveyed, 19% indicated no patient warehousing in the previous 3 years; 81% had warehoused 40% of patients; 92% were able to handle their patient load; and 82% had not changed practices to accommodate more HCV patients in the previous 12 months. Of the 35% of patients who were ledipasvir/sofosbuvir-eligible, 50% already completed/are completing therapy, 21% were not treated due to insurance denial, and 19% were awaiting responses from insurance companies. Launch of a new treatment did not overburden HCV practices. Patients eligible to receive new treatments were being treated, but pre-authorization processes and reimbursement denials reduced the numbers of treated patients.

A preliminary report on histological outcome of pulpotomy with endodontic biomaterials vs calcium hydroxide.

PubMed

Nosrat, Ali; Peimani, Ali; Asgary, Saeed

2013-11-01

The purpose of the study was to evaluate human dental pulp response to pulpotomy with calcium hydroxide (CH), mineral trioxide aggregate (MTA), and calcium enriched mixture (CEM) cement. A total of nine erupted third molars were randomly assigned to each pulpotomy group. The same clinician performed full pulpotomies and coronal restorations. The patients were followed clinically for six months; the teeth were then extracted and prepared for histological assessments. The samples were blindly assessed by an independent observer for pulp vitality, pulp inflammation, and calcified bridge formation. All patients were free of clinical signs/symptoms of pulpal/periradicular diseases during the follow up period. In CH group, one tooth had necrotic radicular pulp; other two teeth in this group had vital uninflamed pulps with complete dentinal bridge formation. In CEM cement and MTA groups all teeth had vital uninflamed radicular pulps. A complete dentinal bridge was formed beneath CEM cement and MTA in all roots. Odontoblast-like cells were present beneath CEM cement and MTA in all samples. This study revealed that CEM cement and MTA were reliable endodontic biomaterials in full pulpotomy treatment. In contrast, the human dental pulp response to CH might be unpredictable.

Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab.

PubMed

Oliveira, Mafalda; Braga, Sofia; Passos-Coelho, José Luís; Fonseca, Ricardo; Oliveira, João

2011-06-01

Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treatment of HER2+ breast cancer. However, its high molecular weight precludes it from crossing the intact blood-brain barrier, making the central nervous system a sanctuary to HER2+ breast cancer metastases. We prospectively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis (LC) and brain metastases from HER2+ breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25 mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung, and liver involvement) previously treated with tamoxifen, letrozole, anthracyclines, taxanes, capecitabine, intravenous trastuzumab, and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after LC diagnosis. A complete leptomeningeal response, with no evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab administration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.

Psychosocial screening at paediatric BEEC clinics: a pilot evaluation study.

PubMed

Hurrell, Ruth A; Fullwood, Catherine; Keys, Joni; Dickson, Alan P; Fishwick, Janet; Whitnall, Beverley; Cervellione, Raimondo M

2015-04-01

Bladder Exstrophy and Epispadias Complex (BEEC) is associated with an increased risk of impaired mental health, quality of life, and psychosocial functioning. Therefore, screening patients to help identify and evaluate potential psychosocial difficulty is arguably an important consideration for BEEC Services. To screen paediatric BEEC patients for a range of general psychosocial difficulties in a multi-disciplinary out-patient clinic setting. This cross-sectional evaluation was conducted between April 2012 and July 2013. Families attending BEEC multi-disciplinary out-patient clinics were asked to complete a range of standardised psychosocial questionnaires, including the Paediatric Quality of Life Inventory (PedsQL 4.0 Generic Core and Family Impact Module), the Strengths and Difficulties Questionnaire (SDQ), the Paediatric Index of Emotional Distress (PI-ED), and the Hospital Anxiety and Depression Scale (HADS). 108 children attended clinic of which 80 (74.1%) patients and their parents/carers completed some or all of the questionnaires. The mean patient age was 8.41 years (SD = 4.46, range = 1-18 years). There were more boys (N = 50, 62.5%) and the majority had a diagnosis of classic bladder exstrophy (N = 51, 63.8%), followed by primary epispadias (N = 22, 27.5%) and cloacal exstrophy (N = 7, 8.7%). Mean total scores fell within the average/normal range on all questionnaires used (See table below). However, variation around these means was high. Age, gender and diagnosis were found to significantly influence certain questionnaire responses with older-age groups, males, and those with classic bladder exstrophy particularly at risk across some domains. The children/adolescents self-reported better health related quality of life (HRQoL) scores than published results for a range of paediatric chronic health conditions. Differences between parent and child responses on both the PedsQL and SDQ favoured a more positive response on the child self-report questionnaire but were not statistically significant. Mean scores on the measures used suggest a relatively optimistic picture of general psychosocial well-being, especially for HRQoL, in the BEEC population studied. Positive HRQoL outcomes have recently been reported for BEEC paediatric populations. Our results reflect this trend with better mean HRQoL scores than paediatric patients with a range of other chronic health conditions. However, this optimism is cautious given the limitations of this evaluation study and the high variation around the means. Limitations included the small sample size (especially for patients with cloacal exstrophy), the lack of a control group, the limited sensitivity of generic questionnaires in respect of BEEC-specific issues, and the low mean age of patients in the study. Future screening programmes may wish to consider measuring BEEC-specific variables (e.g. satisfaction with genital appearance/function); collecting information on medical aspects, such as continence, pubertal stage and frequency/timing of medical intervention; and asking both parents/carers (where possible) to complete the questionnaires. Screening questionnaire responses were used in conjunction with clinical psychology consultations to evaluate a range of psychosocial aspects in BEEC paediatric patients. Whilst mean scores on the measures used suggest a relatively optimistic picture, certain individual scores did fall within the clinical ranges, highlighting the potential need for further assessment. Developmentally tailored consultations with a clinical psychologist can provide detailed information around questionnaire responses and further assess BEEC specific aspects. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report.

PubMed

Mody, Kabir; Strauss, Edward; Lincer, Robert; Frank, Richard C

2010-10-20

Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.

Clinical efficacy and safety of bevacizumab monotherapy in patients with metastatic melanoma: predictive importance of induced early hypertension.

PubMed

Schuster, Cornelia; Eikesdal, Hans P; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E; Akslen, Lars A; Straume, Oddbjørn

2012-01-01

VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12-49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. ClinicalTrials.gov NCT00139360.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma.

PubMed

Yu, Jeong Il; Yoo, Gyu Sang; Cho, Sungkoo; Jung, Sang Hoon; Han, Youngyih; Park, Seyjoon; Lee, Boram; Kang, Wonseok; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Park, Hee Chul

2018-03-01

This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62-92 GyE 10 . Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

PubMed Central

Yu, Jeong Il; Yoo, Gyu Sang; Cho, Sungkoo; Jung, Sang Hoon; Han, Youngyih; Park, Seyjoon; Lee, Boram; Kang, Wonseok; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Park, Hee Chul

2018-01-01

Purpose This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. Materials and Methods HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62–92 GyE10. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. Conclusion PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted. PMID:29580046

Response to DNA damage of CHEK2 missense mutations in familial breast cancer

PubMed Central

Roeb, Wendy; Higgins, Jake; King, Mary-Claire

2012-01-01

Comprehensive sequencing of tumor suppressor genes to evaluate inherited predisposition to cancer yields many individually rare missense alleles of unknown functional and clinical consequence. To address this problem for CHEK2 missense alleles, we developed a yeast-based assay to assess in vivo CHEK2-mediated response to DNA damage. Of 25 germline CHEK2 missense alleles detected in familial breast cancer patients, 12 alleles had complete loss of DNA damage response, 8 had partial loss and 5 exhibited a DNA damage response equivalent to that mediated by wild-type CHEK2. Variants exhibiting reduced response to DNA damage were found in all domains of the CHEK2 protein. Assay results were in agreement with epidemiologic assessments of breast cancer risk for those variants sufficiently common for case–control studies to have been undertaken. Assay results were largely concordant with consensus predictions of in silico tools, particularly for damaging alleles in the kinase domain. However, of the 25 variants, 6 were not consistently classifiable by in silico tools. An in vivo assay of cellular response to DNA damage by mutant CHEK2 alleles may complement and extend epidemiologic and genetic assessment of their clinical consequences. PMID:22419737

Response to DNA damage of CHEK2 missense mutations in familial breast cancer.

PubMed

Roeb, Wendy; Higgins, Jake; King, Mary-Claire

2012-06-15

Comprehensive sequencing of tumor suppressor genes to evaluate inherited predisposition to cancer yields many individually rare missense alleles of unknown functional and clinical consequence. To address this problem for CHEK2 missense alleles, we developed a yeast-based assay to assess in vivo CHEK2-mediated response to DNA damage. Of 25 germline CHEK2 missense alleles detected in familial breast cancer patients, 12 alleles had complete loss of DNA damage response, 8 had partial loss and 5 exhibited a DNA damage response equivalent to that mediated by wild-type CHEK2. Variants exhibiting reduced response to DNA damage were found in all domains of the CHEK2 protein. Assay results were in agreement with epidemiologic assessments of breast cancer risk for those variants sufficiently common for case-control studies to have been undertaken. Assay results were largely concordant with consensus predictions of in silico tools, particularly for damaging alleles in the kinase domain. However, of the 25 variants, 6 were not consistently classifiable by in silico tools. An in vivo assay of cellular response to DNA damage by mutant CHEK2 alleles may complement and extend epidemiologic and genetic assessment of their clinical consequences.

Establishing a clinical pharmacy technician at a United States Army military treatment facility.

PubMed

Evans, Jennifer L; Gladd, Ellen M; Gonzalez, Alicia C; Tranam, Salman; Larrabee, Joni M; Lipphardt, Sarah E; Chen, Tina T; Ronn, Michael D; Spain, John

2016-01-01

To describe the creation of a clinical pharmacy technician position within the U.S. Army and to identify the personal skills and characteristics required to meet the demands of this role. An outpatient military treatment facility located in Maryland. The clinical pharmacy technician position was designed to support clinical pharmacy services within a patient-centered medical home. Funding and a position description were established to hire a clinical pharmacy technician. Expected duties included administrative (45%), patient education (30%), and dispensing (25%). Local policy, in accordance with federal law and U.S. Army regulations, was developed to define the expanded technician responsibility to deliver patient medication education. In the initial 3 months, the clinical pharmacy technician spent 24 hours per week on clinical activities, affording an additional 10-15 hours per week for clinical pharmacists to provide patient care. Completed consults increased from 41% to 56%, and patient-pharmacist encounters increased from 240 to 290 per month. The technician, acting as a clinical pharmacist extender, also completed an average of 90 patient encounters independently each month. As a result of these improvements, the decision was made to hire a second technician. Currently, the technicians spend 28-40 hours per week on clinical activities, offsetting an average of 26 hours per week for the clinical pharmacists. A patient-centered medical home clinical pharmacy technician can reduce the administrative workload for clinical pharmacists, improve their efficiency, and enhance the use of clinical pharmacy services. Several characteristics, particularly medication knowledge, make pharmacy technicians particularly suited for this role. The results from the implementation of a clinical pharmacy technician at this military treatment facility resulted in an Army-wide expansion of the position and suggested applicability in other practice sites, particularly in federal pharmacies. Published by Elsevier Inc.

Patient representatives' views on patient information in clinical cancer trials.

PubMed

Dellson, Pia; Nilbert, Mef; Carlsson, Christina

2016-02-01

Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. Two major themes emerged: emotional responses and cognitive responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development of future simplified and more attractive informed consent forms. The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials.

Honoring Dental Patients' Privacy Rule Right of Access in the Context of Electronic Health Records.

PubMed

Ramoni, Rachel B; Asher, Sheetal R; White, Joel M; Vaderhobli, Ram; Ogunbodede, Eyitope O; Walji, Muhammad F; Riedy, Christine; Kalenderian, Elsbeth

2016-06-01

A person's right to access his or her protected health information is a core feature of the U.S. Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. If the information is stored electronically, covered entities must be able to provide patients with some type of machine-readable, electronic copy of their data. The aim of this study was to understand how academic dental institutions execute the Privacy Rule's right of access in the context of electronic health records (EHRs). A validated electronic survey was distributed to the clinical deans of 62 U.S. dental schools during a two-month period in 2014. The response rate to the survey was 53.2% (N=33). However, three surveys were partially completed, and of the 30 completed surveys, the 24 respondents who reported using axiUm as the EHR at their dental school clinic were the ones on which the results were based (38.7% of total schools at the time). Of the responses analyzed, 86% agreed that clinical modules should be considered part of a patient's dental record, and all agreed that student teaching-related modules should not. Great variability existed among these clinical deans as to whether administrative and financial modules should be considered part of a patient record. When patients request their records, close to 50% of responding schools provide the information exclusively on paper. This study found variation among dental schools in their implementation of the Privacy Rule right of access, and although all the respondents had adopted EHRs, a large number return records in paper format.

Do circulating long non-coding RNAs (lncRNAs) (LincRNA-p21, GAS 5, HOTAIR) predict the treatment response in patients with head and neck cancer treated with chemoradiotherapy?

PubMed

Fayda, Merdan; Isin, Mustafa; Tambas, Makbule; Guveli, Murat; Meral, Rasim; Altun, Musa; Sahin, Dilek; Ozkan, Gozde; Sanli, Yasemin; Isin, Husniye; Ozgur, Emre; Gezer, Ugur

2016-03-01

Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in head and neck cancer (HNC). The aim of the present study was to evaluate plasma levels of three lncRNA molecules (lincRNA-p21, GAS5, and HOTAIR) in the treatment response in HNC patients treated with radical chemoradiotherapy (CRT). Forty-one patients with HNC were enrolled in the study. Most of the patients had nasopharyngeal carcinoma (n = 27, 65.9 %) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5 months after therapy. lncRNAs in plasma were measured by semiquantitative PCR. Treatment response was evaluated according to clinical examination, RECIST and PERCIST criteria based on magnetic resonance imaging (MRI), and positron emission tomography with computed tomography (PET/CT) findings. Complete response (CR) rates were 73.2, 36.6, and 50 % for clinical investigation, PET/CT-, or MRI-based response evaluation, respectively. Predictive value of lncRNAs was investigated in patients with CR vs. those with partial response (PR)/progressive disease (PD). We found that post-treatment GAS5 levels in patients with PR/PD were significantly higher compared with patients with CR based on clinical investigation (p = 0.01). Receiver operator characteristic (ROC) analysis showed that at a cutoff value of 0.3 of GAS5, sensitivity and specificity for clinical tumor response were 82 and 77 %, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (p = 0.042). In contrast to GAS5, pretreatment or post-treatment lincRNA-p21 and HOTAIR levels were not informative for treatment response. Our results suggest that circulating GAS5 could be a biomarker in predicting treatment response in HNC patients.

Immune reconstitution inflammatory syndrome in cancer patients with pulmonary aspergillosis recovering from neutropenia: Proof of principle, description, and clinical and research implications.

PubMed

Miceli, Marisa H; Maertens, Johan; Buvé, Kristel; Grazziutti, Monica; Woods, Gail; Rahman, Mazhar; Barlogie, Bart; Anaissie, Elias J

2007-07-01

Assessing the outcome of patients with invasive pulmonary aspergillosis by using conventional criteria is difficult, particularly when clinical and radiologic worsening coincides with neutrophil recovery. Usually, it is assumed that this deterioration is related to progressive aspergillosis, prompting changes in patient management. However, its temporal relation with neutrophil recovery suggests that it may be caused by an immune reconstitution syndrome (IRIS). Galactomannan is an Aspergillus-specific polysaccharide that is released during aspergillosis and is detected by the serum galactomannan test, which has been approved by the United States Food and Drug Administration for the diagnosis of invasive aspergillosis. In this study, the authors used sequential galactomannan testing to distinguish IRIS responses from progressive aspergillosis. From April 2001 to December 2006, patients with hematologic malignancies underwent galactomannan screening during periods when they were at risk. The clinical and laboratory findings from patients who had >or=2 consecutive positive galactomannan assays (optical density, >or=0.5) were reviewed. Nineteen neutropenic patients with aspergillosis developed clinical and radiologic pulmonary deterioration during neutrophil recovery. Deterioration coincided with microbiologic response, as documented by rapid normalization of serum galactomannan, and, in 16 patients, was followed by complete clinical response and survival at 3 months, although there were no changes in antifungal therapy. The 3 patients who died during the first month had no evidence of aspergillosis at autopsy examination. The authors propose that IRIS was responsible for the current findings and provide a definition for the syndrome. They also recommend serial galactomannan testing to guide aspergillosis management. Declining galactomannan values imply IRIS with an aspergillus response and obviate the need for invasive procedures and alternative antifungal therapies, whereas persistent galactomannan elevation indicates progressive aspergillosis and requires prompt treatment modification. Copyright (c) 2007 American Cancer Society.

DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

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

Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu; Wang Xiaozhe; Niemierko, Andrzej

2012-05-01

Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, withmore » biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need confirmation in an independent data set.« less

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

PubMed

Lacy, B E; Lembo, A J; Macdougall, J E; Shiff, S J; Kurtz, C B; Currie, M G; Johnston, J M

2014-03-01

US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies. © 2013 Ironwood Pharmaceuticals. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

Compliance and Subjective Patient Responses to Eyelid Hygiene.

PubMed

Alghamdi, Yousef A; Camp, Andrew; Feuer, William; Karp, Carol L; Wellik, Sarah; Galor, Anat

2017-07-01

Lid hygiene is a commonly prescribed first-line therapy in patients with lid margin disease, yet compliance with therapy is not well characterized. The goals of this study were to assess patient compliance with lid hygiene and evaluate which factors predict a favorable symptomatic response to treatment. This was a cross-sectional study of patients seen in the Miami Veterans Affairs eye clinic between August and December 2014. An evaluation was performed to assess dry eye symptoms and lid margin signs. All patients were then instructed to perform warm compresses and lid scrubs. A follow-up phone survey assessed compliance and subjective therapeutic response 6 weeks later. Two hundred seven of 211 (98%) patients (94% male, 60% white) completed the survey. Of the 207 patients, 188 (91%) completed the follow-up survey. Compliance with therapy was reported in 104 patients (55%); 66 reported complete improvement, 30 partial improvement, and 8 no improvement in symptoms. Patients who self-reported dry eye symptoms at first visit (n=86, 74%) were more likely to be compliant with lid hygiene than those who did not report symptoms (n=18, 25%) (P<0.0005). The only factor associated with poorer response to lid hygiene was longer time of self-reported dry eye symptoms. None of the other signs studied, including the presence of skin rosacea and lid margin telangiectasia, were associated with a differential response to lid hygiene. Patients with dry eye symptoms were moderately compliant with lid hygiene, and patients who performed the routine noted improvement in symptoms.

Biopsychosocial influence on shoulder pain: rationale and protocol for a pre-clinical trial

PubMed Central

George, Steven Z.; Staud, Roland; Borsa, Paul A.; Wu, Samuel S.; Wallace, Margaret R.; Greenfield, Warren. H.; Mackie, Lauren N.; Fillingim, Roger B.

2017-01-01

Background Chronic musculoskeletal pain conditions are a prevalent and disabling problem. Preventing chronic musculoskeletal pain requires multifactorial treatment approaches that address its complex etiology. Prior cohort studies identified a high risk subgroup comprised of variation in COMT genotype and pain catastrophizing. This subgroup had increased chance of heightened pain responses (in a pre-clinical model) and higher 12 month post-operatives pain intensity ratings (in a clinical model). This pre-clinical trial will test mechanisms and efficacy of personalized pain interventions matched to the genetic and psychological characteristics of the high-risk subgroup. Methods Potential participants will be screened for high risk subgroup membership, appropriateness for exercise-induced muscle injury protocol, and appropriateness for propranolol administration. Eligible participants that consent to the study will then be randomized into one of four treatment groups; 1) personalized pharmaceutical and psychological education; 2) personalized pharmaceutical and general education; 3) placebo pharmaceutical and psychological education; 4) placebo pharmaceutical and psychological education. Over the 5-day study period participants will complete an exercise-induced muscle injury protocol and receive study interventions. Pain and disability assessments will be completed daily, with primary outcomes being duration of shoulder pain (number of days until recovery), peak shoulder pain intensity, and peak shoulder disability. Secondary outcomes include inflammatory markers, psychological mediators, and measures of pain sensitivity regulation. Conclusion This pre-clinical trial builds on prior cohort studies and its completion will provide foundational data supporting efficacy and mechanisms of personalized interventions for individuals that may be at increased risk for developing chronic shoulder pain. Trial Registration ClinicalTrials.gov registry, NCT02620579 (Registered on November 13, 2015) PMID:28315479

Biopsychosocial influence on shoulder pain: Rationale and protocol for a pre-clinical trial.

PubMed

George, Steven Z; Staud, Roland; Borsa, Paul A; Wu, Samuel S; Wallace, Margaret R; Greenfield, Warren H; Mackie, Lauren N; Fillingim, Roger B

2017-05-01

Chronic musculoskeletal pain conditions are a prevalent and disabling problem. Preventing chronic musculoskeletal pain requires multifactorial treatment approaches that address its complex etiology. Prior cohort studies identified a high risk subgroup comprised of variation in COMT genotype and pain catastrophizing. This subgroup had increased chance of heightened pain responses (in a pre-clinical model) and higher 12month post-operatives pain intensity ratings (in a clinical model). This pre-clinical trial will test mechanisms and efficacy of personalized pain interventions matched to the genetic and psychological characteristics of the high-risk subgroup. Potential participants will be screened for high risk subgroup membership, appropriateness for exercise-induced muscle injury protocol, and appropriateness for propranolol administration. Eligible participants that consent to the study will then be randomized into one of four treatment groups; 1) personalized pharmaceutical and psychological education; 2) personalized pharmaceutical and general education; 3) placebo pharmaceutical and psychological education; 4) placebo pharmaceutical and psychological education. Over the 5-day study period participants will complete an exercise-induced muscle injury protocol and receive study interventions. Pain and disability assessments will be completed daily, with primary outcomes being duration of shoulder pain (number of days until recovery), peak shoulder pain intensity, and peak shoulder disability. Secondary outcomes include inflammatory markers, psychological mediators, and measures of pain sensitivity regulation. This pre-clinical trial builds on prior cohort studies and its completion will provide foundational data supporting efficacy and mechanisms of personalized interventions for individuals that may be at increased risk for developing chronic shoulder pain. ClinicalTrials.gov registry, NCT02620579 (Registered on November 13, 2015). Copyright © 2017 Elsevier Inc. All rights reserved.

Standardized synoptic cancer pathology reports - so what and who cares? A population-based satisfaction survey of 970 pathologists, surgeons, and oncologists.

PubMed

Lankshear, Sara; Srigley, John; McGowan, Thomas; Yurcan, Marta; Sawka, Carol

2013-11-01

Cancer Care Ontario implemented synoptic pathology reporting across Ontario, impacting the practice of pathologists, surgeons, and medical and radiation oncologists. The benefits of standardized synoptic pathology reporting include enhanced completeness and improved consistency in comparison with narrative reports, with reported challenges including increased workload and report turnaround time. To determine the impact of synoptic pathology reporting on physician satisfaction specific to practice and process. A descriptive, cross-sectional design was utilized involving 970 clinicians across 27 hospitals. An 11-item survey was developed to obtain information regarding timeliness, completeness, clarity, and usability. Open-ended questions were also employed to obtain qualitative comments. A 51% response rate was obtained, with descriptive statistics reporting that physicians perceive synoptic reports as significantly better than narrative reports. Correlation analysis revealed a moderately strong, positive relationship between respondents' perceptions of overall satisfaction with the level of information provided and perceptions of completeness for clinical decision making (r = 0.750, P < .001) and ease of finding information for clinical decision making (r = 0.663, P < .001). Dependent t tests showed a statistically significant difference in the satisfaction scores of pathologists and oncologists (t169 = 3.044, P = .003). Qualitative comments revealed technology-related issues as the most frequently cited factor impacting timeliness of report completion. This study provides evidence of strong physician satisfaction with synoptic cancer pathology reporting as a clinical decision support tool in the diagnosis, prognosis, and treatment of cancer patients.

