Enhancing Hispanic Participation in Mental Health Clinical Research: Development of a Spanish-speaking Depression Research Site

PubMed Central

Rivera, Vivianne Aponte; Dunlop, Boadie W.; Ramirez, Cynthia; Kelley, Mary E.; Schneider, Rebecca; Blastos, Beatriz; Larson, Jacqueline; Mercado, Flavia; Mayberg, Helen; Craighead, W. Edward

2015-01-01

Background Hispanics, particularly those with limited English proficiency, are underrepresented in psychiatric clinical research studies. We developed a bilingual and bicultural research clinic dedicated to the recruitment and treatment of Spanish-speaking subjects in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study, a large clinical trial of treatment-naïve subjects with major depressive disorder (MDD). Methods Demographic and clinical data derived from screening evaluations of the first 1,174 subjects presenting for participation were compared between the Spanish-speaking site (N=275) and the primary English-speaking site (N=899). Reasons for ineligibility (N=888) for the PReDICT study were tallied for each site. Results Compared to English-speakers, Spanish-speakers had a lower level of education and were more likely to be female, uninsured, and have uncontrolled medical conditions. Clinically, Spanish-speakers demonstrated greater depression severity, with higher mean symptom severity scores, and a greater number of previous suicide attempts. Among the subjects who were not randomized into the PReDICT study, Spanish-speaking subjects were more likely to have an uncontrolled medical condition or refuse participation, whereas English-speaking subjects were more likely to have bipolar disorder or a non-MDD depressive disorder. Conclusion Recruitment of Hispanic subjects with MDD is feasible and may enhance efforts at signal detection, given the higher severity of depression among Spanish-speaking participants presenting for clinical trials. Specific approaches for the recruitment and retention of Spanish-speaking participants are required. PMID:23959771

Enhancing Hispanic participation in mental health clinical research: development of a Spanish-speaking depression research site.

PubMed

Aponte-Rivera, Vivianne; Dunlop, Boadie W; Ramirez, Cynthia; Kelley, Mary E; Schneider, Rebecca; Blastos, Beatriz; Larson, Jacqueline; Mercado, Flavia; Mayberg, Helen; Craighead, W Edward

2014-03-01

Hispanics, particularly those with limited English proficiency, are underrepresented in psychiatric clinical research studies. We developed a bilingual and bicultural research clinic dedicated to the recruitment and treatment of Spanish-speaking subjects in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study, a large clinical trial of treatment-naïve subjects with major depressive disorder (MDD). Demographic and clinical data derived from screening evaluations of the first 1,174 subjects presenting for participation were compared between the Spanish-speaking site (N = 275) and the primary English-speaking site (N = 899). Reasons for ineligibility (N = 888) for the PReDICT study were tallied for each site. Compared to English speakers, Spanish speakers had a lower level of education and were more likely to be female, uninsured, and have uncontrolled medical conditions. Clinically, Spanish speakers demonstrated greater depression severity, with higher mean symptom severity scores, and a greater number of previous suicide attempts. Among the subjects who were not randomized into the PReDICT study, Spanish-speaking subjects were more likely to have an uncontrolled medical condition or refuse participation, whereas English-speaking subjects were more likely to have bipolar disorder or a non-MDD depressive disorder. Recruitment of Hispanic subjects with MDD is feasible and may enhance efforts at signal detection, given the higher severity of depression among Spanish-speaking participants presenting for clinical trials. Specific approaches for the recruitment and retention of Spanish-speaking participants are required. © 2013 Wiley Periodicals, Inc.

A pilot study to evaluate the effects of floatation spa treatment on patients with osteoarthritis.

PubMed

Hill, S; Eckett, M J; Paterson, C; Harkness, E F

1999-12-01

To conduct a preliminary investigation of the effects on floatation spa therapy on quality of life in patients with osteoarthritis to see if controlled trials are warranted. Uncontrolled clinical trial. Private floatation spa therapy centre. Fourteen patients with chronic osteoarthritis of the weight-bearing joints, of whom four dropped out. Six weekly sessions of floatation spa therapy. SF36, AIMS2 and MYMOP quality-of-life questionnaires. All patients improved. Differences between baseline and discharge scores showed statistically significant improvement for MYMOP, but not AIMS2 or SF-36. Controlled trials of floatation spa therapy for patients with osteoarthritis are warranted.

Abdominal and General Adiposity and Level of Asthma Control in Adults with Uncontrolled Asthma

PubMed Central

Lv, Nan; Xiao, Lan; Camargo, Carlos A.; Wilson, Sandra R.; Buist, A. Sonia; Strub, Peg; Nadeau, Kari C.

2014-01-01

Rationale: Abdominal adiposity may be an important risk factor for uncontrolled asthma in adults, controlling for general obesity. Whether the relationship, if present, is explained by other factors (e.g., asthma onset age, sex, and/or coexisting conditions) is unclear. Objectives: To examine whether clinically applicable anthropometric measures of abdominal adiposity—waist circumference and waist-to-height ratio (WHtR)—are related to poorer asthma control in adults with uncontrolled asthma controlling for body mass index (BMI), and whether the relationship (if present) is explained by gastroesophageal reflux disorder (GERD), sleep quality, or obstructive sleep apnea (OSA) or differs by age of asthma onset or sex. Methods: Patients aged 18 to 70 years with uncontrolled asthma (n = 90) participated in a 6-month randomized clinical trial. Measurements and Main Results: Baseline measures included sociodemographics, standardized anthropometrics, Asthma Control Test (ACT), GERD Symptom Assessment Scale, Pittsburgh Sleep Quality Index, and Berlin Questionnaire for Sleep Apnea. Participants (mean [SD] age, 52 [12] yr) were racially and ethnically diverse, 67% women, and 69% overweight or obese, and 71% reported their age of asthma onset was 12 years or older. Participants had uncontrolled asthma (mean [SD] ACT score, 14.9 [3.7]) and low GERD symptoms score (0.6 [0.4]); 67% reported poor sleep quality, and 42% had a high OSA risk. General linear regression results showed that worse ACT scores were significantly associated with every SD increase in waist circumference (β= −1.03; 95% confidence interval [CI], −1.96 to −0.16; P = 0.02) and waist-to-height ratio (β= −1.16; 95% CI, −2.00 to −0.33; P = 0.008), controlling for sociodemographics. Waist-to-height ratio remained correlated with ACT (β= −2.30; 95% CI, −4.16 to −0.45; P = 0.02) after further adjusting for BMI. The BMI-controlled relationship between WHtR and ACT did not differ by age of asthma onset or sex (P > 0.05 for interactions) and persisted after additional adjustment for GERD, sleep quality, or OSA scores. Poor sleep quality was associated with worse ACT scores (β= −0.87; 95% CI, −1.71 to −0.03; P = 0.045) controlling for waist-to-height ratio, BMI, and sociodemographics. Conclusions: Abdominal adiposity by waist-to-height ratio and poor sleep quality correlated with poorer asthma control in adults with uncontrolled asthma, after controlling for BMI and sociodemographics. These results warrant replication in larger studies of diverse populations. Clinical trial registered with www.clinicaltrials.gov (NCT 01725945). PMID:25343191

Immediate effect of couple relationship education on low-satisfaction couples: a randomized clinical trial plus an uncontrolled trial replication.

PubMed

Kim Halford, W; Pepping, Christopher A; Hilpert, Peter; Bodenmann, Guy; Wilson, Keithia L; Busby, Dean; Larson, Jeffry; Holman, Thomas

2015-05-01

Couple relationship education (RE) usually is conceived of as relationship enhancement for currently satisfied couples, with a goal of helping couples sustain satisfaction. However, RE also might be useful as a brief, accessible intervention for couples with low satisfaction. Two studies were conducted that tested whether couples with low relationship satisfaction show meaningful gains after RE. Study 1 was a three-condition randomized controlled trial in which 182 couples were randomly assigned to RELATE with Couple CARE (RCC), a flexible delivery education program for couples, or one of two control conditions. Couples with initially low satisfaction receiving RCC showed a moderate increase in relationship satisfaction (d=0.50) relative to the control. In contrast, couples initially high in satisfaction showed little change and there was no difference between RCC and the control conditions. Study 2 was an uncontrolled trial of the Couple Coping Enhancement Training (CCET) administered to 119 couples. Couples receiving CCET that had initially low satisfaction showed a moderate increase in satisfaction (g=.44), whereas initially highly satisfied couples showed no change. Brief relationship education can assist somewhat distressed couples to enhance satisfaction, and has potential as a cost-effective way of enhancing the reach of couple interventions. Copyright © 2015. Published by Elsevier Ltd.

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

2016-09-20

Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

Telemonitoring-based service redesign for the management of uncontrolled hypertension (HITS): cost and cost-effectiveness analysis of a randomised controlled trial

PubMed Central

Stoddart, Andrew; Hanley, Janet; Wild, Sarah; Pagliari, Claudia; Paterson, Mary; Lewis, Steff; Sheikh, Aziz; Krishan, Ashma; Padfield, Paul; McKinstry, Brian

2013-01-01

Objectives To compare the costs and cost-effectiveness of managing patients with uncontrolled blood pressure (BP) using telemonitoring versus usual care from the perspective of the National Health Service (NHS). Design Within trial post hoc economic evaluation of data from a pragmatic randomised controlled trial using an intention-to-treat approach. Setting 20 socioeconomically diverse general practices in Lothian, Scotland. Participants 401 primary care patients aged 29–95 with uncontrolled daytime ambulatory blood pressure (ABP) (≥135/85, but <210/135 mm Hg). Intervention Participants were centrally randomised to 6 months of a telemonitoring service comprising of self-monitoring of BP transmitted to a secure website for review by the attending nurse/doctor and patient, with optional automated patient decision-support by text/email (n=200) or usual care (n-201). Randomisation was undertaken with minimisation for age, sex, family practice, use of three or more hypertension drugs and self-monitoring history. Main outcome measures Mean difference in total NHS costs between trial arms and blinded assessment of mean cost per 1 mm Hg systolic BP point reduced. Results Home telemonitoring of BP costs significantly more than usual care (mean difference per patient £115.32 (95% CI £83.49 to £146.63; p<0.001)). Increased costs were due to telemonitoring service costs, patient training and additional general practitioner and nurse consultations. The mean cost of systolic BP reduction was £25.56/mm Hg (95% CI £16.06 to £46.89) per patient. Conclusions Over the 6-month trial period, supported telemonitoring was more effective at reducing BP than usual care but also more expensive. If clinical gains are maintained, these additional costs would be very likely to be compensated for by reductions in the cost of future cardiovascular events. Longer-term modelling of costs and outcomes is required to fully examine the cost-effectiveness implications. Trial registration International Standard Randomised Controlled Trials, number ISRCTN72614272. PMID:23793650

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Neely, Jessica A; Kalipatnapu, Sasank

2014-11-14

Haemophilia is a genetic disorder which is characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 06 November 2014. Eligible trials included randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the effects of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Complementary and alternative medicine for the treatment of type 2 diabetes.

PubMed

Nahas, Richard; Moher, Matthew

2009-06-01

To review clinical evidence supporting complementary and alternative medicine interventions for improving glycemic control in type 2 diabetes mellitus. MEDLINE and EMBASE were searched from January 1966 to August 2008 using the term type 2 diabetes in combination with each of the following terms for specific therapies selected by the authors: cinnamon, fenugreek, gymnema, green tea, fibre, momordica, chromium, and vanadium. Only human clinical trials were selected for review. Chromium reduced glycosylated hemoglobin (HbA(1c)) and fasting blood glucose (FBG) levels in a large meta-analysis. Gymnema sylvestre reduced HbA(1c) levels in 2 small open-label trials. Cinnamon improved FBG but its effects on HbA(1c) are unknown. Bitter melon had no effect in 2 small trials. Fibre had no consistent effect on HbA(1c) or FBG in 12 small trials. Green tea reduced FBG levels in 1 of 3 small trials. Fenugreek reduced FBG in 1 of 3 small trials. Vanadium reduced FBG in small, uncontrolled trials. There were no trials evaluating microvascular or macrovascular complications or other clinical end points. Chromium, and possibly gymnema, appears to improve glycemic control. Fibre, green tea, and fenugreek have other benefits but there is little evidence that they substantially improve glycemic control. Further research on bitter melon and cinnamon is warranted. There is no complementary and alternative medicine research addressing microvascular or macrovascular clinical outcomes.

Topical Botanical Agents for the Treatment of Psoriasis: A Systematic Review.

PubMed

Farahnik, Benjamin; Sharma, Divya; Alban, Joseph; Sivamani, Raja K

2017-08-01

Patients with psoriasis often enquire about the use of numerous botanical therapeutics. It is important for dermatologists to be aware of the current evidence regarding these agents. We conducted a systematic literature search using the PubMed, MEDLINE, and EMBASE databases for controlled and uncontrolled clinical trials that assessed the use of topical botanical therapeutics for psoriasis. The search included the following keywords: 'psoriasis' and 'plant' or 'herbal' or 'botanical'. We also reviewed citations within articles to identify additional relevant sources. We then further refined the results by route of administration and the topical botanical agents are reviewed herein. A total of 27 controlled and uncontrolled clinical trials addressing the use of topical botanical agents for psoriasis were assessed in this review. We found that the most highly studied and most efficacious topical botanical therapeutics were Mahonia aquifolium, indigo naturalis, aloe vera, and, to a lesser degree, capsaicin. The most commonly reported adverse effects were local skin irritation, erythema, pruritus, burning, and pain. However, the overall evidence for these therapeutics remains limited in quantity and quality. The literature addresses a large number of studies in regard to botanicals for the treatment of psoriasis. While most agents appear to be safe, further research is necessary before topical botanical agents can be consistently recommended to patients.

Use of fibrin sealants in cardiovascular surgery: a systematic review.

PubMed

Rousou, John A

2013-05-01

Fibrin sealants are used for hemostasis and tissue adherence. This systematic review summarizes published clinical data for fibrin sealant use in cardiovascular surgery. A literature search for the following terms was conducted using PubMed and EMBASE: (TISSEEL or Tissucol or Beriplast P or Evicel or Quixil or Crosseal or Reliseal or Fibringluraas or Bolheal or Tachosil or Vivostat or Vitagel or Artiss or "fibrin glue" or "fibrin sealant" or "fibrin tissue adhesive") and (cardiac or cardiovascular or vascular or heart or coronary or surgery). Case reports and series were excluded; although reports of controlled trials were preferred, uncontrolled trial data were also considered. Clinical trials and chart review analyses of fibrin sealants were identified and summarized. Although clinical trial data were available for other agents, the majority of published studies examined TISSEEL. Overall, TISSEEL and other fibrin sealants showed improvements over standard of care or control groups for a variety of predefined endpoints. Safety findings are also summarized. Data from these studies showed that fibrin sealants were well tolerated and provided effective hemostasis in a range of cardiac and aortic surgeries. © 2013 Wiley Periodicals, Inc.

A 12-year prognosis of adult-onset asthma: Seinäjoki Adult Asthma Study.

PubMed

Tuomisto, Leena E; Ilmarinen, Pinja; Niemelä, Onni; Haanpää, Jussi; Kankaanranta, Terhi; Kankaanranta, Hannu

2016-08-01

Long-term prognosis of adult-onset asthma is poorly known. To evaluate 12-year prognosis of adult-onset asthma and the factors associated with disease prognosis. Seinäjoki Adult-onset Asthma Study (SAAS) is a 12-year real-life single-center follow-up study of new-onset asthma diagnosed at adult age and treated in primary and specialized care. Remission was defined by no symptoms and no asthma medication use for 6 months. Asthma control was evaluated according to Global Initiative for Asthma 2010. Factors associated with current asthma control were analyzed by multinomial multivariate logistic regression. A total of 203 patients (79% of the baseline population) were followed for 12 years. Remission occurred in 6 (3%) patients. In 34% asthma was controlled, in 36% it was partially controlled and in 30% uncontrolled. Uncontrolled asthma was predicted by elevated body-mass index at baseline, smoking (pack-years) and current allergic or persistent rhinitis. Elevated blood eosinophils and good lung function (FEV1) at baseline protected from uncontrolled asthma. In contrast, gender, age at the onset or baseline symptoms (Airways Questionnaire 20) were not significant predictors of uncontrolled disease. During a 12-year follow-up, remission of adult-onset asthma was rare occurring in only 3% of patients. The majority of patients (66%) presented either with uncontrolled or partially controlled asthma. This study is registered at ClinicalTrials.gov with identifier number NCT02733016. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Reiss, Ulrike M

2016-12-20

Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016. Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Complementary and alternative medicine for the treatment of type 2 diabetes

PubMed Central

Nahas, Richard; Moher, Matthew

2009-01-01

ABSTRACT OBJECTIVE To review clinical evidence supporting complementary and alternative medicine interventions for improving glycemic control in type 2 diabetes mellitus. QUALITY OF EVIDENCE MEDLINE and EMBASE were searched from January 1966 to August 2008 using the term type 2 diabetes in combination with each of the following terms for specific therapies selected by the authors: cinnamon, fenugreek, gymnema, green tea, fibre, momordica, chromium, and vanadium. Only human clinical trials were selected for review. MAIN MESSAGE Chromium reduced glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels in a large meta-analysis. Gymnema sylvestre reduced HbA1c levels in 2 small open-label trials. Cinnamon improved FBG but its effects on HbA1c are unknown. Bitter melon had no effect in 2 small trials. Fibre had no consistent effect on HbA1c or FBG in 12 small trials. Green tea reduced FBG levels in 1 of 3 small trials. Fenugreek reduced FBG in 1 of 3 small trials. Vanadium reduced FBG in small, uncontrolled trials. There were no trials evaluating microvascular or macrovascular complications or other clinical end points. CONCLUSION Chromium, and possibly gymnema, appears to improve glycemic control. Fibre, green tea, and fenugreek have other benefits but there is little evidence that they substantially improve glycemic control. Further research on bitter melon and cinnamon is warranted. There is no complementary and alternative medicine research addressing microvascular or macrovascular clinical outcomes. PMID:19509199

Can Family-Based Treatment of Anorexia Nervosa Be Manualized?

PubMed Central

Lock, James; Le Grange, Daniel

2001-01-01

The authors report on the development of a manual for treating adolescents with anorexia nervosa modeled on a family-based intervention originating at the Maudsley Hospital in London. The manual provides the first detailed account of a clinical approach shown to be consistently efficacious in randomized clinical trials for this disorder. Manualized family therapy appears to be acceptable to therapists, patients, and families. Preliminary outcomes are comparable to what would be expected in clinically supervised sessions. These results suggest that through the use of this manual a valuable treatment approach can now be tested more broadly in controlled and uncontrolled settings. PMID:11696652

Translation failure and medical reversal: Two sides to the same coin.

PubMed

Prasad, Vinay

2016-01-01

Translation failure occurs when the results of preclinical, observational and/or early phase studies fail to predict the results of well done (i.e. appropriately controlled, adequately powered, and properly conducted) phase III or randomised clinical trials. Some failures occur when promising basic science findings fail to replicate in human studies, while others happen when promising uncontrolled trial data show an exaggerated effect that vanishes in the setting of a randomised trial. Medical reversals occur when the results of preclinical, observational and/or early phase studies fail to predict the results of subsequent randomized clinical trials, but the practice has already gained widespread acceptance. Oncologic examples include bevacizumab and the use of autologous stem cell transplant in metastatic breast cancer. In a well-intentioned effort to reduce the rate of translation failure, oncologists must be careful that changes to regulatory processes and clinical trial design do not actually work to increase the approval of ineffective compounds. By trying to cure translation failure, we should be careful to avoid medical reversal. The rise of surrogate end-points and role of hard-wired bias in oncology trials suggest that we may be currently ignoring the simple fact that translation failure and medical reversal are two sides to the same coin. Published by Elsevier Ltd.

Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis.

PubMed

Sobieraj, Diana M; Baker, William L; Nguyen, Elaine; Weeda, Erin R; Coleman, Craig I; White, C Michael; Lazarus, Stephen C; Blake, Kathryn V; Lang, Jason E

2018-04-10

Long-acting muscarinic antagonists (LAMAs) are a potential adjunct therapy to inhaled corticosteroids in the management of persistent asthma. To conduct a systematic review and meta-analysis of the effects associated with LAMA vs placebo or vs other controllers as an add-on therapy to inhaled corticosteroids and the use of a LAMA as add-on therapy to inhaled corticosteroids and long-acting β-agonists (LABAs; hereafter referred to as triple therapy) vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma. MEDLINE, EMBASE, Cochrane databases, and clinical trial registries (earliest date through November 28, 2017). Two reviewers selected randomized clinical trials or observational studies evaluating a LAMA vs placebo or vs another controller as an add-on therapy to inhaled corticosteroids or triple therapy vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma reporting on an outcome of interest. Meta-analyses using a random-effects model was conducted to calculate risk ratios (RRs), risk differences (RDs), and mean differences (MDs) with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength-of-evidence grading were completed by 2 independent reviewers. Asthma exacerbations. Of 1326 records identified, 15 randomized clinical trials (N = 7122 patients) were included. Most trials assessed adding LAMA vs placebo or LAMA vs LABA to inhaled corticosteroids. Adding LAMA vs placebo to inhaled corticosteroids was associated with a significantly reduced risk of exacerbation requiring systemic corticosteroids (RR, 0.67 [95% CI, 0.48 to 0.92]; RD, -0.02 [95% CI, -0.04 to 0.00]). Compared with adding LABA, adding LAMA to inhaled corticosteroids was not associated with significant improvements in exacerbation risk (RR, 0.87 [95% CI, 0.53 to 1.42]; RD, 0.00 [95% CI, -0.02 to 0.02]), or any other outcomes of interest. Triple therapy was not significantly associated with improved exacerbation risk vs inhaled corticosteroids and LABA (RR, 0.84 [95% CI, 0.57 to 1.22]; RD, -0.01 [95% CI, -0.08 to 0.07]). In this systematic review and meta-analysis, the use of LAMA compared with placebo as add-on therapy to inhaled corticosteroids was associated with a lower risk of asthma exacerbations; however, the association of LAMA with benefit may not be greater than that with LABA. Triple therapy was not associated with a lower risk of exacerbations.

A Complex Multiherbal Regimen Based on Ayurveda Medicine for the Management of Hepatic Cirrhosis Complicated by Ascites: Nonrandomized, Uncontrolled, Single Group, Open-Label Observational Clinical Study.

PubMed

Patel, Manish V; Patel, Kalapi B; Gupta, Shivenarain; Michalsen, Andreas; Stapelfeldt, Elmar; Kessler, Christian S

2015-01-01

Hepatic cirrhosis is one of the leading causes of death worldwide, especially if complicated by ascites. This chronic condition can be related to the classical disease entity jalodara in Traditional Indian Medicine (Ayurveda). The present paper aims to evaluate the general potential of Ayurvedic therapy for overall clinical outcomes in hepatic cirrhosis complicated by ascites (HCcA). In form of a nonrandomized, uncontrolled, single group, open-label observational clinical study, 56 patients fulfilling standardized diagnostic criteria for HCcA were observed during their treatment at the P. D. Patel Ayurveda Hospital, Nadiad, India. Based on Ayurvedic tradition, a standardized treatment protocol was developed and implemented, consisting of oral administration of single and compound herbal preparations combined with purificatory measures as well as dietary and lifestyle regimens. The outcomes were assessed by measuring liver functions through specific clinical features and laboratory parameters and by evaluating the Child-Pugh prognostic grade score. After 6 weeks of treatment and a follow-up period of 18 weeks, the outcomes showed statistically significant and clinically relevant improvements. Further larger and randomized trials on effectiveness, safety, and quality of the Ayurvedic approach in the treatment of HCcA are warranted to support these preliminary findings.

Dynamics of heart rate variability in patients with type 2 diabetes mellitus during spinal anaesthesia: prospective observational study.

PubMed

Lee, Su Hyun; Lee, Dong Hoon; Ha, Dong Hoon; Oh, Young Jun

2015-10-08

Little is known about the changes in autonomic function during spinal anaesthesia in type 2 diabetic patients. The purpose of the study was to assess the influence of spinal anaesthesia on the heart rate variability in type 2 diabetic patients according to the glycated hemoglobin (HbA1c) level. Sixty-six patients who were scheduled for elective orthostatic lower limb surgery were assigned to three groups (n = 22, each) according to HbA1c; controlled diabetes mellitus (HbA1c < 7 %), uncontrolled diabetes mellitus (HbA1c > 7 %) and the control group. The heart rate variability was measured 10 min before (T0), and at10 min (T1), 20 min (T2) and 30 min (T3) after spinal anaesthesia. Before spinal anaesthesia, total, low-and high-frequency power were significantly lower in the uncontrolled diabetec group than in other group (p < 0.05). During spinal anaesthesia, total, low- and high-frequency powers were did not change in the uncontrolled diabetec group while the low-frequency power in the controlled diabetec group was significantly depressed (p < 0.05). The ratio of low-to high-frequency was comparable among the groups, while it was reduced at T1-2 than at T0 in all the groups. The blood pressures were higher in the uncontrolled diabetec group than in the other groups. Spinal anaesthesia had an influence on the cardiac autonomic modulation in controlled diabetec patients, but not in uncontrolled diabetec patients. There were no differences in all haemodynamic variables during an adequate level of spinal anaesthesia in controlled and uncontrolled type 2 DM. ClinicalTrials.gov NCT02137057.

Improving Urban African Americans’ Blood Pressure Control through Multi-level Interventions in the Achieving Blood Pressure Control Together (ACT) Study: A Randomized Clinical Trial

PubMed Central

Ephraim, Patti L.; Hill-Briggs, Felicia; Roter, Debra; Bone, Lee; Wolff, Jennifer; Lewis-Boyer, LaPricia; Levine, David; Aboumatar, Hanan; Cooper, Lisa A; Fitzpatrick, Stephanie; Gudzune, Kimberly; Albert, Michael; Monroe, Dwyan; Simmons, Michelle; Hickman, Debra; Purnell, Leon; Fisher, Annette; Matens, Richard; Noronha, Gary; Fagan, Peter; Ramamurthi, Hema; Ameling, Jessica; Charlston, Jeanne; Sam, Tanyka; Carson, Kathryn A.; Wang, Nae-Yuh; Crews, Deidra; Greer, Raquel; Sneed, Valerie; Flynn, Sarah J.; DePasquale, Nicole; Boulware, L. Ebony

2014-01-01

Background Given their high rates of uncontrolled blood pressure, urban African Americans comprise a particularly vulnerable subgroup of persons with hypertension. Substantial evidence has demonstrated the important role of family and community support in improving patients’ management of a variety of chronic illnesses. However, studies of multilevel interventions designed specifically to improve urban African American patients’ blood pressure self-management by simultaneously leveraging patient, family, and community strengths are lacking. Methods/Design We report the protocol of the Achieving Blood Pressure Control Together (ACT) study, a randomized controlled trial designed to study the effectiveness of interventions that engage patient, family, and community-level resources to facilitate urban African American hypertensive patients’ improved hypertension self-management and subsequent hypertension control. African American patients with uncontrolled hypertension receiving health care in an urban primary care clinic will be randomly assigned to receive 1) an educational intervention led by a community health worker alone, 2) the community health worker intervention plus a patient and family communication activation intervention, or 3) the community health worker intervention plus a problem-solving intervention. All participants enrolled in the study will receive and be trained to use a digital home blood pressure machine. The primary outcome of the randomized controlled trial will be patients’ blood pressure control at 12 months. Discussion Results from the ACT study will provide needed evidence on the effectiveness of comprehensive multi-level interventions to improve urban African American patients’ hypertension control. PMID:24956323

Improving urban African Americans' blood pressure control through multi-level interventions in the Achieving Blood Pressure Control Together (ACT) study: a randomized clinical trial.

PubMed

Ephraim, Patti L; Hill-Briggs, Felicia; Roter, Debra L; Bone, Lee R; Wolff, Jennifer L; Lewis-Boyer, LaPricia; Levine, David M; Aboumatar, Hanan J; Cooper, Lisa A; Fitzpatrick, Stephanie J; Gudzune, Kimberly A; Albert, Michael C; Monroe, Dwyan; Simmons, Michelle; Hickman, Debra; Purnell, Leon; Fisher, Annette; Matens, Richard; Noronha, Gary J; Fagan, Peter J; Ramamurthi, Hema C; Ameling, Jessica M; Charlston, Jeanne; Sam, Tanyka S; Carson, Kathryn A; Wang, Nae-Yuh; Crews, Deidra C; Greer, Raquel C; Sneed, Valerie; Flynn, Sarah J; DePasquale, Nicole; Boulware, L Ebony

2014-07-01

Given their high rates of uncontrolled blood pressure, urban African Americans comprise a particularly vulnerable subgroup of persons with hypertension. Substantial evidence has demonstrated the important role of family and community support in improving patients' management of a variety of chronic illnesses. However, studies of multi-level interventions designed specifically to improve urban African American patients' blood pressure self-management by simultaneously leveraging patient, family, and community strengths are lacking. We report the protocol of the Achieving Blood Pressure Control Together (ACT) study, a randomized controlled trial designed to study the effectiveness of interventions that engage patient, family, and community-level resources to facilitate urban African American hypertensive patients' improved hypertension self-management and subsequent hypertension control. African American patients with uncontrolled hypertension receiving health care in an urban primary care clinic will be randomly assigned to receive 1) an educational intervention led by a community health worker alone, 2) the community health worker intervention plus a patient and family communication activation intervention, or 3) the community health worker intervention plus a problem-solving intervention. All participants enrolled in the study will receive and be trained to use a digital home blood pressure machine. The primary outcome of the randomized controlled trial will be patients' blood pressure control at 12months. Results from the ACT study will provide needed evidence on the effectiveness of comprehensive multi-level interventions to improve urban African American patients' hypertension control. Copyright © 2014 Elsevier Inc. All rights reserved.

A potential new treatment for rheumatoid arthritis: thunder god vine.

PubMed

Lipsky, P E; Tao, X L

1997-04-01

Various extracts of the vinelike plant Tripterygium wilfordii Hook f have been widely used in China to treat patients with a number of autoimmune diseases. Although most of the clinical experience has derived from uncontrolled trials, one placebo-controlled double-blind trial has clearly demonstrated efficacy in rheumatoid arthritis. Studies in laboratory animals have indicated that extracts of Tripterygium wilfordii Hook f suppress both immune and inflammatory responses and also effectively treat a number of models of autoimmune disease. More detailed in vitro analysis has indicated that components of Tripterygium wilfordii Hook f suppress immune responses by inhibiting transcription of cytokine genes, including interleukin-2 and gamma interferon. The current status of knowledge of the potential clinical benefit of this herbal remedy and possible mechanisms accounting for its utility are considered in this review.

Physiotherapy for adult patients with critical illness: recommendations of the European Respiratory Society and European Society of Intensive Care Medicine Task Force on Physiotherapy for Critically Ill Patients.

PubMed

Gosselink, R; Bott, J; Johnson, M; Dean, E; Nava, S; Norrenberg, M; Schönhofer, B; Stiller, K; van de Leur, H; Vincent, J L

2008-07-01

The Task Force reviewed and discussed the available literature on the effectiveness of physiotherapy for acute and chronic critically ill adult patients. Evidence from randomized controlled trials or meta-analyses was limited and most of the recommendations were level C (evidence from uncontrolled or nonrandomized trials, or from observational studies) and D (expert opinion). However, the following evidence-based targets for physiotherapy were identified: deconditioning, impaired airway clearance, atelectasis, intubation avoidance, and weaning failure. Discrepancies and lack of data on the efficacy of physiotherapy in clinical trials support the need to identify guidelines for physiotherapy assessments, in particular to identify patient characteristics that enable treatments to be prescribed and modified on an individual basis. There is a need to standardize pathways for clinical decision-making and education, to define the professional profile of physiotherapists, and increase the awareness of the benefits of prevention and treatment of immobility and deconditioning for critically ill adult patients.

A systematic review of reboxetine for treating patients with attention deficit hyperactivity disorder.

PubMed

Ghanizadeh, Ahmad

2015-05-01

No published systematic review has ever assessed the efficacy and safety of reboxetine for treating of patients with attention deficit hyperactivity disorder (ADHD). This systematic review aimed to review the available evidence regarding the efficacy of reboxetine for treating ADHD. The databases of Pubmed/Medline, Google scholar, SCOPUS and Web of Science were searched using the Keywords: "reboxetine", "ADHD" and "attention deficit hyperactivity disorder". The reference lists of the included studies were screened to find any possible other relevant articles. All the non-controlled and controlled clinical trials were included. The current evidence mainly consists of un-controlled studies, such as case series. Only three of 33 studies were controlled clinical trials. They are from single sites and included a sub-sample of patients with ADHD. Non-controlled studies and controlled trials support the promising effect of reboxetine for treating ADHD in a sub-sample of patients that are without co-morbid psychiatric disorder and mental retardation. Reboxetine is tolerated well. However, more controlled trials are needed to reach any firm conclusion.

B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design.

PubMed

Reddy, Venkat; Jayne, David; Close, David; Isenberg, David

2013-01-01

B cells are believed to be central to the disease process in systemic lupus erythematosus (SLE), making them a target for new therapeutic intervention. In recent years there have been many publications regarding the experience in SLE of B-cell depletion utilising rituximab, an anti-CD20 mAb that temporarily depletes B cells,reporting promising results in uncontrolled open studies and in routine clinical use. However, the two large randomised controlled trials in extra-renal lupus (EXPLORER study) and lupus nephritis (LUNAR study) failed to achieve their primary endpoints. Based on the clinical experience with rituximab this failure was somewhat unexpected and raised a number of questions and concerns, not only into the true level of benefit of B-cell depletion in a broad population but also how to test the true level of effectiveness of an investigational agent as we seek to improve the design of therapeutic trials in SLE. A better understanding of what went wrong in these trials is essential to elucidate the underlying reasons for the disparate observations noted in open studies and controlled trials. In this review, we focus on various factors that may affect the ability to accurately and confidently establish the level of treatment effect of the investigational agent, in this case rituximab, in the tw studies and explore hurdles faced in the randomised controlled trials investigating the efficacy of ocrelizumab, the humanised anti-CD20 mAb, in SLE. Further, based on the lessons learned from the clinical trials, we make suggestions that could be implemented in future clinical trial design to overcome the hurdles faced.

[Position paper on the results of Symplicity HTN-3 trial. Grupo de estudio de la hipertensión arterial resistente].

PubMed

Azpiri-López, José Ramón; Assad-Morell, José Luis; Ponce de León-Martínez, Enrique; Monreal-Puente, Rogelio; Dávila-Bortoni, Adrián; Vázquez-Díaz, Luis Alberto; Treviño-Frutos, Ramón Javier; Barrera-Oranday, Félix; Del Angel-Soto, Juan Gustavo; Martínez, José Guadalupe; Arellano-Torres, Marcelo

2015-01-01

Renal artery denervation has shown to be an effective treatment for resistant hypertension. Symplicity HTN 1 and 2 trials showed in small and uncontrolled groups, significant systolic blood pressure reductions down to 30 mm Hg. Symplicity HTN-3, a double blind, randomized, placebo controlled clinical trial shaded this initial enthusiasm. Surprisingly, their results showed that renal denervation has a similar effect to placebo. Pre-specified subgroup analysis showed that non-black race individuals, younger than 65 years and with normal renal function, had a statistically significant systolic blood pressure decrease. This manuscript critically appraises the Symplicity HTN-3 trial, proposing possible explanations for the results. Also declares our group position and future actions regarding renal denervation. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

PubMed

Fureman, Brandy E; Friedman, Daniel; Baulac, Michel; Glauser, Tracy; Moreno, Jonathan; Dixon-Salazar, Tracy; Bagiella, Emilia; Connor, Jason; Ferry, Jim; Farrell, Kathleen; Fountain, Nathan B; French, Jacqueline A

2017-10-03

The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here. © 2017 American Academy of Neurology.

Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

PubMed

Hosoya, Tatsuo; Kuriyama, Satoru; Ohno, Iwao; Kawamura, Tetsuya; Ogura, Makoto; Ikeda, Masato; Ishikawa, Masahiro; Hayashi, Fumihiro; Kanai, Tatsuya; Tomonari, Haruo; Soejima, Michimasa; Akaba, Kiyoaki; Tokudome, Goro; Endo, S; Fukui, A; Gomi, H; Hamaguchi, A; Hanaoka, K; Hara, Y; Hara, Y; Hasegawa, T; Hayakawa, H; Hikida, M; Hirano, K; Horiguchi, M; Hosoya, M; Ichida, K; Imai, T; Ishii, T; Ishikawa, H; Kameda, C; Kasai, T; Kobayashi, A; Kobayashi, H; Kurashige, M; Kusama, Y; Maezawa, H; Maezawa, Y; Maruyama, Y; Matsuda, H; Matsuo, N; Matsuo, T; Miura, Y; Miyajima, M; Miyakawa, M; Miyazaki, Y; Mizuguchi, M; Nakao, M; Nokano, H; Ohkido, I; Ohtsuka, Y; Okada, K; Okamoto, H; Okonogi, H; Saikawa, H; Saito, H; Sekiguchi, C; Suetsugu, Y; Sugano, N; Suzuki, T; Suzuki, T; Takahashi, H; Takahashi, Y; Takamizawa, S; Takane, K; Morita, T; Takazoe, K; Tanaka, H; Tanaka, S; Terawaki, H; Toyoshima, R; Tsuboi, N; Udagawa, T; Ueda, H; Ueda, Y; Uetake, M; Unemura, S; Utsunomiya, M; Utsunomiya, Y; Yamada, T; Yamada, Y; Yamaguchi, Y; Yamamoto, H; Yokoo, T; Yokoyama, K; Yonezawa, H; Yoshida, H; Yoshida, M; Yoshizawa, T

2012-04-01

Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

[Cannabinoids in multiple sclerosis -- therapeutically reasonable?].

PubMed

Trebst, C; Stangel, M

2005-08-01

For centuries extracts from the Cannabis sativa plant have been used for recreational use and as remedies. Anecdotal reports from patients with multiple sclerosis (MS) experiencing relief of their spasticity and pain after smoking marihuana have prompted discussions about a potential therapeutic application of cannabis preparations in MS. Only recently the first large, multicenter, double-blind, placebo controlled study was conducted evaluating the use of cannabinoids for treatment of spasticity and other symptoms related to MS. Based on this trial and previous uncontrolled observations together with insights from basic research and animal experiments there is reasonable evidence for the therapeutical employment of cannabinoids in the treatment of MS related symptoms. Furthermore, data are arising that cannabinoids have immunomodulatory and neuroprotective properties. However, results from clinical trials do not allow the recommendation for the general use of cannabinoids in MS. This article summarizes the present knowledge of clinical and experimental research regarding the therapeutic potential of cannabinoids for the treatment of MS.

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients.

PubMed

McFarland, Lynne V

2010-05-14

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler's diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Helicobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn's disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea.

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients

PubMed Central

McFarland, Lynne V

2010-01-01

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler’s diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Heliobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn’s disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea. PMID:20458757

Validity and reliability of a new ankle dorsiflexion measurement device.

PubMed

Gatt, Alfred; Chockalingam, Nachiappan

2013-08-01

The assessment of the maximum ankle dorsiflexion angle is an important clinical examination procedure. Evidence shows that the traditional goniometer is highly unreliable, and various designs of goniometers to measure the maximum ankle dorsiflexion angle rely on the application of a known force to obtain reliable results. Hence, an innovative ankle dorsiflexion measurement device was designed to make this measurement more reliable by holding the foot in a selected posture without the application of a known moment. To report on the comprehensive validity and reliability testing carried out on the new device. Following validity testing, four different trials to test reliability of the ankle dorsiflexion measurement device were performed. These trials included inter-rater and intra-rater testings with a controlled moment, intra-rater reliability testing with knees flexed and extended without a controlled moment, intra-rater testing with a patient population, and inter-rater reliability testing between four raters of varying experience without controlling moment. All raters were blinded. A series of trials to test intra-rater and inter-rater reliabilities. Intra-rater reliability intraclass correlation coefficient was 0.98 and inter-rater reliability intraclass correlation coefficient (2,1) was 0.953 with a controlled moment. With uncontrolled moment, very high reliability for intra-tester was also achieved (intraclass correlation coefficient = 0.94 with knees extended and intraclass correlation coefficient = 0.95 with knees flexed). For the trial investigating test-retest reliability with actual patients, intraclass correlation coefficient of 0.99 was obtained. In the trial investigating four different raters with uncontrolled moment, intraclass correlation coefficient of 0.91 was achieved. The new ankle dorsiflexion measurement device is a valid and reliable device for measuring ankle dorsiflexion in both healthy subjects and patients, with both controlled and uncontrolled moments, even by multiple raters of varying experience when the foot is dorsiflexed to its end of range of motion. An ankle dorsiflexion measuring device has been designed to increase the reliability of ankle dorsiflexion measurement and replace the traditional goniometer. While the majority of similar devices rely on application of a known moment to perform this measurement, it has been shown that this is not required with the new ankle dorsiflexion measurement device and, rather, foot posture should be taken into consideration as this affects the maximum ankle dorsiflexion angle.

Evidence-based veterinary dermatology: a systematic review of interventions for Malassezia dermatitis in dogs.

PubMed

Negre, Amélie; Bensignor, Emmanuel; Guillot, Jacques

2009-02-01

The aim of this systematic review was to evaluate the efficacy of antifungal treatments for Malassezia dermatitis in dogs and, when possible, to propose recommendation for or against their use. Electronic searches were carried out using PubMed MEDLINE(R), CABDirect and CONSULTANT database. The volumes of Advances in Veterinary Dermatology, the proceedings of ESVD/ECVD and AAVD/ACVD congresses were hand-searched for studies relevant to this review. All articles and book chapters discussing treatment of Malassezia dermatitis were scanned for additional citations. Lastly, a request was sent to the Vetderm Listserv to share recent clinical trials. The analysis evaluated study design, methodology quality, subject enrolment quality, type of interventions and outcome measures. The searches identified 35 articles, and 14 trials that fulfilled the following selection criteria: (i) in vivo clinical trials, (ii) dogs showing clinical lesions of Malassezia dermatitis and (iii) enrolment of at least five dogs. Among these, only eight studies fulfilled the following additional criterion: (iv) prospective in vivo clinical trials reporting clinical and mycological outcome measures. A total number of 14 different treatment protocols included four blinded, randomized and controlled trials (quality of evidence grade A), four controlled studies lacking blinding and/or randomization (grade B), five open uncontrolled trials (grade C) and one descriptive study (grade D). This systematic review allowed us to recommend, with good evidence, the use of only one topical treatment of Malassezia dermatitis (2% miconazole nitrate +2% chlorhexidine, twice a week for 3 weeks) and with fair evidence the use of two systemic treatments with azole derivatives (ketoconazole, 10 mg kg(-1) day(-1) and itraconazole, 5 mg kg(-1) day(-1) for 3 weeks).

Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review

PubMed Central

Rosenblat, Christian; McIntyre, Roger S.; Alves, Gilberto S.; Fountoulakis, Konstantinos N.; Carvalho, André F.

2015-01-01

Major depressive disorder (MDD) is a leading cause of disability worldwide. Current first line therapies target modulation of the monoamine system. A large variety of agents are currently available that effectively alter monoamine levels; however, approximately one third of MDD patients remain treatment refractory after adequate trials of multiple monoamine based therapies. Therefore, patients with treatment-resistant depression (TRD) may require modulation of pathways outside of the classic monoamine system. The purpose of this review was thus to discuss novel targets for TRD, to describe their potential mechanisms of action, the available clinical evidence for these targets, the limitations of available evidence as well as future research directions. Several alternate pathways involved in the patho-etiology of TRD have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the hypothalamic-pituitary-adrenal (HPA) axis, the metabolic and bioenergetics system, neurotrophic pathways, the glutamate system, the opioid system and the cholinergic system. For each of these systems, several targets have been assessed in preclinical and clinical models. Preclinical models strongly implicate these pathways in the patho-etiology of MDD. Clinical trials for TRD have been conducted for several novel targets; however, most of the trials discussed are small and several are uncontrolled. Therefore, further clinical trials are required to assess the true efficacy of these targets for TRD. As well, several promising novel agents have been clinically tested in MDD populations, but have yet to be assessed specifically for TRD. Thus, their applicability to TRD remains unknown. PMID:26467412

The role of ECT in posttraumatic stress disorder: A systematic review.

PubMed

Youssef, Nagy A; McCall, W Vaughn; Andrade, Chittaranjan

2017-02-01

Posttraumatic stress disorder (PTSD) is associated with a high burden of disability and mortality and frequently is treatment resistant. There is little to offer patients who are not responding to standard interventions. Thus, the objective of this report is to systematically review human data on whether electroconvulsive therapy (ECT) is effective in PTSD. We performed a systematic literature review from 1958 through August 2016 for clinical studies and case reports published in English examining the efficacy of ECT in improving PTSD symptoms. The literature search generated 3 retrospective studies, 1 prospective uncontrolled clinical trial, and 5 case reports. It is not clear, given the small sample size and lack of a large randomized trial, whether favorable outcomes were attributed to improvement in depression (as opposed to core PTSD symptoms). Current efficacy data do not separate conclusively the effects of ECT on PTSD symptoms from those on depression. Randomized controlled trials are necessary to examine the use of ECT in medication-refractory PTSD patients with and without comorbid depression. Subsequent studies may address response in PTSD subtypes, and the use of novel techniques, such as memory reactivation, before ECT.

Preclinical and clinical experience in vascular gene therapy: advantages over conservative/standard therapy.

PubMed

Nikol, S; Huehns, T Y

2001-04-01

No systemic pharmacological treatment has been shown to convincingly reduce the incidence of restenosis after angioplasty or increase the formation of collaterals in ischemic tissue in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates or in inducing angiogenesis post-angioplasty and following stent implantation has encouraged the development of new technological treatment approaches. Gene therapy is a novel strategy with the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation, and to induce growth of new vessels or remodeling of pre-existing vessel branches, which may help patients with critical ischemia. Gene therapy strategies have the advantage of minimizing systemic side effects and may have a long-term effect as the encoded protein is released. Most clinical trials investigating gene therapy for vascular disease have been uncontrolled phase I and IIa trials. Gene therapy into vessels with the genes for growth factors has been demonstrated to be feasible and efficient. Local drug delivery devices have been used in combination with gene therapy in several trials to maximize safety and efficiency. Data from experimental animal work indicates that gene therapy may modify intimal hyperplasia after arterial injury, but there are few clinical trials on restenosis in patients. Preliminary clinical results show only limited success in altering restenosis rates. In vitro and experimental in vivo investigations into gene therapy for angiogenesis demonstrate increased formation of collaterals and functional improvement of limb ischemia. There is some evidence of increased collateral formation and clinical improvement in patients with critical limb ischemia. Results of placebo-controlled and double-blind trials of gene therapy for vascular disease are awaited.

Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue?

PubMed

Carrion, Flavio A; Figueroa, Fernando E

2011-05-11

Mesenchymal stem cells (MSCs) are now known to display not only adult stem cell multipotency but also robust anti-inflammatory and regenerative properties. After widespread in vitro and in vivo preclinical testing in several autoimmune disease models, allogenic MSCs have been successfully applied in patients with severe treatment-refractory systemic lupus erythematosus. The impressive results of these uncontrolled phase I and II trials - mostly in patients with non-responding renal disease - point to the need to perform controlled multicentric trials. In addition, they suggest that there is much to be learned from the basic and clinical science of MSCs in order to reap the full potential of these multifaceted progenitor cells in the treatment of autoimmune diseases.

Pirfenidone: an anti-fibrotic and cytoprotective agent as therapy for progressive kidney disease

PubMed Central

Cho, Monique E; Kopp, Jeffrey B

2010-01-01

Importance of the field Many chronic diseases of various etiologies universally lead to fibrosis and organ dysfunction. Despite many advances in medicine in recent years, options to slow the progression of fibrotic diseases have remained limited. The recent availability of pirfenidone, an anti-fibrotic and anti-inflammatory investigational agent, thus offers a new hope for treating progressive fibrotic diseases. Areas covered in this review This review provides concise review of the available data regarding mechanism and pharmacokinetics of pirfenidone and preclinical and clinical data regarding efficacy and safety in fibrotic diseases of the kidney. It also reviews results of clinical trials involving pirfenidone in other fibrotic diseases. What the reader will gain The review will provide in-depth review of pirfenidone with a renal focus. Take home message Because many of the available clinical trials have been small and/or uncontrolled, conclusive evidence regarding efficacy and safety of pirfenidone is lacking, particularly in patients with renal or hepatic dysfunction. Larger studies are needed both to better understand long-term efficacy and safety of this medication in various patient populations. PMID:20050822

Intensive Home Hemodialysis: An Eye at the Past Looking for the Hemodialysis of the Future.

PubMed

Naso, Agostino; Scaparrotta, Giuseppe; Naso, Elena; Calò, Lorenzo A

2015-09-01

Multiple observational studies along with a limited number of randomized clinical trials suggest that intensive hemodialysis (IHD) not only improves outcomes for uremic patients undergoing chronic dialysis but does so with a more favorable cost/benefit ratio compared with conventional hemodialysis. As a result of this, there has been a rapid increase in the interest in home hemodialysis (HHD) as HHD represents the easiest means of implementing IHD. While HHD has generated increased interest given its association with better outcomes/reduced hospitalizations, there are very few randomized controlled trials comparing HHD with other hemodialysis methods. Reported HHD-associated increased survival benefits compared with in-center hemodialysis are from uncontrolled studies, which raise patient selection bias as underlying the differences found. Thus, while HHD draws increasing attention, studies that pay careful attention to the psychosocial, demographic, and clinical factors associated with patients selected to undergo HHD will be needed to ultimately demonstrate its benefits, clarify the clinical applications, and determine the limits of IHD use in dialysis patients. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Physician and patient characteristics associated with clinical inertia in blood pressure control.

PubMed

Harle, Christopher A; Harman, Jeffrey S; Yang, Shuo

2013-11-01

Clinical inertia, the failure to adjust antihypertensive medications during patient visits with uncontrolled hypertension, is thought to be a common problem. This retrospective study used 5 years of electronic medical records from a multispecialty group practice to examine the association between physician and patient characteristics and clinical inertia. Hierarchical linear models (HLMs) were used to examine (1) differences in physician and patient characteristics among patients with and without clinical inertia, and (2) the association between clinical inertia and future uncontrolled hypertension. Overall, 66% of patients experienced clinical inertia. Clinical inertia was associated with one physician characteristic, patient volume (odds ratio [OR]=0.998). However, clinical inertia was associated with multiple patient characteristics, including patient age (OR=1.021), commercial insurance (OR=0.804), and obesity (OR=1.805). Finally, patients with clinical inertia had 2.9 times the odds of uncontrolled hypertension at their final visit in the study period. These findings may aid the design of interventions to reduce clinical inertia. ©2013 Wiley Periodicals, Inc.

Engaging stakeholders to design a comparative effectiveness trial in children with uncontrolled asthma.

PubMed

Erwin, Kim; Martin, Molly A; Flippin, Tara; Norell, Sarah; Shadlyn, Ariana; Yang, Jie; Falco, Paula; Rivera, Jaime; Ignoffo, Stacy; Kumar, Rajesh; Margellos-Anast, Helen; McDermott, Michael; McMahon, Kate; Mosnaim, Giselle; Nyenhuis, Sharmilee M; Press, Valerie G; Ramsay, Jessica E; Soyemi, Kenneth; Thompson, Trevonne M; Krishnan, Jerry A

2016-01-01

To present the methods and outcomes of stakeholder engagement in the development of interventions for children presenting to the emergency department (ED) for uncontrolled asthma. We engaged stakeholders (caregivers, physicians, nurses, administrators) from six EDs in a three-phase process to: define design requirements; prototype and refine; and evaluate. Interviews among 28 stakeholders yielded themes regarding in-home asthma management practices and ED discharge experiences. Quantitative and qualitative evaluation showed strong preference for the new discharge tool over current tools. Engaging end-users in contextual inquiry resulted in CAPE (CHICAGO Action Plan after ED discharge), a new stakeholder-balanced discharge tool, which is being tested in a multicenter comparative effectiveness trial.

Nurse-led disease management for hypertension control in a diverse urban community: a randomized trial.

PubMed

Hebert, Paul L; Sisk, Jane E; Tuzzio, Leah; Casabianca, Jodi M; Pogue, Velvie A; Wang, Jason J; Chen, Yingchun; Cowles, Christine; McLaughlin, Mary Ann

2012-06-01

Treated but uncontrolled hypertension is highly prevalent in African American and Hispanic communities. To test the effectiveness on blood pressure of home blood pressure monitors alone or in combination with follow-up by a nurse manager. Randomized controlled effectiveness trial. Four hundred and sixteen African American or Hispanic patients with a history of uncontrolled hypertension. Patients with blood pressure ≥150/95, or ≥140/85 for patients with diabetes or renal disease, at enrollment were recruited from one community clinic and four hospital outpatient clinics in East and Central Harlem, New York City. Patients were randomized to receive usual care or a home blood pressure monitor plus one in-person counseling session and 9 months of telephone follow-up with a registered nurse. During the trial, the home monitor alone arm was added. Change in systolic and diastolic blood pressure at 9 and 18 months. Changes from baseline to 9 months in systolic blood pressure relative to usual care was -7.0 mm Hg (Confidence Interval [CI], -13.4 to -0.6) in the nurse management plus home blood pressure monitor arm, and +1.1 mm Hg (95% CI, -5.5 to 7.8) in the home blood pressure monitor only arm. No statistically significant differences in systolic blood pressure were observed among treatment arms at 18 months. No statistically significant improvements in diastolic blood pressure were found across treatment arms at 9 or 18 months. Changes in prescribing practices did not explain the decrease in blood pressure in the nurse management arm. A nurse management intervention combining an in-person visit, periodic phone calls, and home blood pressure monitoring over 9 months was associated with a statistically significant reduction in systolic, but not diastolic, blood pressure compared to usual care in a high risk population. Home blood pressure monitoring alone was no more effective than usual care.

[Antihypertensive Efficacy of Fixed Combination Azilsartan Medoxomil / Chlorthalidone in Patients With Uncontrolled Arterial Hypertension].

PubMed

Kobalava, Z D; Villevalde, S V; Kulakov, V V

2017-11-01

To study effects of a fixed azilsartan medoxomil/chlorthalidone combination (Edarbi Clo) on clinical, ambulatory and central blood pressure (BP) in patients with uncontrolled arterial hypertension (AH)). Patients (n=25) with uncontrolled AH were given fixed azilsartan medoxomil/chlorthalidone combination (40 / 12.5 mg / day) for 4 weeks. After 4 weeks, in patients who did not achieve target BP levels the dose was increased up to 40 / 25 mg / day. Duration of the study was 12 weeks. After 12 weeks of treatment 88 % of patients achieved target clinical BP (.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2015-12-03

Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection. To determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions. We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data. We found no relevant studies. We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.

Uncontrolled Hypertension and Its Determinants in Patients with Concomitant Type 2 Diabetes Mellitus (T2DM) in Rural South Africa.

PubMed

Adeniyi, Oladele Vincent; Yogeswaran, Parimalaranie; Longo-Mbenza, Benjamin; Ter Goon, Daniel

2016-01-01

Paucity of data on the prevalence, treatment and control of hypertension in individuals living with type 2 diabetes mellitus (T2DM) in the rural communities of South Africa may undermine efforts to reduce the morbidity and mortality associated with cardiovascular diseases. This study examines the socio-demographic and clinical determinants of uncontrolled hypertension among individuals living with T2DM in the rural communities of Mthatha, South Africa. This cross-sectional study involved a serially selected sample of 265 individuals living with T2DM and hypertension at Mthatha General Hospital, Mthatha. Uncontrolled hypertension was defined as systolic blood pressure greater than or equal to 140 mmHg and diastolic blood pressure greater than or equal to 90mmHg in accordance with the Eight Joint National Committee Report (JNC 8) (2014). We performed univariate and multivariate logistic regression analyses to identify the significant determinants of uncontrolled hypertension. Of the total participants (n = 265), the prevalence of uncontrolled hypertension was 75.5% (n = 200). In univariate analysis of all participants, male gender (p = 0.029), age≥65 years (p = 0.016), unemployed status (p<0.0001), excessive alcohol intake (p = 0.005) and consumption of western-type diet (p<0.0001) were positively associated with uncontrolled hypertension. In multivariate logistic regression (LR method) analysis, unemployed status (p<0.0001), excessive alcohol intake (p = 0.007) and consumption of western-type diet (p<0.0001) were independently and significantly associated with uncontrolled hypertension. There is significant association between increasing number and classes of anti-hypertensive drugs and uncontrolled hypertension (p = 0.05 and 0.02, respectively). Prevalence of uncontrolled hypertension was high in individuals with concomitant hypertension and T2DM in the study population. Male sex, aging, clinic inertia, unemployed status and nutritional transitions are the most important determinants of uncontrolled hypertension in T2DM in Mthatha, South Africa. Treatment to blood pressure targets, though feasible in our setting, would require concerted efforts by addressing these determinants and clinic inertia.

Measurement of asthma control according to global initiative for asthma guidelines: a comparison with the asthma control questionnaire

PubMed Central

2012-01-01

Introduction Asthma Control Questionnaire (ACQ) is a validated tool to measure asthma control. Cut-off points that best discriminate “well-controlled” or “not well-controlled” asthma have been suggested from the analysis of a large randomized clinical trial but they may not be adequate for daily clinical practice. Aims To establish cut-off points of the ACQ that best discriminate the level of control according to Global Initiative for Asthma (GINA) 2006 guidelines in patients with asthma managed at Allergology and Pulmonology Departments as well as Primary Care Centers in Spain. Patients and methods An epidemiological descriptive study, with prospective data collection. Asthma control following GINA-2006 classification and 7-item ACQ was assessed. The study population was split in two parts: 2/3 for finding the cut-off points (development population) and 1/3 for validating the results (validation population). Results A total of 1,363 stable asthmatic patients were included (mean age 38 ± 14 years, 60.3% women; 69.1% non-smokers). Patient classification according to GINA-defined asthma control was: controlled 13.6%, partially controlled 34.2%, and uncontrolled 52.3%. The ACQ cut-off points that better agreed with GINA-defined asthma control categories were calculated using receiver operating curves (ROC). The analysis showed that ACQ < 0.5 was the optimal cut-off point for “controlled asthma” (sensitivity 74.1%, specificity 77.5%) and 1.00 for “uncontrolled asthma” (sensitivity 73%, specificity 88.2%). Kappa index between GINA categories and ACQ was 0.62 (p < 0.001). Conclusion The ACQ cut-off points associated with GINA-defined asthma control in a real-life setting were <0.5 for controlled asthma and ≥1 for uncontrolled asthma. PMID:22726416

Measurement of asthma control according to Global Initiative for Asthma guidelines: a comparison with the Asthma Control Questionnaire.

PubMed

Olaguibel, José María; Quirce, Santiago; Juliá, Berta; Fernández, Cristina; Fortuna, Ana María; Molina, Jesús; Plaza, Vicente

2012-06-22

Asthma Control Questionnaire (ACQ) is a validated tool to measure asthma control. Cut-off points that best discriminate "well-controlled" or "not well-controlled" asthma have been suggested from the analysis of a large randomized clinical trial but they may not be adequate for daily clinical practice. To establish cut-off points of the ACQ that best discriminate the level of control according to Global Initiative for Asthma (GINA) 2006 guidelines in patients with asthma managed at Allergology and Pulmonology Departments as well as Primary Care Centers in Spain. An epidemiological descriptive study, with prospective data collection. Asthma control following GINA-2006 classification and 7-item ACQ was assessed. The study population was split in two parts: 2/3 for finding the cut-off points (development population) and 1/3 for validating the results (validation population). A total of 1,363 stable asthmatic patients were included (mean age 38 ± 14 years, 60.3% women; 69.1% non-smokers). Patient classification according to GINA-defined asthma control was: controlled 13.6%, partially controlled 34.2%, and uncontrolled 52.3%. The ACQ cut-off points that better agreed with GINA-defined asthma control categories were calculated using receiver operating curves (ROC). The analysis showed that ACQ < 0.5 was the optimal cut-off point for "controlled asthma" (sensitivity 74.1%, specificity 77.5%) and 1.00 for "uncontrolled asthma" (sensitivity 73%, specificity 88.2%). Kappa index between GINA categories and ACQ was 0.62 (p < 0.001). The ACQ cut-off points associated with GINA-defined asthma control in a real-life setting were <0.5 for controlled asthma and ≥1 for uncontrolled asthma.

[Prevention of therapeutic inertia in the treatment of arterial hypertension by using a program of home blood pressure monitoring].

PubMed

Márquez Contreras, Emilio; Martín de Pablos, José Luis; Espinosa García, Jacinto; Casado Martínez, José Joaquín; Sanchez López, Eugenio; Escribano, José

2012-02-01

To evaluate the efficacy of a program of home blood pressure monitoring (HBPM) on therapeutic Inertia (TI) in mild-to-moderate hypertension (AHT). Controlled, randomised clinical trial. Forty six clinics in 35 primary care centres. Spain. A total of 232 patients with uncontrolled hypertension were included. Two groups with 116 patients were formed: 1) Control group (CG): standard health intervention; 2) Intervention group (IG): patients who were included in the HBPM program. TI was calculated by the ratio: Number of patients whose pharmacological treatment was not changed in each visit/Number of patients with an average BP 140mmHg and/or 90mmHg in the general population or 130 and/or 90 mmHg in diabetics. The mean BPs and the percentage of controlled patients were calculated. The mean number of people that required an intervention in order to avoid TI was calculated (NI). A total of 209 patients completed the study, with TI in 35.64% (95% CI=29.85%-41.43%) of the sample, and in 71.63% (95% CI=63.9-79.36%) of the uncontrolled hypertensive patients. The TI was 22.42% (95% CI=24.2-37%) in the IG and 50% (95% CI=37.75-62.25) in the CG (p<.05) in visit 2, and 25.23% (95% CI=14.84-35.62) and 46.07% (95% CI=33.85-58.29) in the final visit for IG and CG, respectively (P<.05). The NI was 4.3. TI was very significant among the uncontrolled hypertensive patients. The studied interventions are effective for improving TI. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Estimating outcomes and cost effectiveness using a single-arm clinical trial: ofatumumab for double-refractory chronic lymphocytic leukemia.

PubMed

Hatswell, Anthony J; Thompson, Gwilym J; Maroudas, Penny A; Sofrygin, Oleg; Delea, Thomas E

2017-01-01

Ofatumumab (Arzerra ® , Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9 months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. The objective of the study was to present a method to estimate the cost effectiveness of ofatumumab in the treatment of DR-CLL. As no suitable historical control was available for modelling, the outcomes from non-responders to ofatumumab were used to model the effect of best supportive care (BSC). This was done via a Cox regression to control for differences in baseline characteristics between groups. This analysis was included in a partitioned survival model built in Microsoft ® Excel with utilities and costs taken from published sources, with costs and quality-adjusted life years (QALYs) were discounted at a rate of 3.5% per annum. Using the outcomes seen in non-responders, ofatumumab is expected to add approximately 0.62 life years (1.50 vs. 0.88). Using published utility values this translates to an additional 0.30 QALYs (0.77 vs. 0.47). At the list price, ofatumumab had a cost per QALY of £130,563, and a cost per life year of £63,542. The model was sensitive to changes in assumptions regarding overall survival estimates and utility values. This study demonstrates the potential of using data for non-responders to model outcomes for BSC in cost-effectiveness evaluations based on single-arm trials. Further research is needed on the estimation of comparative effectiveness using uncontrolled clinical studies.

COACH trial: A randomized controlled trial of nurse practitioner/community health worker cardiovascular disease risk reduction in urban community health centers: Rationale and design

PubMed Central

Allen, Jerilyn K; Himmelfarb, Cheryl R Dennison; Szanton, Sarah L; Bone, Lee; Hill, Martha N; Levine, David M

2011-01-01

Background Despite well-publicized guidelines on the appropriate management of cardiovascular disease (CVD) and type 2 diabetes, implementation of risk-reducing practices remains poor. This paper describes the rationale and design of a randomized controlled clinical trial evaluating the effectiveness of a comprehensive program of CVD risk reduction delivered by nurse practitioner (NP)/community health worker (CHW) teams versus enhanced usual care in improving the proportion of patients in urban community health centers who achieve goal levels recommended by national guidelines for lipids, blood pressure, HbA1c and prescription of appropriate medications. Methods The COACH (Community Outreach and Cardiovascular Health) trial is a randomized controlled trial in which patients at federally-qualified community health centers were randomly assigned to one of two groups: comprehensive intensive management of CVD risk factors for one year by a NP/CHW team or an enhanced usual care control group. Results A total of 3899 patients were assessed for eligibility and 525 were randomized. Groups were comparable at baseline on sociodemographic and clinical characteristics with the exception of statistically significant differences in total cholesterol and hemoglobin A1c. Conclusions This study is a novel amalgam of multilevel interdisciplinary strategies to translate highly efficacious therapies to low-income federally-funded health centers that care for patients who carry a disproportionate burden of CVD, type 2 diabetes and uncontrolled CVD risk factors. The impact of such a community clinic-based intervention is potentially enormous. PMID:21241828

COACH trial: a randomized controlled trial of nurse practitioner/community health worker cardiovascular disease risk reduction in urban community health centers: rationale and design.

PubMed

Allen, Jerilyn K; Himmelfarb, Cheryl R Dennison; Szanton, Sarah L; Bone, Lee; Hill, Martha N; Levine, David M

2011-05-01

Despite well-publicized guidelines on the appropriate management of cardiovascular disease (CVD) and type 2 diabetes, implementation of risk-reducing practices remains poor. This paper describes the rationale and design of a randomized controlled clinical trial evaluating the effectiveness of a comprehensive program of CVD risk reduction delivered by nurse practitioner (NP)/community health worker (CHW) teams versus enhanced usual care in improving the proportion of patients in urban community health centers who achieve goal levels recommended by national guidelines for lipids, blood pressure, HbA1c and prescription of appropriate medications. The COACH (Community Outreach and Cardiovascular Health) trial is a randomized controlled trial in which patients at federally-qualified community health centers were randomly assigned to one of two groups: comprehensive intensive management of CVD risk factors for one year by a NP/CHW team or an enhanced usual care control group. A total of 3899 patients were assessed for eligibility and 525 were randomized. Groups were comparable at baseline on sociodemographic and clinical characteristics with the exception of statistically significant differences in total cholesterol and hemoglobin A1c. This study is a novel amalgam of multilevel interdisciplinary strategies to translate highly efficacious therapies to low-income federally-funded health centers that care for patients who carry a disproportionate burden of CVD, type 2 diabetes and uncontrolled CVD risk factors. The impact of such a community clinic-based intervention is potentially enormous. Copyright © 2011 Elsevier Inc. All rights reserved.

Engaging stakeholders to design a comparative effectiveness trial in children with uncontrolled asthma

PubMed Central

Erwin, Kim; Martin, Molly A; Flippin, Tara; Norell, Sarah; Shadlyn, Ariana; Yang, Jie; Falco, Paula; Rivera, Jaime; Ignoffo, Stacy; Kumar, Rajesh; Margellos-Anast, Helen; McDermott, Michael; McMahon, Kate; Mosnaim, Giselle; Nyenhuis, Sharmilee M; Press, Valerie G; Ramsay, Jessica E; Soyemi, Kenneth; Thompson, Trevonne M; Krishnan, Jerry A

2016-01-01

Aim: To present the methods and outcomes of stakeholder engagement in the development of interventions for children presenting to the emergency department (ED) for uncontrolled asthma. Methods: We engaged stakeholders (caregivers, physicians, nurses, administrators) from six EDs in a three-phase process to: define design requirements; prototype and refine; and evaluate. Results: Interviews among 28 stakeholders yielded themes regarding in-home asthma management practices and ED discharge experiences. Quantitative and qualitative evaluation showed strong preference for the new discharge tool over current tools. Conclusion: Engaging end-users in contextual inquiry resulted in CAPE (CHICAGO Action Plan after ED discharge), a new stakeholder-balanced discharge tool, which is being tested in a multicenter comparative effectiveness trial. PMID:26690579

Dietary nitrate lowers ambulatory blood pressure in treated, uncontrolled hypertension: a 7-d, double-blind, randomised, placebo-controlled, cross-over trial.

PubMed

Kerley, Conor P; Dolan, Eamon; James, Philip E; Cormican, Liam

2018-03-01

Dietary nitrate has been shown to increase nitrate/nitrite levels and decrease blood pressure (BP) in multiple populations. There are few reports among hypertensives and these reports have provided conflicting evidence. We aimed to assess the effect of daily nitrate compared with placebo in subjects with uncontrolled hypertension (HTN). On day 0, hypertensives wore an ambulatory BP monitor (ABPM) for 24 h and blood was taken. Subjects were then randomised to 7-d nitrate-rich beetroot juice (NO3 -) (12·9 mmol nitrate) followed by 7-d nitrate-depleted beetroot juice (0·5 mmol nitrate) or vice versa. ABPM and blood were assessed before and after both conditions. In all, twenty subjects with treated yet uncontrolled HTN entered and completed the trial (mean age=62·5 years, mean BMI=30·7 kg/m2). Baseline BP was 137/80 (sd 7/7) mmHg. Dietary nitrate was well tolerated and resulted in significantly increased plasma nitrite (P=0·0004) and decreased 24-h systolic BP and diastolic BP compared with placebo (-8 mmHg; P=0·012 and -4 mmHg; P=0·018, respectively). Our results support the existing data suggesting an anti-hypertensive effect of dietary nitrate in treated yet uncontrolled hypertensives. Targeted dietary strategies appear promising contributors to BP control.

[Prognosis and treatment of dry mouth. Systematic review].

PubMed

López-López, José; Jané Salas, Enric; Chimenos Küstner, Eduardo

2014-02-04

There are no clearly established protocols for the treatment of dry mouth. The aim of this paper is a systematic review of the literature of the past 10 years using the words « dry mouth », « prognosis », « treatment » and « dentistry ». The initial search found 1,450 entries and within the restriction « clinical trials OR randomized controlled trial OR systemic reviews » it has been reduced to 522, which 145 were meta-analysis and systematic reviews. Papers not relevant to the issue were removed reducing the entries to 53. Twenty-four were dismissed (8 irrelevant, 7 reviews without adequate information and 9 personal opinions). Of the 29 items tested, 15 were controlled trials, 2 uncontrolled trials, 4 observational studies, 2 systematic reviews and 5 non systematic reviews. The most studied patients were Sjögren's syndrome and the irradiated patients. Treatments are focused on the etiology, prevention, symptomatic, local salivary stimulation and systemic treatments. It can be concluded that treatment must be individualized, salivary substitutes and mechanical stimulation techniques can be applied. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Learned Helplessness and Sexual Risk Taking in Adolescent and Young Adult African American Females.

PubMed

Pittiglio, Laura

2017-08-01

Research involving adolescent and young African American (AA) females has demonstrated that they face uncontrollable obstacles which can interfere with the negotiation of safer sexual behaviors. If these obstacles are perceived as uncontrollable, then these females may be at risk for the development of Learned Helplessness (LH). As the LH model predicts, if these obstacles are believed not to be in their control, it may lead to deficits in motivational or cognitive decision-making, deficits that could certainly influence their sexual risk taking behaviors. Therefore, the primary objective for this pilot study was to trial the Learned Helplessness Scale (LHS) to examine the perceptions of LH in this population. A convenience sample of 50 adolescent and young AA females between the ages of 16 and 21 were recruited from two clinics in Southeast Michigan. Scores on the LHS ranged from 20 to 57, with a mean score of 39.1 (standard deviation = 10.49). The higher range of scores in the sample demonstrates a continuum of LH among the participants in the study.

The Sacubitril/Valsartan, a First-in-Class, Angiotensin Receptor Neprilysin Inhibitor (ARNI): Potential Uses in Hypertension, Heart Failure, and Beyond.

PubMed

Kario, Kazuomi

2018-01-27

Sacubitril/valsartan (LCZ696) is a first-in-class, novel-acting, angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition of neprilysin and the angiotensin (AT 1 ) receptor. A recent clinical trial PRARDIGM-HF demonstrated that this drug is superior to angiotensin-converting enzyme (ACE) inhibitors for improving the prognosis in the patients with heart failure, and this has resulted in the drug being included in clinical practice guidelines for the management of heart failure with reduced ejection fraction (EF). In addition, sacubitril/valsartan has been developed for the management of hypertension, because it has unique anti-aging properties. However, the clinical evidence of mechanism has not been well validated. A recent mechanistic study PARAMETER demonstrated that sacubitril/valsartan (LCZ696) is superior to angiotensin receptor blocker (ARB) monotherapy for reducing central aortic systolic pressure (primary endpoint) as well as for central aortic pulse pressure (secondary endpoint) and nocturnal BP preferentially. Considering these results, sacubitril/valsartan may be an attractive therapeutic agent to treat the elderly with age-related hypertension phenotypes, such as drug-uncontrolled (resistant) hypertension characterized as systolic (central) hypertension (structural hypertension) and/or nocturnal hypertension (salt-sensitive hypertension). These are the high-risk hypertension phenotypes which are prone to develop heart failure with preserved EF and chronic kidney disease. Sacubitril/valsartan may be effective to suppress the age-related continuum from hypertension to heart failure, and it could be clinically useful not only for secondary prevention, but also as primary prevention of heart failure in uncontrolled elderly hypertensive patients.

Digital Clinical Communication for Families and Caregivers of Children or Young People With Short- or Long-Term Conditions: Rapid Review

PubMed Central

Armoiry, Xavier; Sturt, Jackie; Phelps, Emma Elizabeth; Walker, Clare-Louise; Court, Rachel; Taggart, Frances; Sutcliffe, Paul; Atherton, Helen

2018-01-01

Background The communication relationship between parents of children or young people with health conditions and health professionals is an important part of treatment, but it is unclear how far the use of digital clinical communication tools may affect this relationship. Objective The objective of our study was to describe, assess the feasibility of, and explore the impact of digital clinical communication between families or caregivers and health professionals. Methods We searched the literature using 5 electronic databases. We considered all types of study design published in the English language from January 2009 to August 2015. The population of interest included families and caregivers of children and young people aged less than 26 years with any type of health condition. The intervention was any technology permitting 2-way communication. Results We included 31 articles. The main designs were randomized controlled trials (RCTs; n=10), cross-sectional studies (n=9), pre- and postintervention uncontrolled (pre/post) studies (n=7), and qualitative interview studies (n=2); 6 had mixed-methods designs. In the majority of cases, we considered the quality rating to be fair. Many different types of health condition were represented. A breadth of digital communication tools were included: videoconferencing or videoconsultation (n=14), and Web messaging or emails (n=12). Health care professionals were mainly therapists or cognitive behavioral therapists (n=10), physicians (n=8), and nurses (n=6). Studies were very heterogeneous in terms of outcomes. Interventions were mainly evaluated using satisfaction or acceptance, or outcomes relating to feasibility. Clinical outcomes were rarely used. The RCTs showed that digital clinical communication had no impact in comparison with standard care. Uncontrolled pre/post studies showed good rates of satisfaction or acceptance. Some economic studies suggested that digital clinical communication may save costs. Conclusions This rapid review showed an emerging body of literature on the use of digital clinical communication to improve families’ and caregivers’ involvement in the health management of children or young people. Further research with appropriate study designs and longer-term outcome measures should be encouraged. Trial Registration PROSPERO CRD42016035467; http://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD 42016 035467(Archived by WebCite at http://www.webcitation.org/6vpgZU1FU) PMID:29305339

Emotional and uncontrolled eating styles and chocolate chip cookie consumption. A controlled trial of the effects of positive mood enhancement.

PubMed

Turner, Sally Ann; Luszczynska, Aleksandra; Warner, Lisa; Schwarzer, Ralf

2010-02-01

The study tested the effects of positive mood enhancement on chocolate chip cookie consumption in the context of emotional and uncontrolled eating styles. The relationship between emotional eating style and chocolate chip cookie intake was assumed to be mediated by uncontrolled eating style. Further, it was hypothesized that the effectiveness of the positive mood enhancement may be more salient among those who have effective control of their eating. In this experimental study, respondents (N=106, 70% women, aged 16-45 years old) were assigned by means of cluster randomization to the control or positive mood enhancement condition (a comedy movie clip). Compared to the control condition, positive mood enhancement resulted in consuming on average 53.86 kcal less. Relationships between emotional eating style and cookie intake were mediated by uncontrolled eating. Moderated mediation analysis indicated that the effect of a mediator (uncontrolled eating) on cookie intake was moderated by the group assignment. Positive mood enhancement resulted in eating on average 3.3 cookies less among individuals with a more controlled eating style. By contrast, among those who presented uncontrolled eating, positive mood enhancement led to consuming an average of 1.7 cookies more. 2009 Elsevier Ltd. All rights reserved.

Design of a pragmatic trial in minority children presenting to the emergency department with uncontrolled asthma: The CHICAGO Plan.

PubMed

Krishnan, Jerry A; Martin, Molly A; Lohff, Cortland; Mosnaim, Giselle S; Margellos-Anast, Helen; DeLisa, Julie A; McMahon, Kate; Erwin, Kim; Zun, Leslie S; Berbaum, Michael L; McDermott, Michael; Bracken, Nina E; Kumar, Rajesh; Margaret Paik, S; Nyenhuis, Sharmilee M; Ignoffo, Stacy; Press, Valerie G; Pittsenbarger, Zachary E; Thompson, Trevonne M

2017-06-01

Among children with asthma, black children are two to four times as likely to have an emergency department (ED) visit and die from asthma, respectively, compared to white children in the United States. Despite the availability of evidence-based asthma management guidelines, minority children are less likely than white children to receive or use effective options for asthma care. The CHICAGO Plan is a three-arm multi-center randomized pragmatic trial of children 5 to 11years old presenting to the ED with uncontrolled asthma that compares: [1] an ED-focused intervention to improve the quality of care on discharge to home, [2] the same ED-focused intervention together with a home-based community health worker (CHW)-led intervention, and [3] enhanced usual care. All children receive spacers for the metered dose inhaler and teaching about its use. The Patient-Reported Outcomes Measurement Information System (PROMIS) Asthma Impact Scale and Satisfaction with Participation in Social Roles at 6months are the primary outcomes in children and in caregivers, respectively. Other patient-reported outcomes and indicators of healthcare utilization are assessed as secondary outcomes. Innovative features of the CHICAGO Plan include early and continuous engagement of children, caregivers, the Chicago Department of Public Health, and other stakeholders to inform the design and implementation of the study and a shared research infrastructure to coordinate study activities. The objective of this report is to describe the development of the CHICAGO Plan, including the methods and rationale for engaging stakeholders, the shared research infrastructure, and other features of the pragmatic clinical trial design. Published by Elsevier Inc.

Design of a pragmatic trial in minority children presenting to the emergency department with uncontrolled asthma: The CHICAGO Plan

PubMed Central

Krishnan, Jerry A.; Martin, Molly A.; Lohff, Cortland; Mosnaim, Giselle S.; Margellos-Anast, Helen; DeLisa, Julie A.; McMahon, Kate; Erwin, Kim; Zun, Leslie S.; Berbaum, Michael L.; McDermott, Michael; Bracken, Nina E.; Kumar, Rajesh; Paik, S. Margaret; Nyenhuis, Sharmilee M.; Ignoffo, Stacy; Press, Valerie G.; Pittsenbarger, Zachary E.; Thompson, Trevonne M.

2017-01-01

Among children with asthma, black children are two to four times as likely to have an emergency department (ED) visit and die from asthma, respectively, compared to white children in the United States. Despite the availability of evidence-based asthma management guidelines, minority children are less likely than white children to receive or use effective options for asthma care. The CHICAGO Plan is a three-arm multi-center randomized pragmatic trial of children 5 to 11 years old presenting to the ED with uncontrolled asthma that compares: (1) an ED-focused intervention to improve the quality of care on discharge to home, (2) the same ED-focused intervention together with a home-based community health worker (CHW)-led intervention, and (3) enhanced usual care. All children receive spacers for the metered dose inhaler and teaching about its use. The Patient-Reported Outcomes Measurement Information System (PROMIS) Asthma Impact Scale and Satisfaction with Participation in Social Roles at 6 months are the primary outcomes in children and in caregivers, respectively. Other patient-reported outcomes and indicators of healthcare utilization are assessed as secondary outcomes. Innovative features of the CHICAGO Plan include early and continuous engagement of children, caregivers, the Chicago Department of Public Health, and other stakeholders to inform the design and implementation of the study and a shared research infrastructure to coordinate study activities. The objective of this report is to describe the development of the CHICAGO Plan, including the methods and rationale for engaging stakeholders, the shared research infrastructure, and other features of the pragmatic clinical trial design. PMID:28366780

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2013-08-20

Nearly 30% of patients with epilepsy continue to have seizures in spite of several antiepileptic drug (AED) regimens. In such cases they are regarded as having refractory, or uncontrolled epilepsy.There is no universally accepted definition for uncontrolled or medically refractory epilepsy, but for the purpose of this review, we will consider seizures to be drug resistant if they failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age and improve the intellectual and social status of children. There are many types of surgery for refractory epilepsy with subpial transection being one. Our main aim is to determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (8 August 2013), The Cochrane Central Register of Controlled Trials (CENTRAL Issue 7 of 12, The Cochrane Library July 2013), and MEDLINE (1946 to 8 August 2013). We did not impose any language restrictions. We considered all randomised and quasi-randomised parallel group studies either blinded or non-blinded. Two review authors (BK and SR) independently screened the trials identified by the search. The same two authors planned to independently assess the methodological quality of studies. If studies had been identified for inclusion, one author would have extracted the data and the other would have verified it. No relevant studies were found. There is no evidence to support or refute the use of subpial transection surgery for medically refractory cases of epilepsy. Well designed randomised controlled trials are needed in future to guide clinical practice.