Examining effectiveness of tailorable computer-assisted therapy programmes for substance misuse: Programme usage and clinical outcomes data from Breaking Free Online.

PubMed

Elison, Sarah; Jones, Andrew; Ward, Jonathan; Davies, Glyn; Dugdale, Stephanie

2017-11-01

When evaluating complex, tailorable digital behavioural interventions, additional approaches may be required alongside established methodologies such as randomised controlled trials (RCTs). Research evaluating a computer-assisted therapy (CAT) programme for substance misuse, Breaking Free Online (BFO), is informed by Medical Research Council (MRC) guidance recommending examination of 'mechanisms of action' of individual intervention strategies, which is relevant when evaluating digital interventions with content that may evolve over time. To report findings from examination of mechanisms of action of tailoring advice within the BFO programme and outcomes from specific intervention strategies. Analysis of covariance and linear regressions were used to assess intervention completion data, and psychometric and clinical outcomes, for 2311 service users accessing drug and alcohol treatment services across the UK. Tailoring advice provided to users appeared to prompt them to prioritise completion of intervention strategies associated with their areas of highest biopsychosocial impairment. Completion of specific intervention strategies within BFO were associated with specific clinical outcomes, with a dose response also being found. Mechanisms of action analyses revealed the primacy of cognitions, with cognitive restructuring strategies being associated with improvements in mental health, severity of substance dependence, quality of life and global biopsychosocial functioning. The MRC framework provides an evolved research paradigm within the field of digital behavioural change. By assessing baseline profiles of need, BFO can target the most appropriate clinical content for individual users. Mechanisms of action research can be used to inform modifications to BFO to continually update clinical content and the technology platform. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel cancer immunotherapy agents with survival benefit: recent successes and next steps

PubMed Central

Sharma, Padmanee; Wagner, Klaus; Wolchok, Jedd D.; Allison, James P.

2012-01-01

The US Food and Drug Administration (FDA) recently approved two novel immunotherapy agents, sipuleucel-T and ipilimumab, which showed a survival benefit for patients with metastatic prostate cancer and melanoma, respectively. The mechanisms by which these agents provide clinical benefit are not completely understood. However, knowledge of these mechanisms will be crucial for probing human immune responses and tumour biology in order to understand what distinguishes responders from non-responders. The following next steps are necessary: first, the development of immune-monitoring strategies for the identification of relevant biomarkers; second, the establishment of guidelines for the assessment of clinical end points; and third, the evaluation of combination therapy strategies to improve clinical benefit. PMID:22020206

Health departments do it better: prenatal care site and prone infant sleep position.

PubMed

Lahr, Martin B; Rosenberg, Kenneth D; Lapidus, Jodi A

2005-06-01

Reduction of prone infant sleep position has been the main public health effort to reduce the incidence of Sudden Infant Death Syndrome (SIDS). Oregon Pregnancy Risk Assessment Monitoring System (PRAMS) surveys a stratified random sample of women after a live birth. In 1998-1999, 1867 women completed the survey (64.0% unweighted response; 73.5% weighted response). Overall, 9.2% of all women "usually" chose prone infant sleep position, while 24.2% chose side and 66.5% chose supine position. Women receiving care from private physicians or HMOs more often chose prone position (10.6%) than women receiving prenatal care from health department clinics (2.5%), hospital clinics (6.1%) or other sites (8.3%). Compared to health department prenatal clinic patients, private prenatal patients were more likely to choose prone infant sleep position, adjusted odds ratio = 4.78 (95% confidence interval [CI] 1.64-13.92). Health Department clinics have done a better job than private physicians in educating mothers about putting infants to sleep on their backs. Providers-especially private providers-should continue to stress the importance of supine sleep position for infants.

Improving patient recruitment to multicentre clinical trials: the case for employing a data manager in a district general hospital-based oncology centre.

PubMed

Street, A; Strong, J; Karp, S

2001-01-01

One of the most frequently cited reasons for poor recruitment to multicentre randomized clinical trials is the additional workload placed on clinical staff. We report the effect on patient recruitment of employing a data manager to support clinical staff in an English district general hospital (DGH). In addition, we explore the effect data managers have on the quality of data collected, proxied by the number of queries arising with the trial organizers. We estimate that the cost of employing a data manager on a full-time basis is 502 per patient recruited but may amount to 326 if the appointment is part-time. Data quality is high when full responsibility lies with a data manager but falls when responsibility is shared. Whether the costs of employing a data manager to recruit patients from a DGH are worth incurring depends on the value placed on the speed at which multicentre trials can be completed, how important it is to broaden the research base beyond the traditional setting of teaching hospitals, and the amount of evaluative data required.

Treating and Downstaging Hepatocellular Carcinoma in the Caudate Lobe with Yttrium-90 Radioembolization

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

Ibrahim, Saad M.; Kulik, Laura; Baker, Talia

2012-10-15

Purpose: This study was designed to determine the technical feasibility, safety, efficacy, and potential to downstage patients to within transplantation criteria when treating patients with hepatocellular carcinoma (HCC) of the caudate lobe using Y90 radioembolization. Methods: During a 4-year period, 8 of 291 patients treated with radioembolization for unresectable HCC had disease involving the caudate lobe. All patients were followed for treatment-related clinical/biochemical toxicities, serum tumor marker response, and treatment response. Imaging response was assessed with the World Health Organization (WHO) and European Association for the Study of the Liver (EASL) classification schemes. Pathologic response was reported as percent necrosismore » at explantation. Results: Caudate lobe radioembolization was successfully performed in all eight patients. All patients presented with both cirrhosis and portal hypertension. Half were United Network for Organ Sharing (UNOS) stage T3 (n = 4, 50%). Fatigue was reported in half of the patients (n = 4, 50%). One (13%) grade 3/4 bilirubin toxicity was reported. One patient (13%) showed complete tumor response by WHO criteria, and three patients (38%) showed complete response using EASL guidelines. Serum AFP decreased by more than 50% in most patients (n = 6, 75%). Four patients (50%) were UNOS downstaged from T3 to T2, three of who underwent transplantation. One specimen showed histopathologic evidence of 100% complete necrosis, and two specimens demonstrated greater than 50% necrosis. Conclusions: Radioembolization with yttrium-90 appears to be a feasible, safe, and effective treatment option for patients with unresectable caudate lobe HCC. It has the potential to downstage patients to transplantation.« less

Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid.

PubMed

Hillemanns, P; Untch, M; Dannecker, C; Baumgartner, R; Stepp, H; Diebold, J; Weingandt, H; Pröve, F; Korell, M

2000-03-01

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat. Copyright 2000 Wiley-Liss, Inc.

Implementing a pilot leadership course for internal medicine residents: design considerations, participant impressions, and lessons learned.

PubMed

Blumenthal, Daniel M; Bernard, Ken; Fraser, Traci N; Bohnen, Jordan; Zeidman, Jessica; Stone, Valerie E

2014-11-30

Effective clinical leadership is associated with better patient care. We implemented and evaluated a pilot clinical leadership course for second year internal medicine residents at a large United States Academic Medical Center that is part of a multi-hospital health system. The course met weekly for two to three hours during July, 2013. Sessions included large group discussions and small group reflection meetings. Topics included leadership styles, emotional intelligence, and leading clinical teams. Course materials were designed internally and featured "business school style" case studies about everyday clinical medicine which explore how leadership skills impact care delivery. Participants evaluated the course's impact and quality using a post-course survey. Questions were structured in five point likert scale and free text format. Likert scale responses were converted to a 1-5 scale (1 = strongly disagree; 3 = neither agree nor disagree; 5 = strongly agree), and means were compared to the value 3 using one-way T-tests. Responses to free text questions were analyzed using the constant comparative method. All sixteen pilot course participants completed the survey. Participants overwhelmingly agreed that the course provided content and skills relevant to their clinical responsibilities and leadership roles. Most participants also acknowledged that taking the course improved their understanding of their strengths and weaknesses as leaders, different leadership styles, and how to manage interpersonal conflict on clinical teams. 88% also reported that the course increased their interest in pursuing additional leadership training. A clinical leadership course for internal medicine residents designed by colleagues, and utilizing case studies about clinical medicine, resulted in significant self-reported improvements in clinical leadership competencies.

Venetoclax and low-dose cytarabine induced complete remission in a patient with high-risk acute myeloid leukemia: a case report.

PubMed

Liu, Bingshan; Narurkar, Roshni; Hanmantgad, Madhura; Zafar, Wahib; Song, Yongping; Liu, Delong

2018-05-21

Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high-risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies.

Novel pharmacotherapies in diabetic retinopathy: Current status and what's in the horizon?

PubMed Central

Das, Arup; McGuire, Paul G; Monickaraj, Finny

2016-01-01

The blood–retinal barrier (BRB) alteration is the hallmark feature of diabetic retinopathy. Vascular endothelial growth factor (VEGF) is a potent vasopermeability factor that has been implicated in the pathogenesis of BRB alteration. Inflammation also plays a crucial role in this process with involvement of several chemokines and cytokines. Multiple anti-VEGF drugs are widely used as in the treatment of diabetic macular edema (DME) as well as proliferative diabetic retinopathy. Several clinical trials have proved the beneficial effects of these drugs in improvement of vision and prevention of vision loss. However, the response to anti-VEGF drugs in DME is not complete in a significant number of patients. The effect seems transient in this latter group, and many patients do not show complete resolution of fluid. Potential novel therapies targeting molecules beyond VEGF are being developed and examined in clinical trials. PMID:26953018

The Pine Ridge-Mayo National Aeronautics and Space Administration telemedicine project: program activities and participant reactions.

PubMed

Kottke, T E; Little Finger, L; Trapp, M A; Panser, L A; Novotny, P J

1996-04-01

To determine the response of participants to the Pine Ridge-Mayo National Aeronautics and Space Administration telemedicine project. We describe a 3-month demonstration project of medical education and clinical consultations conducted by means of satellite transmission. Postparticipation questionnaires and a postproject survey were used to assess the success of the activity. Patients and employees at the Pine Ridge Indian Health Service Hospital in southwestern South Dakota and employees at Mayo Clinic Rochester participated in a telemedicine project, after which they completed exit surveys and a postproject questionnaire to ascertain the acceptability of this mode of health care. Almost all Pine Ridge and Mayo Clinic participants viewed the project as beneficial. The educational sessions received favorable evaluations, and almost two-thirds of the patients who completed evaluations thought the consultation had contributed to their medical care. More than 90% of the respondents from Pine Ridge and more than 85% of the respondents from Mayo Clinic Rochester said that they would recommend participation in this project to others. More than 90% of respondents from Pine Ridge and 80% of Mayo respondents agreed with the statement that the project should continue. These data suggest that a program of clinical consultation services, professional education, and patient education available by telemedicine might be viewed as beneficial.

Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

PubMed Central

Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

1995-01-01

In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality. PMID:7621588

Intratumoral Epidermal Growth Factor Receptor Antisense DNA Therapy in Head and Neck Cancer: First Human Application and Potential Antitumor Mechanisms

PubMed Central

Lai, Stephen Y.; Koppikar, Priya; Thomas, Sufi M.; Childs, Erin E.; Egloff, Ann Marie; Seethala, Raja R.; Branstetter, Barton F.; Gooding, William E.; Muthukrishnan, Ashok; Mountz, James M.; Lui, Vivian W.Y.; Shin, Dong M.; Agarwala, Sanjiv S.; Johnson, Rita; Couture, Larry A.; Myers, Eugene N.; Johnson, Jonas T.; Mills, Gordon; Argiris, Athanassios; Grandis, Jennifer R.

2009-01-01

Purpose Squamous cell carcinoma of the head and neck (SCCHN) is characterized by upregulation of the epidermal growth factor receptor (EGFR). We developed a novel strategy to target EGFR by using a therapeutic gene that consisted of an EGFR antisense (AS) gene sequence under U6 promoter control. A phase I clinical trial was conducted to evaluate the safety and biologic effects of EGFR AS. Patients and Methods Patients with advanced SCCHN who were refractory to standard therapies and who had at least one assessable and accessible lesion were enrolled. The EGFR AS dose was escalated in successive cohorts (six dose levels; 60 to 1,920 μg/injection). Patients received four weekly intratumoral EGFR AS injections. Tumor biopsies were performed before and after completion of therapy. Treatment response was assessed by tumor volume measurements (positron emission tomography/computed tomography), and levels of target proteins were assessed by immunohistochemistry. Results Seventeen assessable patients were treated. No grades 3 to 4 or dose-limiting toxicities were noted, and a maximum-tolerated dose was not reached. Five patients (29%) achieved a clinical response, which included two complete responses (CRs) and three partial responses (PRs); two additional patients had stable disease (SD) as the best response. Patients with disease control (CR + PR + SD) had tumors with higher EGFR and lower STAT3 expression at baseline compared with patients who had progressive disease (P = .0312 and P = .095, respectively). Conclusion Intratumoral EGFR AS was safe and resulted in antitumor activity in patients with advanced SCCHN. Baseline levels of high EGFR and low STAT3 may be associated with antitumor effects. PMID:19204206

Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma.

PubMed

Loveland, Bruce E; Zhao, Anne; White, Shane; Gan, Hui; Hamilton, Kate; Xing, Pei-Xiang; Pietersz, Geoffrey A; Apostolopoulos, Vasso; Vaughan, Hilary; Karanikas, Vaios; Kyriakou, Peter; McKenzie, Ian F C; Mitchell, Paul L R

2006-02-01

Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy. Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy. Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNgamma Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment. Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.

[Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes].

PubMed

Ruano, R; Ramos, M; García-Talavera, J R; Ramos, T; Rosero, A S; González-Orus, J M; Sancho, M

2014-01-01

To evaluate the influence of the molecular subtype (MS) in the Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (BC) and a complete axillary response (CR). A prospective study involving 70 patients with BC treated with NAC was carried out. An axillary lymph node dissection was performed in the first 48 patients (validation group: VG), and in case of micro- or macrometastases in the therapeutic application phase (therapy group:TG). Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+, 10HER2+ non-luminal, 17 triple-negative. SNB was carried out in 98.6% of the cases, with only one false negative result in the VG (FN=2%). Molecular subtype did not affect SN detection. Despite the existence of axillary CR, statistically significant differences were found in the proportion of macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+. Breast tumor response to NAC varied among the different MS, this being lowest in luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple-negative were the groups with the best axillary histological response both when there was prior clinical involvement and when there was not. Molecular subtype is a predictive factor of the degree of tumor response to NAC in breast cancer. However, it does not affect SNB detection and efficiency. SNB can also be used safely in women with prior node involvement as long as a complete clinical and radiological assessment is made of the node response to NAC. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

The role of clinical toxicologists and poison control centers in public health.

PubMed

Sutter, Mark E; Bronstein, Alvin C; Heard, Stuart E; Barthold, Claudia L; Lando, James; Lewis, Lauren S; Schier, Joshua G

2010-06-01

Poison control centers and clinical toxicologists serve many roles within public health; however, the degree to which these entities collaborate is unknown. The objective of this survey was to identify successful collaborations of public health agencies with clinical toxicologists and poison control centers. Four areas including outbreak identification, syndromic surveillance, terrorism preparedness, and daily public health responsibilities amenable to poison control center resources were assessed. An online survey was sent to the directors of poison control centers, state epidemiologists, and the most senior public health official in each state and selected major metropolitan areas. This survey focused on three areas: service, structure within the local or state public health system, and remuneration. Questions regarding remuneration and poison control center location within the public health structure were asked to assess if these were critical factors of successful collaborations. Senior state and local public health officials were excluded because of a low response rate. The survey was completed in October 2007. A total of 111 respondents, 61 poison control centers and 50 state epidemiologists, were eligible for the survey. Sixty-nine (62%) of the 111 respondents, completed and returned the survey. Thirty-three (54%) of the 61 poison control centers responded, and 36 of the 50 state epidemiologists (72%) responded. The most frequent collaborations were terrorism preparedness and epidemic illness reporting. Additional collaborations also exist. Important collaborations exist outside of remuneration or poison control centers being a formal part of the public health structure. Poison control centers have expanded their efforts to include outbreak identification, syndromic surveillance, terrorism preparedness, and daily public health responsibilities amenable to poison control center resources. Collaboration in these areas and others should be expanded. Published by Elsevier Inc.

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

PubMed Central

Ray, Lara A; Bujarski, Spencer; Courtney, Kelly E; Moallem, Nathasha R; Lunny, Katy; Roche, Daniel; Leventhal, Adam M; Shoptaw, Steve; Heinzerling, Keith; London, Edythe D; Miotto, Karen

2015-01-01

Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatment-seeking individuals meeting DSM-IV criteria for MA abuse or dependence (n=30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of ‘crave drug,' ‘stimulated,' and ‘would like drug access,' decreased the the post-MA administration timecourse of ‘anxious' and increased ratings of ‘bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA. PMID:25801501

Role of curative radiotherapy in the treatment of lung cancer. [Clinical factors effecting efficacy and incidence of complications

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

Coy, P.; Kennelly, G.M.

1980-02-15

From 1963 to 1974, 141 patients with lung cancer were treated with curative intent in the A. Maxwell Evans Clinic in Vancouver. The clinical presentation, age and sex distribution, histology, and reasons for surgery not being carried out are examined. The results of this treatment are presented. An attempt has been made to isolate a group of patients who have a better prognosis so that treatment selection can be improved. Hemoptysis, cough, dyspnea, and incidental finding on routine chest x-ray were the most common manner of presentation. Thirty-four percent of the patients were over 70 years of age and 13%more » were women. The crude overall three- and five-year survival rates were 18 and 10% (19 and 9% in the men, 17 and 14% in the women). Patients presenting with dyspnea had a better survival than those presenting with cough and hemoptysis. Patients with lesions less than 3 cm in diameter had a 28% three-year survival, compared with 14% for lesions greater than 5 cm in diameter. The three- and five-year survival rates in patients over 70 years of age were 23 and 17% respectively. The response to treatment and the survival were better in the patients with squamous cell carcinoma. Twenty-two percent were alive at three years and 12% at five years as compared with 9 and 5% for other histologies. Fifty-four percent of the 35 patients with a complete response and with squamous cell carcinoma were alive at three years, compared with only 8% of the 12 patients with other histologies who showed a complete response.« less

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): the cutaneous sanctuary.

PubMed

Pileri, A; Delfino, C; Grandi, V; Agostinelli, C; Pileri, S A; Pimpinelli, N

2012-12-01

Blastic plasmacytoid dendritic cell neoplasm (BPDNC) is a rare tumour, which stems from plasmacytoid dendritic cells. Although the aetiology is still unclear, in the last few years various reports suggested a potential role of chromosomal aberrations in the oncogenesis. The disease is currently enclosed among "acute myeloid leukemia (AML) and related precursor neoplasms" in the last WHO classification. BPDCN has an aggressive course, however, it has been suggested that an exclusive cutaneous involvement at presentation is related to a better clinical outcome. We review the literature about BPDCN, and we present a series of 11 cases, all characterised by disease limited to the skin at presentation. Furthermore, we examined all cases of the last 10 years stored in the database of the multidisciplinary study group on cutaneous lymphomas of the University of Florence. Basing on the clinical features, patient were classified into two groups: with a single-lesion or multiple eruptive-lesions presentation. The former were treated with radiotherapy (limited field, electron beam therapy). The latter were treated with different therapeutic options, depending on age and co-morbidities. All patients with a single lesion achieved complete response. Five of 6 patients with eruptive lesions achieved a clinical response (2 complete and 3 partial response). Notably, the progression free survival was higher in the single-lesion than in the eruptive-lesion group (23 vs. 9 months). However all patients relapsed and 8 of 11 died. Although the small number of selected patients, we could speculate that the concept of "cutaneous sanctuary" is particularly true in patients with a single lesion-presentation. In these patients, especially if >70 year-old aged, radiotherapy should be encouraged as the treatment of choice.

Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms

PubMed Central

Monsma, David J; Cherba, David M; Eugster, Emily E; Dylewski, Dawna L; Davidson, Paula T; Peterson, Chelsea A; Borgman, Andrew S; Winn, Mary E; Dykema, Karl J; Webb, Craig P; MacKeigan, Jeffrey P; Duesbery, Nicholas S; Nickoloff, Brian J; Monks, Noel R

2015-01-01

Variable clinical responses, tumor heterogeneity, and drug resistance reduce long-term survival outcomes for metastatic melanoma patients. To guide and accelerate drug development, we characterized tumor responses for five melanoma patient derived xenograft models treated with Vemurafenib. Three BRAFV600E models showed acquired drug resistance, one BRAFV600E model had a complete and durable response, and a BRAFV600V model was expectedly unresponsive. In progressing tumors, a variety of resistance mechanisms to BRAF inhibition were uncovered, including mutant BRAF alternative splicing, NRAS mutation, COT (MAP3K8) overexpression, and increased mutant BRAF gene amplification and copy number. The resistance mechanisms among the patient derived xenograft models were similar to the resistance pathways identified in clinical specimens from patients progressing on BRAF inhibitor therapy. In addition, there was both inter- and intra-patient heterogeneity in resistance mechanisms, accompanied by heterogeneous pERK expression immunostaining profiles. MEK monotherapy of Vemurafenib-resistant tumors caused toxicity and acquired drug resistance. However, tumors were eradicated when Vemurafenib was combined the MEK inhibitor. The diversity of drug responses among the xenograft models; the distinct mechanisms of resistance; and the ability to overcome resistance by the addition of a MEK inhibitor provide a scheduling rationale for clinical trials of next-generation drug combinations. PMID:26101714

Promoting clinical competence: using scaffolded instruction for practice-based learning.

PubMed

Tilley, Donna Scott; Allen, Patricia; Collins, Cathie; Bridges, Ruth Ann; Francis, Patricia; Green, Alexia

2007-01-01

Competency-based education is essential for bridging the gap between education and practice. The attributes of competency-based education include an outcomes focus, allowance for increasing levels of competency, learner accountability, practice-based learning, self-assessment, and individualized learning experiences. One solution to this challenge is scaffolded instruction, where collaboration and knowledge facilitate learning. Collaboration refers to the role of clinical faculty who model desired clinical skills then gradually shift responsibility for nursing activity to the student. This article describes scaffolded instruction as applied in a Web-based second-degree bachelor of science in nursing (BSN) program. This second-degree BSN program uses innovative approaches to education, including a clinical component that relies on clinical coaches. Students in the program remain in their home community and complete their clinical hours with an assigned coach. The method will be described first, followed by a description of how the method was applied.

Clinical and imaging evaluation of the response to intravenous steroids in patients with Graves' orbitopathy and analysis on who requires additional therapy.

PubMed

Tsirouki, Theodora; Bargiota, Alexandra; Tigas, Stelios; Vasileiou, Agathi; Kapsalaki, Eftichia; Giotaki, Zoe; Asproudis, Ioannis; Tsatsoulis, Agathokles; Koukoulis, Georgios; Tsironi, Evangelia E

2016-01-01

The aim of this study was to evaluate the safety and efficacy of an individualized steroid regimen in patients with moderate-to-severe Graves' orbitopathy (GO) by monitoring clinical and imaging parameters. In total, 47 patients with active, moderate-to-severe GO were enrolled in this study. All the patients received the proposed treatment regimen by European Group on GO of 4.5 g of intravenous (IV) methylprednisolone for 12 weeks. At the end of the IV treatment, patients with persistent active GO (Group 1) who were assessed by clinical examination and orbital imaging with short tau inversion recovery-sequence magnetic resonance imaging (STIR MRI) received additional treatment with oral prednisolone, and those with inactive GO (Group 2) received no further treatment. Of the 42 patients who completed the study, 22 (52.4%) patients formed Group 1 and 20 (47.6%) patients Group 2. At the 12th week, the overall response to IV treatment was 76.2%, and clinical activity score (CAS) improvement was 69%. At the 24th week, the overall response was 92.8%, and CAS improvement was 97.6%, without statistically significant difference in CAS and total eye score between these two groups ( P =0.157 and P =0.856, respectively). Ophthalmic manifestations were improved, being absent or minimal in 78.6% of patients at the 24th week follow-up. Recurrence of disease activity occurred in 9.5% of patients up to 24 weeks after the completion of treatment, and major adverse events occurred in 6.4% of patients. In patients with moderate-to-severe GO, IV steroid treatment, followed by oral treatment, when needed, is an effective regimen with low rates of adverse events and recurrences. STIR MRI is a significant tool for recognizing patients who need additional steroid treatment.

Clinical and imaging evaluation of the response to intravenous steroids in patients with Graves’ orbitopathy and analysis on who requires additional therapy

PubMed Central

Tsirouki, Theodora; Bargiota, Alexandra; Tigas, Stelios; Vasileiou, Agathi; Kapsalaki, Eftichia; Giotaki, Zoe; Asproudis, Ioannis; Tsatsoulis, Agathokles; Koukoulis, Georgios; Tsironi, Evangelia E

2016-01-01

Objective The aim of this study was to evaluate the safety and efficacy of an individualized steroid regimen in patients with moderate-to-severe Graves’ orbitopathy (GO) by monitoring clinical and imaging parameters. Methods In total, 47 patients with active, moderate-to-severe GO were enrolled in this study. All the patients received the proposed treatment regimen by European Group on GO of 4.5 g of intravenous (IV) methylprednisolone for 12 weeks. At the end of the IV treatment, patients with persistent active GO (Group 1) who were assessed by clinical examination and orbital imaging with short tau inversion recovery-sequence magnetic resonance imaging (STIR MRI) received additional treatment with oral prednisolone, and those with inactive GO (Group 2) received no further treatment. Results Of the 42 patients who completed the study, 22 (52.4%) patients formed Group 1 and 20 (47.6%) patients Group 2. At the 12th week, the overall response to IV treatment was 76.2%, and clinical activity score (CAS) improvement was 69%. At the 24th week, the overall response was 92.8%, and CAS improvement was 97.6%, without statistically significant difference in CAS and total eye score between these two groups (P=0.157 and P=0.856, respectively). Ophthalmic manifestations were improved, being absent or minimal in 78.6% of patients at the 24th week follow-up. Recurrence of disease activity occurred in 9.5% of patients up to 24 weeks after the completion of treatment, and major adverse events occurred in 6.4% of patients. Conclusion In patients with moderate-to-severe GO, IV steroid treatment, followed by oral treatment, when needed, is an effective regimen with low rates of adverse events and recurrences. STIR MRI is a significant tool for recognizing patients who need additional steroid treatment. PMID:27895458

Oxytocin response to youth–mother interactions in clinically anxious youth is associated with separation anxiety and dyadic behavior

PubMed Central

Lebowitz, Eli R.; Silverman, Wendy K.; Martino, Alyssa M.; Zagoory-Sharon, Orna; Feldman, Ruth; Leckman, James F.

2017-01-01

Background Anxiety disorders are common in youth and cause significant distress and impairment to the individual and family. Oxytocin (OT), a nine amino acid peptide, is implicated in anxiety regulation and modulation of close interpersonal and attachment behavior. Anxiety disorders have been linked to low levels of salivary OT in youth. Research has also linked oxytocinergic functioning to social support, warm contact, and bonding, and indicated that contact with attachment figures stimulates OT response. We examined OT response to a brief, positive youth–mother interaction in clinically anxious youth. We investigated whether quality of the youth–mother interaction as well as the presence of particular anxiety disorders, are associated with youth OT response. Method Salivary OT from 41 youth with primary DSM-5 anxiety disorders was assayed before and after a 7-min youth–mother interaction that was later systematically coded by two reliable coders. Youth and mothers also completed rating scales of youth anxiety symptoms. Results Affective touch, maternal sensitivity, maternal intrusiveness, youth engagement, and youth initiative all contributed significantly to predicting youth OT response. Repeated measures analyses showed that when affective touch was high youth had greater OT response. OT response was positively associated with the presence of separation anxiety disorder (SAD) and with child ratings of separation anxiety. Conclusions The findings highlight the importance of maternal and dyadic behavior patterns to oxytocinergic response in clinically anxious youth, shed light on the association between OT and SAD, and point to possible intervention strategies. PMID:28052452

Evaluation systems for clinical governance development: a comparative study.

PubMed

Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Ebrahimipour, Hossein

2014-01-01

Lack of scientific and confirmed researches and expert knowledge about evaluation systems for clinical governance development in Iran have made studies on different evaluation systems for clinical governance development a necessity. These studies must provide applied strategies to design criteria of implementing clinical governance for hospital's accreditation. This is a descriptive and comparative study on development of clinical governance models all over the world. Data have been gathered by reviewing related articles. Models have been studied in comprehensive review method. The evaluated models of clinical governance development were Australian, NHS, SPOCK and OPTIGOV. The final aspects extracted from these models were Responsiveness, Policies and Strategies, Organizational Structure, Allocating Resources, Education and Occupational Development, Performance Evaluation, External Evaluation, Patient Oriented Approach, Risk Management, Personnel's Participation, Information Technology, Human Resources, Research and Development, Evidence Based Medicine, Clinical Audit, Health Technology Assessment and Quality. These results are applicable for completing the present criteria which evaluating clinical governance application and provide practical framework to evaluate country's hospital on the basis of clinical governance elements.

Early non-response to certolizumab pegol in rheumatoid arthritis predicts treatment failure at one year. Data from a randomised phase III clinical trial.

PubMed

Berenbaum, Francis; Pham, Thao; Claudepierre, Pascal; de Chalus, Thibault; Joubert, Jean-Michel; Saadoun, Carine; Riou França, Lionel; Fautrel, Bruno

2018-01-01

To compare different early clinical criteria of non-response determined at three months as predictors of clinical failure at one year in patients with rheumatoid arthritis starting therapy with certolizumab pegol. Data were derived from a randomised Phase III clinical trial in patients with rheumatoid arthritis who failed to respond to methotrexate monotherapy. Patients included in this post-hoc analysis were treated with certolizumab pegol (400mg qd reduced to 200mg qd after one month) and with methotrexate. The study duration was twelve months. Response at three months was determined with the American College of Rheumatology-50, Disease Assessment Score-28 ESR, Health Assessment Questionnaire and the Clinical Disease Activity Index. The performance of these measures at predicting treatment failure at twelve months defined by the American College of Rheumatology-50 criteria was determined, using the positive predictive values as the principal evaluation criterion. Three hundred and eighty two patients were available for analysis and 225 completed the twelve-month follow-up. At Week 52, 149 (38.1%) patients met the American College of Rheumatology-50 response criterion. Positive predictive values ranged from 81% for a decrease in Health Assessment Questionnaire- Disability index score since baseline >0.22 to 95% for a decrease in Disease Assessment Score-28 score since baseline≥1.2. Sensitivity was≤70% in all cases. Performance of these measures was similar irrespective of the definition of treatment failure at 12months. Simple clinical measures of disease activity can predict future treatment failure reliably and are appropriate for implementing treat-to-target treatment strategies in everyday practice. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Effectiveness of betahistine (48 mg/day) in patients with vestibular vertigo during routine practice: The VIRTUOSO study.

PubMed

Parfenov, Vladimir A; Golyk, Volodymyr A; Matsnev, Eduard I; Morozova, Svetlana V; Melnikov, Oleg A; Antonenko, Ludmila M; Sigaleva, Elena E; Situkho, Maksym I; Asaulenko, Olena I; Popovych, Vasyl I; Zamergrad, Maxim V

2017-01-01

Vestibular vertigo is associated with substantially reduced quality of life. Betahistine is effective in improving vertigo-associated symptoms, with longer treatment periods leading to greater improvements; however, it is not known whether these effects persist after treatment cessation. VIRTUOSO was a prospective, multinational, non-comparative, post-marketing observational programme investigating the effectiveness of betahistine (48 mg/day) and the course of vertigo after the discontinuation of treatment. Patients with vestibular vertigo who were prescribed 48 mg/day betahistine were enrolled in Russia and Ukraine. Treatment duration was up to 2 months, and patients were followed up for 2 months after discontinuation of betahistine. Efficacy endpoints included clinical response (assessed by change in vertigo severity), monthly attack frequency, and physician and patient grading of overall clinical response and improvement of vertigo-associated symptoms. Overall, 309 patients were enrolled and 305 completed the study. Clinical response was rated as good, very good or excellent in 74.1% of patients at end of treatment, with vertigo severity significantly decreased from baseline (p < 0.001). Monthly vertigo attack frequency decreased significantly during the 2 months of treatment (p < 0.001 from baseline) and further decreased during the 2-month follow-up (p < 0.001 from end of treatment). Overall, clinical response was graded as good or excellent by 94.4% of physicians and 95.4% of patients. Clinical improvement was considered either good or excellent by 82.6-90.5% of physicians and patients for nausea, vomiting and faintness. Only one adverse event was reported, with no serious adverse events. Our findings suggest that betahistine (48 mg/day) therapy is effective in treating vertigo in routine clinical settings. The observed effects persisted for 2 months after treatment cessation, suggesting that betahistine may facilitate lasting vestibular compensation.

The relaxation response resiliency program (3RP) in patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis: results from a pilot study.

PubMed

Vranceanu, Ana-Maria; Merker, Vanessa L; Plotkin, Scott R; Park, Elyse R

2014-10-01

NF1, NF2, and Schwannomatosis are incurable tumor suppressor syndromes associated with poor quality of life. The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an NF adapted, 8-week group mind body skills based intervention, the relaxation response resiliency program (3RP) aimed at improving resiliency and increasing satisfaction with life. Patients seen at MGH's Neurofibromatosis Clinic were offered participation if they described difficulties coping to a treating physician. Participants completed measures of life satisfaction, resiliency, stress, mood, lifestyle, pain, post-traumatic growth and mindfulness at baseline and after completing the 3RP program. The intervention had relative feasible enrollment rate (48% rate, 32 out of 67 of patients signing the informed consent form). However, out of the 32 patients who signed the informed consent, only 20 started the study (62.5%) and only 16 completed it (50%), suggesting problems with feasibility. The main reason cited for non-participation was burden of travel to the clinic. The intervention was highly acceptable, as evidenced by an 80% completion rate (16/20). Paired t tests showed significant improvement in resiliency, satisfaction with life, depression, stress, anxiety, mindfulness and post traumatic growth, with effect sizes ranging from 0.73-1.33. There was a trend for significance for improvement in somatization and sleepiness (p = 0.06), with effect sizes of 0.54-0.92 respectively. Statistically nonsignificant improvement was observed in all other measures, with effect sizes small to medium. In sum, the 3RP was found to be relatively feasible, highly acceptable and preliminary efficacious in decreasing symptom burden in this population, supporting the need of a randomized controlled trial.

Transition of Care in Adolescents With Cerebral Palsy: A Survey of Current Practices.

PubMed

Bolger, Ashlee; Vargus-Adams, Jilda; McMahon, Mary

2017-03-01

Transition of care from pediatric to adult health care providers for youth with special needs (including cerebral palsy [CP]) is of current interest because these individuals are now living well into adulthood. Studies have attempted to identify barriers to transition, ideal timing for transition of care, and key elements for successful transition programs. These studies often encompass a wide range of diagnoses, and results cannot be fully applied to those with CP. To identify and describe current transition-of-care (TOC) practices and beliefs among physician providers of adolescents with CP in multidisciplinary CP clinics. Descriptive survey. Multidisciplinary CP clinics in the United States. Physician leaders in the aforementioned CP clinics. Respondents completed an electronic survey. Responses were deidentified and reported in aggregate by the use of descriptive statistics. Electronic survey addressing 3 domains: demographics of clinics, current opinions/practices related to TOC processes, and perceived barriers to successful TOC. Fifteen surveys were sent with 11 returned (response rate = 73%). TOC practices varied among clinics surveyed. Fifty-five percent of clinics had a structured transition program, but only one transitioned 100% of their patients to adult providers by 22 years of age. Only one clinic had an absolute upper age limit for seeing patients, and 36% of clinics accepted new patients older than 21 years. No respondent was "completely satisfied" with their transition process, and only one respondent was "moderately satisfied." The majority of respondents felt the ideal care setting for adults with CP was a comprehensive, multidisciplinary adult-focused clinic in an adult hospital/clinic with primarily adult providers. They noted the top 3 perceived barriers to successful TOC were limited adult providers willing to accept CP patients, concern about the level of care in the adult health care system, and lack of financial resources. Current TOC practices vary considerably among multidisciplinary pediatric CP clinics and are not satisfactory to individual physician providers within these clinics. Respondents desired a multidisciplinary clinic in an adult care setting with adult providers; however, the top 3 perceived barriers involved the adult health care system, making it difficult for pediatric providers to develop effective TOC programs. Not applicable. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Molar incisor hypomineralisation: experience and perceived challenges among dentists specialising in paediatric dentistry and a group of general dental practitioners in the UK.

PubMed

Kalkani, M; Balmer, R C; Homer, R M; Day, P F; Duggal, M S

2016-04-01

To assess the views and experience of the UK dentists specialising in paediatric dentistry (trainees) about molar incisor hypomineralisation (MIH) and compare the findings with the responses from a group of UK general dental practitioners. A web-based questionnaire was sent to dentists undergoing specialist training in paediatric dentistry. The same questionnaire was completed by a group of general dentists who stated an interest in treating children, with various levels of experience. The questionnaire sought information on clinical experience and the views of the dentists on the impact of MIH on children and families. Specialty trainees (37) from different paediatric dental departments in the UK completed the online survey, giving a total response rate of 71%. The questionnaire was also completed by 31 general dental practitioners. There was difficulty in distinguishing MIH from other conditions for both groups. Increased sensitivity of affected teeth was the most frequently encountered problem with 51% of the trainees and 76% of the dentists saying this was often or always a challenge. The trainees were particularly concerned about the pain children experienced and about the appearance of the condition. Both groups felt that parental anxiety occurred in almost all cases. Both groups felt that MIH presents several clinical challenges and has a negative effect on the quality of life of the affected children and their families. There were significant differences in the views and perceptions between the two groups.

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

PubMed

Weiss, Glen J; Byron, Sara A; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A; Carpten, John D; Craig, David W; Whitsett, Timothy G

2017-01-01

Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

Evaluation of Magnetic Resonance Imaging Responsiveness in Active Psoriatic Arthritis at Multiple Timepoints during the First 12 Weeks of Antitumor Necrosis Factor Therapy.

PubMed

Feletar, Marie; Hall, Stephen; Bird, Paul

2016-01-01

To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.

Electroconvulsive therapy in pregnant patients.

PubMed

Bulbul, Feridun; Copoglu, Umit Sertan; Alpak, Gokay; Unal, Ahmet; Demir, Bahadır; Tastan, Mehmet Fatih; Savas, Haluk A

2013-01-01

In this study, the aim was to evaluate the clinical characteristics of patients that received electroconvulsive therapy (ECT) during pregnancy due to psychiatric disorders, evaluate the safety and efficacy of ECT in pregnant women, and evaluate the overall status of mothers and babies during the postpartum period. The study included 33 patients who were admitted as inpatients with the indication of ECT due to pregnancy and concurrent psychiatric disorders. Upon ECT administration, a complete response to treatment was seen in 84.21% of patients with major depression (n=16), a partial response to treatment in 15.78% of patients (n=3), a complete response to treatment in 91.66% of patients with bipolar disorder (n=11), a partial response to treatment in 8.33% of the patients(n=1), and a full response to treatment in 50% of patients with schizophrenia (n=1) and a partial response to treatment in 50% of patients with schizophrenia (n=1) were obtained. We had after birth information of 27 infants from total 33. It was learned that two of them had disease, one was stillbirth and 24 of them did not have any health problems. ECT administration during pregnancy to treat psychiatric disorders was found to be an effective treatment method. No risk of preterm birth in mothers treated with ECT during pregnancy was detected. © 2013.

How Imaging Can Impact Clinical Trial Design: Molecular Imaging as a Biomarker for Targeted Cancer Therapy.

PubMed

Mankoff, David A; Farwell, Michael D; Clark, Amy S; Pryma, Daniel A

2015-01-01

The ability to measure biochemical and molecular processes to guide cancer treatment represents a potentially powerful tool for trials of targeted cancer therapy. These assays have traditionally been performed by analysis of tissue samples. However, more recently, functional and molecular imaging has been developed that is capable of in vivo assays of cancer biochemistry and molecular biology and is highly complementary to tissue-based assays. Cancer imaging biomarkers can play a key role in increasing the efficacy and efficiency of therapeutic clinical trials and also provide insight into the biologic mechanisms that bring about a therapeutic response. Future progress will depend on close collaboration between imaging scientists and cancer physicians and on public and commercial sponsors, to take full advantage of what imaging has to offer for clinical trials of targeted cancer therapy. This review will provide examples of how molecular imaging can inform targeted cancer clinical trials and clinical decision making by (1) measuring regional expression of the therapeutic target, (2) assessing early (pharmacodynamic) response to treatment, and (3) predicting therapeutic outcome. The review includes a discussion of basic principles of molecular imaging biomarkers in cancer, with an emphasis on those methods that have been tested in patients. We then review clinical trials designed to evaluate imaging tests as integrated markers embedded in a therapeutic clinical trial with the goal of validating the imaging tests as integral markers that can aid patient selection and direct response-adapted treatment strategies. Examples of recently completed multicenter trials using imaging biomarkers are highlighted.

Psychiatrists’ Comfort Using Computers and Other Electronic Devices in Clinical Practice

PubMed Central

Fochtmann, Laura J.; Clarke, Diana E.; Barber, Keila; Hong, Seung-Hee; Yager, Joel; Mościcki, Eve K.; Plovnick, Robert M.

2015-01-01

This report highlights findings from the Study of Psychiatrists’ Use of Informational Resources in Clinical Practice, a cross-sectional Web- and paper-based survey that examined psychiatrists’ comfort using computers and other electronic devices in clinical practice. One-thousand psychiatrists were randomly selected from the American Medical Association Physician Masterfile and asked to complete the survey between May and August, 2012. A total of 152 eligible psychiatrists completed the questionnaire (response rate 22.2 %). The majority of psychiatrists reported comfort using computers for educational and personal purposes. However, 26 % of psychiatrists reported not using or not being comfortable using computers for clinical functions. Psychiatrists under age 50 were more likely to report comfort using computers for all purposes than their older counterparts. Clinical tasks for which computers were reportedly used comfortably, specifically by psychiatrists younger than 50, included documenting clinical encounters, prescribing, ordering laboratory tests, accessing read-only patient information (e.g., test results), conducting internet searches for general clinical information, accessing online patient educational materials, and communicating with patients or other clinicians. Psychiatrists generally reported comfort using computers for personal and educational purposes. However, use of computers in clinical care was less common, particularly among psychiatrists 50 and older. Information and educational resources need to be available in a variety of accessible, user-friendly, computer and non-computer-based formats, to support use across all ages. Moreover, ongoing training and technical assistance with use of electronic and mobile device technologies in clinical practice is needed. Research on barriers to clinical use of computers is warranted. PMID:26667248

Psychiatrists' Comfort Using Computers and Other Electronic Devices in Clinical Practice.

PubMed

Duffy, Farifteh F; Fochtmann, Laura J; Clarke, Diana E; Barber, Keila; Hong, Seung-Hee; Yager, Joel; Mościcki, Eve K; Plovnick, Robert M

2016-09-01

This report highlights findings from the Study of Psychiatrists' Use of Informational Resources in Clinical Practice, a cross-sectional Web- and paper-based survey that examined psychiatrists' comfort using computers and other electronic devices in clinical practice. One-thousand psychiatrists were randomly selected from the American Medical Association Physician Masterfile and asked to complete the survey between May and August, 2012. A total of 152 eligible psychiatrists completed the questionnaire (response rate 22.2 %). The majority of psychiatrists reported comfort using computers for educational and personal purposes. However, 26 % of psychiatrists reported not using or not being comfortable using computers for clinical functions. Psychiatrists under age 50 were more likely to report comfort using computers for all purposes than their older counterparts. Clinical tasks for which computers were reportedly used comfortably, specifically by psychiatrists younger than 50, included documenting clinical encounters, prescribing, ordering laboratory tests, accessing read-only patient information (e.g., test results), conducting internet searches for general clinical information, accessing online patient educational materials, and communicating with patients or other clinicians. Psychiatrists generally reported comfort using computers for personal and educational purposes. However, use of computers in clinical care was less common, particularly among psychiatrists 50 and older. Information and educational resources need to be available in a variety of accessible, user-friendly, computer and non-computer-based formats, to support use across all ages. Moreover, ongoing training and technical assistance with use of electronic and mobile device technologies in clinical practice is needed. Research on barriers to clinical use of computers is warranted.

Evaluation of a Statewide HIV-HCV-STD Online Clinical Education Program by Healthcare Providers - A Comparison of Nursing and Other Disciplines.

PubMed

Wang, Dongwen; Luque, Amneris E

2016-01-01

The New York State HIV-HCV-STD Clinical Education Initiative (CEI) has developed a large repository of online resources and disseminated them to a wide range of healthcare providers. To evaluate the CEI online education program and in particular to compare the self-reported measures by clinicians from different disciplines, we analyzed the data from 1,558 course completions in a study period of three months. The results have shown that the overall evaluations by the clinicians were very positive. Meanwhile, there were significant differences across the clinical disciplines. In particular, physicians and nurse practitioners were the most satisfied. In contrast, pharmacists and case/care managers recorded lower than average responses. Nurses and counselors had mixed results. Nurse practitioners' responses were very similar to physicians on most measures, but significantly different from nurses in many aspects. For more effective knowledge dissemination, online education programs should consider the unique needs by clinicians from specific disciplines.

Clinical epidemiology of eosinophilic pustular folliculitis: results from a nationwide survey in Japan.

PubMed

Yamamoto, Yosuke; Nomura, Takashi; Kabashima, Kenji; Miyachi, Yoshiki

2015-01-01

No epidemiological study has examined the clinical characteristics, including medication use, of patients with eosinophilic pustular folliculitis (EPF). To describe the clinical characteristics for EPF and to examine the factors associated with the effectiveness of oral indomethacin for EPF. A cross-sectional study was performed of patients with EPF who visited the dermatology departments of the 67 main teaching facilities in Japan. We documented the patient characteristics and examined factors associated with the effectiveness of oral indomethacin. A total of 145 patients with EPF were enrolled; 62.8% were prescribed oral indomethacin. A multivariable analysis revealed that female patients were more likely to exhibit complete response to oral indomethacin after adjustment for confounders (adjusted proportion ratio = 1.93, p = 0.04). Oral indomethacin has been accepted as a first-line treatment in EPF. Our results suggest that there is a sex difference in the treatment response to oral indomethacin. © 2014 S. Karger AG, Basel.