A MULTI-CENTER CLUSTER-RANDOMIZED TRIAL OF A MULTI-FACTORIAL INTERVENTION TO IMPROVE ANTIHYPERTENSIVE MEDICATION ADHERENCE AND BLOOD PRESSURE CONTROL AMONG PATIENTS AT HIGH CARDIOVASCULAR RISK (The COM99 study)*

PubMed Central

Pladevall, Manel; Brotons, Carlos; Gabriel, Rafael; Arnau, Anna; Suarez, Carmen; de la Figuera, Mariano; Marquez, Emilio; Coca, Antonio; Sobrino, Javier; Divine, George; Heisler, Michele; Williams, L Keoki

2010-01-01

Background Medication non-adherence is common and results in preventable disease complications. This study assesses the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. Methods and Results In this multi-center, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients’ pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end-point of all cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62; 95% confidence interval [CI] 0.50–0.78) and were more likely to be adherent (OR 1.91; 95% CI 1.19–3.05) when compared with control group patients at 6 months. After five years 16% of the patients in the intervention group and 19% in the control group met the composite end-point (hazard ratio 0.97; 95% CI 0.67–1.39). Conclusions A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events. PMID:20823391

A targeted decision aid for the elderly to decide whether to undergo colorectal cancer screening: development and results of an uncontrolled trial

PubMed Central

2010-01-01

Background Competing causes of mortality in the elderly decrease the potential net benefit from colorectal cancer screening and increase the likelihood of potential harms. Individualized decision making has been recommended, so that the elderly can decide whether or not to undergo colorectal cancer (CRC) screening. The objective is to develop and test a decision aid designed to promote individualized colorectal cancer screening decision making for adults age 75 and over. Methods We used formative research and cognitive testing to develop and refine the decision aid. We then tested the decision aid in an uncontrolled trial. The primary outcome was the proportion of patients who were prepared to make an individualized decision, defined a priori as having adequate knowledge (10/15 questions correct) and clear values (25 or less on values clarity subscale of decisional conflict scale). Secondary outcomes included overall score on the decisional conflict scale, and preferences for undergoing screening. Results We enrolled 46 adults in the trial. The decision aid increased the proportion of participants with adequate knowledge from 4% to 52% (p < 0.01) and the proportion prepared to make an individualized decision from 4% to 41% (p < 0.01). The proportion that preferred to undergo CRC screening decreased from 67% to 61% (p = 0. 76); 7 participants (15%) changed screening preference (5 against screening, 2 in favor of screening) Conclusion In an uncontrolled trial, the elderly participants appeared better prepared to make an individualized decision about whether or not to undergo CRC screening after using the decision aid. PMID:20849625

Idarucizumab (Praxbind) Formulary Review.

PubMed

Buchheit, Jessica; Reddy, Prabashni; Connors, Jean M

2016-09-01

Idarucizumab (Praxbind), a humanized monoclonal antibody fragment was granted accelerated approval from the Food and Drug Administration in October 2015 as the first agent to reverse the effects of a novel oral anticoagulant. The drug is indicated for dabigatran reversal in patients requiring emergency surgery/urgent procedures or with life-threatening or uncontrolled bleeding. In a randomized study with healthy volunteers, compared with placebo, idarucizumab reduced the clotting times for all tests assays (assessed pre-, end of-, and 24 hours after infusion), while the results for the placebo group remained unchanged. Another randomized clinical trial assessed the safety and efficacy of idarucizumab in patients with either overt bleeding or undergoing emergency surgery where hemostasis was required. This study is ongoing, but preliminary results showed reversal efficacy demonstrated a reasonable safety profile from the time of the infusion to 90 days after. The wholesale acquisition cost of two 2.5 g vials of idarucizumab is currently $3482.50. To treat 10 or 20 patients per year with a single 5 g dose is estimated to cost $34,825 and $69,650, respectively. In the clinical trial described above, approximately 20% of patients required a second dose, which would further increase the cost of use. In this formulary review for a health system's pharmacy and therapeutics committee, idarucizumab clinical trials and medication package insert were summarized and, after consulting with clinical experts from our institutions, practical recommendations for use were generated to ensure appropriate and safe use of this agent.

Prevalence of pseudoresistant hypertension due to inaccurate blood pressure measurement

PubMed Central

Bhatt, Hemal; Siddiqui, Mohammed; Judd, Eric; Oparil, Suzanne; Calhoun, David

2016-01-01

Background The prevalence of pseudoresistant hypertension (HTN) due to inaccurate BP measurement remains unknown. Methods Triage BP measurements and measurements obtained at the same clinic visit by trained physicians were compared in consecutive adult patients referred for uncontrolled resistant HTN (RHTN). Triage BP measurements were taken by the clinic staff during normal intake procedures. BP measurements were obtained by trained physicians using the BpTRU device. The prevalence of uncontrolled RHTN and differences in BP measurements were compared. Results Of 130 patients with uncontrolled RHTN, 33.1% (n=43) were falsely identified as having uncontrolled RHTN based on triage BP measurements. The median (IQR) of differences in systolic BP between pseudoresistant and true resistant groups were 23 (17 – 33) mm Hg and 13 (6 – 21) mm Hg, respectively (P=0.0001). The median (IQR) of differences in diastolic BP between the two groups were 12 (7 – 18) mm Hg and 8 (4 – 11) mm Hg, respectively (P=0.001). Conclusion Triage BP technique overestimated the prevalence of uncontrolled RHTN in approximately 33% of the patients emphasizing the importance of obtaining accurate BP measurements. PMID:27129931

Cupping for stroke rehabilitation: a systematic review.

PubMed

Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Han, Chang-ho; Ernst, Edzard

2010-07-15

Cupping is often used for stroke rehabilitation in Asian countries. Currently, no systematic review of this topic is available. The aim of this systematic review is to summarize and critically evaluate the evidence for and against the effectiveness of cupping for stroke rehabilitation. Thirteen databases were searched from their inception through March of 2010 without language restrictions. Prospective clinical trials were included if cupping was tested as the sole treatment or as an adjunct to other conventional treatments for stroke rehabilitation. We found 43 potentially relevant articles, of which 5 studies including 3 randomized clinical trials (RCTs) and 2 uncontrolled observational studies (UOSs) met our inclusion criteria. Cupping was compared with acupuncture, electro-acupuncture and warm needling. Some superior effects of cupping were found in two of the RCTs when compared to acupuncture in hemiplegic shoulder pain and high upper-limb myodynamia after stroke. The other RCT failed to show favorable effects of cupping when compared to acupuncture and warm needling in patients with hemiplegic hand edema. The two UOSs reported favorable effects of cupping on aphasia and intractable hiccup after stroke. There are not enough trials to provide evidence for the effectiveness of cupping for stroke rehabilitation because most of the included trials compared the effects with unproven evidence and were not informative. Future RCTs seem warranted but must overcome the methodological shortcomings of the existing evidence. Copyright 2010 Elsevier B.V. All rights reserved.

Development of lacosamide for the treatment of partial-onset seizures

PubMed Central

Doty, Pamela; Hebert, David; Mathy, Francois-Xavier; Byrnes, William; Zackheim, James; Simontacchi, Kelly

2013-01-01

Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug–drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic–clonic seizures in those with idiopathic generalized epilepsy. PMID:23859801

Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells

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

Uchiyama, Toru; Kumaki, Satoru; Ishikawa, Yoshinori

Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human {gamma}c chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the {gamma}c chain, the cells were treated with ganciclovir (GCV). The {gamma}c chain positive cells were eliminated under low concentrationmore » without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the {gamma}c chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial.« less

Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement

PubMed Central

MacPherson, Hugh; Altman, Douglas G; Hammerschlag, Richard; Li, Youping; Wu, Taixiang; White, Adrian; Moher, David

2010-01-01

The STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal editors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision. To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face-to-face meeting in Freiburg, a group of 21 participants further revised the STRICTA checklist and planned dissemination. The new STRICTA checklist, which is an official extension of CONSORT, includes 6 items and 17 subitems. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background and the control or comparator interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word ‘controlled’ in STRICTA is replaced by ‘clinical’, to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, including uncontrolled outcome studies and case reports. It is intended that the revised STRICTA checklist, in conjunction with both the main CONSORT statement and extension for non-pharmacological treatment, will raise the quality of reporting of clinical trials of acupuncture. PMID:20615861

Reasons for uncontrolled seizures in children: the impact of pseudointractability.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad

2012-11-01

We investigated the various possible reasons for uncontrolled seizures in patients under 18 years of age to determine the impact of pseudointractability. We also investigated the various forms of pseudointractability in children with uncontrolled seizures. In this cross-sectional retrospective chart review study, all patients under 18 years of age with their first seizure occurring at least 6 months prior to the referral date, taking at least one antiepileptic drug (AED), and having at least one seizure in the past 3 months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: poor adherence; wrong medication; wrong dose of the correct medication; diagnosis other than epilepsy; and finally, medically refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's Exact tests to determine potentially significant differences, and a P value less than 0.05 was considered significant. During the study period, 198 patients were referred to us due to uncontrolled seizures. Ninety patients (45%) were taking one AED, 55 (28%) were taking two AEDs, and 53 (27%) patients were taking more than two AEDs at the time of referral. Four percent of these patients did not have epilepsy. Forty-seven percent of the children with uncontrolled seizures had medically refractory epilepsy; 37% were taking the wrong AEDs; 10% were taking suboptimal doses of AEDs; and 2% had poor drug adherence. Uncontrolled seizures in children are a commonly encountered problem, particularly at epilepsy clinics. One should consider all possible reasons for these uncontrolled seizures, including non-epileptic seizures, pseudointractability, and medically refractory epilepsy. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2012 Elsevier Inc. All rights reserved.

The use of maca (Lepidium meyenii) to improve semen quality: A systematic review.

PubMed

Lee, Myeong Soo; Lee, Hye Won; You, Sooseong; Ha, Ki-Tae

2016-10-01

The aim of this review was to assess the evidence for the effectiveness of maca (Lepidium meyenii) in improving semen quality. We searched 11 databases from their inception to March 2016 and included all clinical trials on the improvement of semen quality parameters in infertile and healthy men, regardless of the study design or the type of maca. The risk of bias for each study was assessed using the Cochrane criteria. The selection of studies, data extraction, and validation were performed independently by the first two authors. Discrepancies were resolved through discussion by the same two authors. Five studies - 3 randomized clinical trials (RCTs) and 2 uncontrolled observational studies (UOSs) - met all of the inclusion criteria. One RCT found favorable effects of maca on sperm mobility in infertile men. The two other RCTs showed positive effects of maca on several semen quality parameters in healthy men. The two UOSs also suggested favorable effects of maca on semen quality. The results of our systematic review provide suggestive evidence for the effectiveness of maca in improving semen quality. However, the total number of trials, the total sample size, and the risk of bias of the included studies prevent the drawing firm conclusions. More rigorous studies are warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force.

PubMed

Martinowitz, U; Michaelson, M

2005-04-01

Recombinant activated factor VII (rFVIIa) has been approved by the U.S. Food and Drug Administration (FDA) for almost a decade for hemophilic patients with inhibitors. Its off-label use as a hemostatic agent in massive bleeding caused by a wide array of clinical scenarios is rapidly expanding. While evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are available for its off-label use. The aim of this study is to develop expert recommendations for the use of rFVIIa in patients suffering from uncontrolled bleeding (with special emphasis on trauma) until randomized, controlled trials allow for the introduction of more established evidence-based guidelines. A multidisciplinary task force comprising representatives of the relevant National Medical Associations, experts from the Medical Corps of the Army, Ministry of Health and the Israel National Trauma Advisory Board was established in Israel. Recommendations were construed based on the analysis of the first 36 multi-trauma patients accumulated in the prospective national registry of the use of rFVIIa in trauma, and an extensive literature search consisting of published and prepublished controlled animal trials, case reports and series. The final consensus guidelines, together with the data of the first 36 trauma patients treated in Israel, are presented in this article. Results of the first 36 trauma patients: The prolonged clotting assays [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened significantly within minutes following administration of rFVIIa. Cessation of bleeding was achieved in 26 of 36 (72%) patients. Acidosis diminished the hemostatic effect of the drug, while hypothermia did not affect it. The survival rate of 61% (22/36) seems to be favorable compared with published series of similar, or less severe, trauma patients (range 30%-57%). As a result of the lack of controlled trials, our guidelines should be considered as suggestive rather than conclusive. However, they provide a valuable tool for physicians using rFVIIa for the expanding off-label clinical uses.

Massage therapy for children with autism spectrum disorders: a systematic review.

PubMed

Lee, Myeong Soo; Kim, Jong-In; Ernst, Edzard

2011-03-01

We aimed to assess the effectiveness of massage as a treatment option for autism. We searched the following electronic databases using the time of their inception through March 2010: MEDLINE, AMED, CINAHL, EMBASE, PsycINFO, Health Technology Assessment, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Psychology and Behavioral Sciences Collection, 6 Korean medical databases (KSI, DBpia, KISTEP, RISS, KoreaMed, and National Digital Library), China Academic Journal (through China National Knowledge Infrastructure), and 3 Japanese medical databases (Journal@rchive, Science Links Japan, and Japan Science & Technology link). The search phrase used was "(massage OR touch OR acupressure) AND (autistic OR autism OR Asperger's syndrome OR pervasive developmental disorder)." The references in all located articles were also searched. No language restrictions were imposed. Prospective controlled clinical studies of any type of massage therapy for autistic patients were included. Trials in which massage was part of a complex intervention were also included. Case studies, case series, qualitative studies, uncontrolled trials, studies that failed to provide detailed results, and trials that compared one type of massage with another were excluded. All articles were read by 2 independent reviewers (M.S.L. and J-I.K.), who extracted data from the articles according to predefined criteria. Risk of bias was assessed using the Cochrane classification. Of 132 articles, only 6 studies met our inclusion criteria. One randomized clinical trial found that massage plus conventional language therapy was superior to conventional language therapy alone for symptom severity (P < .05) and communication attitude (P < .01). Two randomized clinical trials reported a significant benefit of massage for sensory profile (P < .01), adaptive behavior (P < .05), and language and social abilities (P < .01) as compared with a special education program. The fourth randomized clinical trial showed beneficial effects of massage for social communication (P < .05). Two nonrandomized controlled clinical trials suggested that massage therapy is effective. However, all of the included trials have high risk of bias. The main limitations of the included studies were small sample sizes, predefined primary outcome measures, inadequate control for nonspecific effects, and a lack of power calculations or adequate follow-up. Limited evidence exists for the effectiveness of massage as a symptomatic treatment of autism. Because the risk of bias was high, firm conclusions cannot be drawn. Future, more rigorous randomized clinical trials seem to be warranted. © Copyright 2011 Physicians Postgraduate Press, Inc.

Pediatric intensive care treatment of uncontrolled status epilepticus.

PubMed

Wilkes, Ryan; Tasker, Robert C

2013-04-01

The critically ill mechanically ventilated child with ongoing seizures that are refractory to any treatment presents a distinct challenge in pediatric neurocritical care. The evidence base from randomized controlled trials on which anti-epileptic drug (AED) strategy should be used is inadequate. This review of refractory and super-refractory status epilepticus summarizes recent pediatric case series regarding definitions, the second-tier AED therapies once initial anticonvulsants have failed, and the experience of high-dose midazolam, barbiturate anesthesia, and volatile anesthetics for uncontrolled status epilepticus. Copyright © 2013 Elsevier Inc. All rights reserved.

Management of Brain Metastases.

PubMed

Jeyapalan, Suriya A.; Batchelor, Tracy

2004-07-01

Advances in neurosurgery and the development of stereotactic radiosurgery have expanded treatment options available for patients with brain metastases. However, despite several randomized clinical trials and multiple uncontrolled studies, there is not a uniform consensus on the best treatment strategy for all patients with brain metastases. The heterogeneity of this patient population in terms of functional status, types of underlying cancers, status of systemic disease control, and number and location of brain metastases make such consensus difficult. Nevertheless, in certain situations, there is Class I evidence that supports one approach or another. The primary objectives in the management of this patient population include improved duration and quality of survival. Very few patients achieve long-term survival after the diagnosis of a brain metastasis.

Linking clinic and home: a randomized, controlled clinical effectiveness trial of real-time, wireless blood pressure monitoring for older patients with kidney disease and hypertension.

PubMed

Rifkin, Dena E; Abdelmalek, Joseph A; Miracle, Cynthia M; Low, Chai; Barsotti, Ryan; Rios, Phil; Stepnowsky, Carl; Agha, Zia

2013-02-01

Older adults with chronic kidney disease have a high rate of uncontrolled hypertension. Home monitoring of blood pressure (BP) is an integral part of management, but requires that patients bring records to clinic visits. Telemonitoring interventions, however, have not targeted older, less technologically-skilled populations. Veterans with stage 3 or greater chronic kidney disease and uncontrolled hypertension were randomized to a novel telemonitoring device pairing a Bluetooth-enabled BP cuff with an Internet-enabled hub, which wirelessly transmitted readings (n=28), or usual care (n=15). Home recordings were reviewed weekly and telemonitoring participants were contacted if BP was above goal. The prespecified primary endpoints were improved data exchange and device acceptability. Secondary endpoint was BP change. Forty-three participants (average age 68 years, 75% white) completed the 6-month study. Average start-of-study BP was 147/78 mmHg. Those in the intervention arm had a median of 29 (IQR 22, 53) transmitted BP readings per month, with 78% continuing to use the device regularly, whereas only 20% of those in the usual care group brought readings to in-person visits. The median number of telephone contacts triggered by the wireless monitoring was 2 (IQR 1, 4) per patient. Both groups had a significant improvement in systolic BP (P<0.05, for both changes); systolic BP fell a median of 13 mmHg in monitored participants compared with 8.5 mmHg in usual care participants (P for comparison 0.31). This low-cost wireless monitoring strategy led to greater sharing of data between patients and clinic and produced a trend toward improvements in BP control over usual care at 6 months.

A diabetes scorecard does not improve HbA(1c), blood pressure, lipids, aspirin usage, exercise and diabetes knowledge over 9 months: a randomized controlled trial.

PubMed

Irwig, M S; Sood, P; Ni, D; Amass, T; Khurana, P S; Jayanthi, V V; Wang, L; Adler, S M

2012-09-01

To test (1) whether a diabetes scorecard can improve glycaemic control, blood pressure control, LDL cholesterol, aspirin usage and exercise; (2) if the scorecard will motivate and/or educate patients to improve their scores for subsequent visits; and (3) whether the scorecard will improve rates of clinical inertia. Five physicians enrolled 103 patients ≥ 40 years old with uncontrolled Type 2 diabetes [HbA(1c) ≥ 64 mmol/mol (8.0%)] to randomly receive either a diabetes scorecard or not during four clinical visits over a 9-month period. The population was predominantly urban with a disproportionately higher percentage of black people than the general population. Our scorecard assigned points to six clinical variables, with a perfect total score of 100 points corresponding to meeting all targets. The primary outcomes were total scores and HbA(1c) in the scorecard and control groups at 9 months. There were no significant differences between the control and scorecard groups at visits 1 and 4 in total score, HbA(1c) , blood pressure, LDL cholesterol, aspirin usage, exercise or knowledge about diabetic targets. By visit 4 both the control and scorecard groups had statistically significant improvements with their mean total score (9 and 7 points, respectively), HbA(1c) [-9 mmol/mol (-0.8%) and -15 mmol/mol (-1.4%), respectively] and aspirin usage (33% increase and 16% increase, respectively). Rates of clinical inertia were low throughout the study. A diabetes scorecard did not improve glycaemic control, blood pressure control, LDL cholesterol, aspirin usage, exercise or diabetic knowledge in an urban population with uncontrolled Type 2 diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Development and implementation of a navigator-facilitated care coordination algorithm to improve clinical outcomes of underserved Latino patients with uncontrolled diabetes.

PubMed

Congdon, Heather Brennan; Eldridge, Barbara Hoffman; Truong, Hoai-An

2013-11-01

Development and implementation of an interprofessional navigator-facilitated care coordination algorithm (NAVCOM) for low-income, uninsured patients with uncontrolled diabetes at a safety-net clinic resulted in improvement of disease control as evidenced by improvement in hemoglobin A1C. This report describes the process and lessons learned from the development and implementation of NAVCOM and patient success stories.

Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids.

PubMed

Bateman, Eric D; Guerreros, Alfredo G; Brockhaus, Florian; Holzhauer, Björn; Pethe, Abhijit; Kay, Richard A; Townley, Robert G

2017-08-01

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d ) or twice-daily (2, 25, 75 or 150 mg b.i.d ) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. Copyright ©ERS 2017.

Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids

PubMed Central

Guerreros, Alfredo G.; Brockhaus, Florian; Pethe, Abhijit; Kay, Richard A.; Townley, Robert G.

2017-01-01

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS). Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d.) or twice-daily (2, 25, 75 or 150 mg b.i.d.) fevipiprant (n=782), montelukast 10 mg q.d. (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d. Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d. and 75 mg b.i.d. groups, with no clinically meaningful differences between q.d. and b.i.d. Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments. Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. PMID:28838980

One year in review 2016: Behçet's syndrome.

PubMed

Hatemi, Gulen; Seyahi, Emire; Fresko, Izzet; Talarico, Rosaria; Hamuryudan, Vedat

2016-01-01

Several articles highlighting the epidemiology, pathogenesis, clinical features, treatment modalities and disease assessment of Behçet's syndrome (BS) have been published during the last year. Clinical and radiological features of lower extremity deep vein thrombosis due to BS can be quite different than those found in thrombosis due to other causes; additionally, frequency of post-thrombotic syndrome is significantly increased in BS. Some clinical and colonoscopic features are useful in differentiating BS from Crohn's disease. Barkhof criteria may be helpful in differentiating neurologic involvement due to BS from multiple sclerosis. Anatomical localization of papulopustular lesions but not histology has been found to be helpful in differentiating papulopustular lesions of BS from those found in acne vulgaris. Several studies looked at the ovarian reserve with contradicting results. A population-based cohort study found higher risk of hematological malignancies only among female BS patients living in Taiwan. The role of genetic factors and environment is discussed and both autoimmune and autoinflammatory features are underlined in the pathogenesis of BS. New data on the epistatic interactions between ERAP and HLA B51 is available and information on the microbiome have started to appear. New uncontrolled data suggest beneficial effects of anti-TNFs for refractory extra-ocular complications of BS such as pulmonary artery, gastrointestinal and central nervous system involvement. Uncontrolled studies suggest promising results with interleukin-1 inhibition but gevokizumab, a humanised anti IL-1β antibody, failed to meet the primary endpoint of time to first ocular exacerbation in a phase III trial. The debate on anticoagulation continues with new observational data.

How We Identify and Manage Patients with Inadequately Controlled Polycythemia Vera.

PubMed

Reiter, Andreas; Harrison, Claire

2016-10-01

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by an overactive Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway through mutations in JAK2 exons 12 or 14 (JAK2 V617F). The dominant clinical characteristics include erythrocytosis (with or without leukocytosis/thrombocytosis), thrombotic events, and symptoms. Increased risk of mortality is mainly caused by thrombotic events and progression to post-polycythemia vera myelofibrosis (PPV-MF) or secondary acute myeloid leukemia (sAML). The most important prognostic factors include age and a history of thrombotic events, although recent evidence has indicated that leukocytosis and additional cytogenetic aberrations may also be of significant prognostic value. First-line therapies include aspirin and phlebotomies, which significantly reduce the incidence of thrombotic events and prolong survival. Cytoreductive treatment with hydroxyurea (approved) and conventional or pegylated interferon-α (effective, but not approved in many countries) is initiated for high-risk or inadequately controlled disease, e.g., uncontrolled hematocrit, leukocytosis, thrombocytosis, thrombotic events, splenomegaly, or symptoms. However, some patients may not receive initial benefit from first-line therapy or may become resistant or intolerant in due course. Although second-line treatment options are limited, clinical trials have shown the efficacy of ruxolitinib toward improving blood counts, enlarged spleen, and symptoms and potentially reducing thrombotic events. Identification of patients with uncontrolled PV is important for clinical care, as such patients have a high risk of complications, and future studies with JAK inhibitors or other agents alone or in combination are needed to test their potential to reduce rates of thrombotic events and transformation to PPV-MF or sAML.

Role of exercise training in polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Benham, J L; Yamamoto, J M; Friedenreich, C M; Rabi, D M; Sigal, R J

2018-06-12

Preliminary evidence suggests exercise in polycystic ovary syndrome (PCOS) may improve reproductive and cardiometabolic parameters. Our primary aim was to determine the impact of exercise training on reproductive health in women with PCOS. Our secondary aim was to determine the effect of exercise training on cardiometabolic indices. A systematic review of published literature was conducted using MEDLINE and EMBASE based on a pre-published protocol (PROSPERO CRD42017065324). The search was not limited by year. Randomized controlled trials, non-randomized controlled trials and uncontrolled trials that evaluated an exercise intervention in women with PCOS and reported reproductive outcomes were included. Reproductive outcomes were analysed semi-quantitatively and a meta-analysis was conducted for reported cardiometabolic outcomes. Of 517 screened abstracts, 14 studies involving 617 women with PCOS were included: seven randomized controlled trials, one non-randomized controlled trial and six uncontrolled trials. There were insufficient published data to describe the effect of exercise interventions on ovulation quantitatively, but semi-quantitative analysis suggested that exercise interventions may improve menstrual regularity, pregnancy and ovulation rates. Our meta-analysis found that exercise improved lipid profiles and decreased waist circumference, systolic blood pressure and fasting insulin. The impact of exercise interventions on reproductive function remains unclear. However, our meta-analysis suggests that exercise interventions may improve cardiometabolic profiles in women with PCOS. © 2018 World Obesity Federation.

Early clinical observations on the use of imatinib mesylate in FOP: A report of seven cases.

PubMed

Kaplan, Frederick S; Andolina, Jeffrey R; Adamson, Peter C; Teachey, David T; Finklestein, Jerry Z; Ebb, David H; Whitehead, Benjamin; Jacobs, Benjamin; Siegel, David M; Keen, Richard; Hsiao, Edward; Pignolo, Robert J

2018-04-01

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification (HO) for which there is presently no definitive treatment. Research studies have identified multiple potential targets for therapy in FOP, and novel drug candidates are being developed for testing in clinical trials. A complementary approach seeks to identify approved drugs that could be re-purposed for off-label use against defined targets in FOP. One such drug is imatinib mesylate, a tyrosine kinase inhibitor originally developed for use in patients with chronic myeloid leukemia (CML). Imatinib has the desirable effect of attacking multiple targets involved in the early hypoxic and inflammatory stages of FOP flare-ups, including HIF1-α, PDGFRα, c-KIT, and multiple MAP kinases. Based on compelling biologic rationale, strong preclinical data, and a favorable safety profile, imatinib has been prescribed on an off-label basis in a non-trial setting in seven children with continuous FOP flare-ups, predominantly in the axial regions, and which were not responsive to standard-of-care regimens. Anecdotal reports in these seven isolated cases document that the medication was well-tolerated with a ubiquitous reported decrease in the intensity of flare-ups in the six children who took the medication. These early clinical observations support the implementation of clinical trials in children with uncontrolled FOP flare-ups to determine if imatinib may ameliorate symptoms or alter the natural history of this debilitating and life-threatening disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-Management and Clinical Decision Support for Patients With Complex Chronic Conditions Through the Use of Smartphone-Based Telemonitoring: Randomized Controlled Trial Protocol

PubMed Central

Ware, Patrick; Logan, Alexander G; Cafazzo, Joseph A; Chapman, Kenneth R; Segal, Phillip; Ross, Heather J

2017-01-01

Background The rising prevalence of chronic illnesses hinders the sustainability of the health care system because of the high cost of frequent hospitalizations of patients with complex chronic conditions. Clinical trials have demonstrated that telemonitoring can improve health outcomes, but they have generally been limited to single conditions such as diabetes, hypertension, or heart failure. Few studies have examined the impact of telemonitoring on complex patients with multiple chronic conditions, although these patients may benefit the most from this technology. Objective The aim of this study is to investigate the impact of a smartphone-based telemonitoring system on the clinical care and health outcomes of complex patients across several chronic conditions. Methods A mixed-methods, 6-month randomized controlled trial (RCT) of a smartphone-based telemonitoring system is being conducted in specialty clinics. The study will include patients who have been diagnosed with one or more of any of the following conditions: heart failure, chronic obstructive pulmonary disease, chronic kidney disease, uncontrolled hypertension, or insulin-requiring diabetes. The primary outcome will be the health status of patients as measured with SF-36. Patients will be randomly assigned to either the control group receiving usual care (n=73) or the group using the smartphone-based telemonitoring system in addition to usual care (n=73). Results Participants are currently being recruited for the trial. Data collection is anticipated to be completed by the fall of 2018. Conclusions This RCT will be among the first trials to provide evidence of the impact of telemonitoring on costs and health outcomes of complex patients who may have multiple chronic conditions. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 41238563; http://www.isrctn.com/ISRCTN41238563 (Archived by WebCite at http://www.webcitation.org/6ug2Sk0af) and Clinicaltrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852 (Archived by WebCite at http://www.webcitation.org/6uvjNosBC) PMID:29162557

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

PubMed

Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

2017-12-08

Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.

A Review of Ranibizumab for the Treatment of Diabetic Retinopathy.

PubMed

Stewart, Michael W

2017-06-01

Laser photocoagulation has been the standard treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) for several decades. The discovery of vascular endothelial growth factor (VEGF) and the subsequent determination of its critical role in the development DME and PDR has led to the development of VEGF inhibitory drugs. Ranibizumab was the first anti-VEGF drug approved for the treatment of both DME and diabetic retinopathy in eyes with DME. Medline searches with the keywords "ranibizumab," "diabetic macular edema," and "proliferative diabetic retinopathy" were performed to identify pertinent pre-clinical studies and clinical trials. Top-line data, with emphasis on pivotal trials, was identified and incorporated into this manuscript. Findings from small uncontrolled trials were generally not used unless they filled important gaps in our understanding of anti-VEGF therapy. Ranibizumab is a recombinant humanized antibody fragment that binds all isoforms of VEGF-A with high affinity. Three parallel lines of clinical research have produced level I evidence supporting the superiority of ranibizumab over laser photocoagulation for the treatment of DME. Regular injections also lead to improvement in diabetic retinopathy severity scores in a large minority of eyes. Ranibizumab is effective for PDR and produces less visual field loss than laser photocoagulation. It has an excellent safety profile, with low incidence of ocular and systemic adverse events. Ranibizumab has become a frequently used first-line therapy for the treatment of DME. Emerging data suggest that it may become an important treatment for DR and PDR.

Atherosclerotic renovascular disease – epidemiology, treatment and current challenges

PubMed Central

Vassallo, Diana

2017-01-01

The neutral results of recent large randomized controlled trials comparing renal revascularization with optimal medical therapy in patients with atherosclerotic renovascular disease (ARVD) have cast doubt on the role of revascularization in the management of unselected patients with this condition. However, these studies have strengthened the evidence base for the role of contemporary intensive medical vascular protection therapy and aggressive risk factor control in improving clinical outcomes in ARVD. Patients presenting with ‘high-risk’ clinical features such as uncontrolled hypertension, rapidly declining renal function or flash pulmonary oedema are underrepresented in these studies; hence these results may not be applicable to all patients with ARVD. In this ‘high-risk’ subgroup, conservative management may not be sufficient in preventing adverse events, and indeed, observational evidence suggests that this specific patient subgroup may gain benefit from timely renal revascularization. Current challenges include the development of novel diagnostic techniques to establish haemodynamic significance of a stenosis, patient risk stratification and prediction of post-revascularization outcomes to ultimately facilitate patient selection for revascularization. In this paper we describe the epidemiology of this condition and discuss treatment recommendations for this condition in light of the results of recent randomized controlled trials while highlighting important clinical unmet needs and challenges faced by clinicians managing this condition. PMID:29056991

[Mechanical thrombectomy in acute ischemic stroke. What is the position after the latest study results?].

PubMed

Hacke, W; Diener, H-C

2015-06-01

Mechanical devices for the recanalization of vessel occlusions in severe acute ischemic stroke have been developed for more than a decade. Several devices have been approved for clinical use on the basis of uncontrolled case series. Many neurologists have asked for randomized clinical trials comparing the new devices with standard treatment, e.g. thrombolytic therapy within a 4.5 h time window. The first 3 investigator initiated randomized trials published in 2013 failed to show superiority of mechanical thrombectomy over standard treatment. In the aftermath of these negative results several new trials with changes in design (e.g. shorter time window and only proximal vessel occlusions) and the use of modern devices with proven higher recanalization rates, so called stent retrievers, have been launched. In October 2014 the first of these new trials was presented and showed a clear superiority of thrombectomy. Based on this result interim analyses of five other studies were performed and most were prematurely terminated because of overwhelming efficacy. Only one trial testing another type of recanalization device failed to reach a statistically significant result. Currently five studies have already been published and two more studies have been presented at scientific conferences. This article provides an overview of the study protocols and the results of the individual studies, their common features and the characteristics of patients who benefit from this treatment. Finally, the consequences that these results may have for the treatment of patients with severe stroke caused by proximal vessel occlusion are discussed.

Improving hypertension management through pharmacist prescribing; the rural alberta clinical trial in optimizing hypertension (Rural RxACTION): trial design and methods

PubMed Central

2011-01-01

Background Patients with hypertension continue to have less than optimal blood pressure control, with nearly one in five Canadian adults having hypertension. Pharmacist prescribing is gaining favor as a potential clinically efficacious and cost-effective means to improve both access and quality of care. With Alberta being the first province in Canada to have independent prescribing by pharmacists, it offers a unique opportunity to evaluate outcomes in patients who are prescribed antihypertensive therapy by pharmacists. Methods The study is a randomized controlled trial of enhanced pharmacist care, with the unit of randomization being the patient. Participants will be randomized to enhanced pharmacist care (patient identification, assessment, education, close follow-up, and prescribing/titration of antihypertensive medications) or usual care. Participants are patients in rural Alberta with undiagnosed/uncontrolled blood pressure, as defined by the Canadian Hypertension Education Program. The primary outcome is the change in systolic blood pressure between baseline and 24 weeks in the enhanced-care versus usual-care arms. There are also three substudies running in conjunction with the project examining different remuneration models, investigating patient knowledge, and assessing health-resource utilization amongst patients in each group. Discussion To date, one-third of the required sample size has been recruited. There are 15 communities and 17 pharmacists actively screening, recruiting, and following patients. This study will provide high-level evidence regarding pharmacist prescribing. Trial Registration Clinicaltrials.gov NCT00878566. PMID:21834970

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2012-08-15

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition.

Pulmonary Metastasectomy: A Common Practice Based on Weak Evidence

PubMed Central

Treasure, Tom

2007-01-01

The resection of secondary metastases from the lungs is a wide-spread surgical practice. Patients are referred from coloproctology teams to thoracic surgeons specifically for this surgery. What is the expected benefit? I have explored the rationale and searched the literature in order to present these patients with a well-informed opinion for their consideration. I find only weak evidence based on uncontrolled retrospective series which have been interpreted as showing a survival benefit. This has been extrapolated to policy and practice that do not stand up to scrutiny. The practice has never been subjected to randomised trial and I will argue that the present evidence is insufficient to justify the uncontrolled use of an intervention with inescapable short-term morbidity, permanent loss of function, and major cost implications. I propose ways in which the evidence may be improved, including a trial in the areas of most uncertainty. PMID:17999813

A Randomised, Double-Blind, Controlled Efficacy Trial of the LiESP/QA-21 Vaccine in Naïve Dogs Exposed to Two Leishmania infantum Transmission Seasons

PubMed Central

Oliva, Gaetano; Nieto, Javier; Foglia Manzillo, Valentina; Cappiello, Silvia; Fiorentino, Eleonora; Di Muccio, Trentina; Scalone, Aldo; Moreno, Javier; Chicharro, Carmen; Carrillo, Eugenia; Butaud, Therese; Guegand, Laurie; Martin, Virginie; Cuisinier, Anne-Marie; McGahie, David; Gueguen, Sylvie; Cañavate, Carmen; Gradoni, Luigi

2014-01-01

Canine leishmaniasis is an important zoonosis caused by uncontrolled infection with Leishmania infantum, where an inappropriate immune response is not only responsible for permitting this intracellular parasite to multiply, but is also responsible for several of the pathological processes seen in this disease. Effective canine vaccines are therefore a highly desirable prevention tool. In this randomised, double-blinded, controlled trial, the efficacy of the LiESP/QA-21 vaccine (CaniLeish, Virbac, France) was assessed by exposing 90 naïve dogs to natural L. infantum infection during 2 consecutive transmission seasons, in two highly endemic areas of the Mediterranean basin. Regular PCR, culture, serological and clinical examinations were performed, and the infection/disease status of the dogs was classified at each examination. The vaccine was well-tolerated, and provided a significant reduction in the risk of progressing to uncontrolled active infection (p = 0.025) or symptomatic disease (p = 0.046), with an efficacy of 68.4% and a protection rate of 92.7%. The probability of becoming PCR positive was similar between groups, but the probability of returning to a PCR negative condition was higher in the vaccinated group (p = 0.04). In conclusion, we confirmed the interest of using this vaccine as part of a comprehensive control program for canine leishmaniasis, and validated the use of a protocol based on regular in-depth assessments over time to assess the efficacy of a canine leishmaniasis vaccine. PMID:25299614

Reasons for uncontrolled seizures in adults; the impact of pseudointractability.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad; Ashjazadeh, Nahid; Nikseresht, Alireza; Shariat, Abdolhamid; Petramfar, Peyman; Yousefipour, Gholamali; Borhani-Haghighi, Afshin; Izadi, Sadegh; Rahimi-Jaberi, Abbas

2013-05-01

We investigated the various possible reasons for uncontrolled seizures in patients 18 years of age and older to determine the impact of pseudointractability. We also tried to investigate the various forms of pseudointractability. In this cross-sectional study, all patients 18 years of age and older with their first seizure occurring at least six months prior to the referral date, taking at least one antiepileptic drug (AED) and having at least one seizure in the past three months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: Poor compliance; Wrong medication (misclassification); Wrong dose of the correct medication; Diagnosis other than epilepsy; and finally, Medically-refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's exact tests, and a P value less than 0.05 was considered significant. 350 patients were referred to us due to uncontrolled seizures. One hundred ninety-one (55%) were male and 159 (45%) were female. Twelve percent of the patients had diagnoses other than epilepsy, 40% had indeed medically-refractory epilepsy; 29% were taking the wrong AEDs (misclassified epilepsy); 18% were taking suboptimal doses of AEDs; and 1% had poor drug compliance. The most common reason for uncontrolled seizures among patients with idiopathic generalized epilepsy was taking the wrong AED. However, among patients with focal epilepsy, true medically-refractory epilepsy was the most common reason. Uncontrolled seizures are a commonly encountered problem, especially at epilepsy clinics and one should consider all possible reasons for these uncontrolled seizures. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Food insecurity and effectiveness of behavioral interventions to reduce blood pressure, New York City, 2012-2013.

PubMed

Grilo, Stephanie A; Shallcross, Amanda J; Ogedegbe, Gbenga; Odedosu, Taiye; Levy, Natalie; Lehrer, Susan; Chaplin, William; Spruill, Tanya M

2015-02-12

Food insecurity is associated with diet-sensitive diseases and may be a barrier to successful chronic disease self-management. To evaluate the impact of food insecurity on blood pressure reduction in a pilot clinical trial, we tested the effectiveness of 2 behavioral interventions for hypertension in people with and without food security. A group of 28 men and women with type 2 diabetes and uncontrolled hypertension were randomized to either 1) home blood pressure telemonitoring alone or 2) home blood pressure telemonitoring plus telephone-based nurse case management. The primary outcome was 6-month change in systolic blood pressure. The 2 interventions resulted in modest, nonsignificant blood pressure reductions. Food-secure patients experienced clinically and statistically significant reductions in blood pressure, whereas no significant change was seen among food-insecure patients. Screening for food insecurity may help identify patients in need of tailored disease management interventions.

Therapeutic hypothermia: applications in pediatric cardiac arrest.