Clinical phenotype and infertility treatment in a male with hypogonadotropic hypogonadism due to mutations Ala129Asp/Arg262Gln of the gonadotropin-releasing hormone receptor.

PubMed

Layman, Lawrence C; Cohen, David P; Xie, Jun; Smith, Gary D

2002-12-01

To characterize the genotype and phenotype of a man with idiopathic hypogonadism with infertility. Molecular analysis and clinical description. Medical school laboratory and reproductive endocrine clinic.A 40-year-old male with idiopathic hypogonadotropic hypogonadism. Denaturing gradient gel electrophoresis analysis and DNA sequencing of the gonadotropin-releasing hormone receptor (GNRHR) gene were performed. The patient was treated with hCG and FSH. GNRHR mutation detection, genotype/phenotype correlation, and testicular response to exogenous gonadotropin therapy. The proband demonstrated compound heterozygosity for Ala129Asp/Arg262Gln GNRHR mutations. He had a complete form of idiopathic hypogonadotropic hypogonadism, with descended testes and severe oligospermia but little response to exogenous gonadotropins. The phenotype of this patient differs from the one other family described with the same mutations. Exogenous gonadotropin therapy may not be as beneficial for increasing sperm concentration in older men with idiopathic hypogonadotropic hypogonadism.

Toxic effects and antitumor response of gemcitabine in combination with piroxicam treatment in dogs with transitional cell carcinoma of the urinary bladder.

PubMed

Marconato, Laura; Zini, Eric; Lindner, Donna; Suslak-Brown, Lisa; Nelson, Victoria; Jeglum, Ann K

2011-04-15

To investigate whether combined treatment with gemcitabine and piroxicam in dogs with transitional cell carcinoma (TCC) of the urinary bladder is tolerated and provides an advantage in terms of survival time over previously reported treatments. Clinical trial. Animals-38 dogs with TCC of the urinary bladder. Dogs were treated with gemcitabine (800 mg/m(2), IV over 30 to 60 minutes, q 7 d) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). Complete blood cell counts were monitored prior to each gemcitabine treatment. All toxic effects of gemcitabine in dogs were recorded. Primary tumors were ultrasonographically reevaluated after 4 gemcitabine treatments. Dogs received a median of 8 gemcitabine treatments (range, 1 to 38 treatments/dog). In response to treatment, 10 of 38 (26.3%) dogs had grade 1 gastrointestinal tract signs, 11 (28.9%) had grade 2, and 5 (13.2%) had grade 3. Grade 1 neutropenia developed in 6 (15.8%) dogs and grade 2 and 3 neutropenia in 2 (5.3%) dogs each. Thrombocytopenia was rare. All dogs had improvement of clinical signs of disease. Two dogs had a complete tumor response, 8 had a partial response, 19 had stable disease, and 8 had progressive disease. Median survival time with treatment was 230 days. Administration of gemcitabine in combination with piroxicam treatment failed to provide a longer overall survival time in dogs with TCC of the urinary bladder, compared with previously reported treatment strategies. However, this combination of chemotherapy did provide a new treatment alternative with fewer adverse effects.

Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3).

PubMed

Nash, Peter; Mease, Philip J; McInnes, Iain B; Rahman, Proton; Ritchlin, Christopher T; Blanco, Ricardo; Dokoupilova, Eva; Andersson, Mats; Kajekar, Radhika; Mpofu, Shephard; Pricop, Luminita

2018-03-15

The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study ( ClinicalTrials.gov NCT01989468). Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naïve, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ). Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naïve and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported. Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously. ClinicalTrials.gov NCT01989468 . Registered 21 November 2013. EudraCT 2013-004002-25 . Registered 17 December 2013.

Further development of pharmacy student-facilitated diabetes management clinics.

PubMed

Nuffer, Wesley; McCollum, Marianne; Ellis, Samuel L; Turner, Christopher J

2012-04-10

To further develop and evaluate a diabetes disease state management (DSM) program that provided direct patient care responsibilities to advanced pharmacy practice experience (APPE) students as members of healthcare teams. Nine new clinics and 3 established sites that provide self-care management education to patients with diabetes were established and maintained in rural Colorado pharmacies and supported by students in APPE training for 48 weeks per year. The 12 clinics provided 120 APPE student placements in 2010-2011. Students' perceptions of their experiences were positive. Patients who completed the student-supported diabetes self-management education program had improvements in blood glucose, blood pressure, and lipid values. Twelve diabetes DSM clinics provided direct patient care opportunities to APPE students working as part of healthcare teams while expanding healthcare resources in underserved communities in Colorado.

Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180

PubMed Central

Treon, Steven P.; Ioakimidis, Leukothea; Soumerai, Jacob D.; Patterson, Christopher J.; Sheehy, Patricia; Nelson, Marybeth; Willen, Michael; Matous, Jeffrey; Mattern, John; Diener, Jakow G.; Keogh, George P.; Myers, Thomas J.; Boral, Andy; Birner, Ann; Esseltine, Dixie L.; Ghobrial, Irene M.

2009-01-01

Purpose We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenström macroglobulinemia (WM). Patients and Methods A cycle of therapy consisted of bortezomib 1.3 mg/m2 intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m2 on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Twenty-three patients received a median of seven cycles of treatment. Results Median bone marrow disease involvement declined from 55% to 10% (P = .0004), serum immunoglobulin M levels declined from 4,830 to 1,115 mg/dL (P < .0001), and hematocrit increased from 29.8% to 38.2% (P = .0002) at best response. The overall response rates and major response rates were 96% and 83% with three complete responses, two near complete responses, three very good partial responses, 11 partial responses, and three minor responses. Responses occurred at a median of 1.4 months. With a median follow-up of 22.8 months, 18 of 23 patients remained free of disease progression. Peripheral neuropathy was the most common toxicity, and it resolved to grade ≤ 1 in 13 of 16 patients at a median of 6.0 months. Four of the first seven treated patients developed herpes zoster, resulting in the institution of prophylactic antiviral therapy. Conclusion The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued. PMID:19506160

Validating genetic markers of response to recombinant human growth hormone in children with growth hormone deficiency and Turner syndrome: the PREDICT validation study

PubMed Central

Stevens, Adam; Murray, Philip; Wojcik, Jerome; Raelson, John; Koledova, Ekaterina; Chatelain, Pierre

2016-01-01

Objective Single-nucleotide polymorphisms (SNPs) associated with the response to recombinant human growth hormone (r-hGH) have previously been identified in growth hormone deficiency (GHD) and Turner syndrome (TS) children in the PREDICT long-term follow-up (LTFU) study (Nbib699855). Here, we describe the PREDICT validation (VAL) study (Nbib1419249), which aimed to confirm these genetic associations. Design and methods Children with GHD (n = 293) or TS (n = 132) were recruited retrospectively from 29 sites in nine countries. All children had completed 1 year of r-hGH therapy. 48 SNPs previously identified as associated with first year growth response to r-hGH were genotyped. Regression analysis was used to assess the association between genotype and growth response using clinical/auxological variables as covariates. Further analysis was undertaken using random forest classification. Results The children were younger, and the growth response was higher in VAL study. Direct genotype analysis did not replicate what was found in the LTFU study. However, using exploratory regression models with covariates, a consistent relationship with growth response in both VAL and LTFU was shown for four genes – SOS1 and INPPL1 in GHD and ESR1 and PTPN1 in TS. The random forest analysis demonstrated that only clinical covariates were important in the prediction of growth response in mild GHD (>4 to <10 μg/L on GH stimulation test), however, in severe GHD (≤4 μg/L) several SNPs contributed (in IGF2, GRB10, FOS, IGFBP3 and GHRHR). Conclusions The PREDICT validation study supports, in an independent cohort, the association of four of 48 genetic markers with growth response to r-hGH treatment in both pre-pubertal GHD and TS children after controlling for clinical/auxological covariates. However, the contribution of these SNPs in a prediction model of first-year response is not sufficient for routine clinical use. PMID:27651465

Selection of response criteria for clinical trials of sarcoma treatment.

PubMed

Schuetze, Scott M; Baker, Laurence H; Benjamin, Robert S; Canetta, Renzo

2008-01-01

Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal tissues. A large number of new therapies are being evaluated in patients with sarcomas, and consensus criteria defining treatment responses are essential for comparison of results from studies completed by different research groups. The 1979 World Health Organization (WHO) handbook set forth operationally defined criteria for response evaluation in solid tumors that were updated in 2000 with the publication of the Response Evaluation Criteria in Solid Tumors (RECIST). There have been significant advances in tumor imaging, however, that are not reflected in the RECIST. For example, computed tomography (CT) slice thickness has been reduced from 10 mm to < or =2.5 mm, allowing for more reproducible and accurate measurement of smaller lesions. Combination of imaging techniques, such as positron emission tomography with fluorine-18-fluorodeoxyglucose (18FDG-PET) and CT can provide investigators and clinicians with both anatomical and functional information regarding tumors, and there is now a large body of evidence demonstrating the effectiveness of PET/CT and other newer imaging methods for the detection and staging of tumors as well as early determination of responses to therapy. The application of newer imaging methods has the potential to decrease both the sample sizes required for, and duration of, clinical trials by providing an early indication of therapeutic response that is well correlated with clinical outcomes, such as time to tumor progression or overall survival. The results summarized in this review support the conclusion that the RECIST and the WHO criteria for evaluation of response in solid tumors need to be modernized. In addition, there is a current need for prospective trials to compare new response criteria with established endpoints and to validate imaging-based response rates as surrogate endpoints for clinical trials of new agents for sarcoma and other solid tumors.

Validating genetic markers of response to recombinant human growth hormone in children with growth hormone deficiency and Turner syndrome: the PREDICT validation study.

PubMed

Stevens, Adam; Murray, Philip; Wojcik, Jerome; Raelson, John; Koledova, Ekaterina; Chatelain, Pierre; Clayton, Peter

2016-12-01

Single-nucleotide polymorphisms (SNPs) associated with the response to recombinant human growth hormone (r-hGH) have previously been identified in growth hormone deficiency (GHD) and Turner syndrome (TS) children in the PREDICT long-term follow-up (LTFU) study (Nbib699855). Here, we describe the PREDICT validation (VAL) study (Nbib1419249), which aimed to confirm these genetic associations. Children with GHD (n = 293) or TS (n = 132) were recruited retrospectively from 29 sites in nine countries. All children had completed 1 year of r-hGH therapy. 48 SNPs previously identified as associated with first year growth response to r-hGH were genotyped. Regression analysis was used to assess the association between genotype and growth response using clinical/auxological variables as covariates. Further analysis was undertaken using random forest classification. The children were younger, and the growth response was higher in VAL study. Direct genotype analysis did not replicate what was found in the LTFU study. However, using exploratory regression models with covariates, a consistent relationship with growth response in both VAL and LTFU was shown for four genes - SOS1 and INPPL1 in GHD and ESR1 and PTPN1 in TS. The random forest analysis demonstrated that only clinical covariates were important in the prediction of growth response in mild GHD (>4 to <10 μg/L on GH stimulation test), however, in severe GHD (≤4 μg/L) several SNPs contributed (in IGF2, GRB10, FOS, IGFBP3 and GHRHR). The PREDICT validation study supports, in an independent cohort, the association of four of 48 genetic markers with growth response to r-hGH treatment in both pre-pubertal GHD and TS children after controlling for clinical/auxological covariates. However, the contribution of these SNPs in a prediction model of first-year response is not sufficient for routine clinical use. © 2016 European Society of Endocrinology.

Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer.

PubMed

Xu, Yan; Zhu, Lijing; Ru, Tong; Wang, Huanhuan; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-01

Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P < 0.001), whereas tumors significantly decreased in volume at 2 weeks after therapy initiation ( P < 0.05). However, no significant differences in 3D vascular indices values were seen in the PR group during the treatment course (all P > 0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

T-Cell Therapy Using Interleukin-21–Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression

PubMed Central

Chapuis, Aude G.; Roberts, Ilana M.; Thompson, John A.; Margolin, Kim A.; Bhatia, Shailender; Lee, Sylvia M.; Sloan, Heather L.; Lai, Ivy P.; Farrar, Erik A.; Wagener, Felecia; Shibuya, Kendall C.; Cao, Jianhong; Wolchok, Jedd D.; Greenberg, Philip D.

2016-01-01

Purpose Peripheral blood–derived antigen-specific cytotoxic T cells (CTLs) provide a readily available source of effector cells that can be administered with minimal toxicity in an outpatient setting. In metastatic melanoma, this approach results in measurable albeit modest clinical responses in patients resistant to conventional therapy. We reasoned that concurrent cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) checkpoint blockade might enhance the antitumor activity of adoptively transferred CTLs. Patients and Methods Autologous MART1-specific CTLs were generated by priming with peptide-pulsed dendritic cells in the presence of interleukin-21 and enriched by peptide-major histocompatibility complex multimer-guided cell sorting. This expeditiously yielded polyclonal CTL lines uniformly expressing markers associated with an enhanced survival potential. In this first-in-human strategy, 10 patients with stage IV melanoma received the MART1-specific CTLs followed by a standard course of anti–CTLA-4 (ipilimumab). Results The toxicity profile of the combined treatment was comparable to that of ipilimumab monotherapy. Evaluation of best responses at 12 weeks yielded two continuous complete remissions, one partial response (PR) using RECIST criteria (two PRs using immune-related response criteria), and three instances of stable disease. Infused CTLs persisted with frequencies up to 2.9% of CD8+ T cells for as long as the patients were monitored (up to 40 weeks). In patients who experienced complete remissions, PRs, or stable disease, the persisting CTLs acquired phenotypic and functional characteristics of long-lived memory cells. Moreover, these patients also developed responses to nontargeted tumor antigens (epitope spreading). Conclusion We demonstrate that combining antigen-specific CTLs with CTLA-4 blockade is safe and produces durable clinical responses, likely reflecting both enhanced activity of transferred cells and improved recruitment of new responses, highlighting the promise of this strategy. PMID:27269940

T-Cell Therapy Using Interleukin-21-Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression.

PubMed

Chapuis, Aude G; Roberts, Ilana M; Thompson, John A; Margolin, Kim A; Bhatia, Shailender; Lee, Sylvia M; Sloan, Heather L; Lai, Ivy P; Farrar, Erik A; Wagener, Felecia; Shibuya, Kendall C; Cao, Jianhong; Wolchok, Jedd D; Greenberg, Philip D; Yee, Cassian

2016-11-01

Purpose Peripheral blood-derived antigen-specific cytotoxic T cells (CTLs) provide a readily available source of effector cells that can be administered with minimal toxicity in an outpatient setting. In metastatic melanoma, this approach results in measurable albeit modest clinical responses in patients resistant to conventional therapy. We reasoned that concurrent cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) checkpoint blockade might enhance the antitumor activity of adoptively transferred CTLs. Patients and Methods Autologous MART1-specific CTLs were generated by priming with peptide-pulsed dendritic cells in the presence of interleukin-21 and enriched by peptide-major histocompatibility complex multimer-guided cell sorting. This expeditiously yielded polyclonal CTL lines uniformly expressing markers associated with an enhanced survival potential. In this first-in-human strategy, 10 patients with stage IV melanoma received the MART1-specific CTLs followed by a standard course of anti-CTLA-4 (ipilimumab). Results The toxicity profile of the combined treatment was comparable to that of ipilimumab monotherapy. Evaluation of best responses at 12 weeks yielded two continuous complete remissions, one partial response (PR) using RECIST criteria (two PRs using immune-related response criteria), and three instances of stable disease. Infused CTLs persisted with frequencies up to 2.9% of CD8 + T cells for as long as the patients were monitored (up to 40 weeks). In patients who experienced complete remissions, PRs, or stable disease, the persisting CTLs acquired phenotypic and functional characteristics of long-lived memory cells. Moreover, these patients also developed responses to nontargeted tumor antigens (epitope spreading). Conclusion We demonstrate that combining antigen-specific CTLs with CTLA-4 blockade is safe and produces durable clinical responses, likely reflecting both enhanced activity of transferred cells and improved recruitment of new responses, highlighting the promise of this strategy.

Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus

PubMed Central

Md Yusof, Md Yuzaiful; Shaw, Daniel; El-Sherbiny, Yasser M; Dunn, Emma; Rawstron, Andy C; Emery, Paul; Vital, Edward M

2017-01-01

Objective To assess factors associated with primary and secondary non-response to rituximab in systemic lupus erythematosus (SLE) and evaluate management of secondary non-depletion non-response (2NDNR). Methods 125 patients with SLE treated with rituximab over 12 years were studied prospectively. A major clinical response was defined as improvement of all active British Isles Lupus Assessment Group (BILAG)-2004 domains to grade C/better and no A/B flare. Partial responders were defined by one persistent BILAG B. B-cell subsets were measured using highly sensitive flow cytometry. Patients with 2NDNR, defined by infusion reaction and defective depletion, were treated with ocrelizumab or ofatumumab. Results 117 patients had evaluable data. In cycle 1 (C1), 96/117 (82%) achieved BILAG response (major=50%, partial=32%). In multivariable analysis, younger age (OR 0.97, 95% CI 0.94 to 1.00) and B-cell depletion at 6 weeks (OR 3.22, 95% CI 1.24 to 8.33) increased the odds of major response. Complete depletion was predicted by normal complement and lower pre-rituximab plasmablasts and was not associated with increased serious infection post-rituximab. Seventy-seven (with data on 72) C1 responders were retreated on clinical relapse. Of these, 61/72 (85%) responded in cycle 2 (C2). Of the 11 C2 non-responders, nine met 2NDNR criteria (incidence=12%) and tested positive for anti-rituximab antibodies. Lack of concomitant immunosuppressant and higher pre-rituximab plasmablasts predicted 2NDNR. Five were switched to ocrelizumab/ofatumumab, and all depleted and responded. Conclusion Treatment with anti-CD20 agents can be guided by B-cell monitoring and should aim to achieve complete depletion. 2NDNR is associated with anti-rituximab antibodies, and switching to humanised agents restores depletion and response. In SLE, alternative anti-CD20 antibodies may be more consistently effective. PMID:28684557

Correlation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: A multi-institutional retrospective study.

PubMed

Nakamura, Yasuhiro; Tanaka, Ryota; Asami, Yuri; Teramoto, Yukiko; Imamura, Taichi; Sato, Sayuri; Maruyama, Hiroshi; Fujisawa, Yasuhiro; Matsuya, Taisuke; Fujimoto, Manabu; Yamamoto, Akifumi

2017-02-01

Vitiligo is occasionally seen in melanoma patients. Although several studies indicate a correlation between vitiligo occurrence and clinical response in melanoma patients receiving immunotherapy, most studies have included heterogeneous patient and treatment settings. The aim of this study is to investigate the correlation between the occurrence of vitiligo and clinical benefit of nivolumab treatment in advanced melanoma patients. We retrospectively reviewed unresectable stage III or IV melanoma patients treated with nivolumab. Of 35 melanoma patients treated with nivolumab, 25.7% (9/35) developed vitiligo during treatment. The time from the start of nivolumab treatment to occurrence of vitiligo ranged 2-9 months (mean, 5.2). Of nine patients who developed vitiligo, two (22.2%) had a complete response to nivolumab and two (22.2%) had a partial response. The objective response rate was significantly higher in patients with vitiligo than in patients without vitiligo (4/9 [44.4%] vs 2/26 [7.7%]; P = 0.027). The mean time to vitiligo occurrence in patients achieving an objective response was significantly less than that in patients who showed no response (3.1 vs 6.8 months, P = 0.004). Vitiligo occurrence was significantly associated with prolonged progression-free and overall survival (hazard ratio, 0.24 and 0.16; 95% confidence interval, 0.11-0.55 and 0.03-0.79; P = 0.005, and 0.047, respectively). At the 20-week landmark analysis, however, vitiligo was not associated with a statistically significant overall survival benefit (P = 0.28). The occurrence of vitiligo during nivolumab treatment may be correlated with favorable clinical outcome. © 2016 Japanese Dermatological Association.

Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy.

PubMed

Bossuyt, Veerle; Symmans, W Fraser

2016-10-01

The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.

Ivermectin toxicosis in a dog.

PubMed

Hopkins, K D; Marcella, K L; Strecker, A E

1990-07-01

A 5-year-old male Doberman Pinscher was examined after ingesting an equine paste dewormer containing approximately 115 mg of ivermectin. Clinical signs consisted of profound hypothermia, mild dehydration, dilated unresponsive pupils, localized muscle group fasciculations around the face and hind limbs, and no response to any external stimuli. Twelve days after parenteral administration of isotonic fluids and IV administration of dexamethasone and dimethyl sulfoxide, the dog returned to a clinically normal neurologic state. Ivermectin toxicosis has been reported frequently in Collies; however, other breeds may have idiosyncratic reactions to low doses. Patients with severe toxicosis should eventually recover completely if given appropriate intensive care.

Notifiable condition reporting practices: implications for public health agency participation in a health information exchange.

PubMed

Revere, Debra; Hills, Rebecca H; Dixon, Brian E; Gibson, P Joseph; Grannis, Shaun J

2017-03-11

The future of notifiable condition reporting in the United States is undergoing a transformation with the increasing development of Health Information Exchanges which support electronic data-sharing and -transfer networks and the wider adoption of electronic laboratory reporting. Communicable disease report forms originating in clinics are an important source of surveillance data for public health agencies. However, problems of poor data quality and delayed submission of reports to public health agencies are common. In addition, studies of barriers and facilitators to reporting have assumed that the primary reporter is the treating physician, although the extent to which a provider is involved in the reporting workflow is unclear. We sought to better understand the barriers to and burden of notifiable condition reporting from the perspectives of the three primary groups involved in reporting workflow: providers, clinic staff who bear the principal responsibility for reporting, and the public health workers who receive and process reports from clinics. In addition, we sought to situate these findings within the context of the future of notifiable disease reporting and the potential impacts of electronic lab and medical records on the surveillance system. Seven ambulatory care clinics and 3 public health agencies that are part of a Health Information Exchange in the state of Indiana, USA, participated in the study. Data were obtained from a survey of clinic physicians (N = 29), interviews with clinic reporters (N = 11), and interviews with public health workers (N = 9). Survey data were summarized descriptively and interview transcripts underwent qualitative analysis. In both clinics and public health agencies, the laboratory report initiates reporting workflow. Provider involvement with reporting primarily revolves around ordering medications to treat a condition confirmed by the lab result. In clinics, reporting is typically the responsibility of clinic reporters who vary in frequency of reporting. We found an association between frequency of reporting, reporting knowledge and perceptions of reporting burden. In both clinics and public health agencies, interruptions and delays in reporting workflow are encountered due to inaccurate or missing information and impact reporting timeliness, data quality and report completeness. Both providers and clinic reporters lack clarity regarding how data submitted by their reports are used by public health agencies. It is possible that the value of reporting may be diminished when those responsible do not perceive receiving benefit in return. This may account for the low awareness of or recollection of public health communications with clinics that we observed. Despite the high likelihood that public health advisories and guidance are based, in part, on data submitted by clinics, a direct concordance may not be recognized. Unlike most studies of notifiable condition reporting, this study included the clinic reporters who bear primary responsibility for completing and submitting reports to public health agencies. A primary barrier to this reporting is timely and easy access to data. It is possible that expanded adoption of electronic health record and laboratory reporting systems will improve access to this data and reduce reporting the burden. However, a complete reliance on automatic electronic extraction of data requires caution and necessitates continued interfacing with clinic reporters for the foreseeable future-particularly for notifiable conditions that are high-impact, uncommon, prone to false positive readings by labs, or are hard to verify. An important finding of this study is the association between frequency of reporting, reporting knowledge and perceptions of reporting burden. Increased automation could result in even lower reporting knowledge and familiarity with reporting requirements which could actually increase reporters' perception of notifiable condition reporting as burdensome. Another finding was of uncertainty regarding how data sent to public health agencies is used or provides clinical benefit. A strong recommendation generated by these findings is that, given their central role in reporting, clinic reporters are a significant target audience for public health outreach and education that aims to alleviate perceived reporting burden and improve reporting knowledge. In particular, communicating the benefits of public health's use of the data may reduce a perceived lack of information reciprocity between clinical and public health organizations.

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129

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

Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu; Zhang, Qiang; Nguyen-Tan, Phuc Felix

Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive:more » n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local–regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local–regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.« less

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129.

PubMed

Galloway, Thomas J; Zhang, Qiang Ed; Nguyen-Tan, Phuc Felix; Rosenthal, David I; Soulieres, Denis; Fortin, André; Silverman, Craig L; Daly, Megan E; Ridge, John A; Hammond, J Alexander; Le, Quynh-Thu

2016-10-01

To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local-regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local-regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

A Retrospective Review of Pain Control by a Two-Step Irradiance Schedule During Topical ALA-Photodynamic Therapy of Non-melanoma Skin Cancer

PubMed Central

Zeitouni, Nathalie C.; Paquette, Anne D.; Housel, Joseph P.; Shi, Yi; Wilding, Gregory; Foster, Thomas H.; Henderson, Barbara W.

2013-01-01

Background and Objective Photodynamic therapy (PDT) with topical δ-aminolevulinic acid (ALA) of non-melanoma skin cancers is often associated with treatment-limiting pain. A previous study on basal cell carcinomas (BCCs) at Roswell Park Cancer Institute evaluated a two-step irradiance scheme as a means of minimizing pain, preserving outcomes, and limiting treatment time. We used an initial low irradiance until 90% of the protoporphyrin IX was photobleached, followed by a high irradiance interval until the prescribed fluence was delivered. Success of this pilot investigation motivated integration of the protocol into routine practice. Here we present a retrospective review of recent clinical experience in a broad patient population. Study Design/Materials and Methods This was a retrospective review of an existing dermatology data base. Fourteen caucasion patients - 9 men and 5 women, ages 18 to 80, with a total of 51 superficial and 73 nodular BCCs, and three Bowen's disease lesions – were included. ALA was applied to each lesion for approximately 4h. Lesions received an initial irradiance of 30 - 50 mW/cm2 for 20 J/cm2, followed by 150 mW/cm2 for a total fluence of 200-300 J/cm2. Pain was assessed using a visual analog scale (VAS). Clinical outcome was determined at 6-12 months. Results Median VAS scores were 1.0 for both irradiances. Five of 127 lesions required pain control with 1% xylocaine. Pain was strongly influenced by lesion location but not by lesion type, number, or size. Complete responses were achieved in 84.1% of BCCs, which compares favorably with reported results for single ALA-PDT treatments. Two of three Bowen's disease lesions showed a complete response. Complete responses for nodular BCCs were 37%, which are also within the range of reported outcomes. Conclusions A two-step irradiance protocol in ALA-PDT effectively minimizes pain, maintains excellent clinical outcomes in superficial lesions, and adds minimal treatment time. PMID:23390058

Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris.

PubMed

Behzad, M; Möbs, C; Kneisel, A; Möller, M; Hoyer, J; Hertl, M; Eming, R

2012-04-01

Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Common Factor Mechanisms in Clinical Practice and Their Relationship with Outcome.

PubMed

Gaitan-Sierra, Carolina; Hyland, Michael E

2015-01-01

This study investigates three common factor mechanisms that could affect outcome in clinical practice: response expectancy, the affective expectation model and motivational concordance. Clients attending a gestalt therapy clinic (30 clients), a sophrology (therapeutic technique) clinic (33 clients) and a homeopathy clinic (31 clients) completed measures of expectancy and the Positive Affect and Negative Affect Schedule (PANAS) before their first session. After 1 month, they completed PANAS and measures of intrinsic motivation, perceived effort and empowerment. Expectancy was not associated with better outcome and was no different between treatments. Although some of the 54 clients who endorsed highest expectations showed substantial improvement, others did not: 19 had no change or deteriorated in positive affect, and 18 had the same result for negative affect. Intrinsic motivation independently predicted changes in negative affect (β = -0.23). Intrinsic motivation (β = 0.24), effort (β = 0.23) and empowerment (β = 0.20) independently predicted positive affect change. Expectancy (β = -0.17) negatively affected changes in positive affect. Clients found gestalt and sophrology to be more intrinsically motivating, empowering and effortful compared with homeopathy. Greater improvement in mood was found for sophrology and gestalt than for homeopathy clients. These findings are inconsistent with response expectancy as a common factor mechanism in clinical practice. The results support motivational concordance (outcome influenced by the intrinsic enjoyment of the therapy) and the affective expectation model (high expectations can lead for some clients to worse outcome). When expectancy correlates with outcome in some other studies, this may be due to confound between expectancy and intrinsic enjoyment. Common factors play an important role in outcome. Intrinsic enjoyment of a therapeutic treatment is associated with better outcome. Active engagement with a therapeutic treatment improves outcome. Unrealistic expectations about a therapeutic treatment can have a negative impact on outcome. Copyright © 2014 John Wiley & Sons, Ltd.

Clinical investigation of the lesions responsible for sensory disturbance in Minamata disease.

PubMed

Uchino, M; Mita, S; Satoh, H; Hirano, T; Arimura, K; Nakagawa, M; Nakamura, M; Uyama, E; Ando, Y; Wakamiya, J; Futatsuka, M

2001-11-01

To clarify the lesions responsible for sensory disturbance in Minamata disease (MD), we clinically investigated the characteristics of sensory disturbance. In all patients with the classical type MD, two-point discrimination was severely disturbed, but the involvement of superficial sensation was relatively mild. On short-latency somatosensory evoked potential study, the component corresponding to N20 was completely absent with normal N9, N11, and N13 components. Although 14 of 38 chronic MD patients demonstrated intact superficial sensation, 10 of these 14 showed mild to moderate disturbance in two-point discrimination. The two-point discrimination in chronic MD patients was significantly high irrespective of the disturbance of superficial sensation. These findings suggest that the sensory disturbance of MD patients may mainly be caused by a lesion in the sensory cortex rather than in the peripheral nerves. However, other foci could be also responsible for the sensory impairment, since 9 of 38 chronic MD patients showed intact two-point discrimination.

Scintigraphic scoring system for grading severity of gastro-esophageal reflux on 99mTc sulfur colloid gastro-esophageal reflux scintigraphy: A prospective study of 39 cases with pre and post treatment assessment.

PubMed

Puranik, Ameya D; Nair, Gopinathan; Aggarwal, Rajiv; Bandyopadhyay, Abhijit; Shinto, Ajit; Zade, Anand

2013-04-01

The study aimed at developing a scoring system for scintigraphic grading of gastro-esophageal reflux (GER), on gastro-esophageal reflux scintigraphy (GERS) and comparison of clinical and scintigraphic scores, pre- and post-treatment. A total of 39 cases with clinically symptomatic GER underwent 99mTc sulfur colloid GERS; scores were assigned based on the clinical and scintigraphic parameters. Post domperidone GERS was performed after completion of treatment. Follow up GERS was performed and clinical and scintigraphic parameters were compared with baseline parameters. Paired t-test on pre and post domperidone treatment clinical scores showed that the decline in post-treatment scores was highly significant, with P value < 0.001. The scintigraphic scoring system had a sensitivity of 93.9% in assessing treatment response to domperidone, specificity of 83.3% i.e., 83.3% of children with no decline in scintigraphic scores show no clinical response to Domperidone. The scintigraphic scoring system had a positive predictive value of 96.9% and a negative predictive value of 71.4%. GERS with its quantitative parameters is a good investigation for assessing the severity of reflux and also for following children post-treatment.

Clinical Efficacy and Immune Regulation With Peanut Oral Immunotherapy

PubMed Central

Jones, Stacie M.; Pons, Laurent; Roberts, Joseph L.; Scurlock, Amy M.; Perry, Tamara T.; Kulis, Mike; Shreffler, Wayne G.; Steele, Pamela; Henry, Karen A.; Adair, Margaret; Francis, James M.; Durham, Stephen; Vickery, Brian P.; Zhong, Xiaoping; Burks, A. Wesley

2009-01-01

Background Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported. Objective The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT. Methods Peanut-allergic children underwent an OIT protocol including initial day escalation, build-up, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated. Results Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12–18 months, while IgG4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over 6–12 months. Peanut-specific FoxP3 T cells increased until 12 months and then decreased thereafter. Additionally, T cell microarrays showed downregulation of genes in apoptotic pathways. Conclusion OIT induces clinical desensitization to peanut, with significant longer term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT. PMID:19577283

The Utrecht questionnaire (U-CEP) measuring knowledge on clinical epidemiology proved to be valid.

PubMed

Kortekaas, Marlous F; Bartelink, Marie-Louise E L; de Groot, Esther; Korving, Helen; de Wit, Niek J; Grobbee, Diederick E; Hoes, Arno W

2017-02-01

Knowledge on clinical epidemiology is crucial to practice evidence-based medicine. We describe the development and validation of the Utrecht questionnaire on knowledge on Clinical epidemiology for Evidence-based Practice (U-CEP); an assessment tool to be used in the training of clinicians. The U-CEP was developed in two formats: two sets of 25 questions and a combined set of 50. The validation was performed among postgraduate general practice (GP) trainees, hospital trainees, GP supervisors, and experts. Internal consistency, internal reliability (item-total correlation), item discrimination index, item difficulty, content validity, construct validity, responsiveness, test-retest reliability, and feasibility were assessed. The questionnaire was externally validated. Internal consistency was good with a Cronbach alpha of 0.8. The median item-total correlation and mean item discrimination index were satisfactory. Both sets were perceived as relevant to clinical practice. Construct validity was good. Both sets were responsive but failed on test-retest reliability. One set took 24 minutes and the other 33 minutes to complete, on average. External GP trainees had comparable results. The U-CEP is a valid questionnaire to assess knowledge on clinical epidemiology, which is a prerequisite for practicing evidence-based medicine in daily clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Psorinum Therapy in Treating Stomach, Gall Bladder, Pancreatic, and Liver Cancers: A Prospective Clinical Study

PubMed Central

Chatterjee, Aradeep; Biswas, Jaydip; Chatterjee, Ashim; Bhattacharya, Sudin; Mukhopadhyay, Bishnu; Mandal, Syamsundar

2011-01-01

We prospectively studied the clinical efficacy of an alternative cancer treatment “Psorinum Therapy” in treating stomach, gall bladder, pancreatic and liver cancers. Our study was observational, open level and single arm. The participants' eligibility criteria included histopathology/cytopathology confirmation of malignancy, inoperable tumor, and no prior chemotherapy or radiation therapy. The primary outcome measures of the study were (i) to assess the radiological tumor response (ii) to find out how many participants survived at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the beginning of the study considering each type of cancer. Psorinum-6x was administered orally to all the participants up to 0.02 ml/Kg body weight as a single dose in empty stomach per day for 2 years along with allopathic and homeopathic supportive cares. 158 participants (42 of stomach, 40 of gall bladder, 44 of pancreatic, 32 of liver) were included in the final analysis of the study. Complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) cases. Double-blind randomized controlled clinical trial should be conducted for further scientific exploration of this alternative cancer treatment. PMID:21197093

A link prediction approach to cancer drug sensitivity prediction.

PubMed

Turki, Turki; Wei, Zhi

2017-10-03

Predicting the response to a drug for cancer disease patients based on genomic information is an important problem in modern clinical oncology. This problem occurs in part because many available drug sensitivity prediction algorithms do not consider better quality cancer cell lines and the adoption of new feature representations; both lead to the accurate prediction of drug responses. By predicting accurate drug responses to cancer, oncologists gain a more complete understanding of the effective treatments for each patient, which is a core goal in precision medicine. In this paper, we model cancer drug sensitivity as a link prediction, which is shown to be an effective technique. We evaluate our proposed link prediction algorithms and compare them with an existing drug sensitivity prediction approach based on clinical trial data. The experimental results based on the clinical trial data show the stability of our link prediction algorithms, which yield the highest area under the ROC curve (AUC) and are statistically significant. We propose a link prediction approach to obtain new feature representation. Compared with an existing approach, the results show that incorporating the new feature representation to the link prediction algorithms has significantly improved the performance.

Efficacy and Safety of Naftifine HCl Cream 2% in the Treatment of Pediatric Subjects With Tinea Corporis.

PubMed

Gold, Michael; Dhawan, Sunil; Verma, Amit; Kuligowski, Michael; Dobrowski, David

2016-06-01

Tinea corporis is fungal infection of body surfaces other than the feet, groin, scalp, or beard. Naftifine hydrochloride is a topical antifungal of the allylamine class used to treat tinea corporis, displaying fungicidal activity and clinically significant anti-bacterial and anti-inflammatory effects.
To evaluate the efficacy and safety of two-weeks once daily application of naftifine cream 2% in the treatment of tinea corporis among pediatric subjects.
At baseline, 231 subjects were randomly assigned 1:1 to naftifine cream 2% (n=116) and vehicle (n=115). Treatment effect consisting of mycologic determination (KOH and dermatophyte cultures) and scoring of clinical symptom severity was evaluated at baseline, week 2 (end of treatment) and week 3. Efficacy was analyzed in 181 subjects (n=88, naftifine; n=93, vehicle) with a positive baseline dermatophyte culture and KOH for whom week 3 assessments were available. Safety was evaluated by adverse events (AE) and laboratory values in 231 subjects (n=116, naftifine; n=115, vehicle).
Children with tinea corporis treated with naftifine cream 2% demonstrated significantly greater improvements from baseline over vehicle for mycological cure (P<0.0001) and treatment effectiveness (P=0.003) as early as 2 weeks (end of treatment). Response rates continued to increase post-treatment and were the highest 1-week after completion of the therapy (P=0.003 for complete cure; and P<0.001 for mycological cure and treatment effectiveness). Treatment related adverse events were minimal.
Treatment with naftifine cream 2% applied once daily for two weeks was well-tolerated and was effective in treating tinea corporis in children. Further improvement was observed 1-week after treatment completion for all key outcome measures (complete cure, mycological cure, treatment effectiveness, clinical cure, and clinical success) and clinical signs and symptoms (erythema, induration, and pruritus).

J Drugs Dermatol. 2016;15(6):743-748.

FDG-PET metabolic response predicts outcomes in anal cancer managed with chemoradiotherapy.

PubMed

Day, F L; Link, E; Ngan, S; Leong, T; Moodie, K; Lynch, C; Michael, M; Winton, E de; Hogg, A; Hicks, R J; Heriot, A

2011-08-09

The aim was to investigate the correlation between (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic response to chemoradiotherapy and clinical outcomes in squamous cell carcinoma (SCC) of the anus. A total of 48 patients with biopsy-proven anal SCC underwent FDG-PET scans at baseline and post chemoradiotherapy (54 Gy, concurrent 5-FU/mitomycin). Kaplan-Meier analysis was used to determine survival outcomes according to FDG-PET metabolic response. In all, 79% patients (n=38) had a complete metabolic response (CMR) at all sites of disease, 15% (n=7) had a CMR in regional nodes but only partial response in the primary tumour (overall partial metabolic response (PMR)) and 6% (n=3) had progressive distant disease despite CMR locoregionally (overall no response (NR)). The 2-year progression-free survival (PFS) was 95% for patients with a CMR, 71% for PMR and 0% for NR (P<0.0001). The 5-year overall survival (OS) was 88% in CMR, 69% in PMR and 0% in NR (P<0.0001). Cox proportional hazards regression analyses for PFS and OS found significant associations for incomplete (PMR+NR) vs complete FDG-PET response to treatment only, (HR 4.1 (95% CI: 1.5-11.5, P=0.013) and 6.7 (95% CI: 2.1-21.6, P=0.002), respectively). FDG-PET metabolic response to chemoradiotherapy in anal cancer is significantly associated with PFS and OS, and in this cohort incomplete FDG-PET response was a stronger predictor than T or N stage.

How does the outcome of research training fellowships funded via the NHS compare with that from competitively funded fellowships from the MRC and other charities: a cross-sectional retrospective survey of trainees undertaking research training in the West Midlands.

PubMed

Maybury, Charlotte; Morgan, Matthew David; Smith, Russell; Harper, Lorraine

2018-01-23

This study aimed to investigate the impact of research training funded via the National Health Service (NHS) on medical trainees compared with traditional clinical research training fellowships (CRTFs). Online survey of 221 clinical trainees who had completed a period of research during their clinical training between 2009 and 2015 in the West Midlands. Research outcomes. Overall response rate was 59%, of whom 72 participants were funded by CRTFs and 51 funded by the NHS. Although participants with CRTFs were more likely to be awarded a higher degree compared with those on NHS-administered funding (66/72 CRTFs and 37/51 NHS, P=0.005), similar proportions of NHS-funded and CRTF-funded participants entered clinical lecturer posts on completing initial research training (8/51 NHS and 16/72 CRTF, P=0.37). 77% of participants had three or more publications (CRTF 57 and NHS 39, P=0.72). 57 participants had completed clinical training; similar proportions of CRTF-funded and NHS-funded trainees had research included in their consultant contract (12/22 NHS and 14/26 CRTF, P=0.96) or were appointed to academic posts (3 of 25 NHS funded and 6 of 32 CRTF, P>0.05). 95% of participants would recommend to colleagues and 82% of participants felt the research experience improved their provision of clinical care with no difference between CRTF-funded and NHS-funded participants (P=0.49). Continuing to participate in clinical work during the research reduced reports of trainee difficulty on returning to clinical work (23/108 continued clinical work vs 12/22 no clinical work, P=0.001). Research training funded by the NHS provides a quality experience and contributes to the clinical academic capacity within the UK. More needs to be done to support NHS participants to successfully achieve a higher degree. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Complete molecular remission in relapsed and refractory acute myeloid leukaemia with MLL-AF9 treated with chidamide-based chemotherapy.

PubMed

Lun, Y; Yang, J-J; Wu, Y

2017-12-01

The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy. Chidamide (CS055/HBI-8000) is a new histone deacetylase (HDAC) inhibitor that is clinically active in relapsed and refractory peripheral T-cell lymphomas. To the best of our knowledge, successful reinduction treatment on relapsed MLL-AF9 by chidamide-based regimen has not been previously reported. © 2017 John Wiley & Sons Ltd.

APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy.

PubMed

Schnadig, Ian D; Agajanian, Richy; Dakhil, Christopher; Gabrail, Nashat Y; Smith, Robert E; Taylor, Charles; Wilks, Sharon T; Schwartzberg, Lee S; Cooper, William; Mosier, Michael C; Payne, J Yvette; Klepper, Michael J; Vacirca, Jeffrey L

2016-06-01

APF530, extended-release granisetron, provides sustained release for ≥5 days for acute- and delayed-phase chemotherapy-induced nausea and vomiting (CINV). We compared efficacy and safety of APF530 versus ondansetron for delayed CINV after highly emetogenic chemotherapy (HEC), following a guideline-recommended three-drug regimen. HEC patients received APF530 500 mg subcutaneously or ondansetron 0.15 mg/kg intravenously, with dexamethasone and fosaprepitant. Primary end point was delayed-phase complete response (no emesis or rescue medication). A higher percentage of APF530 versus ondansetron patients had delayed-phase complete response (p = 0.014). APF530 was generally well tolerated; treatment-emergent adverse event incidence was similar across arms, mostly mild-to-moderate injection-site reactions. APF530 versus the standard three-drug regimen provided superior control of delayed-phase CINV following HEC. ClinicalTrials.gov : NCT02106494.

Increasing response rates to follow-up questionnaires in health intervention research: Randomized controlled trial of a gift card prize incentive.

PubMed

Morgan, Amy J; Rapee, Ronald M; Bayer, Jordana K

2017-08-01

Background/aims Achieving a high response rate to follow-up questionnaires in randomized controlled trials of interventions is important for study validity. Few studies have tested the value of incentives in increasing response rates to online questionnaires in clinical trials of health interventions. This study evaluated the effect of a gift card prize-draw incentive on response rates to follow-up questionnaires within a trial of an online health intervention. Method The study was embedded in a host randomized controlled trial of an online parenting program for child anxiety. A total of 433 participants were randomly allocated to one of two groups: (1) being informed that they would enter a gift card prize-draw if they completed the final study questionnaire (24-week follow-up) and (2) not informed about the prize-draw. All participants had a 1 in 20 chance of winning an AUD50 gift card after they completed the online questionnaire. Results The odds of the informed group completing the follow-up questionnaire were significantly higher than the uninformed group, (79.6% vs 68.5%, odds ratio = 1.79, 95% confidence interval = 1.15-2.79). This response rate increase of 11.1% (95% confidence interval = 2.8-19.1) occurred in both intervention and control groups in the host randomized controlled trial. The incentive was also effective in increasing questionnaire commencement (84.6% vs 75.9%, odds ratio = 1.74, 95% confidence interval = 1.07-2.84) and reducing the delay in completing the questionnaire (19.9 vs 22.6 days, hazard ratio = 1.34, 95% confidence interval = 1.07-1.67). Conclusion This study adds to evidence for the effectiveness of incentives to increase response rates to follow-up questionnaires in health intervention trials.

Notification and counselling of hepatitis positive blood donors, their immediate emotional response, contact-testing and their follow-up: Study from a tertiary care hospital!

PubMed

Tiwari, Aseem K; Bhardwaj, Gunjan; Dara, Ravi C; Arora, Dinesh; Aggarwal, Geet; Bhargava, Richa; Madan, Kaushal

2018-04-13

Post-donation counselling informs donors of unusual test results. Timely notification and counselling regarding their Transfusion Transmitted Infection (TTI) status is necessary for early clinical intervention in the donor and reducing risk of transmission. We share our experience with respect to Hepatitis B (HBV) and Hepatitis C (HCV) positive donors who were counselled and followed-up for clinical outcome. It was prospective 2-year study in TTI positive blood donors. Confirmed positive HBV/ HCV donors were notified to attend the donor-clinic or to visit local hepatologist for further management. At donor clinic, donor's immediate emotional response was observed; donors were offered contact-testing, associated risk factors were noted, counselled, referred to hepatologist, treated and followed-up for clinical outcome. Of 481 donors (0.91%) confirmed positives, 351 were contacted telephonically; 280 promised to attend donor clinic and 71 were referred to their local hepatologist. 145 donors attended the donor clinic, eventually. Most common immediate emotional response noted were 'feeling of fear' (55.2%) and 'disbelief' (35.2%). Most common associated risk factor was history of medical treatment/ injections without knowledge of sterilisation. Five donors availed contact testing and four (spouses in all four cases) came out positive. Of 98 donors contacted post-counselling; 89 went to hepatologist. No medication was advised to seven donors (low viral load), 59 donors completed treatment course and 23 donors were undergoing treatment at time of follow-up. Nine donors opted for alternative treatment or "no treatment". Donor-clinic proved beneficial to substantial number of donors and their families. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects and Predictive Factors of Immunosuppressive Therapy Combined with Umbilical Cord Blood Infusion in Patients with Severe Aplastic Anemia.