PubMed

Kochanek, Patrick M; Fink, Ericka L; Bell, Michael J; Bayir, Hülya; Clark, Robert S B

2009-03-01

There is a rich history for the use of therapeutic hypothermia after cardiac arrest in neonatology and pediatrics. Laboratory reports date back to 1824 in experimental perinatal asphyxia. Similarly, clinical reports in pediatric cold water drowning victims represented key initiating work in the field. The application of therapeutic hypothermia in pediatric drowning victims represented some of the seminal clinical use of this modality in modern neurointensive care. Uncontrolled application (too deep and too long) and unique facets of asphyxial cardiac arrest in children (a very difficult insult to affect any benefit) likely combined to result in abandonment of therapeutic hypothermia in the mid to late 1980s. Important studies in perinatal medicine have built upon the landmark clinical trials in adults, and are once again bringing therapeutic hypothermia into standard care for pediatrics. Although more work is needed, particularly in the use of mild therapeutic hypothermia in children, there is a strong possibility that this important therapy will ultimately have broad applications after cardiac arrest and central nervous system (CNS) insults in the pediatric arena.

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

Expert opinion: experience with 6-mercaptopurine in the treatment of inflammatory bowel disease.

PubMed

Korelitz, Burton I

2013-05-28

Arbitrarily, modern day treatment of inflammatory bowel disease begins with the introduction of immunosuppressives for ulcerative colitis. Clinical improvement with sulfasalazine had been meaningful but modest. Treatment with adrenocorticotropic hormone and corticosteroids led to clinical responses never before realized but it took much too long to recognize that they were not capable of maintaining remission, that adverse reactions were subtle but potentially devastating and that some other agent would be necessary to capitalize on their transient advantage. This of course was true in the treatment of Crohn's disease as well. Not much was ever made of the role of sulfasalazine for Crohn's disease, but with the severing of the diazobond and the elimination of the sulphur component, the 5-aminosalacylic acid (5-ASA) products clearly led to clinical improvement, especially in cases of Crohn's colitis and those with ileitis where the 5-ASA product was released in the terminal ileum and more proximal in the small bowel as well as in ulcerative colitis. The induction of remission was first demonstrated by 6-mercaptopurine (6-MP) with case reports and uncontrolled trials in patients with ulcerative colitis, but its placebo controlled trial for Crohn's disease firmly established its role in inducing remission. No subsequent trial has confirmed its similar role for ulcerative colitis, but nevertheless clinicians know well that 6-MP works at least as well and probably more effectively for ulcerative colitis than for Crohn's disease. What changes have taken place utilizing 6-MP in the management of inflammatory bowel disease since its introduction in the 1960's and 1970's and its trial for Crohn's disease published in the New England Journal of Medicine in 1980?

Expert opinion: Experience with 6-mercaptopurine in the treatment of inflammatory bowel disease

PubMed Central

Korelitz, Burton I

2013-01-01

Arbitrarily, modern day treatment of inflammatory bowel disease begins with the introduction of immunosuppressives for ulcerative colitis. Clinical improvement with sulfasalazine had been meaningful but modest. Treatment with adrenocorticotropic hormone and corticosteroids led to clinical responses never before realized but it took much too long to recognize that they were not capable of maintaining remission, that adverse reactions were subtle but potentially devastating and that some other agent would be necessary to capitalize on their transient advantage. This of course was true in the treatment of Crohn’s disease as well. Not much was ever made of the role of sulfasalazine for Crohn’s disease, but with the severing of the diazobond and the elimination of the sulphur component, the 5-aminosalacylic acid (5-ASA) products clearly led to clinical improvement, especially in cases of Crohn’s colitis and those with ileitis where the 5-ASA product was released in the terminal ileum and more proximal in the small bowel as well as in ulcerative colitis. The induction of remission was first demonstrated by 6-mercaptopurine (6-MP) with case reports and uncontrolled trials in patients with ulcerative colitis, but its placebo controlled trial for Crohn’s disease firmly established its role in inducing remission. No subsequent trial has confirmed its similar role for ulcerative colitis, but nevertheless clinicians know well that 6-MP works at least as well and probably more effectively for ulcerative colitis than for Crohn’s disease. What changes have taken place utilizing 6-MP in the management of inflammatory bowel disease since its introduction in the 1960’s and 1970’s and its trial for Crohn’s disease published in the New England Journal of Medicine in 1980? PMID:23716977

Percutaneous laser ablation of benign and malignant thyroid nodules.

PubMed

Papini, Enrico; Bizzarri, Giancarlo; Pacella, Claudio M

2008-10-01

Percutaneous image-guided procedures, largely based on thermal ablation, are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. In several uncontrolled clinical trials and in two randomized clinical trials, laser ablation has demonstrated a good efficacy and safety for the shrinkage of benign cold thyroid nodules. In hyperfunctioning nodules, laser ablation induced a nearly 50% volume reduction with a variable frequency of normalization of thyroid-stimulating hormone levels. Laser ablation has been tested for the palliative treatment of poorly differentiated thyroid carcinomas, local recurrences or distant metastases. Laser ablation therapy is indicated for the shrinkage of benign cold nodules in patients with local pressure symptoms who are at high surgical risk. The treatment should be performed only by well trained operators and after a careful cytological evaluation. Laser ablation does not seem to be consistently effective in the long-term control of hyperfunctioning thyroid nodules and is not an alternative treatment to 131I therapy. Laser ablation may be considered for the cytoreduction of tumor tissue prior to external radiation therapy or chemotherapy of local or distant recurrences of thyroid malignancy that are not amenable to surgical or radioiodine treatment.

Oral (Systemic) Botanical Agents for the Treatment of Psoriasis: A Review.

PubMed

Farahnik, Benjamin; Sharma, Divya; Alban, Joseph; Sivamani, Raja

2017-06-01

Patients with psoriasis often use botanical therapies as part of their treatment. It is important for clinicians to be aware of the current evidence regarding these agents as they treat patients. A systematic literature search was conducted using the PubMed, MEDLINE, and EMBASE database for randomized clinical trials assessing the use of botanical therapeutics for psoriasis. The search included the following keywords: "psoriasis" and "plant" or "herbal" or "botanical." Citations within articles were also reviewed to identify relevant sources. The results were then further refined by route of administration, and the oral (systemic) botanical agents are reviewed herein. A total of 12 controlled and uncontrolled clinical trials addressing the use of oral, systemic botanical agents for psoriasis were assessed in this review. While overall evidence is limited in quantity and quality, HESA-A, curcumin, neem extract, and, to a lesser degree, Traditional Chinese Medicine seem to be the most efficacious agents. The literature addresses a large amount of studies in regards to botanicals for the treatment of psoriasis. While most agents appear to be safe, further research is necessary for evidence-based recommendation of oral botanical agents to psoriasis patients.

Development of lacosamide for the treatment of partial-onset seizures.

PubMed

Doty, Pamela; Hebert, David; Mathy, Francois-Xavier; Byrnes, William; Zackheim, James; Simontacchi, Kelly

2013-07-01

Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug-drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures in those with idiopathic generalized epilepsy. © 2013 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Rationale and design of a large registry on renal denervation: the Global SYMPLICITY registry.

PubMed

Böhm, Michael; Mahfoud, Felix; Ukena, Christian; Bauer, Axel; Fleck, Eckart; Hoppe, Uta C; Kintscher, Ulrich; Narkiewicz, Krzysztof; Negoita, Manuela; Ruilope, Luis; Rump, L Christian; Schlaich, Markus; Schmieder, Roland; Sievert, Horst; Weil, Joachim; Williams, Bryan; Zeymer, Uwe; Mancia, Giuseppe

2013-08-22

Hypertension is a global healthcare concern associated with a wide range of comorbidities. The recognition that elevated sympathetic drive plays an important role in the pathogenesis of hypertension led to the use of renal artery denervation to interrupt the efferent and afferent sympathetic nerves between the brain and kidneys to lower blood pressure. Clinical trials of the Symplicity™ renal denervation system have demonstrated that radiofrequency ablation of renal artery nerves is safe and significantly lowers blood pressure in patients with severe resistant (systolic BP >160 mmHg) hypertension. Smaller ancillary studies in hypertensive patients suggest a benefit from renal denervation in a variety of conditions such as chronic kidney disease, glucose intolerance, sleep apnoea and heart failure. The Global SYMPLICITY registry, which incorporates the GREAT SYMPLICITY registry initiated in Germany, is being conducted worldwide to evaluate the safety and efficacy of treatment with the Symplicity renal denervation system in real-world uncontrolled hypertensive patients, looking first at subjects with severe resistant hypertension to confirm the results of prior clinical trials, but then also subjects with a wider range of baseline blood pressure and coexisting comorbidities. The rationale, design and first baseline data from the Global SYMPLICITY registry are presented.

Assessment of asthma control: the SERENA study.

PubMed

Corrado, Antonio; Renda, Teresa; Polese, Guido; Rossi, Andrea

2013-11-01

Several studies suggest that many asthmatic subjects have uncontrolled asthma. The control of asthma is now considered the major goal of therapy. to ascertain the level of asthma control, by Asthma Control Test (ACT), in "real-life" clinical practice and the potential risk factors for uncontrolled disease in patients treated with inhaled corticosteroids (ICS) and long-acting beta-adrenergic agonists (LABA). SERENA is a multi-centre, cross-sectional, 6-month observational, non-interventional study carried out in 16 Pulmonary Units in Italy. Asthmatic outpatients aged over 18, undergoing treatment with ICS at medium-high daily doses associated with LABA, were enrolled. The patients were divided in 3 subgroups according to the level of asthma control by ACT score (25:controlled; 20-24:partly controlled; <20: uncontrolled). Out of a total of 548 patients, 396 met the inclusion criteria. Only 9.1% of patients had asthma controlled, while partly controlled and uncontrolled asthma accounted for 39.6% and 51.3% respectively. The mean age was 54.5 ± 15.8 and the mean duration of asthma was 16.1 ± 14.1 years. There were more females than males (63% vs 37%) and females had highest prevalence of uncontrolled asthma (63.1%). The mean values of FEV1% predicted were lower in the uncontrolled group (p < 0.001). The percentage of patients with at least 1 exacerbation, unscheduled visit and/or admissions was lower in controlled (22.2%, 8.3%, 8.3%) than in partly controlled (50%, 38.6%, 9.2%) and uncontrolled (83.2%, 66.2%, 27.8%) groups (p < 0.0001). The multivariate ordinal logistic regression analysis identified female sex, FEV1 and exacerbations as the strongest independent factors associated with the uncontrolled disease. This study highlights the importance in clinical practice of a periodic assessment by a validated asthma control instrument and exacerbations/health care contacts during previous year. Clinicians should be aware that a significant proportion of patients can have uncontrolled asthma, despite regular pharmacological treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Uncontrolled hypertension among patients managed in primary healthcare facilities in Kinshasa, Democratic Republic of the Congo.

PubMed

Kika, T M; Lepira, F B; Kayembe, P K; Makulo, J R; Sumaili, E K; Kintoki, E V; M'Buyamba-Kabangu, J R

Uncontrolled hypertension remains an important issue in daily clinical practice worldwide. Although the majority of patients are treated in primary care, most of the data on blood pressure control originate from population-based studies or secondary healthcare. The aim of this study was to evaluate the frequency of uncontrolled hypertension and associated risk factors among hypertensive patients followed at primary care facilities in Kinshasa, the capital city of Democratic Republic of the Congo. A sample of 298 hypertensive patients seen at primary healthcare facilities, 90 men and 208 women, aged ≥ 18 years, were consecutively included in this cross-sectional study. The majority (66%) was receiving monotherapy, and diuretics (43%) were the most used drugs. According to 2007 European Society of Hypertension/European Society of Cardiology hypertension guidelines, uncontrolled hypertension was defined as blood pressure ≥ 140/90 or ≥ 130/80 mmHg (diabetes or chronic kidney disease). Logistic regression analysis was used to identify the determinants of uncontrolled hypertension. Uncontrolled hypertension was observed in 231 patients (77.5%), 72 men and 159 women. Uncontrolled systolic blood pressure (SBP) was more frequent than uncontrolled diastolic blood pressure (DBP) and increased significantly with advancing age (p = 0.002). The proportion of uncontrolled SBP and DBP was significantly higher in patients with renal failure (p = 0.01) and those with high (p = 0.03) to very high (p = 0.02) absolute cardiovascular risk. The metabolic syndrome (OR 2.40; 95% CI 1.01-5.74; p = 0.04) emerged as the main risk factor associated with uncontrolled hypertension. Uncontrolled hypertension was common in this case series and was associated with factors related to lifestyle and diet, which interact with blood pressure control.

Acceptability of HIV cure-related trials: the challenges for physicians and people living with HIV (ANRS-APSEC).

PubMed

Preau, Marie; Doumergue, Marjolaine; Protiere, Christel; Goujard, Cécile; Mora, Marion; Meyer, Laurence; Lelievre, Jean-Daniel; Raffi, François; Spire, Bruno; Lambotte, Olivier; Suzan-Monti, Marie

2018-07-01

Essential HIV cure-related clinical trials (HCRCT) have a potentially high-risk profile in terms of participants' health, which could hinder enrollment by people living with HIV (PLWH) and healthcare professionals (HP). The ANRS-APSEC survey is part of the IAS "Towards an HIV cure" initiative, which promotes multidisciplinary research for a safe, affordable and scalable cure. The study objectives were to understand the psychosocial mechanisms underlying PLWH and HP viewpoints about future HCRCT. Six focus group discussions (three with PLWH (n = 21) and three with HP (n = 30)) were held in three French infectious disease units. From these, three perspectives on HCRCT were identified. The first involved beliefs and knowledge associating HCRCT with poorer health and quality of life for PLWH. The second concerned perceptions of HCRCT as a biological and epidemiological flashback to a situation when HIV infection was left uncontrolled. The third was characterized by aspects of historical HIV culture that embrace innovation.

A coordinated PCP-Cardiologist Telemedicine Model (PCTM) in China's community hypertension care: study protocol for a randomized controlled trial.

PubMed

Xu, Lei; Fang, Wei-Yi; Zhu, Fu; Zhang, Hong-Guang; Liu, Kai

2017-05-25

Hypertension is a major risk factor for cardiovascular disease, and its control rate has remained low worldwide. Studies have found that telemonitoring blood pressure (BP) helped control hypertension in randomized controlled trials. However, little is known about its effect in a structured primary care model in which primary care physicians (PCPs) are partnering with cardiology specialists in electronic healthcare data sharing and medical interventions. This study aims to identify the effects of a coordinated PCP-cardiologist model that applies telemedicine tools to facilitate community hypertension control in China. Patients with hypertension receiving care at four community healthcare centers that are academically affiliated to Shanghai Chest Hospital, Shanghai JiaoTong University are eligible if they have had uncontrolled BP in the previous 3 months and access to mobile Internet. Study subjects are randomly assigned to three interventional groups: (1) usual care; (2) home-based BP telemonitor with embedded Global System for Mobile Communications (GSM) module and unlimited data plan, an app to access personal healthcare record and receive personalized lifestyle coaching contents, and proficiency training of their use; or (3) this plus coordinated PCP-cardiologist care in which PCPs and cardiologists share data via a secure CareLinker website to determine interventional approaches. The primary outcome is mean change in systolic blood pressure over a 12-month period. Secondary outcomes are changes of diastolic blood pressure, HbA1C, blood lipids, and medication adherence measured by the eight-item Morisky Medication Adherence Scale. This study will determine whether a coordinated PCP-Cardiologist Telemedicine Model that incorporates the latest telemedicine technologies will improve hypertension care. Success of the model would help streamline the present community healthcare processes and impact a greater number of patients with uncontrolled hypertension. ClinicalTrials.gov, NCT02919033 . Registered on 23 September 2016.

Impact of NGO training and support intervention on diarrhoea management practices in a rural community of Bangladesh: an uncontrolled, single-arm trial.

PubMed

Rahman, Ahmed S; Islam, Mohammad Rafiqul; Koehlmoos, Tracey P; Raihan, Mohammad Jyoti; Hasan, Mohammad Mehedi; Ahmed, Tahmeed; Larson, Charles P

2014-01-01

The evolving Non-Governmental Organization (NGO) sector in Bangladesh provides health services directly, however some NGOs indirectly provide services by working with unlicensed providers. The primary objective of this study was to examine the impact of NGO training of unlicensed providers on diarrhoea management and the scale up of zinc treatment in rural populations. An uncontrolled, single-arm trial for a training and support intervention on diarrhoea outcomes was employed in a rural sub-district of Bangladesh during 2008. Two local NGOs and their catchment populations were chosen for the study. The intervention included training of unlicensed health care providers in the management of acute childhood diarrhoea, particularly emphasizing zinc treatment. In addition, community-based promotion of zinc treatment was carried out. Baseline and endline ecologic surveys were carried out in intervention and control villages to document changes in treatments received for diarrhoea in under-five children. Among surveyed household with an active or recent acute childhood diarrhoea episode, 69% sought help from a health provider. Among these, 62.8% visited an unlicensed private provider. At baseline, 23.9% vs. 22% of control and intervention group children with diarrhoea had received zinc of any type. At endline (6 months later) this had changed to 15.3% vs. 30.2%, respectively. The change in zinc coverage was significantly higher in the intervention villages (p<0.01). Adherence with giving zinc for 10 days or more was significantly higher in the intervention households (9.2% vs. 2.5%; p<0.01). Child's age, duration of diarrhoea, type of diarrhoea, parental year of schooling as well as oral rehydration solution (ORS) and antibiotic usage were significant predictors of zinc usage. Training of unlicensed healthcare providers through NGOs increased zinc coverage in the diarrhoea management of under-five children in rural Bangladesh households. ClinicalTrials.gov NCT02143921.

A controlled time-series trial of clinical reminders: using computerized firm systems to make quality improvement research a routine part of mainstream practice.

PubMed Central

Goldberg, H. I.; Neighbor, W. E.; Cheadle, A. D.; Ramsey, S. D.; Diehr, P.; Gore, E.

2000-01-01

OBJECTIVE: To explore the feasibility of conducting unobtrusive interventional research in community practice settings by integrating firm-system techniques with time-series analysis of relational-repository data. STUDY SETTING: A satellite teaching clinic divided into two similar, but geographically separated, primary care group practices called firms. One firm was selected by chance to receive the study intervention. Forty-two providers and 2,655 patients participated. STUDY DESIGN: A nonrandomized controlled trial of computer-generated preventive reminders. Net effects were determined by quantitatively combining population-level data from parallel experimental and control interrupted time series extending over two-month baseline and intervention periods. DATA COLLECTION: Mean rates at which mammography, colorectal cancer screening, and cholesterol testing were performed on patients due to receive each maneuver at clinic visits were the trial's outcome measures. PRINCIPAL FINDINGS: Mammography performance increased on the experimental firm by 154 percent (0.24 versus 0.61, p = .03). No effect on fecal occult blood testing was observed. Cholesterol ordering decreased on both the experimental (0.18 versus 0.1 1, p = .02) and control firms (0.13 versus 0.07, p = .03) coincident with national guidelines retreating from recommending screening for young adults. A traditional uncontrolled interrupted time-series design would have incorrectly attributed the experimental-firm decrease to the introduction of reminders. The combined analysis properly indicated that no net prompting effect had occurred, as the difference between firms in cholesterol testing remained stochastically stable over time (0.05 versus 0.04, p = .75). A logistic-regression analysis applied to individual-level data produced equivalent findings. The trial incurred no supplementary data collection costs. CONCLUSIONS: The apparent validity and practicability of our reminder implementation study should encourage others to develop computerized firm systems capable of conducting controlled time-series trials. Images Fig. 1 PMID:10737451

Crestal Sinus Augmentation with Recombinant Human Bone Morphogenetic Protein 2: Clinical and Radiographic Outcomes of 2-Year Pilot Trial.

PubMed

Kuchler, Ulrike; Rudelstorfer, Claudia M; Barth, Barbara; Tepper, Gabor; Lidinsky, Dominika; Heimel, Patrick; Watzek, Georg; Gruber, Reinhard

Recombinant human bone morphogenetic protein 2 (rhBMP-2) together with an absorbable collagen carrier (ACS) was approved for augmentation of the maxillary sinus prior to implant placement. The original registration trial was based on a lateral window approach. Clinical outcomes of crestal sinus augmentation with rhBMP-2 have not been reported so far. An uncontrolled pilot trial in which seven patients with a residual maxillary height below 5 mm were enrolled to receive crestal sinus augmentation with rhBMP-2/ACS was conducted. Elevation of the sinus mucosa was performed by gel pressure. Primary endpoints were the gain in augmentation height and volume measured by computed tomography after 6 months. Evaluation of bone quality at the time of implant placement was based on histology. Secondary endpoints were the clinical and radiologic evaluation of the implants and patient satisfaction by visual analog scale (VAS) at the 2-year follow-up. Median gain in augmentation height was 7.2 mm (range 0.0 to 17.5 mm). Five patients gained at least 5 mm of bone height. Two patients with a perforation of the sinus mucosa failed to respond to rhBMP-2/ACS and underwent lateral window augmentation. The median gain in augmentation volume of the five patients was 781.3 mm³ (range 426.9 to 1,242.8 mm³). Biopsy specimens showed a cancellous network consisting of primary plexiform bone with little secondary lamellar bone. After 2 years, implants were in function with no signs of inflammation or peri-implant bone loss. Patients were satisfied with the esthetic outcomes and chewing function. This pilot clinical trial supports the original concept that rhBMP-2/ACS supports bone formation, also in crestal sinus augmentation, and emphasizes the relevance of the integrity of the sinus mucosa to predict the bone gain.

Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant

PubMed Central

Egan, T. M.; Requard, J. J.

2017-01-01

In April 2014, the American Journal of Transplantation published a report on the first lung transplant in the United States recovered from an uncontrolled donation after circulatory determination of death donor (uDCDD), assessed by ex vivo lung perfusion (EVLP). The article identified logistical and ethical issues related to introduction of lung transplant from uDCDDs. In an open clinical trial, we have Food and Drug Administration and Institutional Review Board approval to transplant lungs recovered from uDCDDs judged suitable after EVLP. Through this project and other experiences with lung recovery from uDCDDs, we have identified solutions to many logistical challenges and have addressed ethical issues surrounding lung transplant from uDCDDs that were mentioned in this case report. Here, we discuss those challenges, including issues related to recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs could solve the critical shortage of lungs for transplant. Furthermore, by avoiding the deleterious impact of brain death and days of positive pressure ventilation, and by using opportunities to treat lungs in the decedent or during EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs currently being transplanted from conventional brain-dead organ donors. PMID:25873272

White-Coat Effect Is Uncommon in Patients With Refractory Hypertension.

PubMed

Siddiqui, Mohammed; Judd, Eric K; Oparil, Suzanne; Calhoun, David A

2017-09-01

Refractory hypertension is a recently described phenotype of antihypertensive treatment failure defined as uncontrolled blood pressure (BP) despite the use of ≥5 different antihypertensive agents, including chlorthalidone and spironolactone. Recent studies indicate that refractory hypertension is uncommon, with a prevalence of ≈5% to 10% of patients referred to a hypertension specialty clinic for uncontrolled hypertension. The prevalence of white-coat effect, that is, uncontrolled automated office BP ≥135/85 mm Hg and controlled out-of-office BP <135/85 mm Hg, by awake ambulatory BP monitor in hypertensive patients overall is ≈30% to 40%. The prevalence of white-coat effect among patients with refractory hypertension has not been previously reported. In this prospective evaluation, consecutive patients referred to the University of Alabama at Birmingham Hypertension Clinic for uncontrolled hypertension were enrolled. Refractory hypertension was defined as uncontrolled automated office BP ≥135/85 mm Hg with the use of ≥5 antihypertensive agents, including chlorthalidone and spironolactone. Automated office BP measurements were based on 6 serial readings, done automatically with the use of a BpTRU device unobserved in the clinic. Out-of-office BP measurements were done by 24-hour ambulatory BP monitor. Thirty-four patients were diagnosed with refractory hypertension, of whom 31 had adequate ambulatory BP monitor readings. White-coat effect was present in only 2 patients, or 6.5% of the 31 patients with refractory hypertension, suggesting that white-coat effect is largely absent in patients with refractory hypertension. These findings suggest that white-coat effect is not a common cause of apparent lack of BP control in patients failing maximal antihypertensive treatment. © 2017 American Heart Association, Inc.

A Causal Model for Joint Evaluation of Placebo and Treatment-Specific Effects in Clinical Trials

PubMed Central

Zhang, Zhiwei; Kotz, Richard M.; Wang, Chenguang; Ruan, Shiling; Ho, Martin

2014-01-01

Summary Evaluation of medical treatments is frequently complicated by the presence of substantial placebo effects, especially on relatively subjective endpoints, and the standard solution to this problem is a randomized, double-blinded, placebo-controlled clinical trial. However, effective blinding does not guarantee that all patients have the same belief or mentality about which treatment they have received (or treatmentality, for brevity), making it difficult to interpret the usual intent-to-treat effect as a causal effect. We discuss the causal relationships among treatment, treatmentality and the clinical outcome of interest, and propose a causal model for joint evaluation of placebo and treatment-specific effects. The model highlights the importance of measuring and incorporating patient treatmentality and suggests that each treatment group should be considered a separate observational study with a patient's treatmentality playing the role of an uncontrolled exposure. This perspective allows us to adapt existing methods for dealing with confounding to joint estimation of placebo and treatment-specific effects using measured treatmentality data, commonly known as blinding assessment data. We first apply this approach to the most common type of blinding assessment data, which is categorical, and illustrate the methods using an example from asthma. We then propose that blinding assessment data can be collected as a continuous variable, specifically when a patient's treatmentality is measured as a subjective probability, and describe analytic methods for that case. PMID:23432119

Research on homeopathy: state of the art.

PubMed

Walach, Harald; Jonas, Wayne B; Ives, John; van Wijk, Roel; Weingärtner, Otto

2005-10-01

In this paper, we review research on homeopathy from four perspectives, focusing on reviews and some landmark studies. These perspectives are laboratory studies, clinical trials, observational studies, and theoretical work. In laboratory models, numerous effects and anomalies have been reported. However, no single model has been sufficiently widely replicated. Instead, researchers have focused on ever-new models and experiments, leaving the picture of scattered anomalies without coherence. Basic research, trying to elucidate a purported difference between homeopathic remedies and control solutions has also produced some encouraging results, but again, series of independent replications are missing. While there are nearly 200 reports on clinical trials, few series have been conducted for single conditions. Some of these series document clinically useful effects and differences against placebo and some series do not. Observational research into uncontrolled homeopathic practice documents consistently strong therapeutic effects and sustained satisfaction in patients. We suggest that this scattered picture has to do with the fourth line of research: lack of a good theory. Some of the extant theoretical models are reviewed, including placebo, water structure, silica contamination, energy models, and entanglement models. It emerges that local models, suggesting some change in structure in the solvent, are far from convincing. The nonlocal models proposed would predict that it is impossible to nail down homeopathic effects with direct experimental testing and this places homeopathy in a scientific dilemma. We close with some suggestions for potentially fruitful research.

Prevalence of Recommendations Made Within Dental Research Articles Using Uncontrolled Intervention or Observational Study Designs.

PubMed

Wilson, M K; Chestnutt, I G

2016-03-01

Evidence to inform clinical practice is reliant on research carried out using appropriate study design. The objectives of this work were to (i) identify the prevalence of articles reporting on human studies using uncontrolled intervention or observational research designs published in peer-reviewed dental journals and (ii) determine the nature of recommendations made by these articles. Six peer-reviewed dental journals were selected. Issues published in January to June 2013 were examined and the types of articles published categorized. Following pre-defined inclusion/exclusion criteria, human studies classified as using uncontrolled intervention or observational research designs were subject to detailed review by two independent investigators, to examine if they presented clinical, policy or research recommendations and if these recommendations were supported by the data presented. 52.9% (n = 156) of studies published during the time period met the inclusion criteria. Studies with uncontrolled intervention or observational research designs comprised a larger proportion of the primary research studies published in the journals with lower impact factors (73.3%; n = 107) compared to the high impact journals (38.9%; n = 49). Analysis showed that 60.9% (n = 95) of the included studies made recommendations for clinical practice/dental policy. In 28.2% (n = 44) of studies, the clinical/policy recommendations made were judged to not be fully supported by the data presented. Many studies published in the current dental literature, which are not considered to produce strong evidence, make recommendations for clinical practice or policy. There were some cases when the recommendations were not fully supported by the data presented. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal denervation after Symplicity HTN-3: an update.

PubMed

Persu, Alexandre; Jin, Yu; Fadl Elmula, Fadl Elmula Mohamed; Jacobs, Lotte; Renkin, Jean; Kjeldsen, Sverre

2014-08-01

After three years of excessive confidence, overoptimistic expectations and performance of 15 to 20,000 renal denervation procedures in Europe, the failure of a single well-designed US trial--Symplicity HTN-3--to meet its primary efficacy endpoint has cast doubt on renal denervation as a whole. The use of a sound methodology, including randomisation and blinded endpoint assessment was enough to see the typical 25-30 mmHg systolic blood pressure decrease observed after renal denervation melt down to less than 3 mmHg, the rest being likely explained by Hawthorne and placebo effects, attenuation of white coat effect, regression to the mean and other physician and patient-related biases. The modest blood pressure benefit directly assignable to renal denervation should be balanced with unresolved safety issues, such as potentially increased risk of renal artery stenosis after the procedure (more than ten cases reported up to now, most of them in 2014), unclear long-term impact on renal function and lack of morbidity-mortality data. Accordingly, there is no doubt that renal denervation is not ready for clinical use. Still, renal denervation is supported by a strong rationale and is occasionally followed by major blood pressure responses in at-risk patients who may otherwise have remained uncontrolled. Upcoming research programmes should focus on identification of those few patients with truly resistant hypertension who may derive a substantial benefit from the technique, within the context of well-designed randomised trials and independent registries. While electrical stimulation of baroreceptors and other interventional treatments of hypertension are already "knocking at the door", the premature and uncontrolled dissemination of renal denervation should remain an example of what should not be done, and trigger radical changes in evaluation processes of new devices by national and European health authorities.

Mindfulness-based stress reduction for Tourette Syndrome and Chronic Tic Disorder: a pilot study.

PubMed

Reese, Hannah E; Vallejo, Zayda; Rasmussen, Jessica; Crowe, Katherine; Rosenfield, Elizabeth; Wilhelm, Sabine

2015-03-01

In this pilot study we sought to develop and test a modified form of mindfulness-based stress reduction (MBSR-tics) for the treatment of Tourette Syndrome (TS) and Chronic Tic Disorder (CTD). Our specific aims were: 1) To determine the feasibility and acceptability of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD and 2) To determine the efficacy of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD. Eighteen individuals age 16-67 completed an uncontrolled open trial of MBSR-tics. The intervention consisted of 8 weekly 2-hour classes and one 4hour retreat in the fifth or sixth week of the program. Symptomatic assessments were performed at baseline, post-treatment, and one-month follow-up. MBSR-tics proved to be a feasible and acceptable intervention. It resulted in significant improvement in tic severity and tic-related impairment. 58.8% of subjects were deemed treatment responders. Therapeutic gains were maintained at 1-month follow-up. Improvements in tic severity were correlated with increases in self-reported levels of mindfulness. This small open pilot study provides preliminary support for the feasibility, acceptability, and efficacy of MBSR-tics for individuals 16 or older with TS or CTD. A larger randomized controlled trial with blind assessment is necessary to confirm these initial, promising findings. Trial Registration Partners Clinical Trials Registry Number 2011P000606 (clinicaltrials.partners.org). Copyright © 2014 Elsevier Inc. All rights reserved.

Asthma control in Saudi Arabia: Gender implications.

PubMed

Torchyan, Armen A

2017-05-01

Gender-related factors in asthma control should be considered in clinical consultations to substantially improve asthma control in women. Meanwhile, a limited number of studies have been reported on gender differences in factors related to asthma control, especially in Saudi Arabia. To study the potential gender differences in factors associated with asthma control among adult patients with physician-diagnosed asthma. A cross-sectional study was conducted in adult patients with asthma who attended primary care clinics at three major hospitals in Riyadh, Saudi Arabia. Asthma control was measured by using the Asthma Control Test. Asthma control status was classified as either controlled (Asthma Control Test score of >19) or uncontrolled (Asthma Control Test score of ≤19). Multiple logistic regression analysis was performed. In this study, 58.9% of men and 77.0% of women had uncontrolled asthma (p = 0.002). Factors associated with uncontrolled asthma were different between men and women, except for household income. Reporting higher levels of stress (odds ratio [OR] 4.3 [95% confidence interval {CI}, 1.7-11.1]), daily tobacco smoking (OR 5.8 [95% CI, 1.5-23.5]), and a monthly household income of <15,000 Saudi Arabian Riyals (OR 4.5 [95% CI, 1.9-10.5]) were associated with uncontrolled asthma in men. Being unemployed (OR 3.4 [95% CI, 1.3-9.4]), being obese (OR 3.2 [95% CI, 1.1-9.2]), or having a monthly household income of <15,000 Saudi Arabian Riyals (OR 3.1 [95% CI, 1.2-8.0]) were associated with uncontrolled asthma in women. This study demonstrated that many factors, such as stress, occupation, and obesity, had a differential relationship with uncontrolled asthma among men and women in Saudi Arabia that could provide more insight into methods of improving asthma control, especially in women.

Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

PubMed

Fukushima, Norihide; Tatsumi, Eisuke; Seguchi, Osamu; Takewa, Yoshiaki; Hamasaki, Toshimitsu; Onda, Kaori; Yamamoto, Haruko; Hayashi, Teruyuki; Fujita, Tomoyuki; Kobayashi, Junjiro

2018-06-08

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device and the day of withdrawal of a trial device), and changes in left ventricular diastolic dimension (7 days after implantation of a trial device and the day of withdrawal of a trial device). We will disseminate the findings through regional, national, and international conferences and through peer-reviewed journals. UMIN Clinical Trials Registry (UMIN-CTR; R000033243) registered on 8 September 2017.

Impact of pharmaceutical care interventions on glycemic control and other health-related clinical outcomes in patients with type 2 diabetes: Randomized controlled trial.

PubMed

Wishah, Ruba A; Al-Khawaldeh, Omar A; Albsoul, Abla M

2015-01-01

The primary aim of this study was to evaluate the impact of pharmaceutical care interventions on glycemic control and other health-related clinical outcomes in patients with type 2 diabetes patients in Jordan. A randomized controlled clinical trial was conducted on 106 patients with uncontrolled type 2 diabetes seeking care in the diabetes clinics at Jordan University Hospital. Patients were randomly allocated into control and intervention group. The intervention group patients received pharmaceutical care interventions developed by the clinical pharmacist in collaboration with the physician while the control group patients received usual care without clinical pharmacist's input. Fasting blood glucose and HbA1c were measured at the baseline, at three months, and six months intervals for both intervention and control groups. After the six months follow-up, mean of HbA1c and FBS of the patients in the intervention group decreased significantly compared to the control group patients (P<0.05). Also, the results indicated that mean scores of patients' knowledge about medications, knowledge about diabetes and adherence to medications and diabetes self-care activities of the patients in the intervention group increased significantly compared to the control group (P<0.05). This study demonstrated an improvement in HbA1c, FBS, and lipid profile, in addition to self-reported medication adherence, diabetes knowledge, and diabetes self-care activities in patients with type 2 diabetes who received pharmaceutical care interventions. The results suggest the benefits of integrating clinical pharmacist services in multidisciplinary healthcare team and diabetes management in Jordan. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain

PubMed Central

Al-Saber, Feryal; Aldosari, Waleed; Alselaiti, Mariam; Khalfan, Hesham; Kaladari, Ahmed; Khan, Ghulam; Harb, George; Rehani, Riyadh; Kudo, Sizuka; Koda, Aya; Tanaka, Tohru

2016-01-01

Type 2 diabetes mellitus is prevalent especially in Gulf countries and poses serious long-term risks to patients. A multifaceted treatment approach can include nutritional supplements with antioxidant properties such as 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC). This prospective, randomized, single-blind, placebo-controlled, dose escalating pilot clinical trial assessed the safety of 5-ALA with SFC at doses up to 200 mg 5-ALA/229.42 mg SFC per day in patients living in Bahrain with type 2 diabetes mellitus that was uncontrolled despite the use of one or more antidiabetic drugs. Fifty-three patients (n = 53) from 3 sites at one center were enrolled by Dr. Feryal (Site #01), Dr. Hesham (Site #02), and Dr. Waleed (Site #03) (n = 35, 5-ALA-SFC; n = 18, placebo). There was no significant difference in incidence of adverse events reported, and the most frequent events reported were gastrointestinal in nature, consistent with the known safety profile of 5-ALA in patients with diabetes. No significant changes in laboratory values and no difference in hypoglycemia between patients receiving 5-ALA and placebo were noted. Overall, the current results support that use of 5-ALA-SFC up to 200 mg per day taken as 2 divided doses is safe in patients taking concomitant oral antidiabetic medications and may offer benefits in the diabetic population. This trial is registered with ClinicalTrials.gov NCT02481141. PMID:27738640

Rodent models of depression: learned helplessness induced in mice.

PubMed

Anisman, H; Merali, Z

2001-05-01

Uncontrollable stressors induce a variety of behavioral disturbances that are in many ways reminiscent of the symptoms that characterize clinical depression. These deficits are evident across a range of species, including mice. Given the increasing focus on genetic techniques involving mice to identify the mechanisms subserving these behavioral disturbances (e.g., recombinant, knockout, and transgenic strains), it is of particular interest to provide a detailed description of the method to induce behavioral deficits in response to uncontrollable stressors. This unit describes the procedure used to assess the effects of controllable and uncontrollable shock on subsequent shock escape performance in mice using an escape-delay procedure.

Can virtual reality exposure therapy gains be generalized to real-life? A meta-analysis of studies applying behavioral assessments.

PubMed

Morina, Nexhmedin; Ijntema, Hiske; Meyerbröker, Katharina; Emmelkamp, Paul M G

2015-11-01

In virtual reality exposure therapy (VRET), patients are exposed to virtual environments that resemble feared real-life situations. The aim of the current study was to assess the extent to which VRET gains can be observed in real-life situations. We conducted a meta-analysis of clinical trials applying VRET to specific phobias and measuring treatment outcome by means of behavioral laboratory tests or recordings of behavioral activities in real-life. Data sources were searches of databases (Medline, PsycInfo, and Cochrane). We included in total 14 clinical trials on specific phobias. Results revealed that patients undergoing VRET did significantly better on behavioral assessments following treatment than before treatment, with an aggregated uncontrolled effect size of g = 1.23. Furthermore, patients undergoing VRET performed better on behavioral assessments at post-treatment than patients on wait-list (g = 1.41). Additionally, results of behavioral assessment at post-treatment and at follow-up revealed no significant differences between VRET and exposure in vivo (g = -0.09 and 0.53, respectively). Finally, behavioral measurement effect sizes were similar to those calculated from self-report measures. The findings demonstrate that VRET can produce significant behavior change in real-life situations and support its application in treating specific phobias. Copyright © 2015 Elsevier Ltd. All rights reserved.

The FDA alert on suicidality and antiepileptic drugs: Fire or false alarm?

PubMed

Hesdorffer, Dale C; Kanner, Andres M

2009-05-01

In January 2008, the U.S. Food and Drug Administration (FDA) issued an alert about an increased risk for suicidality in 199 clinical trials of 11 antiepileptic drugs (AEDs) for three different indications, including epilepsy. An advisory panel voted against a black-box warning on AED labels, and the FDA has accepted this recommendation. We discuss three potential problems with the alert. First, adverse event data were used rather than systematically collected data. Second, the 11 drugs grouped together as a single class of AEDs have different mechanisms of action and very different relative risks, many of which were not statistically significant and some of which were smaller than one. These facts suggest that they should not be grouped as a class. Third, the risk of adverse effects from uncontrolled seizures almost certainly outweighs the small risk of suicidality. We place our comments in the context of a review of the literature on suicidality and depression in epilepsy and the sparse literature on AEDs and suicidality. We recommend that all patients with epilepsy be routinely evaluated for depression, anxiety, and suicidality, and that future clinical trials include validated instruments to systematically assess these conditions to determine whether the possible signal observed by the FDA is real.

Mind-body Therapies for Menopausal Symptoms: A Systematic Review

PubMed Central

Innes, Kim E; Selfe, Terry Kit; Vishnu, Abhishek

2010-01-01

Objective To systematically review the peer-reviewed literature regarding the effects of self-administered mind-body therapies on menopausal symptoms. Methods To identify qualifying studies, we searched 10 scientific databases and scanned bibliographies of relevant review papers and all identified articles. The methodological quality of all studies was assessed systematically using predefined criteria. Results Twenty-one papers representing 18 clinical trials from 6 countries met our inclusion criteria, including 12 randomized controlled trials (N=719), 1 non-randomized controlled trial (N=58), and 5 uncontrolled trials (N=105). Interventions included yoga and/or meditation-based programs, tai chi, and other relaxation practices, including muscle relaxation and breath-based techniques, relaxation response training, and low frequency sound-wave therapy. Eight of the nine studies of yoga, tai chi, and meditation-based programs reported improvement in overall menopausal and vasomotor symptoms; six of seven trials indicated improvement in mood and sleep with yoga-based programs, and four studies reported reduced musculoskeletal pain. Results from the remaining nine trials suggest that breath-based and other relaxation therapies also show promise for alleviating vasomotor and other menopausal symptoms, although intergroup findings were mixed. Most studies reviewed suffered methodological or other limitations, complicating interpretation of findings. Conclusions Collectively, findings of these studies suggest that yoga-based and certain other mind-body therapies may be beneficial for alleviating specific menopausal symptoms. However, the limitations characterizing most studies hinder interpretation of findings and preclude firm conclusions regarding efficacy. Additional large, methodologically sound trials are needed to determine the effects of specific mind-body therapies on menopausal symptoms, examine long-term outcomes, and investigate underlying mechanisms. PMID:20167444

Propofol versus thiopental sodium for the treatment of refractory status epilepticus (Review).