PubMed

Zhang, Xia; Li, Zhangzhi; Geng, Wei; Song, Bin; Wan, Chucheng

2018-07-01

To investigate the efficacy and safety of umbilical cord blood (UCB) infusion (UCBI) plus immunosuppressive therapy (IST) treatment in comparison to IST treatment, as well as predictive factors for clinical responses, in severe aplastic anemia (SAA) patients. Totally, 93 patients with SAA were enrolled in this cohort study. In the IST group, rabbit antithymocyte globulin (r-ATG) combined with cyclosporine A (CsA) was administered, while in the IST+UBCI group, r-ATG, CsA, and UCB were used. After 6 months of treatment, UCBI+IST achieved a higher complete response (CR) rate (p=0.002) and an elevated overall response rate (ORR) (p=0.004), compared to IST. Regarding hematopoietic recovery at month 6, platelet responses in the UCBI+IST group were better than those in the IST group (p=0.002), and UCBI+IST treatment facilitated increasing trends in absolute neutrophil count (ANC) response (p=0.056). Kaplan-Meier curves illuminated UCBI+IST achieved faster ANC response (p<0.001) and platelet response (p<0.001), compared with IST therapy. There was no difference in overall survival (OS) between the two groups (p=0.620). Furthermore, logistic regression analysis demonstrated that UCBI+IST was an independent predicting factor for both CR (p=0.001) and ORR (p<0.001), compared to IST; meanwhile, very severe aplastic anemia (VSAA) and ANC could predict clinical responses as well. However, Cox proportional hazard regression indicated that VSAA (p=0.003), but not UCBI+IST, affected OS. Safety profiles showed that UCBI+IST therapy did not elevate adverse events, compared with IST treatment. UCBI+IST achieved better clinical responses and hematopoietic recovery than IST, and was well tolerated in SAA patients. © Copyright: Yonsei University College of Medicine 2018.

Vaccination against hepatitis A and B in persons subject to homelessness in inner Sydney: vaccine acceptance, completion rates and immunogenicity.

PubMed

Poulos, Roslyn G; Ferson, Mark J; Orr, Karen J; McCarthy, Michele A; Botham, Susan J; Stern, Jerome M; Lucey, Adrienne

2010-04-01

To determine acceptance, completion rates and immunogenicity of the standard vaccination schedule for hepatitis A (HAV) and B (HBV) in persons subject to homelessness. A convenience sample of clients (n=201) attending a medical clinic for homeless and disadvantaged persons in Sydney was enrolled. Serological screening for HAV and HBV was undertaken. An appropriate vaccination program was instituted. Post-vaccination serology determined serological response. Although many clients had serological evidence of past infection, at least 138 (69%) clients had the potential to benefit from vaccination. For hepatitis A and B vaccinations, completion rates were 73% (73 of 100 clients) and 75% (69 of 92 clients), respectively; after vaccination, protective antibody was found in 98.2% (56 of 57) and 72% (36 of 50) of clients, respectively. A successful vaccination program can be mounted with a vulnerable population. We consider a clinic with a well-established history of acceptance and utilisation by the target group; a low staff turnover and regular clientele; inclusion of vaccination as part of routine client care; and counselling (part of pre- and post-serological testing) essential components in achieving good vaccination completion rates. © 2010 The Authors. Journal Compilation © 2010 Public Health Association of Australia.

User acceptance of observation and response charts with a track and trigger system: a multisite staff survey.

PubMed

Elliott, Doug; Allen, Emily; McKinley, Sharon; Perry, Lin; Duffield, Christine; Fry, Margaret; Gallagher, Robyn; Iedema, Rick; Roche, Michael

2016-08-01

To examine user acceptance with a new format of charts for recording observations and as a prompt for responding to episodes of clinical deterioration in adult medical-surgical patients. Improving recognition and response to clinical deterioration remains a challenge for acute healthcare institutions globally. Five chart templates were developed in Australia, combining human factors design principles with a track and trigger system for escalation of care. Two chart templates were previously tested in simulations, but none had been evaluated in clinical practice. Prospective multisite survey of user acceptance of the charts in practice. New observation and response charts were trialled in parallel with existing charts for 24 hours across 36 adult acute medical-surgical wards, covering 108 shifts, in five Australian states. Surveys were completed by 477 staff respondents, with open-ended comments and narrative from short informal feedback groups providing elaboration and context of user experiences. Respondents were broadly supportive of the chart format and content for monitoring patients, and as a prompt for escalating care. Some concerns were noted for chart size and style, use of ranges to graph vital signs and with specific human factors design features. Information and training issues were identified to improve usability and adherence to chart guidelines and to support improved detection and response for patients with clinical deterioration. This initial evaluation demonstrated that the charts were perceived as appropriate for documenting observations and as a prompt to detect clinical deterioration. Further evaluation after some minor modifications to the chart is recommended. Explicit training on the principles and rationale of human factors chart design, use of embedded change management strategies and addressing practical issues will improve authentic engagement, staff acceptance and adoption by all clinical users when implementing a similar observation and response chart into practice. © 2016 John Wiley & Sons Ltd.

Chemosensitivity and Endocrine Sensitivity in Clinical Luminal Breast Cancer Patients in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST) Predicted by Molecular Subtyping.

PubMed

Whitworth, Pat; Beitsch, Peter; Mislowsky, Angela; Pellicane, James V; Nash, Charles; Murray, Mary; Lee, Laura A; Dul, Carrie L; Rotkis, Michael; Baron, Paul; Stork-Sloots, Lisette; de Snoo, Femke A; Beatty, Jennifer

2017-03-01

Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity. NBRST IHC/FISH HR+/HER2- breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type. Pathological complete response (pCR) rates were compared with conventional IHC/FISH subtype. The overall pCR rate for 'clinical luminal' patients to NCT was 11 %; however, 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The MammaPrint index was highly associated with the likelihood of pCR (p < 0.001). Fifty-three patients with BluePrint Luminal tumors received NET with an aromatase inhibitor and 36 (68 %) had a clinical response. With BluePrint subtyping, 18 % of clinical 'luminal' patients are classified in a different subgroup, compared with conventional assessment, and these patients have a significantly higher response rate to NCT compared with BluePrint Luminal patients. MammaPrint/BluePrint subtyping can help allocate effective treatment to appropriate patients. In addition, accurate identification of subtype biology is important in the interpretation of neoadjuvant treatment response since lack of pCR in luminal patients does not portend the worse prognosis associated with residual disease in Basal and HER2 subtypes.

Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response.

PubMed

Pizzi, Marco; Silver, Richard T; Barel, Ariella; Orazi, Attilio

2015-10-01

Recombinant interferon-α represents a well-established therapeutic option for the treatment of polycythemia vera and essential thrombocythemia. Recent studies also suggest a role for recombinant interferon-α in the treatment of 'early stage' primary myelofibrosis, but few studies have reported the bone marrow changes after clinically successful interferon therapy. The aim of the present study is to detail the histological responses to recombinant interferon-α in primary myelofibrosis and post-polycythemia vera/post-essential thrombocythemia myelofibrosis and to correlate these with clinical findings. We retrospectively studied 12 patients with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis, who had been treated with recombinant interferon-α. Six patients had received other prior cytoreductive therapies. Bone marrow biopsy was assessed for the following histological parameters: (i) cellularity; (ii) myeloid-to-erythroid ratio; (iii) megakaryocyte tight clusters; (iv) megakaryocyte and naked nuclei density; (v) megakaryocytic atypia; (vi) fibrosis; and (vii) the percentage of blasts. Clinical and laboratory data were included: (i) constitutional symptoms; (ii) splenomegaly, if present; and (iii) complete cell blood count. The clinical response to therapy was evaluated using the International Working Group for Myelofibrosis Research and Treatment/European LeukemiaNet response criteria. The Dynamic International Prognostic Scoring System (DIPSS) score was calculated before and after recombinant interferon-α administration. Successful interferon therapy for myelofibrosis was associated with a significant reduction of marrow fibrosis, cellularity, megakaryocyte density and naked nuclei density. The presence of JAK2(V617F) mutation correlated with improved DIPSS score. JAK2(V617F)-negative cases showed worsening of such score or evolution to acute myeloid leukemia. Cytogenetic analysis documented a normal karyotype in all cases. In conclusion, successful clinical response to interferon-α correlates well with an improvement of bone marrow morphology. The prognostic effect of such therapy may be influenced by the JAK2 mutational status. Additional studies are needed to confirm these preliminary data.

Impulsive responses to emotion as a transdiagnostic vulnerability to internalizing and externalizing symptoms.

PubMed

Johnson, Sheri L; Carver, Charles S; Joormann, Jutta

2013-09-25

This study explored the hypothesis that impulsive reactions to heightened emotion may reflect a transdiagnostic vulnerability to both externalizing and internalizing symptoms. A sample of undergraduates completed self-report measures of aggression, borderline personality disorder symptoms, anxiety symptoms, and alcohol problems, and a subset completed interviews that assessed suicidality. All participants also completed self-report measures relating to impulsivity. We predicted that emotion-reactive impulsivity, but not other aspects of impulsivity, would be related to the set of psychopathology symptoms. Multiple regression analyses found that emotion-reactive impulsivity was uniquely related to each of the psychopathology scales, whereas non-emotion-relevant impulsivity was uniquely related only to alcohol problems. Discussion focuses on limitations and clinical implications. © 2013 Elsevier B.V. All rights reserved.

Metabolomics biomarkers to predict acamprosate treatment response in alcohol-dependent subjects.

PubMed

Hinton, David J; Vázquez, Marely Santiago; Geske, Jennifer R; Hitschfeld, Mario J; Ho, Ada M C; Karpyak, Victor M; Biernacka, Joanna M; Choi, Doo-Sup

2017-05-31

Precision medicine for alcohol use disorder (AUD) allows optimal treatment of the right patient with the right drug at the right time. Here, we generated multivariable models incorporating clinical information and serum metabolite levels to predict acamprosate treatment response. The sample of 120 patients was randomly split into a training set (n = 80) and test set (n = 40) five independent times. Treatment response was defined as complete abstinence (no alcohol consumption during 3 months of acamprosate treatment) while nonresponse was defined as any alcohol consumption during this period. In each of the five training sets, we built a predictive model using a least absolute shrinkage and section operator (LASSO) penalized selection method and then evaluated the predictive performance of each model in the corresponding test set. The models predicted acamprosate treatment response with a mean sensitivity and specificity in the test sets of 0.83 and 0.31, respectively, suggesting our model performed well at predicting responders, but not non-responders (i.e. many non-responders were predicted to respond). Studies with larger sample sizes and additional biomarkers will expand the clinical utility of predictive algorithms for pharmaceutical response in AUD.

Animal model of neuropathic tachycardia syndrome

NASA Technical Reports Server (NTRS)

Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

2001-01-01

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

Cheilitis as a variation of Candida-associated lesions.

PubMed

Terai, H; Shimahara, M

2006-05-01

Occasionally, the clinical diagnosis of Candida-associated lesion is difficult because of a variety of its clinical manifestations. There have been a few reports on Candida-associated lip lesion except angular cheilitis. In this paper, we investigate the relation of Candida in persistent lesions of the lip. The present study includes consecutive nine patients with persistent erosive lip lesion. For each patient the age at presentation, gender, duration of the disease, other symptoms or signs, complete medical history and prior treatment or medications for the symptom were obtained. Then, mycological examination and the direct cytologic examination were performed. The reported average duration of the disease was 7 months. Six of nine patients had received prior treatments with topical steroids at the other clinic, which failed to resolve their symptoms. Six of nine patients had a predisposing factor for candidiasis. In the culture examination, Candida albicans were isolated in seven patients (77.8%). Five of nine patients received the direct cytologic examination, and four of them revealed pseudohyphae of fungi. The anti-fungal treatment was miconazol gel 25 mg four times per day, and average duration of the treatment was 2 weeks. The outcome was as follows: complete remission in five, remarkable response in two and no response in two. Our results suggested that one form of the varieties of Candida-associated lesions might be considered in the case of lip lesion with unknown origin that was persistent and ineffective to the topical steroids treatment.

Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy

PubMed Central

Maus, Marcela V.; June, Carl H.

2016-01-01

Chimeric antigen receptors (CARs) are engineered fusion proteins constructed from antigen recognition, signaling, and costimulatory domains that can be expressed in cytotoxic T cells with the purpose of reprograming the T cells to specifically target tumor cells. CAR T-cell therapy uses gene transfer technology to reprogram a patient's own T cells to stably express CARs, thereby combining the specificity of an antibody with the potent cytotoxic and memory functions of a T cell. In early phase clinical trials, CAR T cells targeting CD19 have resulted in sustained complete responses within a population of otherwise refractory patients with B-cell malignancies and, more specifically, have shown complete response rates of ≈90% in patients with relapsed or refractory acute lymphoblastic leukemia. Given this clinical efficacy, preclinical development of CAR T-cell therapy for a number of cancer indications has been actively investigated, and the future of the CAR T-cell field is extensive and dynamic. Several approaches to increase the feasibility and safety of CAR T cells are currently being explored, including investigation into mechanisms regulating the persistence of CAR T cells. Additionally, numerous early-phase clinical trials are now investigating CAR T-cell therapy beyond targeting CD19, especially in solid tumors. Trials investigating combinations of CAR T cells with immune checkpoint blockade therapies are now beginning and results are eagerly awaited. This review evaluates several of the ongoing and future directions of CAR T-cell therapy. PMID:27084741

Perceived racial discrimination, but not mistrust of medical researchers, predicts the heat pain tolerance of African Americans with symptomatic knee osteoarthritis.

PubMed

Goodin, Burel R; Pham, Quyen T; Glover, Toni L; Sotolongo, Adriana; King, Christopher D; Sibille, Kimberly T; Herbert, Matthew S; Cruz-Almeida, Yenisel; Sanden, Shelley H; Staud, Roland; Redden, David T; Bradley, Laurence A; Fillingim, Roger B

2013-11-01

Studies have shown that perceived racial discrimination is a significant predictor of clinical pain severity among African Americans. It remains unknown whether perceived racial discrimination also alters the nociceptive processing of painful stimuli, which, in turn, could influence clinical pain severity. This study examined associations between perceived racial discrimination and responses to noxious thermal stimuli among African Americans and non-Hispanic Whites. Mistrust of medical researchers was also assessed given its potential to affect responses to the noxious stimuli. One-hundred and 30 (52% African American, 48% non-Hispanic White) community-dwelling older adults with symptomatic knee osteoarthritis completed two study sessions. In session one, individuals provided demographic, socioeconomic, physical and mental health information. They completed questionnaires related to perceived lifetime frequency of racial discrimination and mistrust of medical researchers. In session two, individuals underwent a series of controlled thermal stimulation procedures to assess heat pain sensitivity, particularly heat pain tolerance. African Americans were more sensitive to heat pain and reported greater perceived racial discrimination as well as greater mistrust of medical researchers compared with non-Hispanic Whites. Greater perceived racial discrimination significantly predicted lower heat pain tolerance for African Americans but not non-Hispanic Whites. Mistrust of medical researchers did not significantly predict heat pain tolerance for either racial group. These results lend support to the idea that perceived racial discrimination may influence the clinical pain severity of African Americans via the nociceptive processing of painful stimuli.

Switching to second-generation tyrosine kinase inhibitor improves the response and outcome of frontline imatinib-treated patients with chronic myeloid leukemia with more than 10% of BCR-ABL/ABL ratio at 3 months

PubMed Central

Casado, Luis-Felipe; García-Gutiérrez, José-Valentín; Massagué, Isabel; Giraldo, Pilar; Pérez-Encinas, Manuel; de Paz, Raquel; Martínez-López, Joaquín; Bautista, Guiomar; Osorio, Santiago; Requena, María-José; Palomera, Luis; Peñarrubia, María-Jesús; Calle, Carmen; Hernández-Rivas, José-Ángel; Burgaleta, Carmen; Maestro, Begoña; García-Ormeña, Nuria; Steegmann, Juan-Luis

2015-01-01

Chronic myeloid leukemia patients display heterogeneous responses to imatinib. Survival depends on baseline clinical characteristics (including prognostic scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3 months of therapy). The results of switching to second-generation tyrosine kinase inhibitors (2GTKIs) may contain a bias since, in the majority of these studies, patients who switch treatment due to intolerance or failure are censored or excluded. We analyzed the Spanish Registry data on switching in an intention-to-treat analysis of patients in standard clinical practice. Switching to 2GTKIs improves responses from 45% to 75% of complete cytogenetic response (CCyR) and from 15% to 45% of major molecular response (MMR) in the group without molecular response 1 (MR1) at 3 months and from 70% to 87% in CCyR and from 52% to 87% in MMR in the group with MR1. The final response rate is poorer in the group with no MR1 at 3 months. Nevertheless, the differences in the rates of response were not translated into differences in major events (transformations or deaths), and the final progression-free survival and overall survival were similar. PMID:25756742

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

PubMed Central

Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

The long-term impacts of group treatment for partner abuse.

PubMed

Mcgregor, Marla; Tutty, Leslie M; Babins-Wagner, Robbie; Gill, Marlyn

2002-01-01

This paper evaluates Responsible Choices for Men, a 14-week therapy group for abusive men based on feminist perspectives using narrative methods. Pre-test and post-test information was available for 76 program completers measuring physical and non-physical abuse, self-esteem, perceived stress, family relations, depression, assertiveness, and sex-role beliefs. The men significantly improved on all variables. A further focus was following up with 22 group members, contacted 5 to 28 months post treatment and asked to complete the same measures. The results indicated not only maintenance of the post-group changes, but continued improvement. Clinical implications and recommendations for group programming with abusive men are presented.

The prognostic role of hemoglobin levels in patients undergoing concurrent chemo-radiation for anal cancer.

PubMed

Franco, Pierfrancesco; Montagnani, Francesco; Arcadipane, Francesca; Casadei, Chiara; Andrikou, Kalliopi; Martini, Stefania; Iorio, Giuseppe Carlo; Scartozzi, Mario; Mistrangelo, Massimiliano; Fornaro, Lorenzo; Cassoni, Paola; Cascinu, Stefano; Ricardi, Umberto; Casadei Gardini, Andrea

2018-05-02

Concurrent chemo-radiation (CT-RT) is a standard therapy for squamous cell carcinoma of anal canal. Different clinical and biological factors may potentially affect outcome. We investigated the prognostic role of baseline hemoglobin (Hb) in a cohort of anal cancer patients submitted to CT-RT with 5-fluorouracil and mitomycin C. Up to 161 patients with clinical stage T1-T4/N0-N3/M0 were treated. Response was assessed at 6 weeks and thereafter at 3, 6 and 12 months. Two different approaches were used:a)simultaneous integrated boost following RTOG 05-29 indications;b)first sequence of 45Gy/25 fractions to the pelvis followed by 9-14.4 Gy/5-8 fractions to the macroscopic disease. Primary endpoints were progression-free survival (PFS) and overall survival (OS). On multivariate analysis, pre-treatment Hb level had a significant correlation to OS (HR:0.53;95% CI:0.33-0.87; p = 0.001), but not to PFS (HR:0.78;95% CI:0.53-1.15; p = 0.12) Patients with pre-treatment Hb ≥ 12 g/dl had 5-year PFS and OS of 82.2%, compared to 29.3% and 32.8% for those below the threshold. The likelihood to achieve a complete remission increased by 5.6% for every single-unit (g/dl) increase in baseline Hb level over 11 g/dl. On multivariate analysis, response to treatment had a significant correlation to PFS (incomplete vs complete response - HR:5.43;95% CI:2.75-10.7; p < 0.0001) and OS (HR: 6.96;95% CI:2.96-16.5; p < 0.0001). We showed that baseline Hb level is a strong indicator for poor response to RT-CT in anal cancer patients. A close clinical monitoring for incomplete response to treatment should be advised in patients with low pre-treatment Hb. The hypothesis that the preservation of adequate Hb level during treatment may lead to a better outcome needs prospective evaluation.

Experience of Comamonas Acidovorans Keratitis with Delayed Onset and Treatment Response in Immunocompromised Cornea

PubMed Central

Lee, Sang Mok; Lee, Jae Lim; Wee, Won Ryang; Lee, Jin Hak

2008-01-01

Purpose To report 2 cases of Comamonas Acidovorans keratitis in immunocompromised cornea. Methods A complete review of the medical records of the two cases of Comamonas acidovorans keratitis. Results We found some similarities in clinical courses of two cases. Both of them showed development of keratitis during the management with corticosteroids, delayed onset, slow response to antibiotics, and relatively less affected corneal epithelium. Conclusions Comamonas Acidovorans is known as a less virulent organism. However it can cause an indolent infection that responds slowly even to adequate antibiotics therapy in immunocompromised corneas. PMID:18323706

Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.

PubMed

Mattingly, Greg W; Weisler, Richard H; Young, Joel; Adeyi, Ben; Dirks, Bryan; Babcock, Thomas; Lasser, Robert; Scheckner, Brian; Goodman, David W

2013-01-29

Despite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD. In a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an "optimal" LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission. Four hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days (P<.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits. In the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months. Clinical Trial Numbers: NCT00334880 and NCT01070394CLINICAL TRIAL REGISTRY: clinicaltrials.gov.

Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder

PubMed Central

2013-01-01

Background Despite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD. Methods In a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an “optimal” LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission. Results Four hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days (P<.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits. Conclusion In the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months. Trial registration Clinical Trial Numbers: NCT00334880 and NCT01070394 Clinical Trial Registry: clinicaltrials.gov URLs http://www.clinicaltrials.gov/show/NCT00334880 http://www.clinicaltrials.gov/ct2/show/NCT01070394?term=NCT01070394&rank=1 PMID:23356790

Construct Validity and Responsiveness of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and Infant Scales in the PICU.

PubMed

Aspesberro, François; Fesinmeyer, Megan D; Zhou, Chuan; Zimmerman, Jerry J; Mangione-Smith, Rita

2016-06-01

To assess the construct validity and the responsiveness of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and Infant Scales in the medical-surgical (PICU) and cardiac PICU. Prospective cohort study of 367 inpatients admitted either to the PICU or the cardiac ICU at Seattle Children's Hospital from January 2012 to June 2013. Parent/caregiver and child (≥ 8 yr old, developmentally appropriate, and critical illness resolved) Pediatric Quality of Life Inventory scores were obtained within 24 hours of PICU/cardiac ICU discharge and subsequently at 4-12 weeks following hospital discharge. Of the 491 eligible participants invited to participate, 367 (74.7% response rate) completed the Pediatric Quality of Life Inventory survey at ICU discharge, and of these, 263 (71.7% follow-up response rate) completed the follow-up survey 4-12 weeks after hospital discharge. Responsiveness was assessed by calculating improvement scores (difference between follow-up and ICU discharge scores, Δ Pediatric Quality of Life Inventory). Construct validity was examined by comparing mean improvement scores for known groups differing by medical complexity. At follow-up, [INCREMENT] Pediatric Quality of Life Inventory scores were as follows (mean ± SD): physical domain, 34.8 ± 32.0; and psychosocial domain, 23.1 ± 23.5. Patients with complex chronic or noncomplex chronic disease had physical functioning improvement scores that were 17.4 points (95% CI, -28.3 to -6.5; p < 0.001) and 19.5 points (95% CI, -30.4 to -8.5; p < 0.002) lower than children with no chronic illness, respectively. Patients with complex chronic disease exhibited psychosocial improvement scores that were 9.6 points (95% CI, -18.4 to -0.8; p < 0.033) lower than patients without chronic disease. Patients with noncomplex chronic disease had similar psychosocial improvement scores when compared with patients without chronic disease. As a measure of health-related quality of live, Pediatric Quality of Life Inventory demonstrated responsiveness and construct validity in a broad population of critically ill children. This measure represents a patient-centered clinically meaningful patient-or-parent-reported outcome measure for pediatric research assessing the clinical effectiveness of PICU/cardiac ICU interventions. When using health-related quality of life recovery as an outcome measure to assess clinical effectiveness in the PICU/cardiac ICU setting, measuring and controlling for the level of medical complexity is important in order to understand the true impact of clinical interventions.