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2013-07-01

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.

PubMed

Niess, Hanno; von Einem, Jobst C; Thomas, Michael N; Michl, Marlies; Angele, Martin K; Huss, Ralf; Günther, Christine; Nelson, Peter J; Bruns, Christiane J; Heinemann, Volker

2015-04-08

Adenocarcinoma originating from the digestive system is a major contributor to cancer-related deaths worldwide. Tumor recurrence, advanced local growth and metastasis are key factors that frequently prevent these tumors from curative surgical treatment. Preclinical research has demonstrated that the dependency of these tumors on supporting mesenchymal stroma results in susceptibility to cell-based therapies targeting this stroma. TREAT-ME1 is a prospective, uncontrolled, single-arm phase I/II study assessing the safety and efficacy of genetically modified autologous mesenchymal stromal cells (MSC) as delivery vehicles for a cell-based gene therapy for advanced, recurrent or metastatic gastrointestinal or hepatopancreatobiliary adenocarcinoma. Autologous bone marrow will be drawn from each eligible patient after consent for bone marrow donation has been obtained (under a separate EC-approved protocol). In the following ~10 weeks the investigational medicinal product (IMP) is developed for each patient. To this end, the patient's MSCs are stably transfected with a gamma-retroviral, replication-incompetent and self-inactivating (SIN) vector system containing a therapeutic promoter - gene construct that allows for tumor-specific expression of the therapeutic gene. After release of the IMP the patients are enrolled after given informed consent for participation in the TREAT-ME 1 trial. In the phase I part of the study, the safety of the IMP is tested in six patients by three treatment cycles consisting of re-transfusion of MSCs at different concentrations followed by administration of the prodrug Ganciclovir. In the phase II part of the study, sixteen patients will be enrolled receiving IMP treatment. A subgroup of patients that qualifies for surgery will be treated preoperatively with the IMP to verify homing of the MSCs to tumors as to be confirmed in the surgical specimen. The TREAT-ME1 clinical study involves a highly innovative therapeutic strategy combining cell and gene therapy and is conducted at a high level of pharmaceutical quality ensuring patient safety. This patient-tailored approach represents the first clinical study worldwide utilizing genetically engineered MSCs in humans. EU Clinical Trials Register/European Union Drug Regulating Authorities Clinical Trials Database number: 2012-003741-15.

Effectiveness of a medical education intervention to treat hypertension in primary care.

PubMed

Martínez-Valverde, Silvia; Castro-Ríos, Angélica; Pérez-Cuevas, Ricardo; Klunder-Klunder, Miguel; Salinas-Escudero, Guillermo; Reyes-Morales, Hortensia

2012-04-01

In Mexico, hypertension is among the top five causes for visits to primary care clinics; its complications are among the main causes of emergency and hospital care. The present study reports the effectiveness of a continuing medical education (CME) intervention to improve appropriate care for hypertension, on blood pressure control of hypertensive patients in primary care clinics. A secondary data analysis was carried out using data of hypertensive patients treated by family doctors who participated in the CME intervention. The evaluation was designed as a pre-/post-intervention study with control group in six primary care clinics. The effect of the CME intervention was analysed using multiple logistic regression modelling in which the dependent variable was uncontrolled blood pressure in the post-intervention patient measurement. After the CME intervention, the net reduction of uncontrolled blood pressure between stages in the intervention group was 10.3%. The model results were that being treated by a family doctor who participated in the CME intervention reduced by 53% the probability of lack of control of blood pressure; receiving dietary recommendations reduced 57% the probability of uncontrolled blood pressure. Having uncontrolled blood pressure at the baseline stage increased the probability of lack of control in 166%, and per each unit of increase in body mass index the lack of control increased 7%. CME intervention improved the medical decision-making process to manage hypertension, thus increasing the probability of hypertensive patients to have blood pressure under control. © 2010 Blackwell Publishing Ltd.

Desferrithiocin: A Search for Clinically Effective Iron Chelators

PubMed Central

2015-01-01

The successful search for orally active iron chelators to treat transfusional iron-overload diseases, e.g., thalassemia, is overviewed. The critical role of iron in nature as a redox engine is first described, as well as how primitive life forms and humans manage the metal. The problems that derive when iron homeostasis in humans is disrupted and the mechanism of the ensuing damage, uncontrolled Fenton chemistry, are discussed. The solution to the problem, chelator-mediated iron removal, is clear. Design options for the assembly of ligands that sequester and decorporate iron are reviewed, along with the shortcomings of the currently available therapeutics. The rationale for choosing desferrithiocin, a natural product iron chelator (a siderophore), as a platform for structure–activity relationship studies in the search for an orally active iron chelator is thoroughly developed. The study provides an excellent example of how to systematically reengineer a pharmacophore in order to overcome toxicological problems while maintaining iron clearing efficacy and has led to three ligands being evaluated in human clinical trials. PMID:25207964

Genetic and epigenetic instability of stem cells.

PubMed

Rajamani, Karthyayani; Li, Yuan-Sheng; Hsieh, Dean-Kuo; Lin, Shinn-Zong; Harn, Horng-Jyh; Chiou, Tzyy-Wen

2014-01-01

Recently, research on stem cells has been receiving an increasing amount of attention, both for its advantages and disadvantages. Genetic and epigenetic instabilities among stem cells have been a recurring obstacle to progress in regenerative medicine using stem cells. Various reports have stated that these instabilities can transform stem cells when transferred in vivo and thus have the potential to develop tumors. Previous research has shown that various extrinsic and intrinsic factors can contribute to the stability of stem cells. The extrinsic factors include growth supplements, growth factors, oxygen tension, passage technique, and cryopreservation. Controlling these factors based on previous reports may assist researchers in developing strategies for the production and clinical application of "safe" stem cells. On the other hand, the intrinsic factors can be unpredictable and uncontrollable; therefore, to ensure the successful use of stem cells in regenerative medicine, it is imperative to develop and implement appropriate strategies and technique for culturing stem cells and to confirm the genetic and epigenetic safety of these stem cells before employing them in clinical trials.

Levetiracetam induced acute reversible psychosis in a patient with uncontrolled seizures

PubMed Central

Kumar, Nithin; Swaroop, H. S.; Chakraborty, Ananya; Chandran, Suhas

2014-01-01

Levetiracetam (LEV) is a relatively newer antiepileptic drug with novel mechanism of action. It was introduced to the market in the year 2000. Pre-marketing clinical trials of the drug reported good tolerability with a wide safety margin. On post-marketing updates, there are few reports of psychosis after treatment with the drug. Here, we report a case of 52-year-old epileptic man who developed acute, reversible psychosis within 3 days of initiation of treatment. The drug was prescribed at a dose of 500 mg per day. After 3 days of treatment, the patient developed visual hallucinations, mood swings, withdrawal and suspicious behavior. Delirium was ruled out as there was no fluctuation in his sensorium or focal neurological deficits. His lab investigations for electrolytes, renal function test, thyroid, liver function and other related tests levels were within normal limits. A diagnosis of LEV induced psychosis was reached based on clinical judgment and causality assessment. PMID:25298593

Young-age gender differences in mathematics mediated by independent control or uncontrollability.

PubMed

Zirk-Sadowski, Jan; Lamptey, Charlotte; Devine, Amy; Haggard, Mark; Szűcs, Dénes

2014-05-01

We studied whether the origins of math anxiety can be related to a biologically supported framework of stress induction: (un)controllability perception, here indicated by self-reported independent efforts in mathematics. Math anxiety was tested in 182 children (8- to 11-year-olds). Latent factor modeling was used to test hypotheses on plausible causal processes and mediations within competing models in quasi-experimental contrasts. Uncontrollability perception in mathematics, or (in)dependence of efforts, best fit the data as an antecedent of math anxiety. In addition, the relationship of math anxiety with gender was fully mediated by adaptive perception of control (i.e. controllability). That is, young boys differ from girls in terms of their experience of control in mathematics learning. These differences influence math anxiety. Our findings are consistent with recent suggestions in clinical literature according to which uncontrollability makes women more susceptible to fear and anxiety disorders. © 2014 John Wiley & Sons Ltd.

Health coaching by medical assistants to improve control of diabetes, hypertension, and hyperlipidemia in low-income patients: a randomized controlled trial.

PubMed

Willard-Grace, Rachel; Chen, Ellen H; Hessler, Danielle; DeVore, Denise; Prado, Camille; Bodenheimer, Thomas; Thom, David H

2015-03-01

Health coaching by medical assistants could be a financially viable model for providing self-management support in primary care if its effectiveness were demonstrated. We investigated whether in-clinic health coaching by medical assistants improves control of cardiovascular and metabolic risk factors when compared with usual care. We conducted a 12-month randomized controlled trial of 441 patients at 2 safety net primary care clinics in San Francisco, California. The primary outcome was a composite measure of being at or below goal at 12 months for at least 1 of 3 uncontrolled conditions at baseline as defined by hemoglobin A1c, systolic blood pressure, and low-density lipoprotein (LDL) cholesterol. Secondary outcomes were meeting all 3 goals and meeting individual goals. Data were analyzed using χ(2) tests and linear regression models. Participants in the coaching arm were more likely to achieve both the primary composite measure of 1 of the clinical goals (46.4% vs 34.3%, P = .02) and the secondary composite measure of reaching all clinical goals (34.0% vs 24.7%, P = .05). Almost twice as many coached patients achieved the hemoglobin A1c goal (48.6% vs 27.6%, P = .01). At the larger study site, coached patients were more likely to achieve the LDL cholesterol goal (41.8% vs 25.4%, P = .04). The proportion of patients meeting the systolic blood pressure goal did not differ significantly. Medical assistants serving as in-clinic health coaches improved control of hemoglobin A1c and LDL levels, but not blood pressure, compared with usual care. Our results highlight the need to understand the relationship between patients' clinical conditions, interventions, and the contextual features of implementation. © 2015 Annals of Family Medicine, Inc.

Health Coaching by Medical Assistants to Improve Control of Diabetes, Hypertension, and Hyperlipidemia in Low-Income Patients: A Randomized Controlled Trial

PubMed Central

Willard-Grace, Rachel; Chen, Ellen H.; Hessler, Danielle; DeVore, Denise; Prado, Camille; Bodenheimer, Thomas; Thom, David H.

2015-01-01

PURPOSE Health coaching by medical assistants could be a financially viable model for providing self-management support in primary care if its effectiveness were demonstrated. We investigated whether in-clinic health coaching by medical assistants improves control of cardiovascular and metabolic risk factors when compared with usual care. METHODS We conducted a 12-month randomized controlled trial of 441 patients at 2 safety net primary care clinics in San Francisco, California. The primary outcome was a composite measure of being at or below goal at 12 months for at least 1 of 3 uncontrolled conditions at baseline as defined by hemoglobin A1c, systolic blood pressure, and low-density lipoprotein (LDL) cholesterol. Secondary outcomes were meeting all 3 goals and meeting individual goals. Data were analyzed using χ2 tests and linear regression models. RESULTS Participants in the coaching arm were more likely to achieve both the primary composite measure of 1 of the clinical goals (46.4% vs 34.3%, P = .02) and the secondary composite measure of reaching all clinical goals (34.0% vs 24.7%, P = .05). Almost twice as many coached patients achieved the hemoglobin A1c goal (48.6% vs 27.6%, P = .01). At the larger study site, coached patients were more likely to achieve the LDL cholesterol goal (41.8% vs 25.4%, P = .04). The proportion of patients meeting the systolic blood pressure goal did not differ significantly. CONCLUSIONS Medical assistants serving as in-clinic health coaches improved control of hemoglobin A1c and LDL levels, but not blood pressure, compared with usual care. Our results highlight the need to understand the relationship between patients’ clinical conditions, interventions, and the contextual features of implementation. PMID:25755034

Treatment of Carpal Tunnel Syndrome in pregnancy with Polarized Polychromatic Non-coherent Light (Bioptron Light): A Preliminary, Prospective, Open Clinical Trial.

PubMed

Dimitrios, Stasinopoulos; Stasinopoulos, Loannis

2017-12-31

The aim of this trial was to assess the efficacy of polarized polychromatic noncoherent light (Bioptron light) in the treatment of Carpal Tunnel Syndrome (CTS) in pregnancy. An uncontrolled experimental study was conducted in pregnant patients with CTS who visited our clinic from January 2006 to January 2010. Bioptron light (480-3400 nm; 95% polarization; 40 mW/cm 2 ; and 2.4 J/cm 2 ) was administered perpendicular to the carpal tunnel area. The irradiation time for each session was 6 min at an operating distance of 5-10 cm from the carpal tunnel area, twice each day, five days per week for 2 weeks. Pain and paraesthesia using a visual analogue scale (VAS) and finger pinch strength were evaluated at the end of treatment (week 2) and 1-month (week 6) after the end of treatment. The Student'sttest was used and p values < 0.05 were accepted as statistically significant. 46 patients participated in the study. The mean age of subjects was 27.6 years (range 22-37). The patient population had a mean duration of CTS of 2.3 months (range 1-4). All patients were in the third trimester. Pain and paraesthesia decreased at the end of treatment and at the 1-month follow-up, whereas the finger pinch strength increased at the end of treatment and at the 1-month follow-up. In conclusion, the results of the present study suggest that Bioptron light is a reliable, safe, and effective treatment option in pregnant patients with CTS. Controlled clinical trials are needed to establish the absolute and relative effectiveness of this intervention.

Observational study of Arctium lappa in the treatment of acne vulgaris.

PubMed

Miglani, Anjali; Manchanda, Raj K

2014-07-01

Arctium lappa (Lappa) is used in traditional Western and Chinese medicine for acne. It is mentioned in homeopathic literature for acne, but its effect has not previously been evaluated. To determine the effectiveness of homeopathic medicine Lappa in treatment of acne vulgaris. An uncontrolled observational interventional study was conducted on human subjects who fulfilled the inclusion criteria and gave written informed consent. Lappa was prescribed in potencies starting from 6c rising to 1M as required, over a period of 6 months. Objective assessment was change in acne lesion counts supplemented with Global Acne Grading System (GAGS) and subjective assessment by using Acne-Specific Quality of Life questionnaire (Acne-QoL). Out of 34 human subjects, 32 completed the follow-up. Statistical significant results were seen in lesion counts, GAGS and Acne-QoL score (p value <0.001). Lappa has shown positive effects in the treatment of acne especially of inflammatory type. Further controlled, randomized studies with larger sample size are desirable. Trial is registered at ClinicalTrials.gov Identifier: NCT01040390. Copyright © 2013 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

A Multiinstitutional Phase 2 Trial of Pazopanib Monotherapy in Advanced Anaplastic Thyroid Cancer

PubMed Central

Suman, Vera J.; Menefee, Michael E.; Smallridge, Robert C.; Molina, Julian R.; Maples, William J.; Karlin, Nina J.; Traynor, Anne M.; Kumar, Priya; Goh, Boon Cher; Lim, Wan-Teck; Bossou, Ayoko R.; Isham, Crescent R.; Webster, Kevin P.; Kukla, Andrea K.; Bieber, Carolyn; Burton, Jill K.; Harris, Pamela; Erlichman, Charles

2012-01-01

Context/Objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). Design/Setting/Patients/Interventions/Outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45–77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC. PMID:22774206

Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial.

PubMed

Nowak, Albina; Boesch, Lukas; Andres, Erik; Battegay, Edouard; Hornemann, Thorsten; Schmid, Christoph; Bischoff-Ferrari, Heike A; Suter, Paolo M; Krayenbuehl, Pierre-Alexandre

2016-12-01

Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials. This is the first double-blind placebo-controlled clinical trial to investigate the efficacy of per os vitamin D3 (cholecalciferol) in treating fatigue among otherwise healthy persons with low serum 25-hydroxyvitamin D (25(OH)D) levels. We enrolled 120 individuals (mean age 29 ± 6 years, 53% women) presenting with fatigue and vitamin D deficiency (serum 25(OH)D < 20 μg/L). Participants were randomized to a single oral dose of 100,000 units of vitamin D or placebo. The primary endpoint was intra-individual change in the fatigue assessment scale (FAS) at 4 weeks after treatment. The mean age of the participants was 29 ± 6 years, 53% were women. Mean FAS decreased significantly more in the vitamin D group (-3.3 ± 5.3; 95% confidence interval [CI] for change -14.1 to 4.1) compared with placebo (-0.8 ± 5.3; 95% CI for change -9.0 to 8.7); (P = 0.01). Amelioration of fatigue was reported more frequently in vitamin D than in placebo group (42 [72%] vs. 31 [50%]; P = 0.01; odds ratio [OR] 2.63, 95% CI for OR 1.23-5.62). Among all participants, improvement in fatigue score correlated with the rise in 25(OH)D level (R = -0.22, P = 0.02). Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency.This study was registered at the www.ClinicalTrials.gov Protocol ID NCT02022475.

Multidisciplinary approach to management of maternal asthma (MAMMA [copyright]): the PROTOCOL for a randomized controlled trial.

PubMed

Lim, Angelina; Stewart, Kay; Abramson, Michael J; Walker, Susan P; George, Johnson

2012-12-19

Uncontrolled asthma during pregnancy is associated with the maternal hazards of disease exacerbation, and perinatal hazards including intrauterine growth restriction and preterm birth. Interventions directed at achieving better asthma control during pregnancy should be considered a high priority in order to optimise both maternal and perinatal outcomes. Poor compliance with prescribed asthma medications during pregnancy and suboptimal prescribing patterns to pregnant women have both been shown to be contributing factors that jeopardise asthma control. The aim is to design and evaluate an intervention involving multidisciplinary care for women experiencing asthma in pregnancy. A pilot single-blinded parallel-group randomized controlled trial testing a Multidisciplinary Approach to Management of Maternal Asthma (MAMMA©) which involves education and regular monitoring. Pregnant women with asthma will be recruited from antenatal clinics in Victoria, Australia. Recruited participants, stratified by disease severity, will be allocated to the intervention or the usual care group in a 1:1 ratio. Both groups will be followed prospectively throughout pregnancy and outcomes will be compared between groups at three and six months after recruitment to evaluate the effectiveness of this intervention. Outcome measures include Asthma Control Questionnaire (ACQ) scores, oral corticosteroid use, asthma exacerbations and asthma related hospital admissions, and days off work, preventer to reliever ratio, along with pregnancy and neonatal adverse events at delivery. The use of FEV(1)/FEV(6) will be also investigated during this trial as a marker for asthma control. If successful, this model of care could be widely implemented in clinical practice and justify more funding for support services and resources for these women. This intervention will also promote awareness of the risks of poorly controlled asthma and the need for a collaborative, multidisciplinary approach to asthma management during pregnancy. This is also the first study to investigate the use of FEV1/FEV6 as a marker for asthma control during pregnancy. Australian New Zealand Clinical Trials Registry (ACTRN12612000681853).

Effect of Black Tea Intake on Blood Cholesterol Concentrations in Individuals with Mild Hypercholesterolemia: A Diet-Controlled Randomized Trial

PubMed Central

Troup, Rasa; Hayes, Jennifer H.; Raatz, Susan K.; Thyagarajan, Bharat; Khaliq, Waseem; Jacobs, David R.; Key, Nigel S.; Morawski, Bozena M.; Kaiser, Daniel; Bank, Alan J.; Gross, Myron

2014-01-01

Habitual intake of black tea has been associated with relatively lower serum cholesterol concentrations in observational studies. However, clinical trial results evaluating the effects of black tea on serum cholesterol have been inconsistent. Several factors could explain these mixed results, in particular, uncontrolled confounding caused by lifestyle factors, e.g. diet. This diet-controlled clinical trial estimates the effect of black tea flavonoid consumption on cholesterol concentrations in 57 borderline hypercholesterolemic individuals (total cholesterol concentrations between 190 and 260 mg/dl (4.9 and 6.7 mmol/L)). A double blind, randomized crossover trial was conducted in Minneapolis, MN from April 2002 through April 2004, wherein key conditions were tightly controlled to minimize possible confounding. Participants consumed a controlled low-flavonoid diet plus 5 cups per day of black tea or tea-like placebo over two 4-week treatment periods. The flavonoid-free caffeinated placebo matched the tea in color and taste. Differences in cholesterol concentrations at the end of each treatment period were evaluated via linear mixed models. Differences (95% CI) in mg/dl among those treated with tea versus placebo were 3.43 (−7.08, 13.94) for total cholesterol, −1.02 (−11.34, 9.30) for low-density lipoprotein cholesterol (LDL-C), 0.58 (−2.98, 4.14) for high-density lipoprotein cholesterol (HDL-C), 15.22 (−40.91, 71.35) for triglycerides, and −0.39 (−11.16, 10.38) for LDL plus HDL cholesterol fraction. The LCL-C/HDL-C ratio decreased by −0.1 units (95% CI −0.41, 0.21). No results were statistically or clinically significant. Thus, the intake of 5 cups of black tea per day did not significantly alter the lipid profile of borderline hypercholesterolemic subjects. PMID:25266246

[Primary care physicians behaviour on hypertensive patients with poor blood pressure control. The PRESCAP 2006 study].

PubMed

Alonso-Moreno, F J; Llisterri Caro, J L; Rodríguez-Roca, G C; Ferreiro Madueño, M; González-Segura Alsina, D; Divisón Garrote, J A; Banegas, J R; Barrios Alonso, V; Lou Arnal, S; Sánchez Ruiz, T; Santos Rodríguez, J A; Durá Belinchón, R

2008-09-01

There is little information available on Therapeutic Inertia in Primary Care (PC). This study aimed to know the therapeutic behavior of the physician for uncontrolled hypertensive patients. Cross-sectional, multicenter study that included hypertensive patients of both genders, under pharmacological treatment who were recruited consecutively in the PC out-patient clinic in all of Spain. Social-demographic, clinical and treatment data were recorded, as well as the motives for eventual therapeutic modification. Adequate BP control was considered when BP values were below 140/90 mmHg in general, and below 130/80 mmHg in diabetes, renal insufficiency or cardiovascular disease. A total of 10,520 patients (53.7% women) were included with average age of 64.6 (11.3 years). Of these, 44.4% the patients were receiving monotherapy and 55.6% were treated with combined therapy (two drugs 41.2%, three drugs 11.7%, and more than three 2.8%). Uncontrolled hypertension was found in 58.6% (95% CI. 57.6-59.5) of the patients. Treatment was modified by physicians in 30.4% (95% CI. 29.2-31.6) of the uncontrolled patients, combination with another drug being the most frequent behavior (46.3%), followed by dose increase (26.1%), and antihypertensive drug switch (22.8%). The perception of the physician of good BP control was the factor most associated with not modifying the treatment in uncontrolled patients. Study results showed that the PC physician modified antihypertensive treatment in only 3 out of 10 uncontrolled patients. When treatment modification was made, association of drugs was the most frequent behavior.

Effects of Diaphragmatic Breathing Patterns on Balance: A Preliminary Clinical Trial.

PubMed

Stephens, Rylee J; Haas, Mitchell; Moore, William L; Emmil, Jordan R; Sipress, Jayson A; Williams, Alex

The purpose of this study was to determine the feasibility of performing a larger study to determine if training in diaphragmatic breathing influences static and dynamic balance. A group of 13 healthy persons (8 men, 5 women), who were staff, faculty, or students at the University of Western States participated in an 8-week breathing and balance study using an uncontrolled clinical trial design. Participants were given a series of breathing exercises to perform weekly in the clinic and at home. Balance and breathing were assessed at the weekly clinic sessions. Breathing was evaluated with Liebenson's breathing assessment, static balance with the Modified Balance Error Scoring System, and dynamic balance with OptoGait's March in Place protocol. Improvement was noted in mean diaphragmatic breathing scores (1.3 to 2.6, P < .001), number of single-leg stance balance errors (7.1 to 3.8, P = .001), and tandem stance balance errors (3.2 to 0.9, P = .039). A decreasing error rate in single-leg stance was associated with improvement in breathing score within participants over the 8 weeks of the study (-1.4 errors/unit breathing score change, P < .001). Tandem stance performance did not reach statistical significance (-0.5 error/unit change, P = .118). Dynamic balance was insensitive to balance change, being error free for all participants throughout the study. This proof-of-concept study indicated that promotion of a costal-diaphragmatic breathing pattern may be associated with improvement in balance and suggests that a study of this phenomenon using an experimental design is feasible. Copyright © 2017. Published by Elsevier Inc.

Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

PubMed

Hoffman, Andrew M; Dow, Steven W

2016-07-01

Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. © 2016 AlphaMed Press.

Care manager to control cardiovascular risk factors in primary care: the Raffaello cluster randomized trial.

PubMed

Deales, A; Fratini, M; Romano, S; Rappelli, A; Penco, M; Perna, G Piero; Beccaceci, G; Borgia, R; Palumbo, W; Magi, M; Vespasiani, G; Bronzini, M; Musilli, A; Nocciolini, M; Mezzetti, A; Manzoli, L

2014-05-01

This cluster randomized trial evaluated the efficacy of a disease and care management (D&CM) model in cardiovascular (CVD) prevention in primary care. Eligible subjects had ≥ 1 among: blood pressure ≥ 140/90 mmHg; glycated hemoglobin ≥ 7%; LDL-cholesterol ≥ 160 or ≥ 100 mg/dL (primary or secondary prevention, respectively); BMI ≥ 30; current smoking. The D&CM intervention included a teamwork including nurses as care managers for the implementation of tailored care plans. Control group was allocated to usual-care. The main outcome was the proportion of subjects achieving recommended clinical targets for ≥ 1 of uncontrolled CVD risk factors at 12-month. During 2008-2009 we enrolled 920 subjects in the Abruzzo/Marche regions, Italy. Following the exclusion of L'Aquila due to 2009 earthquake, final analyses included 762 subjects. The primary outcome was achieved by 39.1% (95%CI: 34.2-44.2) and 25.2% (95%CI: 20.9-29.9) of subjects in the intervention and usual-care group, respectively (p < 0.001). The D&CM intervention significantly increased the proportion of subjects who achieved clinical targets for both diabetes and hypertension, with no differences in hypercholesterolemia, smoking status and obesity. The D&CM intervention was effective in controlling cardiovascular risk factors, in particular hypertension and diabetes. Numbers needed to treat were small. Such intervention may deserve further consideration in clinical practice. ACTRN12611000813987. Copyright © 2013 Elsevier B.V. All rights reserved.

What Happens After Health Coaching? Observational Study 1 Year Following a Randomized Controlled Trial

PubMed Central

Sharma, Anjana E.; Willard-Grace, Rachel; Hessler, Danielle; Bodenheimer, Thomas; Thom, David H.

2016-01-01

PURPOSE Health coaching is effective for chronic disease self-management in the primary care safety-net setting, but little is known about the persistence of its benefits. We conducted an observational study evaluating the maintenance of improved cardiovascular risk factors following a health coaching intervention. METHODS We performed a naturalistic follow-up to the Health Coaching in Primary Care Study, a 12-month randomized controlled trial (RCT) comparing health coaching to usual care for patients with uncontrolled diabetes, hypertension, or hyperlipidemia. Participants were followed up 24 months from RCT baseline. The primary outcome was the proportion at goal for at least 1 measure (hemoglobin A1c, systolic blood pressure, or LDL cholesterol) that had been above goal at enrollment; secondary outcomes included each individual clinical goal. Chi-square tests and paired t-tests compared dichotomous and continuous measures. RESULTS 290 of 441 participants (65.8%) participated at both 12 and 24 months. The proportion of patients in the coaching arm of the RCT who achieved the primary outcome dropped only slightly from 47.1% at 12 to 45.9% at 24 months (P = .80). The proportion at goal for hemoglobin A1c dropped from 53.4% to 36.2% (P = .03). All other clinical metrics had small, nonsignificant changes between 12 and 24 months. CONCLUSIONS Results support the conclusion that most improved clinical outcomes persisted 1 year after the completion of the health coaching intervention. PMID:27184989

What Happens After Health Coaching? Observational Study 1 Year Following a Randomized Controlled Trial.

PubMed

Sharma, Anjana E; Willard-Grace, Rachel; Hessler, Danielle; Bodenheimer, Thomas; Thom, David H

2016-05-01

Health coaching is effective for chronic disease self-management in the primary care safety-net setting, but little is known about the persistence of its benefits. We conducted an observational study evaluating the maintenance of improved cardiovascular risk factors following a health coaching intervention. We performed a naturalistic follow-up to the Health Coaching in Primary Care Study, a 12-month randomized controlled trial (RCT) comparing health coaching to usual care for patients with uncontrolled diabetes, hypertension, or hyperlipidemia. Participants were followed up 24 months from RCT baseline. The primary outcome was the proportion at goal for at least 1 measure (hemoglobin A1c, systolic blood pressure, or LDL cholesterol) that had been above goal at enrollment; secondary outcomes included each individual clinical goal. Chi-square tests and paired t-tests compared dichotomous and continuous measures. 290 of 441 participants (65.8%) participated at both 12 and 24 months. The proportion of patients in the coaching arm of the RCT who achieved the primary outcome dropped only slightly from 47.1% at 12 to 45.9% at 24 months (P = .80). The proportion at goal for hemoglobin A1c dropped from 53.4% to 36.2% (P = .03). All other clinical metrics had small, nonsignificant changes between 12 and 24 months. Results support the conclusion that most improved clinical outcomes persisted 1 year after the completion of the health coaching intervention. © 2016 Annals of Family Medicine, Inc.

Design of a randomized controlled trial of zinc supplementation to improve markers of mortality and HIV disease progression in HIV-positive drinkers in St. Petersburg, Russia.

PubMed

Gnatienko, Natalia; Freiberg, Matthew S; Blokhina, Elena; Yaroslavtseva, Tatiana; Bridden, Carly; Cheng, Debbie M; Chaisson, Christine E; Lioznov, Dmitry; Bendiks, Sally; Koerbel, Glory; Coleman, Sharon M; Krupitsky, Evgeny; Samet, Jeffrey H

2018-06-01

Background Russia continues to have an uncontrolled HIV epidemic and its per capita alcohol consumption is among the highest in the world. Alcohol use among HIV-positive individuals is common and is associated with worse clinical outcomes. Alcohol use and HIV each lead to microbial translocation, which in turn results in inflammation. Zinc supplementation holds potential for lowering levels of biomarkers of inflammation, possibly as a consequence of its impact on intestinal permeability. This paper describes the protocol of a double-blinded randomized placebo-controlled trial of zinc supplementation in St. Petersburg, Russia. Methods Participants (n = 254) were recruited between October 2013 and June 2015 from HIV and addiction clinical care sites, and non-clinical sites in St. Petersburg, Russia. Participants were randomly assigned, to receive either zinc (15 mg for men; 12 mg for women) or placebo, daily for 18 months. The following outcomes were assessed at 6, 12, and 18 months: (1) mortality risk (primary outcome at 18 months); (2) HIV disease progression; (3) cardiovascular risk; and (4) microbial translocation and inflammation. Adherence was assessed using direct (riboflavin) and indirect (pill count, self-report) measures. Conclusion Given the limited effectiveness of current interventions to reduce alcohol use, zinc supplementation merits testing as a simple, low-cost intervention to mitigate the consequences of alcohol use in HIV-positive persons despite ongoing drinking.

Cosmetics for acne: indications and recommendations for an evidence-based approach.

PubMed

Dall'oglio, F; Tedeschi, A; Fabbrocini, G; Veraldi, S; Picardo, M; Micali, G

2015-02-01

The aim of this review was to evaluate, by a thorough revision of the literature, the true efficacy of currently available topic and systemic cosmetic acne agents. The efficacy of currently available cosmetic acne agents has been retrospectively evaluated via thorough revision of the literature on matched electronic databases (PubMed). All retrieved studies, either randomized clinical trials or clinical trials, controlled or uncontrolled were considered. Scientific evidence suggests that most cosmetic products for acne may enhance the clinical outcome. Cleansers should be indicated to all acne patients; those containing benzoyl peroxide or azelaic/salicylic acid/triclosan show the best efficacy profile. Sebum-controlling agents containing nicotinamide or zinc acetate may minimize excessive sebum production. Cosmetics with antimicrobial and anti-inflammatory substances such as, respectively, ethyl lactate or phytosphingosine and nicotinamide or resveratrol, may speed acne recovery. Topical corneolytics, including retinaldehyde/glycolic acid or lactic acid, induce a comedolytic effect and may also facilitate skin absorption of topical drugs. Finally, the use of specific moisturizers should be strongly recommended in all acne patients. Cosmetics, if correctly prescribed, may improve the performance of the therapy, whereas wrong procedures and/or inadequate cosmetics may worsen acne. Cosmetological recommendations may allow clinicians to make informed decisions about the role of various cosmetics and to indentify the appropriate indications and precautions. The choice of the most effective product should take into consideration the ongoing pharmacological therapy and acne type/severity as well.

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.

Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant.

PubMed

Egan, T M; Requard, J J

2015-08-01

In April 2014, the American Journal of Transplantation published a report on the first lung transplant in the United States recovered from an uncontrolled donation after circulatory determination of death donor (uDCDD), assessed by ex vivo lung perfusion (EVLP). The article identified logistical and ethical issues related to introduction of lung transplant from uDCDDs. In an open clinical trial, we have Food and Drug Administration and Institutional Review Board approval to transplant lungs recovered from uDCDDs judged suitable after EVLP. Through this project and other experiences with lung recovery from uDCDDs, we have identified solutions to many logistical challenges and have addressed ethical issues surrounding lung transplant from uDCDDs that were mentioned in this case report. Here, we discuss those challenges, including issues related to recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs could solve the critical shortage of lungs for transplant. Furthermore, by avoiding the deleterious impact of brain death and days of positive pressure ventilation, and by using opportunities to treat lungs in the decedent or during EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs currently being transplanted from conventional brain-dead organ donors. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma.

PubMed

Castro, Mario; Corren, Jonathan; Pavord, Ian D; Maspero, Jorge; Wenzel, Sally; Rabe, Klaus F; Busse, William W; Ford, Linda; Sher, Lawrence; FitzGerald, J Mark; Katelaris, Constance; Tohda, Yuji; Zhang, Bingzhi; Staudinger, Heribert; Pirozzi, Gianluca; Amin, Nikhil; Ruddy, Marcella; Akinlade, Bolanle; Khan, Asif; Chao, Jingdong; Martincova, Renata; Graham, Neil M H; Hamilton, Jennifer D; Swanson, Brian N; Stahl, Neil; Yancopoulos, George D; Teper, Ariel

2018-05-21

Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. Methods We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV 1 ) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV 1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. Results The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV 1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. Conclusions In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .).

Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients

PubMed Central

Pizzini, Patrizia; Cutrupi, Sebastiano; Tripepi, Rocco; Vilasi, Antonio; Tripepi, Giovanni; Mallamaci, Francesca

2017-01-01

Vitamin D receptor (VDR) activation has been reported to increase circulating levels of the advanced glycation end products (AGE) and their decoy receptor (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not been tested in the setting of a randomized, double-blind clinical trial. We have therefore analyzed the effect of VDR activation by paricalcitol on pentosidine, S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like myeloperoxidase in CKD patients in the PENNY trial. At baseline, human S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase (r = 0.71, P < 0.001) was the strongest among these correlations. Paricalcitol failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in unadjusted and adjusted analyses by the generalized linear model (GLM). No effect modification by other risk factors was registered. Paricalcitol does not modify biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The apparent increase in RAGE levels by VDR activation reported in previous uncontrolled studies is most likely due to confounding factors rather than to VDR activation per se. This trial is registered with NCT01680198. PMID:29362665

Benefits of microprocessor-controlled prosthetic knees to limited community ambulators: systematic review.

PubMed

Kannenberg, Andreas; Zacharias, Britta; Pröbsting, Eva

2014-01-01

The benefits of microprocessor-controlled prosthetic knees (MPKs) have been well established in community ambulators (Medicare Functional Classification Level [MFCL]-3) with a transfemoral amputation (TFA). A systematic review of the literature was performed to analyze whether limited community ambulators (MFCL-2) may also benefit from using an MPK in safety, performance-based function and mobility, and perceived function and satisfaction. We searched 10 scientific databases for clinical trials with MPKs and identified six publications with 57 subjects with TFA and MFCL-2 mobility grade. Using the criteria of a Cochrane Review on prosthetic components, we rated methodological quality moderate in four publications and low in two publications. MPK use may significantly reduce uncontrolled falls by up to 80% as well as significantly improve indicators of fall risk. Performance-based outcome measures suggest that persons with MFCL-2 mobility grade may be able to walk about 14% to 25% faster on level ground, be around 20% quicker on uneven surfaces, and descend a slope almost 30% faster when using an MPK. The results of this systematic review suggest that trial fittings may be used to determine whether or not individuals with TFA and MFCL-2 mobility grade benefit from MPK use. Criteria for patient selection and assessment of trial fitting success or failure are proposed.

Shared decision-making in antihypertensive therapy: a cluster randomised controlled trial

PubMed Central

2013-01-01

Background Hypertension is one of the key factors causing cardiovascular diseases. A substantial proportion of treated hypertensive patients do not reach recommended target blood pressure values. Shared decision making (SDM) is to enhance the active role of patients. As until now there exists little information on the effects of SDM training in antihypertensive therapy, we tested the effect of an SDM training programme for general practitioners (GPs). Our hypotheses are that this SDM training (1) enhances the participation of patients and (2) leads to an enhanced decrease in blood pressure (BP) values, compared to patients receiving usual care without prior SDM training for GPs. Methods The study was conducted as a cluster randomised controlled trial (cRCT) with GP practices in Southwest Germany. Each GP practice included patients with treated but uncontrolled hypertension and/or with relevant comorbidity. After baseline assessment (T0) GP practices were randomly allocated into an intervention and a control arm. GPs of the intervention group took part in the SDM training. GPs of the control group treated their patients as usual. The intervention was blinded to the patients. Primary endpoints on patient level were (1) change of patients’ perceived participation (SDM-Q-9) and (2) change of systolic BP (24h-mean). Secondary endpoints were changes of (1) diastolic BP (24h-mean), (2) patients’ knowledge about hypertension, (3) adherence (MARS-D), and (4) cardiovascular risk score (CVR). Results In total 1357 patients from 36 general practices were screened for blood pressure control by ambulatory blood pressure monitoring (ABPM). Thereof 1120 patients remained in the study because of uncontrolled (but treated) hypertension and/or a relevant comorbidity. At T0 the intervention group involved 17 GP practices with 552 patients and the control group 19 GP practices with 568 patients. The effectiveness analysis could not demonstrate a significant or relevant effect of the SDM training on any of the endpoints. Conclusion The study hypothesis that the SDM training enhanced patients’ perceived participation and lowered their BP could not be confirmed. Further research is needed to examine the impact of patient participation on the treatment of hypertension in primary care. Trial registration German Clinical Trials Register (DRKS): DRKS00000125 PMID:24024587

Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorder: Results of an 18-Month Feasibility Study

ERIC Educational Resources Information Center

Eack, Shaun M.; Greenwald, Deborah P.; Hogarty, Susan S.; Bahorik, Amber L.; Litschge, Maralee Y.; Mazefsky, Carla A.; Minshew, Nancy J.

2013-01-01

Adults with autism experience significant impairments in social and non-social information processing for which few treatments have been developed. This study conducted an 18-month uncontrolled trial of Cognitive Enhancement Therapy (CET), a comprehensive cognitive rehabilitation intervention, in 14 verbal adults with autism spectrum disorder to…

Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and bone mineral density in post-menopausal women with type 2 diabetes: a randomized controlled trial.

PubMed

Vianna, Andre Gustavo Daher; de Lacerda, Claudio Silva; Pechmann, Luciana Muniz; Polesel, Michelle Garcia; Marino, Emerson Cestari; Borba, Victoria Zeghbi Cochenski; Barreto, Fellype de Carvalho

2017-01-01

Several antidiabetic therapies affect bone metabolism. Sulfonylureas have the lowest impact on bone among oral antidiabetics. The objective of this study is to compare the effects of vildagliptin and gliclazide modified release (MR) on bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women with uncontrolled type 2 diabetes (T2D). Forty-two postmenopausal women with uncontrolled T2D were randomly allocated into vildagliptin or gliclazide MR (control) groups. The primary endpoint was the change in the BTMs in months 6 and 12 compared with the baseline. The secondary endpoint was the variation in the BMD, which was assessed via dual-energy X-ray absorptiometry at the lumbar spine, femoral neck and total hip at baseline and month 12. After a 12-month treatment, the BTM serum carboxy-terminal telopeptide of type 1 collagen increased 0.001 ± 0.153 ng/mL in the vildagliptin group versus 0.008 ± 0.060 ng/mL in the gliclazide MR group ( p  = 0.858). The serum osteocalcin, serum amino-terminal propeptide of procollagen type I and urinary amino-terminal telopeptide of type 1 collagen remained stable in both groups, and there was no statistically significant difference between the effect of vildagliptin and gliclazide MR on these variables. The lumbar spine BMD did not change in the vildagliptin or gliclazide MR groups after a 12-month treatment (0.000 ± 0.025 g/cm 2 versus -0.008 ± 0.036, respectively, p  = 0.434). Furthermore, there was a similar lack of change in the femoral neck and total hip BMD values in both treatments. Bone turnover markers and BMD remained unchanged after a 12-month treatment in both groups, which suggests that vildagliptin has the same safety profile as gliclazide MR on bone metabolism. Trial Registration ClinicalTrials.gov number NCT01679899.

Yoga as a Therapeutic Intervention: A Bibliometric Analysis of Published Research Studies from 1967 to 2013

PubMed Central

Slutsky, Jeremiah; Singh, Nilkamal; Khalsa, Sat Bir S.

2015-01-01

Abstract Objective: A comprehensive bibliometric analysis was conducted on publications for yoga therapy research in clinical populations. Methods: Major electronic databases were searched for articles in all languages published between 1967 and 2013. Databases included PubMed, PsychInfo, MEDLINE, IndMed, Indian Citation Index, Index Medicus for South-East Asia Region, Web of Knowledge, Embase, EBSCO, and Google Scholar. Nonindexed journals were searched manually. Key search words included yoga, yoga therapy, pranayama, asana. All studies met the definition of a clinical trial. All styles of yoga were included. The authors extracted the data. Results: A total of 486 articles met the inclusion criteria and were published in 217 different peer-reviewed journals from 29 different countries on 28,080 study participants. The primary result observed is the three-fold increase in number of publications seen in the last 10 years, inclusive of all study designs. Overall, 45% of the studies published were randomized controlled trials, 18% were controlled studies, and 37% were uncontrolled studies. Most publications originated from India (n=258), followed by the United States (n=122) and Canada (n=13). The top three disorders addressed by yoga interventions were mental health, cardiovascular disease, and respiratory disease. Conclusion: A surge in publications on yoga to mitigate disease-related symptoms in clinical populations has occurred despite challenges facing the field of yoga research, which include standardization and limitations in funding, time, and resources. The population at large has observed a parallel surge in the use of yoga outside of clinical practice. The use of yoga as a complementary therapy in clinical practice may lead to health benefits beyond traditional treatment alone; however, to effect changes in health care policy, more high-quality, evidence-based research is needed. PMID:26196166

Blood Pressure Control in Hypertensive Patients, Cardiovascular Risk Profile and the Prevalence of Masked Uncontrolled Hypertension (MUCH).

PubMed

Naser, Nabil; Dzubur, Alen; Durak, Azra; Kulic, Mehmed; Naser, Nura

2016-07-27

The term masked hypertension (MH) should be used for untreated individuals who have normal office blood pressure but elevated ambulatory blood pressure. For treated patients, this condition should be termed masked uncontrolled hypertension (MUCH). Masked uncontrolled hypertension (MUCH) has gone unrecognized because few studies have used 24-h ABPM to determine the prevalence of suboptimal BP control in seemingly well-treated patients, and there are few such studies in large cohorts of treated patients attending usual clinical practice. This is important because masked hypertension is associated with a high risk of cardiovascular events. This study was conducted to obtain more information about the association between hypertension and other CV risk factors, about office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients, also to define the prevalence and characteristics of masked uncontrolled hypertension (MUCH) among treated hypertensive patients in routine clinical practice. In this study 2514 male and female patients were included during a period of 5 years follow up. All patients have ambulatory blood pressure monitoring (ABPM) for at least 24h. We identified patients with treated and controlled BP according to current international guidelines (clinic BP, 140/90mmHg). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Masked uncontrolled hypertension (MUCH) was diagnosed in these patients if despite controlled clinic BP, the mean 24-h ABPM average remained elevated (24-h systolic BP ≥130mmHg and/or 24-h diastolic BP ≥80mmHg). Patients had a mean age of 60.2+10 years, and the majority of them (94.6%) were followed by specialist physicians. Average clinic BP was 150.4+16/89.9+12 mmHg. About 70% of patients displayed a very high-risk profile. Ambulatory blood pressure monitoring (ABPM) was performed in all recruited patients for at least 24h. Despite the combined medical treatment (78% of the patients), clinic control (<140/90 mmHg) was achieved in only 26.2% of patients, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 32.7%. From 2514 patients with treated BP, we identified 803 with treated and controlled office BP control (<140/90 mmHg), of whom 258 patients (32.1%) had MUCH according to 24-h ABPM criteria (mean age 57.2 years, 54.7% men). The prevalence of MUCH was slightly higher in males, patients with borderline clinic and office BP (130-139/80-89 mmHg), and patients at high cardiovascular risk (smokers, diabetes, obesity). Masked uncontrolled hypertension (MUCH) was most often due to poor control of nocturnal BP, with the proportion of patients in whom MUCH was solely attributable to an elevated nocturnal BP almost double that solely attributable to daytime BP elevation (22.3 vs. 10.1%, P 0.001). The prevalence of masked suboptimal BP control in patients with treated and well-controlled clinic BP is high. The characteristics of patients with MUCH (male, longer duration of hypertension, obesity, smoking history, and diabetes) indicate that this is a higher-risk group with most to gain from improved BP.

An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions

PubMed Central

Pattee, Gary L.; Wymer, James P.; Lomen-Hoerth, Catherine; Appel, Stanley H.; Formella, Andrea E.; Pope, Laura E.

2014-01-01

Abstract Background: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient’s emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. Objective: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Methods: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Clinical trial registration: #NCT00056524. Results: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. Conclusions: DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions. PMID:25062507

Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma

PubMed Central

Happold, Caroline; Gorlia, Thierry; Chinot, Olivier; Gilbert, Mark R.; Nabors, L. Burt; Wick, Wolfgang; Pugh, Stephanie L.; Hegi, Monika; Cloughesy, Timothy; Roth, Patrick; Reardon, David A.; Perry, James R.; Mehta, Minesh P.; Stupp, Roger

2016-01-01

Purpose Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. Patients and Methods To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV). Results VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use. Conclusion The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials. PMID:26786929

Effect of YH0618 soup on chemotherapy-induced toxicity in patients with cancer who have completed chemotherapy: study protocol for a randomized controlled trial.

PubMed

You, Jie-Shu; Chen, Jian-Ping; Chan, Jessie S M; Lee, Ho-Fun; Wong, Mei-Kuen; Yeung, Wing-Fai; Lao, Li-Xing

2016-07-26

The incidence of cancer has been staying at a high level worldwide in recent years. With advances in cancer diagnosis and therapy strategy, the survival rate of patients with cancer has been increasing, but the side effects of these treatments, especially chemotherapy, are obvious even when the chemotherapy ceases. YH0618, a prescription, has showed efficacy in reducing chemotherapy-induced toxicity through long clinical practice. However, there is no scientific research exploring the effects of YH0618 in patients with cancer. Therefore, using a randomized controlled trial, this study will explore the efficacy of YH0618 on ameliorating chemotherapy-induced toxicity including dermatologic toxicity, myelosuppression, hepatotoxicity and nephrotoxicity and improving fatigue in cancer patients who have completed chemotherapy. This is a prospective assessor-blinded, parallel, randomized controlled trial. Patients with cancer at any stage who have completed chemotherapy within two weeks will be randomly divided into group A (YH0618) and group B (wait-list) using a 1:1 allocation ratio. The chemotherapeutic agents include taxanes or anthracyclines. Subjects assigned to group A will receive YH0618 soup 6 days a week for 6 weeks and uncontrolled follow-up for 6 weeks, while group B are required to wait for 6 weeks before receiving YH0618 intervention. The primary outcome of this study is the incidence of protocol-specified grade ≥2 dermatologic toxicities graded by NCI CTCAE Chinese version 4.0 and changes of fingernail color, face skin color and tongue color evaluated by the L*a*b system within 6 weeks. There are some secondary outcomes associated with dermatologic toxicity including fatigue and clinical objective examination. There are few scientific and safe methods in ameliorating chemotherapy-induced toxicity. The proposed study may provide direct and convincing evidence to support YH0618 as an adjuvant treatment for reducing chemotherapy-induced toxicity, which could be introduced into clinical settings. Chinese Clinical Trial Registry: ChiCTR-IOR-15006486 . Registered on 21 May 2015.

Stem cell transplantation and mesenchymal cells to treat autoimmune diseases.

PubMed

Tyndall, Alan; van Laar, Jacob M

2016-06-01

Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjögren's disease, polymyositis/dermatomyositis and type II diabetes mellitus have received MSC therapeutically. The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Comparison of ambulatory blood pressure-lowering effects of higher doses of different calcium antagonists in uncontrolled hypertension: the Calcium Antagonist Controlled-Release High-Dose Therapy in Uncontrolled Refractory Hypertensive Patients (CARILLON) Study.

PubMed

Mizuno, Hiroyuki; Hoshide, Satoshi; Tomitani, Naoko; Kario, Kazuomi

2017-10-01

Data are sparse regarding ambulatory blood pressure (BP) reduction of up-titration from a standard dose to a high dose in both nifedipine controlled-release (CR) and amlodipine. This was a prospective, randomized, multicenter, open-label trial. Fifty-one uncontrolled hypertensives medicated by two or more antihypertensive drugs including a renin-angiotensin system inhibitor and a calcium antagonist were randomly assigned to either the nifedipine CR (80 mg)/candesartan (8 mg) group or the amlodipine (10 mg)/candesartan (8 mg) group. The changes in 24-hr BP were comparable between the groups. The nifedipine group demonstrated a significant decrease in their urinary albumin creatinine ratio, whereas the amlodipine group demonstrated a significant decrease in their NTproBNP level. However, there was no significant difference in any biomarkers between the two groups. Nifedipine showed an almost equal effect on ambulatory blood pressure as amlodipine. Their potentially differential effects on renal protection and NTproBNP should be tested in larger samples.

Shiga Toxin-Producing Escherichia coli O104:H4: a New Challenge for Microbiology

PubMed Central

Muniesa, Maite; Hammerl, Jens A.; Hertwig, Stefan; Appel, Bernd

2012-01-01

In 2011, Germany experienced the largest outbreak with a Shiga toxin-producing Escherichia coli (STEC) strain ever recorded. A series of environmental and trace-back and trace-forward investigations linked sprout consumption with the disease, but fecal-oral transmission was also documented. The genome sequences of the pathogen revealed a clonal outbreak with enteroaggregative E. coli (EAEC). Some EAEC virulence factors are carried on the virulence plasmid pAA. From an unknown source, the epidemic strains acquired a lambdoid prophage carrying the gene for the Shiga toxin. The resulting strains therefore possess two different mobile elements, a phage and a plasmid, contributing essential virulence genes. Shiga toxin is released by decaying bacteria in the gut, migrates through the intestinal barrier, and is transported via the blood to target organs, like the kidney. In a mouse model, probiotic bifidobacteria interfered with transport of the toxin through the gut mucosa. Researchers explored bacteriophages, bacteriocins, and low-molecular-weight inhibitors against STEC. Randomized controlled clinical trials of enterohemorrhagic E. coli (EHEC)-associated hemolytic uremic syndrome (HUS) patients found none of the interventions superior to supportive therapy alone. Antibodies against one subtype of Shiga toxin protected pigs against fatal neurological infection, while treatment with a toxin receptor decoy showed no effect in a clinical trial. Likewise, a monoclonal antibody directed against a complement protein led to mixed results. Plasma exchange and IgG immunoadsoprtion ameliorated the condition in small uncontrolled trials. The epidemic O104:H4 strains were resistant to all penicillins and cephalosporins but susceptible to carbapenems, which were recommended for treatment. PMID:22504816

Autonomy and Fear of Synthetic Biology: How Can Patients' Autonomy Be Enhanced in the Field of Synthetic Biology? A Qualitative Study with Stable Patients.

PubMed

Rakic, Milenko; Wienand, Isabelle; Shaw, David; Nast, Rebecca; Elger, Bernice S

2017-04-01

We analyzed stable patients' views regarding synthetic biology in general, the medical application of synthetic biology, and their potential participation in trials of synthetic biology in particular. The aim of the study was to find out whether patients' views and preferences change after receiving more detailed information about synthetic biology and its clinical applications. The qualitative study was carried out with a purposive sample of 36 stable patients, who suffered from diabetes or gout. Interviews were transcribed verbatim, translated and fully anonymized. Thematic analysis was applied in order to examine stable patients' attitudes towards synthetic biology, its medical application, and their participation in trials. When patients were asked about synthetic biology in general, most of them were anxious that something uncontrollable could be created. After a concrete example of possible future treatment options, patients started to see synthetic biology in a more positive way. Our study constitutes an important first empirical insight into stable patients' views on synthetic biology and into the kind of fears triggered by the term "synthetic biology." Our results show that clear and concrete information can change patients' initial negative feelings towards synthetic biology. Information should thus be transmitted with great accuracy and transparency in order to reduce irrational fears of patients and to minimize the risk that researchers present facts too positively for the purposes of persuading patients to participate in clinical trials. Potential participants need to be adequately informed in order to be able to autonomously decide whether to participate in human subject research involving synthetic biology.

Different effectiveness of closed embryo culture system with time-lapse imaging (EmbryoScope(TM)) in comparison to standard manual embryology in good and poor prognosis patients: a prospectively randomized pilot study.

PubMed

Wu, Yan-Guang; Lazzaroni-Tealdi, Emanuela; Wang, Qi; Zhang, Lin; Barad, David H; Kushnir, Vitaly A; Darmon, Sarah K; Albertini, David F; Gleicher, Norbert

2016-08-24

Previously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated. We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScope™) and standard embryology. We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScope™ and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScope™ and standard embryology. We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo. Part A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScope™ and standard embryology. The EmbryoScope™, however, more than doubled embryology staff time (P < 0.0001). In Part B, embryos grown in the EmbyoScope™ demonstrated significantly poorer day-3 quality (depending on embryo parameter between P = 0.005 and P = 0.01). Suspicion that conical culture dishes of the EmbryoScope™ (EmbryoSlide™) may be the cause was disproven when standard culture dishes demonstrated no outcome difference in standard incubation. Though due to small patient numbers preliminary, this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology. Appropriately designed and powered prospectively randomized studies appear urgently needed in well-defined patient populations before the uncontrolled utilization of these instruments further expands. NCT02246309 Registered September 18, 2014.

Patient perspectives: Kundalini yoga meditation techniques for psycho-oncology and as potential therapies for cancer.

PubMed

Shannahoff-Khalsa, David S

2005-03-01

The ancient system of Kundalini Yoga (KY) includes a vast array of meditation techniques. Some were discovered to be specific for treating psychiatric disorders and others are supposedly beneficial for treating cancers. To date, 2 clinical trials have been conducted for treating obsessive-compulsive disorder (OCD). The first was an open uncontrolled trial and the second a single-blinded randomized controlled trial (RCT) comparing a KY protocol against the Relaxation Response and Mindfulness Meditation (RRMM) techniques combined. Both trials showed efficacy on all psychological scales using the KY protocol; however, the RCT showed no efficacy on any scale with the RRMM control group. The KY protocol employed an OCD-specific meditation technique combined with other techniques that are individually specific for anxiety, low energy, fear, anger, meeting mental challenges, and turning negative thoughts into positive thoughts. In addition to OCD symptoms, other symptoms, including anxiety and depression, were also significantly reduced. Elements of the KY protocol other than the OCD-specific technique also may have applications for psycho-oncology patients and are described here. Two depression-specific KY techniques are described that also help combat mental fatigue and low energy. A 7-part protocol is described that would be used in KY practice to affect the full spectrum of emotions and distress that complicate a cancer diagnosis. In addition, there are KY techniques that practitioners have used in treating cancer. These techniques have not yet been subjected to formal clinical trials but are described here as potential adjunctive therapies. A case history demonstrating rapid onset of acute relief of intense fear in a terminal breast cancer patient using a KY technique specific for fear is presented. A second case history is reported for a surviving male diagnosed in 1988 with terminal prostate cancer who has used KY therapy long term as part of a self-directed integrative care approach.

Effects of Vildagliptin Add-on Insulin Therapy on Nocturnal Glycemic Variations in Uncontrolled Type 2 Diabetes.

PubMed

Li, Feng-Fei; Shen, Yun; Sun, Rui; Zhang, Dan-Feng; Jin, Xing; Zhai, Xiao-Fang; Chen, Mao-Yuan; Su, Xiao-Fei; Wu, Jin-Dan; Ye, Lei; Ma, Jian-Hua

2017-10-01

To investigate whether vildagliptin add-on insulin therapy improves glycemic variations in patients with uncontrolled type 2 diabetes (T2D) compared to patients with placebo therapy. This was a 24-week, single-center, double-blind, placebo-controlled trial. Inadequately controlled T2D patients treated with insulin therapy were recruited between June 2012 and April 2013. The trial included a 2-week screening period and a 24-week randomized period. Subjects were randomly assigned to a vildagliptin add-on insulin therapy group (n = 17) or a matched placebo group (n = 16). Scheduled visits occurred at weeks 4, 8, 12, 16, 20, and 24. Continuous glucose monitoring (CGM) was performed before and at the endpoint of the study. A total of 33 subjects were admitted, with 1 patient withdrawing from the placebo group. After 24 weeks of therapy, HbA1c values were significantly reduced at the endpoint in the vildagliptin add-on group. CGM data showed that patients with vildagliptin add-on therapy had a significantly lower 24-h mean glucose concentration and mean amplitude of glycemic excursion (MAGE). At the endpoint of the study, patients in the vildagliptin add-on group had a significantly lower MAGE and standard deviation compared to the control patients during the nocturnal period (0000-0600). A severe hypoglycemic episode was not observed in either group. Vildagliptin add-on therapy to insulin has the ability to improve glycemic variations, especially during the nocturnal time period, in patients with uncontrolled T2D.

Endo-Perio Lesion and Uncontrolled Diabetes.

PubMed

Dhoum, Sara; Laslami, Kaoutar; Rouggani, Fatimazahraa; El Ouazzani, Amal; Jabri, Mouna

2018-01-01

This work is to discuss the management of an endo-perio lesion, which represents a challenge to clinicians when it comes to diagnosis and prognosis of the involved teeth and especially with an altered general condition. A 50-year-old female patient with uncontrolled diabetes type 2 is suffering from a purulent discharge coming from the upper right canine. Endodontic and periodontal treatments were realized with 36 months radiological and clinical follow-up with the collaboration of her internist doctor.

Recognizing Disordered Eating in Primary Care Patients with Obesity

PubMed Central

Chacko, Sara A.; Chiodi, Sarah N.; Wee, Christina C.

2015-01-01

Objective In clinical practice, behavioral approaches to obesity treatment focus heavily on diet and exercise recommendations. However, these approaches may not be effective for patients with disordered eating behaviors. Little is known about the prevalence of disordered eating behaviors in primary care patients with obesity or whether they affect difficulty making dietary changes. Methods We conducted a telephone interview of 337 primary care patients aged 18–65 years with BMI≥35kg/m2 in Greater-Boston, 2009–2011 (58% response rate, 69% women). We administered the Three-Factor Eating Questionnaire R-18 (Scores 0–100) and the Impact of Weight on Quality of Life-Lite (IWQOL-lite) (Scores 0–100). We measured difficulty making dietary changes using four questions regarding perceived difficulty changing diet (Scores 0–10). Results 50% of patients reported high emotional eating (score>50) and 28% reported high uncontrolled eating (score>50). Women were more likely to report emotional [OR=4.14 (2.90, 5.92)] and uncontrolled eating [OR=2.11 (1.44, 3.08)] than men. African Americans were less likely than Caucasians to report emotional [OR=0.29 (95% CI: 0.19, 0.44)] and uncontrolled eating [OR=0.11 (0.07, 0.19)]. For every 10-point reduction in QOL score (IWQOL-lite), emotional and uncontrolled eating scores rose significantly by 7.82 and 5.48, respectively. Furthermore, participants who reported emotional and uncontrolled eating reported greater difficulty making dietary changes. Conclusions Disordered eating behaviors are prevalent among obese primary care patients and disproportionately affect women, Caucasians, and patients with poor QOL. These eating behaviors may impair patients' ability to make clinically recommended dietary changes. Clinicians should consider screening for disordered eating behaviors and tailoring obesity treatment accordingly. PMID:25572624

Current concepts in the pharmacotherapy of pseudobulbar affect.

PubMed

Pioro, Erik P

2011-06-18

Arising in settings of CNS insult, pseudobulbar affect (PBA) consists of uncontrollable episodes of crying or laughter incongruent to the patient's mood. The syndrome has been described by a plethora of names, including pathological laughing and crying, emotional lability, emotionalism and emotional incontinence, which hampers efforts to survey published assessments of pharmacological intervention. Still, until quite recently, all treatment has unavoidably been off-label, chiefly involving antidepressants. Using PBA and other syndrome names as search terms, a PubMed search for English-language case reports and therapeutic trials involving at least five patients identified 22 such publications from 1980 through to 2010. Among the seven randomized, double-blind, antidepressant studies with placebo control, two trials assessed 106 and 123 subjects, respectively. However, the other five assessed only 12-28 subjects, and only one of these seven trials (with 28 subjects) measured change in syndrome severity using a validated scale. The three randomized, double-blind studies of dextromethorphan plus quinidine assessed 129, 150 and 326 subjects. Among these studies, two were placebo-controlled and all three used a validated severity scale. Across all placebo-controlled trials, response to active treatment - either an antidepressant or dextromethorphan/quinidine - has in general been significantly greater than response to placebo, but placebo response has sometimes been substantial, suggesting caution in interpreting uncontrolled findings. In October 2010, dextromethorphan/quinidine received approval from the US FDA as first-in-class PBA pharmacotherapy. Advocates of a continuing role for antidepressants, notably selective serotonin reuptake inhibitors, can point to numerous positive case reports and trials, the potential benefit of attempting to treat PBA and concomitant depression without using multiple drugs, and the ever-present need to tailor treatment to the individual patient.

Renal angioplasty and stenting: is it still indicated after ASTRAL and STAR studies?

PubMed

Henry, M; Benjelloun, A; Henry, I; Polydorou, A; Hugel, M

2010-10-01

A renal artery stenosis (RAS) is common among patients with atherosclerosis, up to a third of patients undergoing cardiac catheterization. Fibromuscular dysplasia is the next cause of RAS, commonly found in young women. Atherosclerosis RAS generally progresses overtime and is often associated with loss of renal mass and worsening renal function (RF). Percutaneous renal artery stent placement is the preferred method of revascularization for hemodynamically significant RAS according to ACC and AHA guidelines. Several randomized trials have shown the superiority of endovascular procedures to medical therapy alone. However, two studies ASTRAL and STAR studies were recently published and did not find any difference between renal stenting and medical therapy. But these studies have a lot of limitations and flaws as we will discuss (poor indications, poor results, numerous complications, failures, poor technique, inexperienced operators, ecc.). Despite these questionable studies, renal stenting keeps indications in patients with: uncontrolled hypertension; ischemic nephropathy; cardiac disturbance syndrome (e.g. "flash" pulmonary edema, uncontrolled heart failure or uncontrolled angina pectoris); solitary kidney. To improve the clinical response rates, a better selection of the patients and lesions is mandatory with: good non-invasive or invasive imaging; physiologic lesion assessment using transluminal pressure gradients; measurements of biomarkers (e.g., BNP); fractional flow reserve study. A problem remains after renal angioplasty stenting, the deterioration of the RF in 20-30% of the patients. Atheroembolism seems to play an important role and is probably the main cause of this R.F deterioration. The use of protection devices alone or in combination with IIb IIa inhibitors has been proposed and seems promising as shown in different recent reports. Renal angioplasty and stenting is still indicated but we need: a better patient and lesion selection; improvements in techniques and maybe the use of protection devices to reduce the risk of RF deterioration after renal stenting.

Effects of climate on growth traits of river red gum are determined by respiration parameters

Treesearch

Richard S. Criddle; Thimmappa S. Anekonda; Sharon Tong; John N. Church; F. Thomas Ledig; Lee D. Hansen

2000-01-01

Temperature is the major uncontrollable climate variable in plantation forestry. Matching plants to climate is essential for optimizing growth. Matching is usually done with field trials because of the lack of a predictive relation between laboratory measurements of physiological responses and climatic factors affecting growth. This paper evaluates the potential of...

Cognitive behaviour therapy for common mental disorders in people with Multiple Sclerosis: A bench marking study.

PubMed

Askey-Jones, S; David, A S; Silber, E; Shaw, P; Chalder, T

2013-10-01

Mental health problems such as depression and anxiety are common in Multiple Sclerosis (MS) and are often under treated. This paper reports on the clinical effectiveness of a cognitive behaviour therapy service for common mental disorders in people with MS and compares it to previous randomised controlled trials (RCTs) of cognitive behaviour therapy (CBT) in this population. 49 patients were deemed appropriate for CBT and 29 accepted treatment. Assessments were completed at baseline and end of treatment and included the Hospital Anxiety & Depression Scale. Results in the form of a standardized effect of treatment were compared with five previous RCTs. The results from this clinical service indicated statistically significant outcomes with reductions in depression and anxiety. The uncontrolled effect size was large but inferior to those found in published RCTs. Cognitive behaviour therapy is effective for people with MS in routine clinical practice. Possible limits on effectiveness include more liberal patient selection, lack of specificity in rating scales and heterogeneity of target problems. Given the high rates of distress in this population, routine psychological interventions within neurology services are justifiable. Future research should aim to maximise CBT in such settings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of a Community Health Worker-Led Multicomponent Intervention on Blood Pressure Control in Low-income Patients in Argentina: A Randomized Clinical Trial

PubMed Central

He, Jiang; Irazola, Vilma; Mills, Katherine T.; Poggio, Rosana; Beratarrechea, Andrea; Dolan, Jacquelyn; Chen, Chung-Shiuan; Gibbons, Luz; Krousel-Wood, Marie; Bazzano, Lydia A.; Nejamis, Analia; Gulayin, Pablo; Santero, Marilina; Augustovski, Federico; Chen, Jing; Rubinstein, Adolfo

2017-01-01

Importance Despite extensive knowledge of hypertension treatment, the prevalence of uncontrolled hypertension is high and increasing in low- and middle-income countries. Objective To test whether a community health worker (CHW)-led multicomponent intervention would improve blood pressure (BP) control among low-income patients with hypertension. Design, Setting, and Participants A cluster randomized trial was conducted in 18 centers for primary healthcare within a national public system providing free medications and healthcare to uninsured patients in Argentina. A total of 1,432 low-income adult patients with uncontrolled hypertension were recruited between June 2013 and April 2015 and followed to October 2016. Intervention Nine centers (743 patients) were randomized to the multicomponent intervention, which included a CHW-led home intervention (health coaching, home BP monitoring, and BP audit and feedback), a physician intervention, and a text-messaging intervention over 18 months. Nine centers (689 patients) were randomized to usual care without study intervention. Main Outcomes and Measures The co-primary outcomes were the differences between the intervention and control groups in systolic and diastolic BP changes from baseline to end of follow-up in patients with hypertension. Secondary outcomes included the proportion of patients with controlled hypertension (BP<140/90 mmHg). Three BP measurements were obtained at each of two baseline and two termination visits using a standard protocol, and the means were used for analyses. Results Among 1,432 participants (mean age, 55.8 years; 772 [53.0%] women), 1,357 (94.8%) completed the trial. Baseline mean BP was 151.7 and 149.8 mmHg for systolic, and 92.2 and 90.1 mmHg for diastolic in the intervention and control groups, respectively. Systolic BP reduction from baseline to month 18 was 19.3 mmHg (95% confidence interval [CI]: 17.9, 20.8) in the intervention group and 12.7 mmHg (95% CI: 11.3, 14.2) in the control group; difference in the reduction was 6.6 mmHg (95% CI: 4.6, 8.6; p<0.001). Diastolic BP decreased by 12.2 mmHg (95% CI: 11.2, 13.2) in the intervention group and 6.9 mmHg (95% CI: 5.9, 7.8) in the control group; difference in the reduction was 5.4 mmHg (95% CI: 4.0, 6.8; p<0.001). The proportion of controlled hypertension increased from 17.0% at baseline to 72.9% at 18 months in the intervention group and from 17.6% to 52.2% in the control group; difference in the increase was 20.6% (95% CI: 15.4, 25.9%; p<0.001). No adverse events were reported. Conclusion and Relevance Among low-income patients with uncontrolled hypertension in Argentina, a CHW-led multicomponent intervention compared with usual care resulted in a greater decrease in systolic and diastolic BP over 18 months. Further research is needed to assess generalizability and cost-effectiveness of this intervention, and to understand which components may have contributed most to the outcome. Trial Registration clinicaltrials.gov Identifier: NCT01834131 PMID:28975305

Endo-Perio Lesion and Uncontrolled Diabetes

PubMed Central

Laslami, Kaoutar; Rouggani, Fatimazahraa; El Ouazzani, Amal; Jabri, Mouna

2018-01-01

This work is to discuss the management of an endo-perio lesion, which represents a challenge to clinicians when it comes to diagnosis and prognosis of the involved teeth and especially with an altered general condition. A 50-year-old female patient with uncontrolled diabetes type 2 is suffering from a purulent discharge coming from the upper right canine. Endodontic and periodontal treatments were realized with 36 months radiological and clinical follow-up with the collaboration of her internist doctor. PMID:29888011

Efficacy and safety profile evaluation of acarbose alone and in association with other antidiabetic drugs: a systematic review.

PubMed

Derosa, Giuseppe; Maffioli, Pamela

2012-06-01

Epidemiologic studies have revealed that postprandial hyperglycemia significantly contributes to high glycated hemoglobin concentrations and could be linked to the development of chronic diabetic complications. The purpose of our review was to evaluate the clinical efficacy and safety profile of treatment with acarbose alone and combined with other antidiabetic drugs. A systematic search strategy was developed to identify randomized controlled trials included in MEDLINE and the Cochrane Register of Controlled Trials. The terms acarbose, α-glucosidase inhibitors, type 2 diabetes, adverse events, combination therapy, and postprandial glucose were incorporated into an electronic search strategy that included the Dickersin filter for randomized controlled trials. To qualify for inclusion, clinical trials had to be randomized trials comparing treatment with acarbose at any dosage with any other antidiabetic drug in patients with type 2 diabetes mellitus or impaired glucose tolerance. Eligible trials had to present results on glycemic control or adverse events. Trial participants needed to be affected by type 2 diabetes mellitus or have impaired glucose tolerance, and the intervention had to include acarbose at any dosage as monotherapy or combined with other antidiabetic drugs. A validated 3-item scale was used to evaluate the overall reporting quality of the trials selected for inclusion in the present review. Nineteen trials were included. Treatment with acarbose significantly reduced glycated hemoglobin levels when given as monotherapy and as an add-on to other antidiabetic drug treatment (P < 0.0001). Acarbose treatment was effective in patients with uncontrolled type 2 diabetes and in patients with apparently good metabolic control owing to its positive effect on postprandial hyperglycemia (P < 0.0001). Treatment with acarbose seemed to improve the lipid profile (P < 0.05), reduce circulating levels of cell adhesion molecules (P < 0.05), reduce intima-media thickness progression (P = 0.01), and reverse impaired glucose tolerance to normal glucose tolerance (P < 0.0001). When current therapy is not adequate to obtain glycemic control, acarbose could be an option as monotherapy and as an add-on to other antidiabetic drug treatment, especially when postprandial hyperglycemia is the main concern. Long-term studies are needed to determine whether the effects observed with acarbose use are maintained over the years. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Overview of clinical research design.

PubMed

Hartung, Daniel M; Touchette, Daniel

2009-02-15

Basic concepts and terminology of clinical research design are presented for new clinical investigators. Clinical research, research involving human subjects, can be described as either observational or experimental. The findings of all clinical research can be threatened by issues of bias and confounding. Biases are systematic errors in how study subjects are selected or measured, which result in false inferences. Confounding is a distortion in findings that is attributable to mixing variable effects. Uncontrolled observation research is generally more prone to bias and confounding than experimental research. Observational research includes designs such as the cohort study, case-control study, and cross-sectional study, while experimental research typically involves a randomized controlled trial (RCT). The cohort study, which includes the RCT, defines subject allocation on the basis of exposure interest (e.g., drug, disease-management program) and follows the patients to assess the outcomes. The case-control study uses the primary outcome of interest (e.g., adverse event) to define subject allocation, and different exposures are assessed in a retrospective manner. Cross-sectional research evaluates both exposure and outcome concurrently. Each of these design methods possesses different strengths and weaknesses in answering research questions, as well as underlying many study subtypes. While experimental research is the strongest method for establishing causality, it can be difficult to accomplish under many scenarios. Observational clinical research offers many design alternatives that may be appropriate if planned and executed carefully.

Helplessness and perceived pain intensity: relations to cortisol concentrations after electrocutaneous stimulation in healthy young men

PubMed Central

2011-01-01

Background Uncontrollable aversive events are associated with feelings of helplessness and cortisol elevation and are suitable as a model of depression. The high comorbidity of depression and pain symptoms and the importance of controllability in both conditions are clinically well-known but empirical studies are scarce. The study investigated the relationship of pain experience, helplessness, and cortisol secretion after controllable vs. uncontrollable electric skin stimulation in healthy male individuals. Methods Sixty-four male volunteers were randomly assigned to receive 30 controllable (self-administered) or uncontrollable (experimenter-administered) painful electric skin stimuli. Perceived pain intensity (PPI), subjective helplessness ratings, and salivary cortisol concentrations were assessed. PPI was assessed after stress exposure. For salivary cortisol concentrations and subjective helplessness ratings, areas under the response curve (AUC) were calculated. Results After uncontrollable vs. controllable stress exposure significantly higher PPI ratings (P = 0.023), higher subjective helplessness AUC (P < 0.0005) and higher salivary cortisol AUC (P = 0.004, t-tests) were found. Correlation analyses revealed a significant correlation between subjective helplessness AUC and PPI (r = 0.500, P < 0.0005), subjective helplessness AUC and salivary cortisol AUC (r = 0.304, P = 0.015) and between PPI and salivary cortisol AUC (r = 0.298, P = 0.017). Conclusions The results confirm the impact of uncontrollability on stress responses in humans; the relationship of PPI with subjective helplessness and salivary cortisol suggests a cognitive-affective sensitization of pain perception, particularly under uncontrollable conditions. PMID:21718526

Systemic lupus erythematosus: an update.

PubMed

Golder, Vera; Hoi, Alberta

2017-03-20

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease predominantly affecting women of childbearing age. New classification criteria for SLE have greater sensitivity and therefore improve the diagnostic certainty for some patients, especially those who may previously have been labelled as having undifferentiated symptoms. Uncontrolled disease activity leads to irreversible end-organ damage, which in turn increases the risk of premature death; early and sustained control of disease activity can usually be achieved by conventional immunosuppressant therapy. The development of biological therapy lags behind that for other rheumatic diseases, with belimumab being the only targeted therapy approved by the Therapeutic Goods Administration. "Treat-to-target" concepts are changing trial design and clinical practice, with evidence-based definition of response criteria in the form of remission and low disease activity now on the horizon. While new therapies are awaited, research should also focus on optimising the use of current therapy and improving the quality of care of patients with SLE.

Indications and applications of arterial stents for stroke prevention in atherosclerotic intracranial stenosis.

PubMed

Fields, Jeremy D; Liu, Kenneth C; Barnwell, Stanley L; Clark, Wayne M; Lutsep, Helmi L

2010-01-01

Intracranial stenosis accounts for 8-10% of all ischemic strokes in North America, a frequency slightly less than that of extracranial carotid stenosis. Among patients presenting with transient ischemic attack or stroke due to intracranial stenosis, the risk of recurrent stroke in the first year after initial symptoms is about 14%. Those with high-risk features (recent stroke and severe stenosis) have up to a 23% rate of recurrent stroke in the year after their initial event. Angioplasty with stenting has emerged as a potential treatment strategy, particularly in high-risk patients, although evidence is currently limited to uncontrolled prospective trials and retrospective case series. In this article, we critically review the clinical results supporting the use of stenting and highlight some key considerations in the application of this technology, including patient selection, procedural management, technical issues, and risk factors for complications and in-stent restenosis.

[Massage with aromatherapy: effectiveness on anxiety of users with personality disorders in psychiatric hospitalization].

PubMed

Domingos, Thiago da Silva; Braga, Eliana Mara

2015-06-01

To investigate the effectiveness of aromatherapy massage using the essential oils (0.5%) of Lavandula angustifolia and Pelargonium graveolens for anxiety reduction in patients with personality disorders during psychiatric hospitalization. Uncontrolled clinical trial with 50 subjects submitted to six massages with aromatherapy, performed on alternate days, on the cervical and the posterior thoracic regions. Vital data (heart and respiratory rate) were collected before and after each session and an anxiety scale (Trait Anxiety Inventory-State) was applied at the beginning and end of the intervention. The results were statistically analyzed with the chi square test and paired t test. There was a statistically significant decrease (p < 0.001) of the heart and respiratory mean rates after each intervention session, as well as in the inventory score. Aromatherapy has demonstrated effectiveness in anxiety relief, considering the decrease of heart and respiratory rates in patients diagnosed with personality disorders during psychiatric hospitalization.

Progress in the understanding and utilization of biologic response modifiers in the treatment of uveitis.

PubMed

Maleki, Arash; Meese, Halea; Sahawneh, Haitham; Foster, C Stephen

2016-07-01

Uveitis is the third most common cause of blindness in developed countries. Considering the systemic and local complications of long-term corticosteroid therapy and the intolerance due to side effects and ineffectiveness of conventional chemotherapy, use of biologic response modifiers is a reasonable alternative in the treatment of non-infectious uveitis and persistent uveitic macular edema. The majority of the evidence presented here comes from open uncontrolled analyses. Based on these studies, tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, have been shown to be effective in the treatment of non-infectious uveitis in numerous studies. More research is necessary, particularly multi-center randomized clinical trials, to address the choice of biologic response modifier agent and the length of treatment as we employ biologic response modifiers in different types of uveitis and persistent uveitic macular edema.

An overview on Leishmania vaccines: A narrative review article.

PubMed

Rezvan, Hossein; Moafi, Mohammad

2015-01-01

Leishmaniasis is one of the major health problems and categorized as a class I disease (emerging and uncontrolled) by World Health Organization (WHO), causing highly significant morbidity and mortality. Indeed, more than 350 million individuals are at risk of Leishmania infection, and about 1.6 million new cases occur causing more than 50 thousands death annually. Because of the severe toxicity and drug resistance, present chemotherapy regimen against diverse forms of Leishmania infections is not totally worthwhile. However, sound immunity due to natural infection, implies that vigor cellular immunity against Leishmania parasites, via their live, attenuated or killed forms, can be developed in dogs and humans. Moreover, genetically conserved antigens (in most of Leishmania species), and components of sand fly saliva confer potential immunogenic molecules for Leishmania vaccination. Vaccines successes in animal studies and some clinical trials clearly justify more researches and investments illuminating opportunities in suitable vaccine designation.

An overview on Leishmania vaccines: A narrative review article

PubMed Central

Rezvan, Hossein; Moafi, Mohammad

2015-01-01

Leishmaniasis is one of the major health problems and categorized as a class I disease (emerging and uncontrolled) by World Health Organization (WHO), causing highly significant morbidity and mortality. Indeed, more than 350 million individuals are at risk of Leishmania infection, and about 1.6 million new cases occur causing more than 50 thousands death annually. Because of the severe toxicity and drug resistance, present chemotherapy regimen against diverse forms of Leishmania infections is not totally worthwhile. However, sound immunity due to natural infection, implies that vigor cellular immunity against Leishmania parasites, via their live, attenuated or killed forms, can be developed in dogs and humans. Moreover, genetically conserved antigens (in most of Leishmania species), and components of sand fly saliva confer potential immunogenic molecules for Leishmania vaccination. Vaccines successes in animal studies and some clinical trials clearly justify more researches and investments illuminating opportunities in suitable vaccine designation. PMID:25992245

In patients with severe uncontrolled asthma, does knowledge of adherence and inhaler technique using electronic monitoring improve clinical decision making? A protocol for a randomised controlled trial.