Pilot Testing Behavior Therapy for Chronic Tic Disorders in Neurology and Developmental Pediatrics Clinics.

PubMed

Ricketts, Emily J; Gilbert, Donald L; Zinner, Samuel H; Mink, Jonathan W; Lipps, Tara D; Wiegand, Geoffrey A; Vierhile, Amy E; Ely, Laura J; Piacentini, John; Walkup, John T; Woods, Douglas W

2016-03-01

Comprehensive Behavioral Intervention for Tics (CBIT) is an efficacious treatment with limited regional availability. As neurology and pediatric clinics are often the first point of therapeutic contact for individuals with tics, the present study assessed preliminary treatment response, acceptability, and feasibility of an abbreviated version, modified for child neurology and developmental pediatrics clinics. Fourteen youth (9-17) with Tourette disorder across 2 child neurology clinics and one developmental pediatrics clinic participated in a small case series. Clinician-rated tic severity (Yale Global Tic Severity Scale) decreased from pre- to posttreatment, z = -2.0, P < .05, r = -.48, as did tic-related impairment, z = -2.4, P < .05, r = -.57. Five of the 9 completers (56%) were classified as treatment responders. Satisfaction ratings were high, and therapeutic alliance ratings were moderately high. Results provide guidance for refinement of this modified CBIT protocol. © The Author(s) 2015.

Boron neutron capture therapy for malignant melanoma: first clinical case report in China

PubMed Central

Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

2016-01-01

A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

Clinical outcomes of gastrointestinal stromal tumor in southern Thailand

PubMed Central

Pornsuksiri, Kittima; Chewatanakornkul, Siripong; Kanngurn, Samornmas; Maneechay, Wanwisa; Chaiyapan, Walawee; Sangkhathat, Surasak

2012-01-01

AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whom received upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients. PMID:23444235

Effectiveness of surgical treatment in chronic migraine.

PubMed

Amaya-Blas, Francisco Javier; Mecott, Gabriel A; Marfil-Rivera, Alejandro; Tamayo-Esquivel, María de Lourdes; García-Pérez, Mauricio Manuel; Chacón-Moreno, Hernán; Pérez-Porras, Sergio; Coutiño, Rosa; Castro-Góvea, Yanko

2018-01-01

Migraine affects more than 35 million people in the United States of America, and 10% of the population in the world. The purpose of this study was to evaluate the effectiveness of surgical treatment in chronic migraine with frontal or occipital trigger areas. We designed a pilot, proof of concept, and prospective study to analyze the effectiveness of surgical release of trigger nerves in severe frontal or occipital chronic migraines. The study was approved by the Ethics and Investigation Committee of Hospital Universitario Dr. José Eleuterio González (Monterrey, N.L., Mexico). We included patients diagnosed with chronic migraine by the neurology service of Hospital Universitario Dr. José Eleuterio González that attended our consult from March to December 2012. The patients were assessed by the MIDAS questionnaire and the diagnosis confirmed by injecting 2% lidocaine in the trigger sites. We realized a superior palpebral approach in frontal migraines to resection the glabellar muscles and an occipital approach to free the greater occipital nerve bilaterally. We evaluated complete and partial clinical response measuring the frequency, intensity, and duration of migraine episodes. We included three patients with Stage IV (severe incapacitating) frontal or occipital chronic migraines. Two were occipital trigger sites and one frontal. We obtained complete clinical response in two patients and a partial response in one. Pain intensity decreased in all patients. Surgical treatment is effective in Stage IV (severe incapacitating) frontal or occipital trigger chronic migraines. Copyright: © 2018 Permanyer.

Efficacy of Vismodegib (Erivedge) for Basal Cell Carcinoma Involving the Orbit and Periocular Area.

PubMed

Demirci, Hakan; Worden, Francis; Nelson, Christine C; Elner, Victor M; Kahana, Alon

2015-01-01

Evaluate the effectiveness of vismodegib in the management of basal cell carcinoma with orbital extension and/or extensive periocular involvement. Retrospective chart review of 6 consecutive patients with biopsy-proven orbital basal cell carcinoma and 2 additional patients with extensive periocular basal cell carcinoma who were treated with oral vismodegib (150 mg/day) was performed. Basal cell carcinoma extended in the orbit in 6 of 8 patients (involving orbital bones in 1 patient), and 2 of 8 patients had extensive periocular involvement (1 with basal cell nevus syndrome). Vismodegib therapy was the only treatment in 6 patients, off-label neoadjuvant in 1 patient, and adjuvant treatment in 1 patient. Orbital tumors in all 4 patients who received vismodegib as sole treatment showed partial response with a mean 83% shrinkage in tumor size after a median of 7 months of therapy. In the 2 patients receiving vismodegib as neoadjuvant or adjuvant therapies, there was complete response after a median of 7 months of therapy and no evidence of clinical recurrence after discontinuing therapy for a median of 15 months. The 2 patients with extensive periocular involvement experienced complete clinical response after a median 14 months of treatment. During treatment, the most common side effects were muscle spasm (75%) followed by alopecia (50%), dysgeusia (25%), dysosmia, and episodes of diarrhea and constipation (13%). Basal cell carcinoma with orbital extension and extensive periocular involvement responds to vismodegib therapy. The long-term prognosis remains unknown, and additional prospective studies are indicated.

Clinical features of avian vacuolar myelinopathy in American coots

USGS Publications Warehouse

Larsen, R.S.; Nutter, F.B.; Augspurger, T.; Rocke, T.E.; Tomlinson, L.; Thomas, N.J.; Stoskopf, M.K.

2002-01-01

Objectivea??To characterize clinical features of avian vacuolar myelinopathy (AVM) in American coots. Designa??Case-control study. Animalsa??26 AVM-affected American coots and 12 unaffected coots. Proceduresa??Complete physical, neurologic, hematologic, and plasma biochemical evaluations were performed. Affected coots received supportive care. All coots died or were euthanatized, and AVM status was confirmed via histopathologic findings. Resultsa??3 severely affected coots were euthanatized immediately after examination. Seventeen affected coots were found dead within 7 days of admission, but 5 affected coots survived > 21 days and had signs of clinical recovery. Abnormal physical examination findings appeared to be related to general debilitation. Ataxia (88%), decreased withdrawal reflexes (88%), proprioceptive deficits (81%), decreased vent responses (69%), beak or tongue weakness (42%), and head tremors (31%), as well as absent pupillary light responses (46%), anisocoria (15%), apparent blindness (4%), nystagmus (4%), and strabismus (4%) were detected. Few gross abnormalities were detected at necropsy, but histologically, all AVM-affected coots had severe vacuolation of white matter of the brain. None of the control coots had vacuolation. Conclusions and Clinical Relevancea??Although there was considerable variability in form and severity of clinical neurologic abnormalities, clinical signs common in AVM-affected birds were identified. Clinical recovery of some AVM-affected coots can occur when supportive care is administered. Until the etiology is identified, caution should be exercised when rehabilitating and releasing coots thought to be affected by AVM.

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

PubMed Central

Schuster, Cornelia; Eikesdal, Hans P.; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E.; Akslen, Lars A.; Straume, Oddbjørn

2012-01-01

Background VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. Trial Registration ClinicalTrials.gov NCT00139360. PMID:22719881

Curriculum time compared to clinical procedures in amalgam and composite posterior restorations in U.S. dental schools: a preliminary study.

PubMed

Rey, Rosalia; Nimmo, Susan; Childs, Gail S; Behar-Horenstein, Linda S

2015-03-01

Dental clinicians have an expanding range of biomaterial choices for restoring tooth structure. Scientific developments in cariology, advances in dental biomaterials, and patients' esthetic concerns have led to a reduction in amalgam restorations and an increase in composite restorations. The aim of this study was to compare teaching time with students' clinical procedures in amalgam and composite posterior restorations in dental schools across the United States. Academic deans in 60 schools were invited to complete a survey that asked for the amount of instructional time for amalgam and composite posterior restorations and the number of clinical restorations performed by their Classes of 2009, 2010, and 2011. Of these 60, 12 returned surveys with complete data, for a 20% response rate. Responses from these schools showed little change in lecture and preclinical laboratory instruction from 2009 to 2011. There was a slight increase in two-surface restorations for both amalgam and composites; however, the total number of reported composite and amalgam restorations remained the same. Of 204,864 restorations reported, 53% were composite, and 47% were amalgam. There were twice as many multisurface large or complex amalgam restorations as composites. One-surface composite restorations exceeded amalgams. Among the participating schools, there was little to no change between curriculum time and clinical procedures. Findings from this preliminary study reflect a modest increase in two-surface resin-based restorations placed by dental students from 2009 to 2011 and little change in curricular time devoted to teaching amalgam restorations. The total number of posterior composite restorations placed by students in these schools was slightly higher than amalgams.

Assessing the clinical outcome of Vim radiosurgery with voxel-based morphometry: visual areas are linked with tremor arrest!

PubMed

Tuleasca, Constantin; Witjas, Tatiana; Najdenovska, Elena; Verger, Antoine; Girard, Nadine; Champoudry, Jerome; Thiran, Jean-Philippe; Van de Ville, Dimitri; Cuadra, Meritxell Bach; Levivier, Marc; Guedj, Eric; Régis, Jean

2017-11-01

Radiosurgery (RS) is an alternative to open standard stereotactic procedures (deep-brain stimulation or radiofrequency thalamotomy) for drug-resistant essential tremor (ET), aiming at the same target (ventro-intermediate nucleus, Vim). We investigated the Vim RS outcome using voxel-based morphometry by evaluating the interaction between clinical response and time. Thirty-eight patients with right-sided ET benefited from left unilateral Vim RS. Targeting was performed using 130 Gy and a single 4-mm collimator. Neurological and neuroimaging assessment was completed at baseline and 1 year. Clinical responders were considered those with at least 50% improvement in tremor score on the treated hand (TSTH). Interaction between clinical response and time showed the left temporal pole and occipital cortex (Brodmann area 19, including V4, V5 and the parahippocampal place area) as statistically significant. A decrease in gray matter density (GMD) 1 year after Vim RS correlated with higher TSTH improvement (Spearman = 0.01) for both anatomical areas. Higher baseline GMD within the left temporal pole correlated with better TSTH improvement (Spearman = 0.004). Statistically significant structural changes in the relationship to clinical response after Vim RS are present in remote areas, advocating a distant neurobiological effect. The former regions are mainly involved in locomotor monitoring toward the local and distant environment, suggesting the recruiting requirement in targeting of the specific visuomotor networks.

Sebaceous adenitis and mural folliculitis in a cat responsive to topical fatty acid supplementation.

PubMed

Glos, Katharina; von Bomhard, Wolf; Bettenay, Sonya; Mueller, Ralf S

2016-02-01

To describe a case of feline sebaceous adenitis and mural folliculitis, and its successful treatment with topical fatty acids. A 5-year-old, male castrated Norwegian Forest cat was presented with a progressive seborrhoeic dermatitis. Clinical examination and histopathological examination of skin biopsies. There was severe, multifocal, lymphocytic mural folliculitis and perifollicular dermatitis, moderate hyperkeratosis and sebaceous adenitis on histopathology. Sebaceous glands were either absent or almost completely effaced by a dense lymphocytic infiltrate. Clinical signs began in spring on the face and neck and progressed over an 18 month period to involve the legs. Initially, topical and systemic antibacterial therapy for a mild bacterial overgrowth resulted in partial clinical response. There was no improvement with oral omega 6 fatty acids and surface cleaning. Treatment with a spot-on product containing essential oils, smoothing agents and vitamin E as the sole therapy was associated with a good--but incomplete--clinical response over a 6 month period, with hair regrowth and a marked decrease in seborrhoeic dermatitis. This improvement was sustained until 12 months later when a severe deep pyoderma with associated anorexia and depression occurred. This was symptomatically treated and the cat remained clinically stable for a further 18 months. Periocular and perinasal seborrhoea was a persistent feature. Topical essential fatty acid therapy may offer a viable alternative to ciclosporin, which has been reported for the successful treatment of this rare disease in cats. © 2015 ESVD and ACVD.

A conceptual model for the development process of confirmatory adaptive clinical trials within an emergency research network.

PubMed

Mawocha, Samkeliso C; Fetters, Michael D; Legocki, Laurie J; Guetterman, Timothy C; Frederiksen, Shirley; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

2017-06-01

Adaptive clinical trials use accumulating data from enrolled subjects to alter trial conduct in pre-specified ways based on quantitative decision rules. In this research, we sought to characterize the perspectives of key stakeholders during the development process of confirmatory-phase adaptive clinical trials within an emergency clinical trials network and to build a model to guide future development of adaptive clinical trials. We used an ethnographic, qualitative approach to evaluate key stakeholders' views about the adaptive clinical trial development process. Stakeholders participated in a series of multidisciplinary meetings during the development of five adaptive clinical trials and completed a Strengths-Weaknesses-Opportunities-Threats questionnaire. In the analysis, we elucidated overarching themes across the stakeholders' responses to develop a conceptual model. Four major overarching themes emerged during the analysis of stakeholders' responses to questioning: the perceived statistical complexity of adaptive clinical trials and the roles of collaboration, communication, and time during the development process. Frequent and open communication and collaboration were viewed by stakeholders as critical during the development process, as were the careful management of time and logistical issues related to the complexity of planning adaptive clinical trials. The Adaptive Design Development Model illustrates how statistical complexity, time, communication, and collaboration are moderating factors in the adaptive design development process. The intensity and iterative nature of this process underscores the need for funding mechanisms for the development of novel trial proposals in academic settings.

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Thecua, Elise; Lecomte, Fabienne; Vicentini, Claire; Abi-Rached, Henry; Mortier, Laurent; Mordon, Serge

2018-04-18

Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient. This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage. The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment. The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and local damage. However, no association between the complete response rate at 3 months and the effective light dose or local damage was found. Protocols that achieve high complete response rates at 3 months and low pain scores should be preferred regardless of the effective light dose and local damage. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results.

PubMed

Amin, Asim; Dudek, Arkadiusz Z; Logan, Theodore F; Lance, Raymond S; Holzbeierlein, Jeffrey M; Knox, Jennifer J; Master, Viraj A; Pal, Sumanta K; Miller, Wilson H; Karsh, Lawrence I; Tcherepanova, Irina Y; DeBenedette, Mark A; Williams, W Lee; Plessinger, Douglas C; Nicolette, Charles A; Figlin, Robert A

2015-01-01

AGS-003 is an autologous immunotherapy prepared from fully matured and optimized monocyte-derived dendritic cells, which are co-electroporated with amplified tumor RNA plus synthetic CD40L RNA. AGS-003 was evaluated in combination with sunitinib in an open label phase 2 study in intermediate and poor risk, treatment naïve patients with metastatic clear cell renal cell carcinoma (mRCC). Twenty-one intermediate and poor risk patients were treated continuously with sunitinib (4 weeks on, 2 weeks off per 6 week cycle). After completion of the first cycle of sunitinib, patients were treated with AGS-003 every 3 weeks for 5 doses, then every 12 weeks until progression or end of study. The primary endpoint was to determine the complete response rate. Secondary endpoints included clinical benefit, safety, progression free survival (PFS) and overall survival (OS). Immunologic response was also monitored. Thirteen patients (62%) experienced clinical benefit (9 partial responses, 4 with stable disease); however there were no complete responses in this group of intermediate and poor risk mRCC patients and enrollment was terminated early. Median PFS from registration was 11.2 months (95% CI 6.0, 19.4) and the median OS from registration was 30.2 months (95% CI 9.4, 57.1) for all patients. Seven (33%) patients survived for at least 4.5 years, while five (24%) survived for more than 5 years, including 2 patients who remain progression-free with durable responses for more than 5 years at the time of this report. AGS-003 was well tolerated with only mild injection-site reactions. The most common adverse events were related to expected toxicity from sunitinib therapy. In patients who had sequential samples available for immune monitoring, the magnitude of the increase in the absolute number of CD8(+) CD28(+) CD45RA(-) effector/memory T cells (CTLs) after 5 doses of AGS-003 relative to baseline, correlated with overall survival. AGS-003 in combination with sunitinib was well tolerated and yielded supportive immunologic responses coupled with extension of median and long-term survival in an unselected, intermediate and poor risk prognosis mRCC population. #NCT00678119.

Implementing a Measurement Feedback System: A Tale of Two Sites

PubMed Central

Douglas, Susan R.; Vides De Andrade, Ana Regina; Tomlinson, Michele; Gleacher, Alissa; Olin, Serene; Hoagwood, Kimberly

2015-01-01

A randomized experiment was conducted in two outpatient clinics evaluating a measurement feedback system called contextualized feedback systems. The clinicians of 257 Youth 11–18 received feedback on progress in mental health symptoms and functioning either every 6 months or as soon as the youth’s, clinician’s or caregiver’s data were entered into the system. The ITT analysis showed that only one of the two participating clinics (Clinic R) had an enhanced outcome because of feedback, and only for the clinicians’ ratings of youth symptom severity on the SFSS. A dose–response effect was found only for Clinic R for both the client and clinician ratings. Implementation analyses showed that Clinic R had better implementation of the feedback intervention. Clinicians’ questionnaire completion rate and feedback viewing at Clinic R were 50 % higher than clinicians at Clinic U. The discussion focused on the differences in implementation at each site and how these differences may have contributed to the different outcomes of the experiment. PMID:25876736

Activity of thalidomide and capecitabine in patients with advanced hepatocellular carcinoma.

PubMed

Ang, Soo-Fan; Tan, Sze-Huey; Toh, Han-Chong; Poon, Donald Y H; Ong, Simon Y K; Foo, Kian-Fong; Choo, Su-Pin

2012-06-01

Thalidomide has shown modest activity in advanced hepatocellular carcinomas (HCCs). Single-agent capecitabine has also been used in patients with HCC, with objective responses being reported. In our study, we review the use of thalidomide and capecitabine combination in advanced HCC. From November 2003 and September 2008, 42 patients with advanced HCC who were not eligible for clinical trial or conventional chemotherapy were treated with oral capecitabine (2000 mg/m/d) for 14 days every 3 weeks and oral thalidomide at the doses of 50 to 200 mg/d. Almost 50% of patients had Child-Pugh B or C liver cirrhosis and a history of regional or systemic therapy. Three patients achieved complete responses lasting more than 52 weeks, including 1 patient who achieved pathological complete response and underwent curative resection. There were 3 patients with partial responses and 13 with stable disease. Median overall survival of all 42 patients was 9.9 months. The median progression-free survival was 5.1 months. The presence of ascites, portal vein thrombosis, and poorer Child-Pugh liver cirrhosis status also resulted in significantly poorer survival outcome. Treatment was well tolerated. Fatigue was the most common side effect occurring in 16 (38%) patients, but only 1 patient had grade 3 toxicity and had to stop treatment. Two other patients developed grade 3 palmar-plantar erythrodysesthesia from capecitabine. The combination of thalidomide and capecitabine has activity in advanced HCC and can result in complete pathological response. Treatment is well tolerated even in less-fit patients who have been pretreated and deserve further study.

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

Mimura, Hidefumi, E-mail: mimura@marianna-u.ac.jp; Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp; Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp

PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a furthermore » 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.« less

Efficacy of topical resin lacquer, amorolfine and oral terbinafine for treating toenail onychomycosis: a prospective, randomized, controlled, investigator-blinded, parallel-group clinical trial.

PubMed

Auvinen, T; Tiihonen, R; Soini, M; Wangel, M; Sipponen, A; Jokinen, J J

2015-10-01

Norway spruce (Picea abies) produces resin to protect against decomposition by microbial pathogens. In vitro tests have shown that spruce resin has antifungal properties against dermatophytes known to cause nearly 90% of onychomycosis in humans. To confirm previous in vivo observations that a topical resin lacquer provides mycological and clinical efficacy, and to compare this lacquer with topical amorolfine hydrochloride lacquer and systemic terbinafine for treating dermatophyte toenail onychomycosis. In this prospective, randomized, controlled, investigator-blinded study, 73 patients with onychomycosis were randomized to receive topical 30% resin lacquer once daily for 9 months, topical 5% amorolfine lacquer once weekly for 9 months, or 250 mg oral terbinafine once daily for 3 months. The primary outcome measure was complete mycological cure at 10 months. Secondary outcomes were clinical efficacy, cost-effectiveness and patient compliance. At 10 months, complete mycological cure rates with the resin, amorolfine and terbinafine treatments were 13% [95% confidence interval (CI) 0-28], 8% (95% CI 0-19) and 56% (95% CI 35-77), respectively (P ≤ 0·002). At 10 months, clinical responses were complete in four patients (16%) treated with terbinafine, and partial in seven (30%), seven (28%) and nine (36%) patients treated with resin, amorolfine and terbinafine, respectively (P < 0·05). Resin, amorolfine and terbinafine treatments cost €41·6, €56·3 and €52·1, respectively, per patient (P < 0·001). Topical 30% resin lacquer and topical 5% amorolfine lacquer provided similar efficacy for treating dermatophyte toenail onychomycosis. However, orally administered terbinafine was significantly more effective in terms of mycological cure and clinical outcome than either topical therapy at the 10-month follow-up. © 2015 British Association of Dermatologists.

Evaluation of a Topical Anti-inflammatory/Antifungal Combination Cream in Mild-to-moderate Facial Seborrheic Dermatitis: An Intra-subject Controlled Trial Examining Treated vs. Untreated Skin Utilizing Clinical Features and Erythema-directed Digital Photography.

PubMed

Dall'Oglio, Federica; Tedeschi, Aurora; Guardabasso, Vincenzo; Micali, Giuseppe

2015-09-01

To evaluate if nonprescription topical agents may provide positive outcomes in the management of mild-to-moderate facial seborrheic dermatitis by reducing inflammation and scale production through clinical evaluation and erythema-directed digital photography. Open-label, prospective, not-blinded, intra-patient, controlled, clinical trial (target area). Twenty adult subjects affected by mild-to-moderate facial seborrheic dermatitis were enrolled and instructed to apply the study cream two times daily, initially on a selected target area only for seven days. If the subject developed visible improvement, it was advised to extend the application to all facial affected area for 21 additional days. Efficacy was evaluated by measuring the grade of erythema (by clinical examination and by erythema-directed digital photography), desquamation (by clinical examination), and pruritus (by subject-completed visual analog scale). Additionally, at the end of the protocol, a Physician Global Assessment was carried out. Eighteen subjects completed the study, whereas two subjects were lost to follow-up for nonadherence and personal reasons, respectively. Day 7 data from target areas showed a significant reduction in erythema. At the end of study, a significant improvement was recorded for erythema, desquamation, and pruritus compared to baseline. Physician Global Assessment showed improvement in 89 percent of patients, with a complete response in 56 percent of cases. These preliminary results indicate that the study cream may be a viable nonprescription therapeutic option for patients affected by facial seborrheic dermatitis able to determine early and significant improvement. This study also emphasizes the advantages of using an erythema-directed digital photography system for assisting in a simple, more accurate erythema severity grading and therapeutic monitoring in patients affected by seborrheic dermatitis.