PubMed

Mokoka, Matshediso C; Lombard, Lorna; MacHale, Elaine M; Walsh, Joanne; Cushen, Breda; Sulaiman, Imran; Carthy, Damien Mc; Boland, Fiona; Doyle, Frank; Hunt, Eoin; Murphy, Desmond M; Faul, John; Butler, Marcus; Hetherington, Kathy; Mark FitzGerald, J; Boven, Job Fm van; Heaney, Liam G; Reilly, Richard B; Costello, Richard W

2017-06-15

Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes. This prospective, randomised, multicentre study will compare the impact of using information on adherence to influence asthma treatment. Patients with severe uncontrolled asthma will be included. Data on adherence, inhaler technique and electronically recorded peak expiratory flow rate will be used to promote adherence and guide a clinical decision protocol to guide management in the active group. The control group will receive standard inhaler and adherence education. Medications will be adjusted using a protocol based on Global Initiativefor Asthma (GINA) recommendations. The primary outcome is the between-group difference in the proportion of patients who have refractory disease and are prescribed appropriate medications at the end of 32 weeks. A co-primary outcome is the difference between groups in the rate of adherence to salmeterol/fluticasone inhaler over the last 12 weeks. Secondary outcomes include changes in symptoms, lung function, type-2 cytokine biomarkers and clinical outcomes between both groups. Cost-effectiveness and cost-utility analyses of the INCA device intervention will be performed. The economic impact of a national implementation of the INCA-SUN programme will be evaluated. The results of the study will be published as a manuscript in peer-reviewed journals. The study has been approved by the ethics committees in the five participating hospitals. NCT02307669; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Therapeutic use of dextromethorphan: key learnings from treatment of pseudobulbar affect.

PubMed

Miller, Ariel; Panitch, Hillel

2007-08-15

A variety of neurological conditions and disease states are accompanied by pseudobulbar affect (PBA), an emotional disorder characterized by uncontrollable outbursts of laughing and crying. The causes of PBA are unclear but may involve lesions in neural circuits regulating the motor output of emotional expression. Several agents used in treating other psychiatric disorders have been applied in the treatment of PBA with some success but data are limited and these agents are associated with unpleasant side effects due to nonspecific activity in diffuse neural networks. Dextromethorphan (DM), a widely used cough suppressant, acts at receptors in the brainstem and cerebellum, brain regions implicated in the regulation of emotional output. The combination of DM and quinidine (Q), an enzyme inhibitor that blocks DM metabolism, has recently been tested in phase III clinical trials in patients with multiple sclerosis and amyotrophic lateral sclerosis and was both safe and effective in palliating PBA symptoms. In addition, clinical studies pertaining to the safety and efficacy of DM/Q in a variety of neurological disease states are ongoing.

Associations of metabolic disorder factors with the risk of uncontrolled hypertension: a follow-up cohort in rural China.

PubMed

Xiao, Jing; Hua, Tianqi; Shen, Huan; Zhang, Min; Wang, Xiao-Jian; Gao, Yue-Xia; Lu, Qinyun; Wu, Chuanli

2017-04-07

We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15-70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend <0.01). The presence of ≥3 metabolic disorder factors was associated with higher risks of poor BP control. The associations of metabolic factors and uncontrolled hypertension were stronger for the standard and modified ATP III criteria, compared to the IDF and JIS criteria. Metabolic factors were associated with less effective antihypertension therapy, and all definitions of metabolic syndrome helped identify patients with elevated risks of uncontrolled hypertension.

Post-traumatic stress disorder in older adults: a systematic review of the psychotherapy treatment literature.

PubMed

Dinnen, Stephanie; Simiola, Vanessa; Cook, Joan M

2015-01-01

Older adults represent the fastest growing segment of the US and industrialized populations. However, older adults have generally not been included in randomized clinical trials of psychotherapy for post-traumatic stress disorder (PTSD). This review examined reports of psychological treatment for trauma-related problems, primarily PTSD, in studies with samples of at least 50% adults aged 55 and older using standardized measures. A systematic review of the literature was conducted on psychotherapy for PTSD with older adults using PubMed, Medline, PsychInfo, CINAHL, PILOTS, and Google Scholar. A total of 42 studies were retrieved for full review; 22 were excluded because they did not provide at least one outcome measure or results were not reported by age in the case of mixed-age samples. Of the 20 studies that met review criteria, there were: 13 case studies or series, three uncontrolled pilot studies, two randomized clinical trials, one non-randomized concurrent control study and one post hoc effectiveness study. Significant methodological limitations in the current older adult PTSD treatment outcome literature were found reducing its internal validity and generalizability, including non-randomized research designs, lack of comparison conditions and small sample sizes. Select evidence-based interventions validated in younger and middle-aged populations appear acceptable and efficacious with older adults. There are few treatment studies on subsets of the older adult population including cultural and ethnic minorities, women, the oldest old (over 85), and those who are cognitively impaired. Implications for clinical practice and future research directions are discussed.

Feasibility Study of an Interactive Multimedia Electronic Problem Solving Treatment Program for Depression: A Preliminary Uncontrolled Trial

PubMed Central

Berman, Margit I.; Jr., Jay C. Buckey; Hull, Jay G.; Linardatos, Eftihia; Song, Sueyoung L.; McLellan, Robert K.; Hegel, Mark T.

2014-01-01

Computer-based depression interventions lacking live therapist support have difficulty engaging users. This study evaluated the usability, acceptability, credibility, therapeutic alliance and efficacy of a stand-alone multimedia, interactive, computer-based Problem Solving Treatment program (ePST™) for depression. The program simulated live treatment from an expert PST therapist, and delivered 6 ePST™ sessions over 9 weeks. Twenty-nine participants with moderate-severe symptoms received the intervention; 23 completed a mini mally adequate dose of ePST™ (at least 4 sessions). Program usability, acceptability, credibility, and therapeutic alliance were assessed at treatment midpoint and endpoint. Depressive symptoms and health-related functioning were assessed at baseline, treatment midpoint (4 weeks), and study endpoint (10 weeks). Depression outcomes and therapeutic alliance ratings were also compared to previously published research on live PST and computer-based depression therapy. Participants rated the program as highly usable, acceptable, and credible, and reported a therapeutic alliance with the program comparable to that observed in live therapy. Depressive symptoms improved significantly over time. These findings also provide preliminary evidence that ePST™ may be effective as a depression treatment. Larger clinical trials with diverse samples are indicated. PMID:24680231

Written exposure therapy for veterans diagnosed with PTSD: a pilot study.

PubMed

Sloan, Denise M; Lee, Daniel J; Litwack, Scott D; Sawyer, Alice T; Marx, Brian P

2013-12-01

There is a need to identify alternative treatment options for posttraumatic stress disorder (PTSD), especially among veterans where PTSD tends to be more difficult to treat and dropout rates are especially high. One potential alternative is written exposure therapy, a brief intervention shown to treat PTSD among civilians effectively. This study investigated the feasibility and tolerability of written exposure therapy in an uncontrolled trial with a sample of 7 male veterans diagnosed with PTSD. Findings indicated that written exposure therapy was well tolerated and well received. Only 1 of the 7 veterans dropped out of treatment, no adverse events occurred during the course of treatment, and veterans provided high treatment satisfaction ratings. Clinically significant improvements in PTSD symptom severity were observed for 4 veterans at posttreatment and 6 veterans at the 3-month follow up. Moreover, 5 of the 7 veterans no longer met diagnostic criteria for PTSD 3 months following treatment. These findings suggest that written exposure therapy holds promise as a brief, well tolerated treatment for veterans with PTSD. However, additional research using randomized controlled trial methodology is needed to confirm its efficacy. Published 2013. This article is a US Government work and is in the public domain in the USA.

Comparative Effects of an Angiotensin II Receptor Blocker (ARB)/Diuretic vs. ARB/Calcium-Channel Blocker Combination on Uncontrolled Nocturnal Hypertension Evaluated by Information and Communication Technology-Based Nocturnal Home Blood Pressure Monitoring　- The NOCTURNE Study.

PubMed

Kario, Kazuomi; Tomitani, Naoko; Kanegae, Hiroshi; Ishii, Hajime; Uchiyama, Kazuaki; Yamagiwa, Kayo; Shiraiwa, Toshihiko; Katsuya, Tomohiro; Yoshida, Tetsuro; Kanda, Kiyomi; Hasegawa, Shinji; Hoshide, Satoshi

2017-06-23

Nocturnal blood pressure (BP) is an independent risk factor of cardiovascular events. The NOCTURNE study, a multicenter, randomized controlled trial (RCT) using our recently developed information and communication technology (ICT) nocturnal home BP monitoring (HBPM) device, was performed to compare the nocturnal HBP-lowering effects of differential ARB-based combination therapies in 411 Japanese patients with nocturnal hypertension (HT).Methods and Results:Patients with nocturnal BP ≥120/70 mmHg at baseline even under ARB therapy (100 mg irbesartan daily) were enrolled. The ARB/CCB combination therapy (irbesartan 100 mg+amlodipine 5 mg) achieved a significantly greater reduction in nocturnal home systolic BP (primary endpoint) than the ARB/diuretic combination (daily irbesartan 100 mg+trichlormethiazide 1 mg) (-14.4 vs. -10.5 mmHg, P<0.0001), independently of urinary sodium excretion and/or nocturnal BP dipping status. However, the change in nocturnal home systolic BP was comparable among the post-hoc subgroups with higher salt sensitivity (diabetes, chronic kidney disease, and elderly patients). This is the first RCT demonstrating the feasibility of clinical assessment of nocturnal BP by ICT-nocturnal HBPM. The ARB/CCB combination was shown to be superior to ARB/diuretic in patients with uncontrolled nocturnal HT independently of sodium intake, despite the similar impact of the 2 combinations in patients with higher salt sensitivity.

Effects of aerobic dance training on blood pressure in individuals with uncontrolled hypertension on two antihypertensive drugs: a randomized clinical trial.

PubMed

Maruf, Fatai Adesina; Akinpelu, Aderonke Omobonike; Salako, Babatunde Lawal; Akinyemi, Joshua Odunayo

2016-04-01

There is a dearth of reports on possible additive blood pressure (BP)-reducing effect of aerobic exercise on antihypertensive drug in humans. This study investigated the additive BP-reducing effect of aerobic exercise on BP in individuals with uncontrolled hypertension. In this 12-week double-blind study, 120 new-diagnosed individuals with mild-to-moderate hypertension were randomized to receive coamilozide + 5/10 mg of amlodipine + aerobic dance or coamilozide + 5/10 mg of amlodipine alone. Forty-five and 43 participants in exercise and control groups, respectively, completed the 12-week intervention. Addition of aerobic exercise to antihypertensive drug therapy significantly reduced systolic BP (7.1 mm Hg [95% confidence interval: 5.0, 9.3]; P < .001) and diastolic BP (1.7 mm Hg [95% confidence interval: 0.4, 3.0]; P = .009) at 12 weeks. BP control rate differed significantly between exercise (53.9%) and control (35.3%) groups, P < .001. Postintervention, proportion of participants in exercise group who had their number of antihypertensive drug reduced to one (20.3%) differed from that in control group (11.1%); (χ(2) = 11.0; P = .001). Combination of aerobic dance and antihypertensive drugs reduces number of antihypertensive drugs needed to achieve BP control and enhances BP control in individuals with hypertension on two antihypertensive drugs. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

A systematic review and meta-analysis of the effectiveness of food safety education interventions for consumers in developed countries.

PubMed

Young, Ian; Waddell, Lisa; Harding, Shannon; Greig, Judy; Mascarenhas, Mariola; Sivaramalingam, Bhairavi; Pham, Mai T; Papadopoulos, Andrew

2015-08-26

Foodborne illness has a large public health and economic burden worldwide, and many cases are associated with food handled and prepared at home. Educational interventions are necessary to improve consumer food safety practices and reduce the associated burden of foodborne illness. We conducted a systematic review and targeted meta-analyses to investigate the effectiveness of food safety education interventions for consumers. Relevant articles were identified through a preliminary scoping review that included: a comprehensive search in 10 bibliographic databases with verification; relevance screening of abstracts; and extraction of article characteristics. Experimental studies conducted in developed countries were prioritized for risk-of-bias assessment and data extraction. Meta-analysis was conducted on data subgroups stratified by key study design-intervention-population-outcome categories and subgroups were assessed for their quality of evidence. Meta-regression was conducted where appropriate to identify possible sources of between-trial heterogeneity. We identified 79 relevant studies: 17 randomized controlled trials (RCTs); 12 non-randomized controlled trials (NRTs); and 50 uncontrolled before-and-after studies. Several studies did not provide sufficient details on key design features (e.g. blinding), with some high risk-of-bias ratings due to incomplete outcome data and selective reporting. We identified a moderate to high confidence in results from two large RCTs investigating community- and school-based educational training interventions on behaviour outcomes in children and youth (median standardized mean difference [SMD] = 0.20, range: 0.05, 0.35); in two small RCTs evaluating video and written instructional messaging on behavioural intentions in adults (SMD = 0.36, 95% confidence interval [CI]: 0.02, 0.69); and in two NRT studies for university-based education on attitudes of students and staff (SMD = 0.26, 95% CI: 0.10, 0.43). Uncontrolled before-and-after study outcomes were very heterogeneous and we have little confidence that the meta-analysis results reflect the true effect. Some variation in outcomes was explained in meta-regression models, including a dose effect for behaviour outcomes in RCTs. In controlled trials, food safety education interventions showed significant effects in some contexts; however, many outcomes were very heterogeneous and do not provide a strong quality of evidence to support decision-making. Future research in this area is needed using more robust experimental designs to build on interventions shown to be effective in uncontrolled before-and-after studies.

Review article: gut-directed hypnotherapy in the management of irritable bowel syndrome and inflammatory bowel disease.

PubMed

Peters, S L; Muir, J G; Gibson, P R

2015-06-01

Gut-directed hypnotherapy is being increasingly applied to patients with irritable bowel syndrome (IBS) and to a lesser extent, inflammatory bowel disease (IBD). To review the technique, mechanisms of action and evidence for efficacy, and to identify gaps in the understanding of gut-directed hypnotherapy as a treatment for IBS and IBD. A review of published literature and a systematic review of clinical trials in its application to patients with IBS and IBD were performed. Gut-directed hypnotherapy is a clearly described technique. Its potential mechanisms of action on the brain-gut axis are multiple with evidence spanning psychological effects through to physiological gastrointestinal modifications. Six of seven randomised IBS studies reported a significant reduction (all P < 0.05) in overall gastrointestinal symptoms following treatment usually compared to supportive therapy only. Response rates amongst those who received gut-directed hypnotherapy ranged between 24% and 73%. Efficacy was maintained long-term in four of five studies. A therapeutic effect was also observed in the maintenance of clinical remission in patients with ulcerative colitis. Uncontrolled trials supported the efficacy and durability of gut-directed hypnotherapy in IBS. Gaps in understanding included to whom and when it should be applied, the paucity of adequately trained hypnotherapists, and the difficulties in designing well controlled-trials. Gut-directed hypnotherapy has durable efficacy in patients with IBS and possibly ulcerative colitis. Whether it sits in the therapeutic arsenal as a primary and/or adjunctive therapy cannot be ascertained on the current evidence base. Further research into efficacy, mechanisms of action and predictors of response is required. © 2015 John Wiley & Sons Ltd.

Design, rationale, and baseline characteristics of a cluster randomized controlled trial of pay for performance for hypertension treatment: study protocol

PubMed Central

2011-01-01

Background Despite compelling evidence of the benefits of treatment and well-accepted guidelines for treatment, hypertension is controlled in less than one-half of United States citizens. Methods/design This randomized controlled trial tests whether explicit financial incentives promote the translation of guideline-recommended care for hypertension into clinical practice and improve blood pressure (BP) control in the primary care setting. Using constrained randomization, we assigned 12 Veterans Affairs hospital outpatient clinics to four study arms: physician-level incentive; group-level incentive; combination of physician and group incentives; and no incentives (control). All participants at the hospital (cluster) were assigned to the same study arm. We enrolled 83 full-time primary care physicians and 42 non-physician personnel. The intervention consisted of an educational session about guideline-recommended care for hypertension, five audit and feedback reports, and five disbursements of incentive payments. Incentive payments rewarded participants for chart-documented use of guideline-recommended antihypertensive medications, BP control, and appropriate responses to uncontrolled BP during a prior four-month performance period over the 20-month intervention. To identify potential unintended consequences of the incentives, the study team interviewed study participants, as well as non-participant primary care personnel and leadership at study sites. Chart reviews included data collection on quality measures not related to hypertension. To evaluate the persistence of the effect of the incentives, the study design includes a washout period. Discussion We briefly describe the rationale for the interventions being studied, as well as the major design choices. Rigorous research designs such as the one described here are necessary to determine whether performance-based payment arrangements such as financial incentives result in meaningful quality improvements. Trial Registration http://www.clinicaltrials.gov NCT00302718 PMID:21967830

Double-blind, controlled, clinical trial planned in germany to investigate the efficacy of psychotherapy combined with triptorelin in adult male patients with severe pedophilic disorders: presentation of the study protocol.

PubMed

Briken, Peer; Berner, Wolfgang

2012-01-01

The treatment of paraphilias, especially of pedophilia, centers upon cognitive-behavioral psychotherapy and pharmacologic interventions. Two open, uncontrolled clinical studies using the synthetic LHRH-agonist triptorelin suggested that, combined with psychotherapy, antiandrogen treatment reduced deviant sexual fantasies, urges, and behaviors in paraphilic patients. There is a need for further research using controlled, randomized trials to examine the effectiveness of sexual offender treatment including psychotherapeutic and pharmacologic interventions. The aim of this pilot study is to evaluate the efficacy and tolerability of cognitive-behavioral psychotherapy together with intramuscular (IM) 3-monthly injections of triptorelin in adult men with severe pedophilia. In this multicenter, forensic psychiatric hospital-based, double-blind, controlled, parallel group phase IV trial conducted in Germany, convicted male sexual offenders aged ≥ 18 years with pedophilia, as defined by DSM-IV-TR criteria, will be randomized to receive study-specific psychotherapy together either with triptorelin or placebo for 12 months (total of 4 injections). This is a pilot study, therefore exploratory data analyses will be carried out of three different target parameters: 1. Changes in psychosexual characteristics using the Multiphasic Sex Inventory (scale: sexual abuse of children) 2. Changes in the risk of violent sexual behavior using the Sexual Violence Risk-20 total score 3. Changes in serum testosterone concentration Treatment effects will be assessed by comparing baseline values with those at the final examination (month 12). The absence of real-life stimulants to test for actual recidivism limits possible findings. The study will be conducted in agreement with the European GCP-guideline, all relevant legal requirements, and the legal framework for voluntary treatment of convicted sexual offenders in Germany.

A Randomized Trial of Peer-Delivered Self-Management Support for Hypertension

PubMed Central

Schapira, Marilyn M.; Fletcher, Kathlyn E.; Hayes, Avery; Morzinski, Jeffrey; Laud, Purushottam; Eastwood, Dan; Ertl, Kristyn; Patterson, Leslie; Mosack, Katie E.

2014-01-01

BACKGROUND Peer-led interventions to improve chronic disease self-management can improve health outcomes but are not widely used. Therefore, we tested a peer-led hypertension self-management intervention delivered at regular meetings of community veterans’ organizations. METHODS We randomized 58 organizational units (“posts”) of veterans’ organizations in southeast Wisconsin to peer-led vs. professionally delivered self-management education. Volunteer peer leaders at peer-led posts delivered monthly presentations regarding hypertension self-management during regular post meetings. Volunteer post representatives at seminar posts encouraged post members to attend 3 didactic seminars delivered by health professionals at a time separate from the post meeting. Volunteers in both groups encouraged members to self-monitor using blood pressure cuffs, weight scales, and pedometers. Our primary outcome was change in systolic blood pressure (SBP) at 12 months. RESULTS We measured SBP in 404 participants at baseline and in 379 participants at 12 months. SBP decreased significantly (4.4mm Hg; P < 0.0001) overall; the decrease was similar in peer-led and seminar posts (3.5mm Hg vs. 5.4mm Hg; P = 0.24). Among participants with uncontrolled BP at baseline, SBP decreased by 10.1mm Hg from baseline to 12 months but was again similar in the 2 groups. This pattern was also seen at 6 months and with diastolic blood pressure. CONCLUSIONS Our peer-led educational intervention was not more effective than didactic seminars for SBP control. Although peer-led educational programs have had important impacts in a number of studies, we did not find our intervention superior to a similar intervention delivered by healthcare professionals. Clinical trial registration ClinicalTrials.gov NCT00571038. PMID:24755206

Therapeutic Devices for Epilepsy

PubMed Central

Fisher, Robert S.

2011-01-01

Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

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.

[Clinical utility of home blood pressure monitoring in patients under treatment].

PubMed

Bauk, L; Costa, H A; Caligiuri, S I

2015-01-01

A low number of patients who are treated with antihypertensive drugs achieve therapeutic goals. Home blood pressure monitoring is an excellent tool for studying this population. To determine the prevalence of patients with controlled and uncontrolled hypertension, as well as white-coat-effect and masked hypertension, and to evaluate the relationship with target organ damage in different groups. Blood pressure readings were performed simultaneously in the clinic and in the home using the same validated oscillometric equipment on 83 hypertensive patients on treatment with 2 or more antihypertensive drugs. They were then classified into 4 groups according to the cut-off values of the clinic and home blood pressure measurements. Left ventricular mass index, carotid intima media thickness, and microalbuminuria as markers of target organ damage, were also evaluated. Controlled blood pressure was present in 32.5%, 30.2% had sustained hypertension. The white coat effect was seen in 26.5%, while 10.8% were masked uncontrolled hypertension. Left ventricular mass index was higher in patients with no ambulatory control compared to controlled patients, and carotid IMT was also higher too in uncontrolled and white coat effect groups than controlled patients. More than one third of our patients who were treated with 2 or more drugs were not properly controlled, and they had significantly greater target organ damage than controlled patients. Copyright © 2014 SEHLELHA. Published by Elsevier Espana. All rights reserved.

Twelve-Week 24/7 Ambulatory Artificial Pancreas With Weekly Adaptation of Insulin Delivery Settings: Effect on Hemoglobin A1c and Hypoglycemia.

PubMed

Dassau, Eyal; Pinsker, Jordan E; Kudva, Yogish C; Brown, Sue A; Gondhalekar, Ravi; Dalla Man, Chiara; Patek, Steve; Schiavon, Michele; Dadlani, Vikash; Dasanayake, Isuru; Church, Mei Mei; Carter, Rickey E; Bevier, Wendy C; Huyett, Lauren M; Hughes, Jonathan; Anderson, Stacey; Lv, Dayu; Schertz, Elaine; Emory, Emma; McCrady-Spitzer, Shelly K; Jean, Tyler; Bradley, Paige K; Hinshaw, Ling; Laguna Sanz, Alejandro J; Basu, Ananda; Kovatchev, Boris; Cobelli, Claudio; Doyle, Francis J

2017-12-01

Artificial pancreas (AP) systems are best positioned for optimal treatment of type 1 diabetes (T1D) and are currently being tested in outpatient clinical trials. Our consortium developed and tested a novel adaptive AP in an outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks. Thirty adults with T1D completed a continuous glucose monitor (CGM)-augmented 1-week sensor-augmented pump (SAP) period. After the AP was started, basal insulin delivery settings used by the AP for initialization were adapted weekly, and carbohydrate ratios were adapted every 4 weeks by an algorithm running on a cloud-based server, with automatic data upload from devices. Adaptations were reviewed by expert study clinicians and patients. The primary end point was change in hemoglobin A 1c (HbA 1c ). Outcomes are reported adhering to consensus recommendations on reporting of AP trials. Twenty-nine patients completed the trial. HbA 1c , 7.0 ± 0.8% at the start of AP use, improved to 6.7 ± 0.6% after 12 weeks (-0.3, 95% CI -0.5 to -0.2, P < 0.001). Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved during the day from 5.0 to 1.9% (-3.1, 95% CI -4.1 to -2.1, P < 0.001) and overnight from 4.1 to 1.1% (-3.1, 95% CI -4.2 to -1.9, P < 0.001). Whereas carbohydrate ratios were adapted to a larger extent initially with minimal changes thereafter, basal insulin was adapted throughout. Approximately 10% of adaptation recommendations were manually overridden. There were no protocol-related serious adverse events. Use of our novel adaptive AP yielded significant reductions in HbA 1c and hypoglycemia. © 2017 by the American Diabetes Association.

Home blood pressure monitoring with nurse-led telephone support among patients with hypertension and a history of stroke: a community-based randomized controlled trial

PubMed Central

Kerry, Sally M.; Markus, Hugh S.; Khong, Teck K.; Cloud, Geoffrey C.; Tulloch, Jenny; Coster, Denise; Ibison, Judith; Oakeshott, Pippa

2013-01-01

Background: Adequate control of blood pressure reduces the risk of recurrent stroke. We conducted a randomized controlled study to determine whether home blood pressure monitoring with nurse-led telephone support would reduce blood pressure in patients with hypertension and a history of stroke. Methods: We recruited 381 participants (mean age 72 years) from outpatient and inpatient stroke clinics between Mar. 1, 2007, and Aug. 31, 2009. Nearly half (45%, 170) of the participants had some disability due to stroke. Participants were visited at home for a baseline assessment and randomly allocated to home blood pressure monitoring (n = 187) or usual care (n = 194). Those in the intervention group were given a monitor, brief training and telephone support. Participants who had home blood pressure readings consistently over target (target < 130/80 mm Hg) were advised to consult their family physician. The main outcome measure was a fall in systolic blood pressure after 12 months, measured by an independent researcher unaware of group allocation. Results: Despite more patients in the intervention group than in the control group having changes to antihypertensive treatment during the trial period (60.1% [98/163] v. 47.6% [78/164], p = 0.02), the fall in systolic blood pressure from baseline did not differ significantly between the groups (adjusted mean difference 0.3 mm Hg, 95% confidence interval –3.6 to 4.2 mm Hg). Subgroup analysis showed significant interaction with disability due to stroke (p = 0.03 at 6 months) and baseline blood pressure (p = 0.03 at 12 months). Interpretation: Overall, home monitoring did not improve blood pressure control in patients with hypertension and a history of stroke. It was associated with a fall in systolic pressure in patients who had uncontrolled blood pressure at baseline and those without disability due to stroke. Trial registration: ClinicalTrials.gov registration NCT00514800 PMID:23128283

An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions.

PubMed

Pattee, Gary L; Wymer, James P; Lomen-Hoerth, Catherine; Appel, Stanley H; Formella, Andrea E; Pope, Laura E

2014-11-01

Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient's emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. #NCT00056524. A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions.

Interventions for vaginismus.

PubMed

Melnik, Tamara; Hawton, Keith; McGuire, Hugh

2012-12-12

Vaginismus is an involuntary contraction of the vaginal muscles which makes sexual intercourse difficult or impossible. It is one of the more common female psychosexual problems. Various therapeutic strategies for vaginismus, such as sex therapy and desensitisation, have been proposed, and uncontrolled case series appear promising. To assess the effects of different interventions for vaginismus. We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialised Register (CCDANCTR-Studies and CCDANCTR-References) to August 2012. This register contains relevant randomised controlled trials from: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). We searched reference lists and conference abstracts. We contacted experts in the field regarding unpublished material. Controlled trials comparing treatments for vaginismus with another treatment, a placebo treatment, treatment as usual or waiting list control. The review authors extracted data which we verified with the trial investigator where possible. Five studies were included, of which four with a total of 282 participants provided data. No meta-analysis was possible due to heterogeneity of comparisons within included studies as well as inadequate reporting of data. All studies were considered to be at either moderate or high risk of bias. The results of this systematic review indicate that there is no clinical or statistical difference between systematic desensitisation and any of the control interventions (either waiting list control, systematic desensitisation combined with group therapy or in vitro (with women under instruction by the therapist) desensitisation) for the treatment of vaginismus. The drop-out rates were higher in the waiting list groups. A clinically relevant effect of systematic desensitisation when compared with any of the control interventions cannot be ruled out. None of the included trials compared other behaviour therapies (e.g. cognitive behaviour therapy, sex therapy) to pharmacological interventions. The findings are limited by the evidence available and as such conclusions about the efficacy of interventions for the treatment of vaginismus should be drawn cautiously.

[Hematopoietic reconstitution after transplantation of uncontrolled-rate cryopreservation autologous peripheral blood hematopoietic stem cells using -80 °C mechanical freezer].

PubMed

Liu, Mo; Zhao, Yu; Sun, Jing-Fen; Zhao, Wei; Wang, Li-Li; Yu, Li

2015-02-01

This study was to identify the efficacy of -80°C cryopreservated peripheral blood hemato-poietic stem cell (PBHSC) transplantation for hematopoietic reanstitution in patients. The efficacy of 104 patients underwent autologous peripheral blood hematopoietic stem cell transplantation using uncontrolled-rate freezing and storage at -80°C was evaluated. This cryopreservation method could effectively cryopreserve peripheral blood stem cells. Out of 104 patients only 2 patients died, other patients got hematologic reconstition satisfactorily, the median engrafement times of neutrophils and platelet were 12 and 14 days respectively, the activity of cells after rehabilitation was 94%, the mean recovery rates of CD34(+) cells and mononuclear cells (MNC) were 86% and 80.3% respectively. There were no significant influences on engrafement time in sex, chemotherapy circles and radiotherapy. The engrafement of leukocytes associated with amount of CD34(+) cells. This simple uncontrolled-rate freezing PBHSC at -80°C is safe, effective and economic, and can meet clinical needs. As compared with the classical cryopreservation, there were no significant differences in hematopoietic reconstitution. Therefore, this method worth to popularize and apply in clinic.

Evaluation of a novel supplement to reduce blood glucose through the use of a modified oral glucose tolerance test

PubMed Central

Smith, Adam J; Giunta, Brian; Shytle, R Douglas; Blum, James M

2011-01-01

Elevated blood glucose is a major component in metabolic syndrome and pre-diabetes, sometimes leading to type 2 diabetes mellitus (DM II). Additionally, it may lead to adipose deposits when left elevated for long periods. The epidemiology of DM II clearly shows that uncontrolled blood glucose levels leads to many adverse conditions including heart disease, retinal damage, renal failure, erectile dysfunction, and other significant medical conditions. Here we conducted a single-center, prospective, randomized, double-blinded, placebo-controlled, parallel-group- clinical trial of a nutraceutical supplement vs. placebo to measure its glucose lowering effect in generally healthy adults before and after a simple sugars meal. Subjects reported to the test clinic on multiple days to receive placebo or treatment, a simple sugars meal, as well as pre-and postprandial blood glucose measurement (modified oral glucose tolerance test). Each subject served as his or her own control and thirty-one subjects completed the trial with at least one oral glucose tolerance test (OGTT) with the nutraceutical supplement and placebo. Statistical analysis revealed the nutraceutical supplement significantly lowered postprandial glucose levels by 36% and 59% at 45 and 60 minutes, respectively (***P<.001). The study was limited by its composition of primarily overweight females. Future studies will be required over longer periods in more heterogeneous and larger groups to determine the long-term effect of this supplement on blood glucose levels in terms of prophylaxis or treatment for DM II. PMID:21416063

Hawthorn: pharmacology and therapeutic uses.

PubMed

Rigelsky, Janene M; Sweet, Burgunda V

2002-03-01

The uses, pharmacology, clinical efficacy, dosage and administration, adverse effects, and drug interactions of hawthorn are discussed. Hawthorn (Crataegus oxyacantha) is a fruit-bearing shrub with a long history as a medicinal substance. Uses have included the treatment of digestive ailments, dyspnea, kidney stones, and cardiovascular disorders. Today, hawthorn is used primarily for various cardiovascular conditions. The cardiovascular effects are believed to be the result of positive inotropic activity, ability to increase the integrity of the blood vessel wall and improve coronary blood flow, and positive effects on oxygen utilization. Flavonoids are postulated to account for these effects. Hawthorn has shown promise in the treatment of New York Heart Association (NYHA) functional class II congestive heart failure (CHF) in both uncontrolled and controlled clinical trials. There are also suggestions of a beneficial effect on blood lipids. Trials to establish an antiarrhythmic effect in humans have not been conducted. The recommended daily dose of hawthorn is 160-900 mg of a native water-ethanol extract of the leaves or flowers (equivalent to 30-169 mg of epicatechin or 3.5-19.8 mg of flavonoids) administered in two or three doses. At therapeutic dosages, hawthorn may cause a mild rash, headache, sweating, dizziness, palpitations, sleepiness, agitation, and gastrointestinal symptoms. Hawthorn may interact with vasodilating medications and may potentiate or inhibit the actions of drugs used for heart failure, hypertension, angina, and arrhythmias. The limited data about hawthorn suggest that it may be useful in the treatment of NYHA functional class II CHF.

A randomized breast-feeding promotion intervention did not reduce child obesity in Belarus.

PubMed

Kramer, Michael S; Matush, Lidia; Vanilovich, Irina; Platt, Robert W; Bogdanovich, Natalia; Sevkovskaya, Zinaida; Dzikovich, Irina; Shishko, Gyorgy; Collet, Jean-Paul; Martin, Richard M; Smith, George Davey; Gillman, Matthew W; Chalmers, Beverley; Hodnett, Ellen; Shapiro, Stanley

2009-02-01

The evidence that breast-feeding protects against obesity is based on observational studies, with potential for confounding and selection bias. This article summarizes a previously published study in which we assessed whether an intervention designed to promote exclusive and prolonged breast-feeding affects children's height, weight, adiposity, and blood pressure (BP) at age 6.5 y. The Promotion of Breastfeeding Intervention Trial (PROBIT) is a cluster-randomized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy breast-fed infants were enrolled from 31 Belarussian maternity hospitals and affiliated clinics, of whom 13,889 (81.5%) were followed up at 6.5 y with duplicate measurements of height, weight, waist circumference, triceps and subscapular skinfold thicknesses, systolic and diastolic BP. Analysis was based on intention to treat, with statistical adjustment for clustering within hospitals/clinics to permit inferences at the individual level. The experimental intervention led to a large increase in exclusive breast-feeding at 3 mo (43.3% vs. 6.4%, P < 0.001) and a significantly higher prevalence of any breast-feeding throughout infancy. No significant intervention effects were observed on height, BMI, adiposity measures, or BP. The breast-feeding promotion intervention resulted in substantial increases in the duration and exclusivity of breast-feeding yet did not reduce measures of adiposity at age 6.5 y. Previous reports of protective effects against obesity may reflect uncontrolled bias caused by confounding and selection.

Factors Associated with Uncontrolled Hypertension among Renal Transplant Recipients Attending Nephrology Clinics in Nairobi, Kenya

PubMed Central

Kubo, Mary N.; Kayima, Joshua K.; Were, Anthony J.; McLigeyo, Seth O.; Ogola, Elijah N.

2015-01-01

Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP ≥ 130/80 mmHg). On univariate analysis, male sex (OR 3.7, 95% CI 1.4–9.5, p = 0.006), higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensives (OR 18, 95% CI 5.2–65.7, p < 0.001) were associated with uncontrolled hypertension. On logistic regression analysis, male sex (adjusted OR 4.6, 95% CI 1.1–19.0, p = 0.034) and nonadherence (adjusted OR 33.8, 95% CI 8.6–73.0, p < 0.001) were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population. PMID:26257920

Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

NASA Technical Reports Server (NTRS)

Kramer, George C.; Wade, Charles E.; Dubick, Michael A.; Atkins, James L.

2004-01-01

Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure < 70 mmHg, head trauma, and penetrating injury requiring surgery. HSD and HSS have received regulatory approval in 14 and 3 countries, respectively, with 81,000+ units sold. The primary reported use was head injury and trauma resuscitation. Complications and reported adverse events are surprisingly rare and not significantly different from other solutions.HBOCs are potent volume expanders in addition to oxygen carriers with volume expansion greater than standard colloids. Several investigators have evaluated small volume hyperoncotic HBOCs or HS-HBOC formulations for hypotensive and normotensive resuscitation in animals. A consistent finding in resuscitation with HBOCs is depressed cardiac output. There is some evidence that HBOCs more efficiently unload oxygen from plasma hemoglobin as well as facilitate RBC unloading. We analyzed one volunteer study, 15 intraoperative trials, and 3 trauma studies using HBOCs. Perioperative studies generally suggest ability to deliver oxygen, but one trauma trial using HBOCs (HemAssist) for treatment of trauma resulted in a dramatic increase in mortality, while an intraoperative trauma study using Polyheme demonstrated reductions in blood use and lower mortality compared to historic controls of patients refusing blood. Transfusion reductions with HBOC use have been modest. Two HBOCs (Hemopure and Polyheme) are now in new or planned large-scale multicenter prehospital trials of trauma treatment. A new implementation of small volume resuscitation is closed-loop resuscitation (CLR), which employs microprocessors to titrate just enough fluid to reach a physiologic target . Animal studies suggest less risk of rebleeding in uncontrolled hemorrhage and a reduction in fluid needs with CLR. The first clinical application of CLR was treatment of burn shock and the US Army. Conclusions: Independently sponsored civilian trauma trials and clinical evaluations in operational combat conditions of different small volume strategies are warranted.

Effects of Individual Physician-Level and Practice-Level Financial Incentives on Hypertension Care: A Cluster Randomized Trial

PubMed Central

Petersen, Laura A.; Simpson, Kate; Pietz, Kenneth; Urech, Tracy H.; Hysong, Sylvia J.; Profit, Jochen; Conrad, Douglas A.; Dudley, R. Adams; Woodard, LeChauncy D.

2014-01-01

Importance Pay for performance is intended to align incentives to promote high quality care, but results have been contradictory. Objective To test the effect of explicit financial incentives to reward guideline-recommended hypertension care. Design, Setting, and Participants Cluster randomized controlled trial of 12 Veterans Affairs hospital-based outpatient clinics with five performance periods and a 12-month washout. We enrolled 83 primary care physicians and 42 non-physician personnel (e.g., nurses, pharmacists) working with physicians to deliver hypertension care. Interventions Clinics randomized to one of four groups: physician-level (individual) incentives; practice-level incentives; individual- plus practice-level incentives (combined); or none. Intervention participants received up to five payments every four months; all participants could access feedback reports. Main outcome measures For each four-month period, the number of hypertensive patients among a random sample who achieved guideline-recommended blood pressure thresholds or received an appropriate response to uncontrolled blood pressure; and/or been prescribed guideline-recommended medications and the number who developed hypotension. Results Mean (standard deviation) total payments over the study were $4,270 ($459), $2,672 ($153), and $1,648 ($248) for the combined, individual, and practice-level interventions, respectively. The adjusted change over the study in patients meeting the combined blood pressure/appropriate response measure was 8.84 percentage points (95% confidence interval [CI], 4.20–11.80) for the individual-level, 3.70 (95% CI, 0.24–7.68) for the practice-level, 5.54 (95% CI, 1.92–9.52) for the combined, and 0.47 (95% CI, −3.12–4.04) for the control groups. For medications, the change was 9.07 (95% CI, 4.52–13.44), 4.98 (95% CI, 0.64–10.08), 7.26 (95% CI, 2.92–12.48), and 4.35 (95% CI, −0.28–9.28) percentage points, respectively. The adjusted estimated difference in the change between the proportion of patients with blood pressure control/appropriate response for individual incentive and control groups was 8.36 percentage points (95% CI, 2.40–13.00; P=.005). Use of guideline-recommended medications did not significantly change compared to controls, nor did the incidence of hypotension. The effect of the incentive was not sustained after a washout. Conclusions and Relevance Individual financial incentives, but not practice-level or combined incentives, resulted in greater blood pressure control or appropriate response to uncontrolled blood pressure; none of the incentives resulted in greater use of guideline-recommended medications or increased incidence of hypotension compared to controls. Further research is needed to understand the factors that contributed to our findings. Trial registration NCT00302718; www.clinicaltrials.gov PMID:24026599

Burden of uncontrolled epilepsy in patients requiring an emergency room visit or hospitalization.

PubMed

Manjunath, Ranjani; Paradis, Pierre Emmanuel; Parisé, Hélène; Lafeuille, Marie-Hélène; Bowers, Brian; Duh, Mei Sheng; Lefebvre, Patrick; Faught, Edward

2012-10-30

To quantify the clinical and economic burden of uncontrolled epilepsy in patients requiring emergency department (ED) visit or hospitalization. Health insurance claims from a 5-state Medicaid database (1997Q1-2009Q2) and 55 self-insured US companies ("employer," 1999Q1 and 2008Q4) were analyzed. Adult patients with epilepsy receiving antiepileptic drugs (AED) were selected. Using a retrospective matched-cohort design, patients were categorized into cohorts of "uncontrolled" (≥ 2 changes in AED therapy, then ≥ 1 epilepsy-related ED visit/hospitalization within 1 year) and "well-controlled" (no AED change, no epilepsy-related ED visit/hospitalization) epilepsy. Matched cohorts were compared for health care resource utilization and costs using multivariate conditional regression models and nonparametric methods. From 110,312 (Medicaid) and 36,529 (employer) eligible patients, 3,454 and 602 with uncontrolled epilepsy were matched 1:1 to patients with well-controlled epilepsy, respectively. In both populations, uncontrolled epilepsy cohorts presented about 2 times more fractures and head injuries (all p values < 0.0001) and higher health care resource utilization (ranges of adjusted incidence rate ratios [IRRs] [all-cause utilization]: AEDs = 1.8-1.9, non-AEDs = 1.3-1.5, hospitalizations = 5.4-6.7, length of hospital stays = 7.3-7.7, ED visits = 3.7-5.0, outpatient visits = 1.4-1.7, neurologist visits = 2.3-3.1; all p values < 0.0001) than well-controlled groups. Total direct health care costs were higher in patients with uncontrolled epilepsy (adjusted cost difference [95% confidence interval (CI)] Medicaid = $12,258 [$10,482-$14,083]; employer = $14,582 [$12,019-$17,097]) vs well-controlled patients. Privately insured employees with uncontrolled epilepsy lost 2.5 times more work days, with associated indirect costs of $2,857 (95% CI $1,042-$4,581). Uncontrolled epilepsy in patients requiring ED visit or hospitalization was associated with significantly greater health care resource utilization and increased direct and indirect costs compared to well-controlled epilepsy in both publicly and privately insured settings.