Efficacy of MaZiRenWan, a Chinese Herbal Medicine, in Patients With Functional Constipation in a Randomized Controlled Trial.

PubMed

Zhong, Linda L D; Cheng, Chung-Wah; Kun, Wai; Dai, Liang; Hu, Dong-Dong; Ning, Zi-Wan; Xiao, Hai-Tao; Lin, Cheng-Yuan; Zhao, Ling; Huang, Tao; Tian, Ke; Chan, King-Hong; Lam, Ting-Wa; Chen, Xiao-Rui; Wong, Chi-Tak; Li, Min; Lu, Ai-Ping; Wu, Justin C Y; Bian, Zhao-Xiang

2018-04-12

The Chinese herbal medicine, MaZiRenWan (MZRW), has been used for more than 2000 years to treat constipation, but it has not been tested in a randomized controlled trial. We performed a trial to evaluate the efficacy and safety of MZRW, compared with the stimulant laxative senna or placebo, for patients with functional constipation (FC). We performed a double-blind, double-dummy, trial of 291 patients with FC based on Rome III criteria, seen at 8 clinics in Hong Kong from June 2013 through August 2015. Patients were observed for 2 weeks and then assigned randomly (1:1:1) to groups given MZRW (7.5 g, twice daily), senna (15 mg daily), or placebo for 8 weeks. Patients were then followed for 8 weeks and evaluated at baseline and weeks 4, 8 (end of treatment), and 16 (end of follow up). Participants recorded information on stool form and frequency, feeling of complete evacuation, and research medication taken. Data on individual bowel symptoms, global symptom improvement, and adverse events were collected. A complete response was defined as an increase ≥1 complete spontaneous bowel movement (CSBM)/week from baseline (the primary outcome). Secondary outcomes included response during the follow-up period, colonic transit, individual and global symptom assessments, quality of life measured with 36-item short form Chinese version, and adverse events. Although there was no statistically significant difference in proportions of patients with a complete response to MZRW (68%) vs. senna (57.7%) (P = .14) at week 8, there was a statistically significant difference vs. placebo (33.0%) (P < .005). At the 16-week timepoint (after the 8-week follow-up period), 47.4% of patients had a complete response to MZRW, 20.6% had a complete response to senna, and 17.5% had a complete response to placebo (P < .005 for MZRW vs. placebo). The group that received MZRW group also had significant increases in colonic transit and reduced severity of constipation, straining, incomplete evacuation, and global constipation symptoms compared with the groups that received placebo or senna in (P < .05 for all comparisons). In a randomized controlled trial of 291 patients with FC, we found MZRW to be well-tolerated and effective in increasing CSBM/week. MZRW did not appear to be more effective than senna and might be considered as an alternative to this drug. ClincialTrials.gov no: NCT01695850. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Clinical characteristics of the respiratory subtype in panic disorder patients.

PubMed

Song, Hye-Min; Kim, Ji-Hae; Heo, Jung-Yoon; Yu, Bum-Hee

2014-10-01

Panic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients. Among the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D). The prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group. Panic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs.

Clinical Characteristics of the Respiratory Subtype in Panic Disorder Patients

PubMed Central

Song, Hye-Min; Kim, Ji-Hae; Heo, Jung-Yoon

2014-01-01

Objective Panic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients. Methods Among the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D). Results The prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group. Conclusion Panic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs. PMID:25395972

High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

PubMed

Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

2014-08-21

The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response to metronomic chemotherapy as well the quality of life in pets with advanced cancer. Further studies are warranted to assess the efficacy of this strategy in patients with advanced cancers in companion animals as well as in humans.

Experience with using second life for medical education in a family and community medicine education unit

PubMed Central

2012-01-01

Background The application of new technologies to the education of health professionals is both a challenge and a necessity. Virtual worlds are increasingly being explored as a support for education. Aim: The aim of this work is to study the suitability of Second Life (SL) as an educational tool for primary healthcare professionals. Methods Design: Qualitative study of accredited clinical sessions in SL included in a continuing professional development (CPD) programme for primary healthcare professionals. Location: Zaragoza I Zone Family and Community Medicine Education Unit (EU) and 9 health centres operated by the Aragonese Health Service, Aragon, Spain. Method: The EU held two training workshops in SL for 16 healthcare professionals from 9 health centres by means of two workshops, and requested them to facilitate clinical sessions in SL. Attendance was open to all personnel from the EU and the 9 health centres. After a trail period of clinical sessions held at 5 health centres between May and November 2010, the CPD-accredited clinical sessions were held at 9 health centres between February and April 2011. Participants: 76 healthcare professionals attended the CPD-accredited clinical sessions in SL. Main measurements: Questionnaire on completion of the clinical sessions. Results Response rate: 42-100%. Questionnaire completed by each health centre on completion of the CPD-accredited clinical sessions: Access to SL: 2 centres were unable to gain access. Sound problems: 0% (0/9). Image problems: 0% (0/9). Voice/text chat: used in 100% (10/9); 0 incidents. Questionnaire completed by participants in the CPD-accredited clinical sessions: Preference for SL as a tool: 100% (76/76). Strengths of this method: 74% (56/76) considered it eliminated the need to travel; 68% (52/76) believed it made more effective use of educational resources; and 47% (36/76) considered it improved accessibility. Weaknesses: 91% (69/76) experienced technical problems, while; 9% (7/76) thought it was impersonal and with little interaction. 65.79% (50/76) believed it was better than other distance learning methods and 38.16% (29/76) believed it was better than face-to-face learning. Conclusions SL is a tool that allows educational activities to be designed that involve a number of health centres in different geographical locations, consequently eliminating the need to travel and making more effective use of educational resources. PMID:22587562

Experience with using second life for medical education in a family and community medicine education unit.

PubMed

Melús-Palazón, Elena; Bartolomé-Moreno, Cruz; Palacín-Arbués, Juan Carlos; Lafuente-Lafuente, Antonio; García, Inmaculada García; Guillen, Sara; Esteban, Ana B; Clemente, Silvia; Marco, Angeles M; Gargallo, Pilar M; López, Carlos; Magallón-Botaya, Rosa

2012-05-15

The application of new technologies to the education of health professionals is both a challenge and a necessity. Virtual worlds are increasingly being explored as a support for education. The aim of this work is to study the suitability of Second Life (SL) as an educational tool for primary healthcare professionals. Qualitative study of accredited clinical sessions in SL included in a continuing professional development (CPD) programme for primary healthcare professionals. Zaragoza I Zone Family and Community Medicine Education Unit (EU) and 9 health centres operated by the Aragonese Health Service, Aragon, Spain. The EU held two training workshops in SL for 16 healthcare professionals from 9 health centres by means of two workshops, and requested them to facilitate clinical sessions in SL. Attendance was open to all personnel from the EU and the 9 health centres. After a trail period of clinical sessions held at 5 health centres between May and November 2010, the CPD-accredited clinical sessions were held at 9 health centres between February and April 2011. 76 healthcare professionals attended the CPD-accredited clinical sessions in SL. Questionnaire on completion of the clinical sessions. Response rate: 42-100%. Questionnaire completed by each health centre on completion of the CPD-accredited clinical sessions: Access to SL: 2 centres were unable to gain access. Sound problems: 0% (0/9). Image problems: 0% (0/9). Voice/text chat: used in 100% (10/9); 0 incidents. Questionnaire completed by participants in the CPD-accredited clinical sessions: Preference for SL as a tool: 100% (76/76). Strengths of this method: 74% (56/76) considered it eliminated the need to travel; 68% (52/76) believed it made more effective use of educational resources; and 47% (36/76) considered it improved accessibility. Weaknesses: 91% (69/76) experienced technical problems, while; 9% (7/76) thought it was impersonal and with little interaction. 65.79% (50/76) believed it was better than other distance learning methods and 38.16% (29/76) believed it was better than face-to-face learning. SL is a tool that allows educational activities to be designed that involve a number of health centres in different geographical locations, consequently eliminating the need to travel and making more effective use of educational resources.

Clinical characteristics and disposition kinetics of the hepatomegaly associated with acute, uncomplicated, Plasmodium falciparum malaria in children.

PubMed

Sowunmi, A; Adedeji, A A; Sowunmi, C O; Falade, C O; Falade, A G; Ohaeri, B; Happi, T C; Oduola, A M

2001-01-01

The clinical characteristics and the kinetics of the disposition of the hepatomegaly associated with acute, uncomplicated Plasmodium falciparum malaria were investigated in 162 children in an endemic area of Nigeria. Hepatomegaly was significantly more common in the younger than in the older children. Complete resolution occurred in 48% following antimalarial chemotherapy. In the children in whom hepatomegaly did not resolve, a reduction in liver size of < 17% by the time parasitaemia was cleared (usually on day 3) was associated with non-resolution of hepatomegaly by days 7 or 14 of follow-up. An increase in liver size to at least 125% of the baseline value by day 4 or 5 was associated with a lack of therapeutic response, providing the child involved was aged < 5 years. In the children who had complete clearance of parasitaemia and resolution of hepatomegaly, there was no significant relationship between the parasitaemia-derived conventional indices of therapeutic response [i.e. time to clearance of 50% (PC50) or 90% (PC90) of the parasitaemia, and the parasite-clearance time (PCT)] and the corresponding parameters derived from measurement of liver size [i.e. time for resolution of 50% (HR50) or 90% (HR90) of the hepatomegaly and the hepatomegaly-resolution time (HRT)] in the same patients. However, as the HR50:PC50, HR90:PC90 and HRT:PCT ratios were similar (range = 1.6-2.1), the liver parameters may have therapeutic application. In the children with drug-sensitive P. falciparum infections and in whom hepatomegaly completely resolved, the area produced by plotting liver size against time (i.e. the area under the curve of hepatomegaly v. time, or AUChp) increased in proportion to the liver size below the costal margin (P = 0.02, from analysis of variance), but there was no significant difference in the half-lives of hepatomegaly (t1/2hp) or in the ratios of liver size to AUChp, indicating that the kinetics of the resolution of hepatomegaly were linear in the range examined. Comparison of the kinetic indices of hepatomegaly and parasitaemia showed that, although the half-lives of parasitaemia and hepatomegaly and the corresponding clearance values were similar, there was no correlation between these parameters among those in whom hepatomegaly completely resolved and parasitaemia completely cleared. These results indicate that routine clinical measurement of the liver size in children with hepatomegaly during acute, uncomplicated, P. falciparum malaria may have some use in evaluating and monitoring the therapeutic responses of infections. The resolution of hepatomegaly, a reflection of pathological changes, lags behind clearance of parasitaemia in children with P. falciparum malaria, and supports the use of the liver 'rate' as a malariometric index for assessing the intensity of transmission in endemic areas.

Modeling Efficacy of Bevacizumab Treatment for Metastatic Colon Cancer

PubMed Central

Islam, Rezwan; Chyou, Po-Huang; Burmester, James K

2013-01-01

Purpose: Bevacizumab, an FDA-approved adjuvant treatment for metastatic colon cancer, has extended survival for many patients. However, factors predicting response to treatment remain undefined. Patients and Methods: Relevant clinical and environmental data were abstracted from medical records of 149 evaluable patients treated with bevacizumab for metastatic colon cancer at a multi-specialty clinic. Tumor response was calculated from radiologic reports using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and verified by oncologist review. Patients with at least one occurrence of complete or partial response or stable disease were classified as responders; those exhibiting progressive disease were classified as non-responders. Results: Univariate analysis demonstrated that blood in stool (P<0.05), unexplained weight loss (P<0.05), primary colon cancer site (P<0.05), chemotherapy treatment of primary tumor site (P<0.05), and adenocarcinoma versus adenoma subtype (P<0.05) was associated with tumor responsiveness. Factors remaining statistically significant following multivariate modeling included adenocarcinoma as tumor cell type versus other adenocarcinoma subtypes (OR=6.35, 95% CI: 1.08-37.18), chemotherapy treatment applied to primary tumor (OR= 0.07, 95% CI: 0.0-0.76,), tumor localization to cecal/ascending colon (OR=0.061, 95% CI: 0.006-0.588,), and unexplained weight loss (OR=0.1, 95% CI: 0.02-0.56,). Chemotherapy treatment of primary tumor, unexplained weight loss, and cecal/ascending localization of the tumor were associated with poorer outcomes. Adenocarcinoma as cell type compared to other adenocarcinoma subtypes was associated with better response to bevacizumab treatment. Conclusion: Results suggest that response to bevacizumab therapy may be predicted by modeling clinical factors including symptomology on presentation, tumor location and type, and initial response to chemotherapy. PMID:23678369

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era

PubMed Central

Ambler, Kimberley L. S.; Vickars, Linda M.; Leger, Chantal S.; Foltz, Lynda M.; Montaner, Julio S. G.; Harris, Marianne; Dias Lima, Viviane; Leitch, Heather A.

2012-01-01

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 109/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 109/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed. PMID:22693513

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era.

PubMed

Ambler, Kimberley L S; Vickars, Linda M; Leger, Chantal S; Foltz, Lynda M; Montaner, Julio S G; Harris, Marianne; Dias Lima, Viviane; Leitch, Heather A

2012-01-01

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 10(9)/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 10(9)/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.

The treatment of human cancer with agents prepared from bovine cartilage.

PubMed

Prudden, J F

1985-12-01

Oral and subcutaneous administration of specific preparations of bovine tracheal cartilage rings (Catrix), a nontoxic agent, has resulted in a high response rate in 31 cases of a variety of clinical malignancies (response rate 90%, 61% complete). The demonstrated responder include present therapeutic disasters such as glioblastoma multiforme and cancers of the pancreas and lung. Other types which were treated with success included cancers of the ovary, rectum, prostate, cervix, thyroid, and an inoperable squamous cancer of the nose. These responses were observed when full dose therapy was given over prolonged courses of treatment (years). This wide range of Catrix efficacy now invites investigation by others to confirm the effectiveness of the material and to isolate the molecular entities responsible for these unexpectedly favorable results.

Balancing commercial and public interests

PubMed Central

Furberg, Curt D; Hall, Mark A; Sevick, Mary Ann

2004-01-01

A large number of randomized clinical trials with important health outcomes are completed each year. Those with favorable findings are typically reported and published rapidly, while the publication of those with unfavorable results is often delayed or given a positive "spin." This observation applies primarily to industry-sponsored trials. Our objectives are to discuss the responsibility of pharmaceutical firms to the public with respect to timely, complete, and unbiased information from all randomized clinical trials and to propose solutions for improvements. We believe that in addition to financial obligations to their shareholders, pharmaceutical companies have social responsibilities to the public and to health care providers. However, private markets do not reward or compel optimal disclosure of drug safety or inferiority information on a voluntary basis. A problem which has not previously been identified relates to non-comparability of drugs. A case report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) illustrates how public interests may be violated due to failure to inform about drug inferiority. The current system for dissemination of relevant medical information could be improved if all involved parties collaborated fully. However, full disclosure of trial results is unlikely when research results are unfavorable to the firm. We conclude that expanded government regulations will be required for a satisfactory solution to the problem. PMID:15239846

Webcam delivery of the Camperdown Program for adolescents who stutter: a phase II trial.

PubMed

Carey, Brenda; O'Brian, Sue; Lowe, Robyn; Onslow, Mark

2014-10-01

This Phase II clinical trial examined stuttering adolescents' responsiveness to the Webcam-delivered Camperdown Program. Sixteen adolescents were treated by Webcam with no clinic attendance. Primary outcome was percentage of syllables stuttered (%SS). Secondary outcomes were number of sessions, weeks and hours to maintenance, self-reported stuttering severity, speech satisfaction, speech naturalness, self-reported anxiety, self-reported situation avoidance, self-reported impact of stuttering, and satisfaction with Webcam treatment delivery. Data were collected before treatment and up to 12 months after entry into maintenance. Fourteen participants completed the treatment. Group mean stuttering frequency was 6.1 %SS (range, 0.7-14.7) pretreatment and 2.8 %SS (range, 0-12.2) 12 months after entry into maintenance, with half the participants stuttering at 1.2 %SS or lower at this time. Treatment was completed in a mean of 25 sessions (15.5 hr). Self-reported stuttering severity ratings, self-reported stuttering impact, and speech satisfaction scores supported %SS outcomes. Minimal anxiety was evident either pre- or post-treatment. Individual responsiveness to the treatment varied, with half the participants showing little reduction in avoidance of speech situations. The Webcam service delivery model was appealing to participants, although it was efficacious and efficient for only half. Suggestions for future stuttering treatment development for adolescents are discussed.

Signature program: a platform of basket trials.

PubMed

Slosberg, Eric D; Kang, Barinder P; Peguero, Julio; Taylor, Matthew; Bauer, Todd M; Berry, Donald A; Braiteh, Fadi; Spira, Alexander; Meric-Bernstam, Funda; Stein, Steven; Piha-Paul, Sarina A; Salvado, August

2018-04-20

Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and an actionable mutation. The primary endpoint of each study was the clinical benefit rate (ie, complete or partial response, or stable disease) at 16 weeks. A total of 192 individual sites were opened in the United States, with a median start-up time of 3.6 weeks. The most common tumor types among the 595 treated patients were colorectal (9.2%), non-small cell lung adenocarcinoma (9.1%), and ovarian (8.4%). Frequent genetic alterations were in PIK3CA , RAS , p16 , and PTEN . Overall, 30 partial or complete responses were observed with 6 compounds in 16 tumor types. The Signature Program presents a unique and successful approach for rapid signal finding across multiple tumors and allowed various agents to be evaluated in patients with rare alterations. Incorporating these program features in conventional studies could lead to improved trial efficiencies and patient outcomes.

Signature program: a platform of basket trials

PubMed Central

Peguero, Julio; Taylor, Matthew; Bauer, Todd M.; Berry, Donald A.; Braiteh, Fadi; Spira, Alexander; Meric-Bernstam, Funda; Stein, Steven; Piha-Paul, Sarina A.; Salvado, August

2018-01-01

Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and an actionable mutation. The primary endpoint of each study was the clinical benefit rate (ie, complete or partial response, or stable disease) at 16 weeks. A total of 192 individual sites were opened in the United States, with a median start-up time of 3.6 weeks. The most common tumor types among the 595 treated patients were colorectal (9.2%), non-small cell lung adenocarcinoma (9.1%), and ovarian (8.4%). Frequent genetic alterations were in PIK3CA, RAS, p16, and PTEN. Overall, 30 partial or complete responses were observed with 6 compounds in 16 tumor types. The Signature Program presents a unique and successful approach for rapid signal finding across multiple tumors and allowed various agents to be evaluated in patients with rare alterations. Incorporating these program features in conventional studies could lead to improved trial efficiencies and patient outcomes. PMID:29765547

New Therapeutic Targets in Idiopathic Pulmonary Fibrosis. Aiming to Rein in Runaway Wound-Healing Responses

PubMed Central

Ahluwalia, Neil; Shea, Barry S.

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a devastating disease, with a median survival as short as 3 years from the time of diagnosis and no pharmacological therapies yet approved by the U.S. Food and Drug Administration. To address the great unmet need for effective IPF therapy, a number of new drugs have recently been, or are now being, evaluated in clinical trials. The rationales for most of these therapeutic candidates are based on the current paradigm of IPF pathogenesis, in which recurrent injury to the alveolar epithelium is believed to drive aberrant wound healing responses, resulting in fibrosis rather than repair. Here we discuss drugs in recently completed or currently ongoing phase II and III IPF clinical trials in the context of their putative mechanisms of action and the aberrant repair processes they are believed to target: innate immune activation and polarization, fibroblast accumulation and myofibroblast differentiation, or extracellular matrix deposition and stiffening. Placed in this context, the positive results of recently completed trials of pirfenidone and nintedanib, and results that will come from ongoing trials of other agents, should provide valuable insights into the still-enigmatic pathogenesis of this disease, in addition to providing benefits to patients with IPF. PMID:25090037

A preliminary report on histological outcome of pulpotomy with endodontic biomaterials vs calcium hydroxide

PubMed Central

Peimani, Ali; Asgary, Saeed

2013-01-01

Objectives The purpose of the study was to evaluate human dental pulp response to pulpotomy with calcium hydroxide (CH), mineral trioxide aggregate (MTA), and calcium enriched mixture (CEM) cement. Materials and Methods A total of nine erupted third molars were randomly assigned to each pulpotomy group. The same clinician performed full pulpotomies and coronal restorations. The patients were followed clinically for six months; the teeth were then extracted and prepared for histological assessments. The samples were blindly assessed by an independent observer for pulp vitality, pulp inflammation, and calcified bridge formation. Results All patients were free of clinical signs/symptoms of pulpal/periradicular diseases during the follow up period. In CH group, one tooth had necrotic radicular pulp; other two teeth in this group had vital uninflamed pulps with complete dentinal bridge formation. In CEM cement and MTA groups all teeth had vital uninflamed radicular pulps. A complete dentinal bridge was formed beneath CEM cement and MTA in all roots. Odontoblast-like cells were present beneath CEM cement and MTA in all samples. Conclusions This study revealed that CEM cement and MTA were reliable endodontic biomaterials in full pulpotomy treatment. In contrast, the human dental pulp response to CH might be unpredictable. PMID:24303358

Responsiveness of the numeric pain rating scale in patients with shoulder pain and the effect of surgical status.

PubMed

Michener, Lori A; Snyder, Alison R; Leggin, Brian G

2011-02-01

The Numeric Pain Rating Scale (NPRS) is commonly used to assess pain. Change in the NPRS across time can be interpreted with responsiveness indices. To determine the minimal clinically important difference (MCID) of the NPRS. Single-group repeated measures. Outpatient rehabilitation clinics. Patients with shoulder pain (N = 136). At the initial evaluation patients completed the Penn Shoulder Score (PSS), which includes pain, satisfaction, and function sections. Pain was measured using an 11-point NPRS for 3 conditions of pain: at rest, with normal daily activities, and with strenuous activities. The NPRS average was calculated by averaging the NPRS scores for 3 conditions of pain. The final PSS was completed after 3-4 wk of rehabilitation. To determine the MCID for the NPRS average, the minimal detectible change of 8.6 points for the PSS function scale (0-60 points) was used as an external criterion anchor to classify patients as meaningfully improved (≥8.6 point change) or not improved (<8.6-point change). The MCID for the NPRS average was also determined for subgroups of surgical and nonsurgical patients. Cohen's effect sizes were calculated as a measure of group responsiveness for the NPRS average. Using a receiver-operating-characteristic analysis, the MCID for the average NPRS for all patients was 2.17, and it was 2.17 for both the surgical and nonsurgical subgroup: area-under-the-curve range .74-.76 (95%CI: .55-.95). The effect size for all patients was 1.84, and it was 1.51 and 1.94 for the surgical and nonsurgical groups, respectively. The NPRS average of 3 pain questions demonstrated responsiveness with an MCID of 2.17 in patients with shoulder pain receiving rehabilitation for 3-4 wk. The effect sizes indicated a large effect. However, responsiveness values are not static. Further research is indicated to assess responsiveness of the NPRS average in different types of patients with shoulder pain.