Text Messaging to Improve Hypertension Medication Adherence in African Americans From Primary Care and Emergency Department Settings: Results From Two Randomized Feasibility Studies

PubMed Central

Hirzel, Lindsey; Dawood, Rachelle M; Dawood, Katee L; Nichols, Lauren P; Artinian, Nancy T; Schwiebert, Loren; Yarandi, Hossein N; Roberson, Dana N; Plegue, Melissa A; Mango, LynnMarie C; Levy, Phillip D

2017-01-01

Background Hypertension (HTN) is an important problem in the United States, with an estimated 78 million Americans aged 20 years and older suffering from this condition. Health disparities related to HTN are common in the United States, with African Americans suffering from greater prevalence of the condition than whites, as well as greater severity, earlier onset, and more complications. Medication adherence is an important component of HTN management, but adherence is often poor, and simply forgetting to take medications is often cited as a reason. Mobile health (mHealth) strategies have the potential to be a low-cost and effective method for improving medication adherence that also has broad reach. Objective Our goal was to determine the feasibility, acceptability, and preliminary clinical effectiveness of BPMED, an intervention designed to improve medication adherence among African Americans with uncontrolled HTN, through fully automated text messaging support. Methods We conducted two parallel, unblinded randomized controlled pilot trials with African-American patients who had uncontrolled HTN, recruited from primary care and emergency department (ED) settings. In each trial, participants were randomized to receive either usual care or the BPMED intervention for one month. Data were collected in-person at baseline and one-month follow-up, assessing the effect on medication adherence, systolic and diastolic blood pressure (SBP and DBP), medication adherence self-efficacy, and participant satisfaction. Data for both randomized controlled pilot trials were analyzed separately and combined. Results A total of 58 primary care and 65 ED participants were recruited with retention rates of 91% (53/58) and 88% (57/65), respectively. BPMED participants consistently showed numerically greater, yet nonsignificant, improvements in measures of medication adherence (mean change 0.9, SD 2.0 vs mean change 0.5, SD 1.5, P=.26), SBP (mean change –12.6, SD 24.0 vs mean change –11.3, SD 25.5 mm Hg, P=.78), and DBP (mean change –4.9, SD 13.1 mm Hg vs mean change –3.3, SD 14.3 mm Hg, P=.54). Control and BPMED participants had slight improvements to medication adherence self-efficacy (mean change 0.8, SD 9.8 vs mean change 0.7, SD 7.0) with no significant differences found between groups (P=.92). On linear regression analysis, baseline SBP was the only predictor of SBP change; participants with higher SBP at enrollment exhibited significantly greater improvements at one-month follow-up (β=–0.63, P<.001). In total, 94% (51/54) of BPMED participants agreed/strongly agreed that they were satisfied with the program, regardless of pilot setting. Conclusions Use of text message reminders to improve medication adherence is a feasible and acceptable approach among African Americans with uncontrolled HTN. Although differences in actual medication adherence and blood pressure between BPMED and usual care controls were not significant, patterns of improvement in the BPMED condition suggest that text message medication reminders may have an effect and fully powered investigations with longer-term follow-up are warranted. Trial Registration Clinicaltrials.gov NCT01465217; https://clinicaltrials.gov/ct2/show/NCT01465217 (Archived by WebCite at http://www.webcitation.org/6V0tto0lZ). PMID:28148474

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes.

PubMed

Oster, Gerry; Sullivan, Sean D; Dalal, Mehul R; Kazemi, Mahmood R; Rojeski, Maria; Wysham, Carol H; Sung, Jennifer; Johnstone, Bryan; Cali, Anna M G; Wei, L J; Traylor, Louise; Anhalt, Henry; Hull, Michelle; Van Vleet, John; Meneghini, Luigi F

2016-11-01

This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites. Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. www.clinicaltrials.gov identifier is NCT02451137.

Digital Clinical Communication for Families and Caregivers of Children or Young People With Short- or Long-Term Conditions: Rapid Review.

PubMed

Armoiry, Xavier; Sturt, Jackie; Phelps, Emma Elizabeth; Walker, Clare-Louise; Court, Rachel; Taggart, Frances; Sutcliffe, Paul; Griffiths, Frances; Atherton, Helen

2018-01-05

The communication relationship between parents of children or young people with health conditions and health professionals is an important part of treatment, but it is unclear how far the use of digital clinical communication tools may affect this relationship. The objective of our study was to describe, assess the feasibility of, and explore the impact of digital clinical communication between families or caregivers and health professionals. We searched the literature using 5 electronic databases. We considered all types of study design published in the English language from January 2009 to August 2015. The population of interest included families and caregivers of children and young people aged less than 26 years with any type of health condition. The intervention was any technology permitting 2-way communication. We included 31 articles. The main designs were randomized controlled trials (RCTs; n=10), cross-sectional studies (n=9), pre- and postintervention uncontrolled (pre/post) studies (n=7), and qualitative interview studies (n=2); 6 had mixed-methods designs. In the majority of cases, we considered the quality rating to be fair. Many different types of health condition were represented. A breadth of digital communication tools were included: videoconferencing or videoconsultation (n=14), and Web messaging or emails (n=12). Health care professionals were mainly therapists or cognitive behavioral therapists (n=10), physicians (n=8), and nurses (n=6). Studies were very heterogeneous in terms of outcomes. Interventions were mainly evaluated using satisfaction or acceptance, or outcomes relating to feasibility. Clinical outcomes were rarely used. The RCTs showed that digital clinical communication had no impact in comparison with standard care. Uncontrolled pre/post studies showed good rates of satisfaction or acceptance. Some economic studies suggested that digital clinical communication may save costs. This rapid review showed an emerging body of literature on the use of digital clinical communication to improve families' and caregivers' involvement in the health management of children or young people. Further research with appropriate study designs and longer-term outcome measures should be encouraged. PROSPERO CRD42016035467; http://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD 42016 035467(Archived by WebCite at http://www.webcitation.org/6vpgZU1FU). ©Xavier Armoiry, Jackie Sturt, Emma Elizabeth Phelps, Clare-Louise Walker, Rachel Court, Frances Taggart, Paul Sutcliffe, Frances Griffiths, Helen Atherton. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.01.2018.

The Clinical Potential of Exhaled Breath Analysis For Diabetes Mellitus

PubMed Central

Minh, Timothy Do Chau; Blake, Donald Ray; Galassetti, Pietro Renato

2012-01-01

Summary Various compounds in present human breath have long been loosely associated with pathological states (including acetone smell in uncontrolled diabetes). Only recently, however, the precise measurement of exhaled volatile organic compounds (VOCs) and aerosolized particles was made possible at extremely low concentrations by advances in several analytical methodologies, described in detail in the international literature and each suitable for specific subsets of exhaled compounds. Exhaled gases may be generated endogenously (in the pulmonary tract, blood, or peripheral tissues), as metabolic byproducts of human cells or colonizing micro-organisms, or may be inhaled as atmospheric pollutants; growing evidence indicates that several of these molecules have distinct cell-to-cell signaling functions. Independent of origin and physiological role, exhaled VOCs are attractive candidates as biomarkers of cellular activity/metabolism, and could be incorporated in future non-invasive clinical testing devices. Indeed, several recent studies reported altered exhaled gas profiles in dysmetabolic conditions and relatively accurate predictions of glucose concentrations, at least in controlled experimental conditions, for healthy and diabetic subjects over a broad range of glycemic values. Optimization of this methodology and validation in large-scale trials under a wider range of conditions is needed to determine its true potential to transition into practical clinical use. PMID:22410396

Review of the neurological benefits of phytocannabinoids.

PubMed

Maroon, Joseph; Bost, Jeff

2018-01-01

Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS. In 1980, Cunha et al . reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts. Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson's disease, Alzheimer's disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids. In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes.

Therapy of hearing disorders - conservative procedures

PubMed Central

Plontke, Stefan

2005-01-01

A wide range of therapeutic strategies are available for the therapy of hearing disorders including pharmaceutical, acoustic, electrical, surgical, radiological, cognitive-behavioural and so-called "alternative" strategies. This review focuses on general conservative strategies and specific therapeutic approaches mainly for inner ear disorders, whereas surgical and device-based therapies including hearing aids and cochlear implants are described in other chapters in this volume. In addition to the systemic medication-based therapies for the treatment of hearing disorders, the rapidly growing field of local drug delivery to the inner ear as a promising therapeutic strategy is discussed on the background of unresolved issues. After description of non-drug-based therapeutic procedures, the conservative therapy of specific diseases and syndromes is reviewed. In general, there is a major discrepancy between promising animal studies up to regeneration and stem-cell transplantation, and uncontrolled experimental studies in humans on the one hand and the shortage of randomized controlled clinical trials with a high level of evidence on the other hand. Therefore, the review and comments on published clinical studies should assist the reader in making his/her own decision about the effectiveness of various, especially pharmaceutical treatments. From a critical analysis - particularly of the clinical studies presented - conclusions are drawn for the therapy of hearing disorders in the future. PMID:22073049

Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea.

PubMed

Masab, Muhammad; Saif, Muhammad Wasif

2017-12-01

Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed. This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome. Telotristat ethyl has already been approved for the treatment of inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on SSA therapy. Results from multiple phase I-III clinical studies of telotristat ethyl therapy have reported a significant decrease in the daily bowel movement frequency, increase in quality of life and the subsequent decrease in annual health costs related to carcinoid syndrome symptoms in NET patients. The associated decrease in urinary 5-hydroxyindoleacetic acid (u5-HIAA) provides evidence that telotristat ethyl effectively decreases serotonin production, and therefore, offers a rationale to investigate this agent to mitigate serotonin-mediated complications in this patient population, especially cardiac valvular disease or mesenteric fibrosis.

A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma.

PubMed

Harris, Jeffrey M; Maciuca, Romeo; Bradley, Mary S; Cabanski, Christopher R; Scheerens, Heleen; Lim, Jeremy; Cai, Fang; Kishnani, Mona; Liao, X Charlene; Samineni, Divya; Zhu, Rui; Cochran, Colette; Soong, Weily; Diaz, Joseph D; Perin, Patrick; Tsukayama, Miguel; Dimov, Dimo; Agache, Ioana; Kelsen, Steven G

2016-03-18

Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller. Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide). Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment. Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy. ClinicalTrials.gov NCT01582503.

Safety and Efficacy of PDpoetin for Management of Anemia in Patients with end Stage Renal Disease on Maintenance Hemodialysis: Results from a Phase IV Clinical Trial.

PubMed

Javidan, Abbas Norouzi; Shahbazian, Heshmatollah; Emami, Amirhossein; Yekaninejad, Mir Saeed; Emami-Razavi, Hassan; Farhadkhani, Masoumeh; Ahmadzadeh, Ahmad; Gorjipour, Fazel

2014-08-26

Recombinant human erythropoietin (rHuEPO) is available for correcting anemia. PDpoetin, a new brand of rHuEPO, has been certified by Food and Drug Department of Ministry of Health and Medical Education of Iran for clinical use in patients with chronic kidney disease. We conducted this post-marketing survey to further evaluate the safety and efficacy of PDpoetin for management of anemia in patients on maintenance hemodialysis. Patients from 4 centers in Iran were enrolled for this multicenter, open-label, uncontrolled phase IV clinical trial. Changes in blood chemistry, hemoglobin and hematocrit levels, renal function, and other characteristics of the patients were recorded for 4 months; 501 of the patients recruited, completed this study. Mean age of the patients was 50.9 (±16.2) years. 48.7% of patients were female. Mean of the hemoglobin value in all of the 4 centers was 9.29 (±1.43) g/dL at beginning of the study and reached 10.96 (±2.23) g/dL after 4 months and showed significant increase overall (P<0.001). PDpoetin dose was stable at 50-100 U/kg thrice weekly. Hemorheologic disturbancesand changes in blood electrolytes was not observed. No case of immunological reactions to PDpoetin was observed. Our study, therefore, showed that PDpoetin has significantly raised the level of hemoglobin in the hemodialysis patients (about 1.7±0.6 g/dL). Anemia were successfully corrected in 49% of patients under study. Use of this biosimilar was shown to be safe and effective for the maintenance of hemoglobin in patients on maintenance hemodialysis.

Pharmacological and clinical properties of calcimimetics: calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism.

PubMed

Nagano, Nobuo

2006-03-01

Circulating levels of calcium ion (Ca2+) are maintained within a narrow physiological range mainly by the action of parathyroid hormone (PTH) secreted from parathyroid gland (PTG) cells. PTG cells can sense small fluctuations in plasma Ca2+ levels by virtue of a cell surface Ca2+ receptor (CaR) that belongs to the superfamily of G protein-coupled receptors (GPCR). Compounds that activate the CaR and inhibit PTH secretion are termed 'calcimimetics' because they mimic or potentiate the effects of extracellular Ca2+ on PTG cell function. Preclinical studies with NPS R-568, a first generation calcimimetic compound that acts as a positive allosteric modulator of the CaR, have demonstrated that oral administration decreases serum levels of PTH and calcium, with a leftward shift in the set-point for calcium-regulated PTH secretion in normal rats. NPS R-568 also suppresses the elevation of serum PTH levels and PTG hyperplasia and can improve bone mineral density (BMD) and strength in rats with chronic renal insufficiency (CRI). Clinical trials with cinacalcet hydrochloride (cinacalcet), a compound with an improved metabolic profile, have shown that long-term treatment continues to suppress the elevation of serum levels of calcium and PTH in patients with primary hyperparathyroidism (1HPT). Furthermore, clinical trials in patients with uncontrolled secondary hyperparathyroidism (2HPT) have demonstrated that cinacalcet not only lowers serum PTH levels, but also the serum phosphorus and calcium x phosphorus product; these are a hallmark of an increased risk of cardiovascular disease and mortality in dialysis patients with end-stage renal disease. Indeed, cinacalcet has already been approved for marketing in several countries. Calcimimetic compounds like cinacalcet have great potential as an innovative medical approach to manage 1HPT and 2HPT.

Creatinine plasma at uncontrolled type 2 diabetes mellitus and controlled type 2 diabetes mellitus patients at primary health care in Binjai city, Indonesia

NASA Astrophysics Data System (ADS)

Rusdiana; Savira, M.; Syahputra, M.; Santoso, A.

2018-03-01

The aim of the study knowing the comparison creatinine plasma levels at uncontrolled type 2 diabetes mellitus and controlled type 2 diabetes mellitus patients at Primary Health Care in Binjai city of North Sumatera in Indonesia. This cross-sectional study was conductedon 40 type 2 Diabetes Mellitus patients who attended Primary Health Care in Binjai. Patients with age > 40 years old, (both sexes) were included in the study. We recorded different demographic parameter as age, Body Mass Index, Blood Pressure, and personal history status. And we examined the biochemicalparameters including Hba1c, Fasting Blood Sugar Levels (FBL) and creatinine serum. We separated into two groups base on HbA1c test, controlled type 2 diabetes mellitus and uncontrolled type 2 diabetes mellitus. We measured FBL by using the portable measuring instrument, and Thamrin clinical laboratory measured Hba1c, andwe measured creatinine plasmaby spectrophotometry in Biochemistry laboratory. With statistical analysis using T-test found that there was asignificant differencein creatinine plasma levels between uncontrolled type 2 diabetes mellitus with controlled type 2 diabetes mellitus (p<0.005).

A novel community-based study to address disparities in hypertension and colorectal cancer: a study protocol for a randomized control trial

PubMed Central

2013-01-01

Background Black men have the greatest burden of premature death and disability from hypertension (HTN) in the United States, and the highest incidence and mortality from colorectal cancer (CRC). While several clinical trials have reported beneficial effects of lifestyle changes on blood pressure (BP) reduction, and improved CRC screening with patient navigation (PN), the effectiveness of these approaches in community-based settings remains understudied, particularly among Black men. Methods/design MISTER B is a two-parallel-arm randomized controlled trial that will compare the effect of a motivational interviewing tailored lifestyle intervention (MINT) versus a culturally targeted PN intervention on improvement of BP and CRC screening among black men aged ≥50 with uncontrolled HTN who are eligible for CRC screening. Approximately 480 self-identified black men will be randomly assigned to one of the two study conditions. This innovative research design allows each intervention to serve as the control for the other. Specifically, the MINT arm is the control condition for the PN arm, and vice-versa. This novel, simultaneous testing of two community-based interventions in a randomized fashion is an economical and yet rigorous strategy that also enhances the acceptability of the project. Participants will be recruited during scheduled screening events at barbershops in New York City. Trained research assistants will conduct the lifestyle intervention, while trained community health workers will deliver the PN intervention. The primary outcomes will be 1) within-patient change in systolic and diastolic BP from baseline to six months and 2) CRC screening rates at six months. Discussion This innovative study will provide a unique opportunity to test two interventions for two health disparities simultaneously in community-based settings. Our study is one of the first to test culturally targeted patient navigation for CRC screening among black men in barbershops. Thus, our study has the potential to improve the reach of hypertension control and cancer prevention efforts within a high-risk population that is under-represented in primary care settings. Trial registration ClinicalTrials.gov, NCT01092078 PMID:24011142

Risk factors for obstetric anal sphincter injuries and postpartum anal and urinary incontinence: a case-control trial.

PubMed

Burrell, Madeline; Dilgir, Sapna; Patton, Vicki; Parkin, Katrina; Karantanis, Emmanuel

2015-03-01

Obstetric anal sphincter injuries (OASIS) cause serious maternal morbidity for mothers. A clearer understanding of aetiological factors is needed. We aimed to determine the risk factors for OASIS . Birth details of 222 primiparous women sustaining OASIS were compared with 174 women who did not sustain OASIS (controls) to determine the relevant risk factors. The data underwent univariate analysis and logistic regression analysis. Asian or Indian ethnicity, operative vaginal birth (p = 0.00), persistent occipito-posterior position (p = 0.038) and rapid uncontrolled delivery of the head were identified as risk factors for OASIS. Pushing time, use of epidural, episiotomy and head circumference were not predictors of OASIS. Women with Asian or Indian ethnicity, operative vaginal birth, persistent occipito-posterior position and rapid uncontrolled delivery of the fetal head were likely to sustain OASIS. Awareness of these factors may help to minimise the incidence of OASIS.

New-onset epilepsy in the elderly.

PubMed

Vu, Lily Chi; Piccenna, Loretta; Kwan, Patrick; O'Brien, Terence J

2018-06-01

People who are 60 years old and older have the highest incidence of developing new-onset epilepsy. The increase of the ageing population has resulted in a greater number of patients with new-onset epilepsy or at risk of developing the condition. Previously published review articles regarding epilepsy in older patients have had a broad focus, including people who were diagnosed with epilepsy in childhood or in middle age. This review focuses on the causes, treatment, prognosis and psychosocial impact of new-onset epilepsy in people aged 60 years and over. Following a search of the medical electronic databases and relevant references, we identified 22 studies overall that met the inclusion criteria. Only four randomised clinical trials (RCTs) were identified comparing different antiepileptic drug treatments in this population, demonstrating that newer generation antiepileptic drugs, e.g. lamotrigine and levetiracetam, were generally better tolerated. One uncontrolled study provided promising evidence of good outcomes and safety for surgical resection as a treatment for people with uncontrolled seizures. Five studies reported that people 60 years and over with new-onset epilepsy have significant cognitive impairments, e.g. memory, and psychological issues including depression, anxiety and fatigue. We found that there is very limited evidence to guide treatment in people with Alzheimer's disease and epilepsy. The specific features of new-onset epilepsy in this target population significantly influences the choice of treatment. Cognitive and psychiatric screening before treatment may be useful for management. Two studies with proposed guidelines were identified, but no formal clinical practice guidelines exist for this special population to assist with appropriate management. There is a need for more RCTs that investigate effective treatments with limited side effects. More research studies on the psychosocial effects of new onset epilepsy, and long-term outcomes, for people aged 60 years are also required. This article is protected by copyright. All rights reserved.

Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women’s Health Initiative Memory Study

PubMed Central

Wu, Chunyuan; Coker, Laura H.; Seth, Arjun; Snetselaar, Linda; Manson, JoAnn E.; Rossouw, Jacques E.; Wassertheil-Smoller, Sylvia

2016-01-01

BACKGROUND To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. METHODS Prospective follow-up of 6,426 cognitively intact women aged 65–79 years enrolled in the Women’s Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140mm Hg or diastolic BP ≥ 90mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). RESULTS Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). CONCLUSIONS Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056 PMID:26137952

A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in patients with uncontrolled type 2 diabetes.

PubMed

Safren, Steven A; Gonzalez, Jeffrey S; Wexler, Deborah J; Psaros, Christina; Delahanty, Linda M; Blashill, Aaron J; Margolina, Aleksandra I; Cagliero, Enrico

2014-01-01

To test cognitive behavioral therapy for adherence and depression (CBT-AD) in type 2 diabetes. We hypothesized that CBT-AD would improve adherence; depression; and, secondarily, hemoglobin A1c (A1C). Eighty-seven adults with unipolar depression and uncontrolled type 2 diabetes received enhanced treatment as usual (ETAU), including medication adherence, self-monitoring of blood glucose (SMBG), and lifestyle counseling; a provider letter documented psychiatric diagnoses. Those randomized to the intervention arm also received 9-11 sessions of CBT-AD. Immediately after acute treatment (4 months), adjusting for baseline, CBT-AD had 20.7 percentage points greater oral medication adherence on electronic pill cap (95% CI -31.14 to -10.22, P = 0.000); 30.2 percentage points greater SMBG adherence through glucometer downloads (95% CI -42.95 to -17.37, P = 0.000); 6.44 points lower depression scores on the Montgomery-Asberg Depression Rating Scale (95% CI 2.33-10.56, P = 0.002); 0.74 points lower on the Clinical Global Impression (95% CI 0.16-1.32, P = 0.01); and 0.72 units lower A1C (95% CI 0.29-1.15, P = 0.001) relative to ETAU. Analyses of 4-, 8-, and 12-month follow-up time points indicated that CBT-AD maintained 24.3 percentage points higher medication adherence (95% CI -38.2 to -10.3, P = 0.001); 16.9 percentage points greater SMBG adherence (95% CI -33.3 to -0.5, P = 0.043); and 0.63 units lower A1C (95% CI 0.06-1.2, P = 0.03) after acute treatment ended. For depression, there was some evidence of continued improvement posttreatment, but no between-group differences. CBT-AD is an effective intervention for adherence, depression, and glycemic control, with enduring and clinically meaningful benefits for diabetes self-management and glycemic control in adults with type 2 diabetes and depression.

Smartphone-based vs paper-based asthma action plans for adolescents.

PubMed

Perry, Tamara T; Marshall, Alexandra; Berlinski, Ariel; Rettiganti, Mallikarjuna; Brown, Rita H; Randle, Shemeka M; Luo, Chunqiao; Bian, Jiang

2017-03-01

Adolescents with asthma are at risk of poor outcomes and are traditionally difficult to reach. To examine adolescents' use of and asthma outcomes associated with smartphone- vs paper-based asthma action plans (AAPs). We conducted a 6-month randomized clinical trial with adolescents (12-17 years old) with persistent asthma. Participants used their respective smartphone or paper AAPs for medication instructions and peak flow or asthma symptoms logging. AAP use was measured electronically for smartphone users and via mail-in diaries for the paper group. Changes in Asthma Control Test (ACT) and self-efficacy scores were examined. Thirty-four adolescents participated in this study (median age, 15.4 years). Participants were mostly African American (62%) with state-issued insurance (71%). Adolescents in the smartphone group accessed the AAP a median of 12.17 times per week or 4.36 days per week but only recorded medications or symptoms and peak flow data in the electronic diary a median of 10 days per month during the 6-month period. Participants in the paper group recorded data a median of 23.5 days per month on their paper diaries. Overall, there were no changes in ACT and self-efficacy scores between groups. Adolescents with uncontrolled asthma (baseline ACT score ≤19) had an improvement in ACT for the smartphone group (before, 11; after, 20) ([P = .04) compared with no change in the paper group (before, 17; after, 17) (P = .64). Adolescent satisfaction with the application was high, with 100% stating they would recommend the smartphone AAP to a friend. Adolescents were frequent and highly satisfied users of the smartphone AAP with a subset of participants with uncontrolled asthma demonstrating possible clinical benefit. Findings suggest a need for larger-scale studies to determine the effectiveness of smartphone-based AAPs among high-risk patients with asthma. clinicaltrials.gov Identifier: NCT02091869. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Detecting Motor Impairment in Early Parkinson’s Disease via Natural Typing Interaction With Keyboards: Validation of the neuroQWERTY Approach in an Uncontrolled At-Home Setting

PubMed Central

Ledesma-Carbayo, María J; Butterworth, Ian; Matarazzo, Michele; Montero-Escribano, Paloma; Puertas-Martín, Verónica; Gray, Martha L

2018-01-01

Background Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease and one of the most common forms of movement disorder. Although there is no known cure for PD, existing therapies can provide effective symptomatic relief. However, optimal titration is crucial to avoid adverse effects. Today, decision making for PD management is challenging because it relies on subjective clinical evaluations that require a visit to the clinic. This challenge has motivated recent research initiatives to develop tools that can be used by nonspecialists to assess psychomotor impairment. Among these emerging solutions, we recently reported the neuroQWERTY index, a new digital marker able to detect motor impairment in an early PD cohort through the analysis of the key press and release timing data collected during a controlled in-clinic typing task. Objective The aim of this study was to extend the in-clinic implementation to an at-home implementation by validating the applicability of the neuroQWERTY approach in an uncontrolled at-home setting, using the typing data from subjects’ natural interaction with their laptop to enable remote and unobtrusive assessment of PD signs. Methods We implemented the data-collection platform and software to enable access and storage of the typing data generated by users while using their computer at home. We recruited a total of 60 participants; of these participants 52 (25 people with Parkinson’s and 27 healthy controls) provided enough data to complete the analysis. Finally, to evaluate whether our in-clinic-built algorithm could be used in an uncontrolled at-home setting, we compared its performance on the data collected during the controlled typing task in the clinic and the results of our method using the data passively collected at home. Results Despite the randomness and sparsity introduced by the uncontrolled setting, our algorithm performed nearly as well in the at-home data (area under the receiver operating characteristic curve [AUC] of 0.76 and sensitivity/specificity of 0.73/0.69) as it did when used to evaluate the in-clinic data (AUC 0.83 and sensitivity/specificity of 0.77/0.72). Moreover, the keystroke metrics presented a strong correlation between the 2 typing settings, which suggests a minimal influence of the in-clinic typing task in users’ normal typing. Conclusions The finding that an algorithm trained on data from an in-clinic setting has comparable performance with that tested on data collected through naturalistic at-home computer use reinforces the hypothesis that subtle differences in motor function can be detected from typing behavior. This work represents another step toward an objective, user-convenient, and quasi-continuous monitoring tool for PD. PMID:29581092

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Kalaivani, Mani

2015-06-25

This is an updated version of the original Cochrane review published in Issue 8, 2012.Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is a substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (26 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 2, February 2015) and MEDLINE (1946 to 26 March 2015). We also searched ClinicalTrials.gov (26 March 2015), the South Asian Database of Controlled Clinical Trials and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol in patients of any age and gender. Two review authors screened the search results and reviewed the abstracts of relevant and eligible trials before retrieving the full-text publications. One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study cannot be considered of high methodological quality. This study was terminated early due to recruitment problems. This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. Days of mechanical ventilation were more in patients receiving thiopental sodium when compared with propofol. At three months there was no evidence of a difference between the drugs with respect to outcome measures such as control of seizure activity and functional outcome. Adverse events reported in this study were infection, hypotension and intestinal ischaemia. Since the last version of this review we have found no new studies.There is a lack of robust, randomised, controlled evidence that can clarify the efficacy of propofol and thiopental sodium compared to each other in the treatment of RSE. There is a need for large randomised controlled trials for this serious condition.

Comorbid sleep disorders and suicide risk among children and adolescents with bipolar disorder.

PubMed

Stanley, Ian H; Hom, Melanie A; Luby, Joan L; Joshi, Paramjit T; Wagner, Karen D; Emslie, Graham J; Walkup, John T; Axelson, David A; Joiner, Thomas E

2017-12-01

Children and adolescents with bipolar disorder are at increased risk for suicide. Sleep disturbances are common among youth with bipolar disorder and are also independently implicated in suicide risk; thus, comorbid sleep disorders may amplify suicide risk in this clinical population. This study examined the effects of comorbid sleep disorders on suicide risk among youth with bipolar disorder. We conducted secondary analyses of baseline data from the Treatment of Early Age Mania (TEAM) study, a randomized controlled trial of individuals aged 6-15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (N = 379). Sleep disorders (i.e., nightmare, sleep terror, and sleepwalking disorders) and suicide risk were assessed via the WASH-U-KSADS and the CDRS-R, respectively. We constructed uncontrolled logistic regression models as well as models controlling for trauma history, a generalized anxiety disorder (GAD) diagnosis, and depression symptoms. Participants with a current comorbid nightmare disorder versus those without were nearly twice as likely to screen positive for suicide risk in an uncontrolled model and models controlling for trauma history, a GAD diagnosis, and depression symptoms. Neither a current comorbid sleep terror disorder nor a sleepwalking disorder was significantly associated with suicide risk. This pattern of findings remained consistent for both current and lifetime sleep disorder diagnoses. Youth with bipolar I disorder and a comorbid nightmare disorder appear to be at heightened suicide risk. Implications for assessment and treatment are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Renal sympathetic denervation in uncontrolled arterial hypertension after successful repair for aortic coarctation.

PubMed

Lurz, Philipp; Okon, Thomas; Riede, Thomas; Wagner, Robert; Schuler, Gerhard; Daehnert, Ingo; Desch, Steffen

2016-01-01

Uncontrolled arterial hypertension is a frequent problem after successful repair of CoA and has been attributed to increased central sympathetic drive as well as a blunted baroreceptor reflex. RSD is a promising therapy to reduce central sympathetic drive and improve baroreflex sensitivity. 8 patients (age: 27±6 years) with previous surgical and/or percutaneous repair of CoA, absence of any relevant restenosis (invasive gradient across the site of previous treatment 3±4 mmHg) and resistant arterial hypertension (daytime SBP≥140 mmHg on 24 hour ambulatory blood pressure measurements [ABPM] in spite of the concurrent use of 3 antihypertensive agents of different classes or intolerance to BP medications) were included. Bilateral RSD was performed using the Symplicity Flex™ catheter (Medtronic, MN, USA). RSD was successful in all patients with no procedural complications and no evidence for renal artery stenosis 6 months post procedure. From baseline to 6 month follow-up, RSD was followed by a significant reduction in average daytime systolic BP (150.4±7.8 to 143.1±8.0 mmHg; p=0.0117) as well as systolic BP throughout 24 h (146.8±7.3 vs. 140.5±7.8, p=0.04). The BP reductions observed in these patients justify engaging in a larger clinical trial on the efficacy of RSD in this specific type of secondary hypertension and bares the hope that RSD might extend the currently very limited armory against arterial hypertension in young adults with previous repair of CoA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized, double-blind, 8-week study.

PubMed

Cheung, Deanna G; Aizenberg, Diego; Gorbunov, Vladimir; Hafeez, Kudsia; Chen, Chien-Wei; Zhang, Jack

2018-01-01

A majority of patients with hypertension fail to achieve blood pressure (BP) control despite treatment with commonly prescribed drugs. This randomized, double-blind phase III trial assessed the superiority of sacubitril/valsartan 200 mg (97/103 mg) to continued olmesartan 20 mg in reducing ambulatory systolic BP after 8-week treatment in patients with mild to moderate essential hypertension uncontrolled with olmesartan 20 mg alone. A total of 376 patients were randomized to receive either sacubitril/valsartan (n = 188) or olmesartan (n = 188). Superior reductions in 24-hour mean ambulatory systolic BP were observed in the sacubitril/valsartan group vs the olmesartan group (-4.3 mm Hg vs -1.1 mm Hg, P < .001). Reductions in 24-hour mean ambulatory diastolic BP and pulse pressure and office systolic BP and diastolic BP were significantly greater with sacubitril/valsartan vs olmesartan (P < .014). A greater proportion of patients achieved BP control with sacubitril/valsartan vs olmesartan. The overall incidence of adverse events was comparable between the groups. Compared with continued olmesartan, sacubitril/valsartan was more effective and generally safe in patients with hypertension uncontrolled with olmesartan 20 mg. ©2018 Wiley Periodicals, Inc.

Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management.

PubMed

Arvin, Ann M; Wolinsky, Jerry S; Kappos, Ludwig; Morris, Michele I; Reder, Anthony T; Tornatore, Carlo; Gershon, Anne; Gershon, Michael; Levin, Myron J; Bezuidenhoudt, Mauritz; Putzki, Norman

2015-01-01

Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity. To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management. Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated. In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-years at the time of analysis). Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting. Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical Bayes geometric mean, 1.88 [90% CI, 0.87-3.70]). Corticosteroid treatment for relapses might be a risk factor for VZV reactivation. Rates of VZV infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipients. Rates reported in the postmarketing setting are comparable. We found no sign of risk accumulation with longer exposure. Serious or complicated cases of herpes zoster were uncommon. We recommend establishing the patient's VZV immune status before initiating fingolimod therapy and immunization for patients susceptible to primary VZV infection. Routine antiviral prophylaxis is not needed, but using concomitant pulsed corticosteroid therapy beyond 3 to 5 days requires an individual risk-benefit assessment. Vigilance to identify early VZV symptoms is important to allow timely antiviral treatment.

Resistant Hypertension: Time to Consider the Best Fifth Anti-Hypertensive Treatment.

PubMed

Pio-Abreu, Andrea; Drager, Luciano F

2018-06-16

Resistant hypertension (RH) is a growing clinical condition worldwide associated with target-organ damage and poor prognosis compared to non-resistant counterparts. The purpose of this review is to perform a critical evaluation of preferable drug choices for managing RH highlighting the evidence that significant proportion of patients remained uncontrolled despite using four anti-hypertensive drugs. Until recently, the fourth drug therapy was main derived from personal opinion or small interventional studies. The recent data derived from two multicentric randomized trials, namely PATHWAY-2 and ReHOT, pointed spironolactone as the preferable fourth drug therapy in patients with confirmed RH as compared to bisoprolol and doxazosin (PATHWAY-2) as well as clonidine (ReHOT). However, significant proportion of patients (especially observed in ReHOT trial that used 24-h ambulatory blood pressure monitoring) did not achieve optimal blood pressure with the fourth drug. This finding underscores the need of new approaches and treatment options in this important research area. The current evidence pointed that significant proportion of RH patients are requiring more than four drugs for controlling BP. This statement is particularly true considering the new criteria proposed by the 2017 Guidelines for diagnosing RH (> 130 × 80 mmHg). New combinations, drugs, or treatments should be tested aiming to reduce the RH burden. Based on the aforementioned multicentric trials, we proposed the first five preferable anti-hypertensive classes in the overall context of RH.

An expert opinion on PANDAS/PANS: highlights and controversies.

PubMed

Chiarello, Francesca; Spitoni, Silvia; Hollander, Eric; Matucci Cerinic, Marco; Pallanti, Stefano

2017-06-01

'Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections' (PANDAS) identified a unique subgroup of patients with abrupt onset of obsessive compulsive disorder (OCD) symptoms clinically related to Streptococcus infection and accompanied by neuropsychological and motor symptoms. After almost 20 years, PANDAS has not been accepted as distinct disorder and new criteria for paediatric acute-onset neuropsychiatric syndrome (PANS) have been replaced it, highlighting the fact that several agents rather than only Streptococcus might be involved. Extensive review of the PANDAS/PANS literature was performed on PubMed. Although antibiotics have been reported to be effective for acute and prophylactic phases in several uncontrolled studies and non-steroidal anti-inflammatory drugs (NSAID) are used during exacerbations, clinical multicenter trials are still missing. Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT) are still the first line of recommendation for acute onset OCD spectrum. Immunological therapies should be restricted to a few cases. While PANDAS has found no confirmation as a distinct syndrome, and it is not presented in DSM-5, patients with acute onset OCD spectrum, neurocognitive and motor symptoms should be evaluated for inflammatory, infective, immunological and metabolic abnormalities with a comprehensive diagnostic algorithm.

The Adolescent Behavioral Activation Program: Adapting Behavioral Activation as a Treatment for Depression in Adolescence.

PubMed

McCauley, Elizabeth; Gudmundsen, Gretchen; Schloredt, Kelly; Martell, Christopher; Rhew, Isaac; Hubley, Samuel; Dimidjian, Sona

2016-01-01

This study aimed to examine implementation feasibility and initial treatment outcomes of a behavioral activation (BA) based treatment for adolescent depression, the Adolescent Behavioral Activation Program (A-BAP). A randomized, controlled trial was conducted with 60 clinically referred adolescents with a depressive disorder who were randomized to receive either 14 sessions of A-BAP or uncontrolled evidenced-based practice for depression. The urban sample was 64% female, predominantly Non-Hispanic White (67%), and had an average age of 14.9 years. Measures of depression, global functioning, activation, and avoidance were obtained through clinical interviews and/or through parent and adolescent self-report at preintervention and end of intervention. Intent-to-treat linear mixed effects modeling and logistic regression analysis revealed that both conditions produced statistically significant improvement from pretreatment to end of treatment in depression, global functioning, and activation and avoidance. There were no significant differences across treatment conditions. These findings provide the first step in establishing the efficacy of BA as a treatment for adolescent depression and support the need for ongoing research on BA as a way to enhance the strategies available for treatment of depression in this population.

Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis

PubMed Central

Wex, Eva; Pautsch, Alexander; Schnapp, Gisela; Hostettler, Katrin E.; Stowasser, Susanne; Kolb, Martin

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease characterised by fibrosis of the lung parenchyma and loss of lung function. Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. A number of profibrotic mediators including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and transforming growth factor-β are believed to play important roles in the pathogenesis of IPF. Nintedanib is a potent small molecule inhibitor of the receptor tyrosine kinases PDGF receptor, FGF receptor and vascular endothelial growth factor receptor. Data from in vitro studies have shown that nintedanib interferes with processes active in fibrosis such as fibroblast proliferation, migration and differentiation, and the secretion of ECM. In addition, nintedanib has shown consistent anti-fibrotic and anti-inflammatory activity in animal models of lung fibrosis. These data provide a strong rationale for the clinical efficacy of nintedanib in patients with IPF, which has recently been demonstrated in phase III clinical trials. PMID:25745043

Baseline Characteristics of African Americans in the Systolic Blood Pressure Intervention Trial (SPRINT)

PubMed Central

Still, Carolyn H.; Craven, Timothy E.; Freedman, Barry I.; Van Buren, Peter; Sink, Kaycee M.; Killeen, Anthony A.; Bates, Jeffrey T.; Bee, Alberta; Contreras, Gabriel; Oparil, Suzanne; Pedley, Carolyn; Wall, Barry; White, Suzanne; Woods, Delia; Rodriguez, Carlos; Wright, Jackson T.

2015-01-01

The Systolic Blood Pressure Intervention Trial (SPRINT) will compare treatment to a systolic blood pressure goal of <120 mmHg to treatment to the currently recommended goal of <140 mmHg for effects on incident cardiovascular, renal, and neurologic outcomes including cognitive decline. Objectives The objectives of this analysis are to compare baseline characteristics of African American (AA) and non-AA SPRINT participants and explore factors associated with uncontrolled blood pressure (BP) by race. Methods SPRINT enrolled 9,361 hypertensive participants over age 50. This cross-sectional analysis examines sociodemographics, baseline characteristics, and study measures among AAs compared to non-AAs. Results AAs made up 31% of participants. AAs (compared to non-AAs) were younger and less frequently male, had less education, and were more likely uninsured or covered by Medicaid. In addition, AAs scored lower on the cognitive screening test when compared to non-AAs. Multivariable logistic regression analysis found BP control rates to <140/90 mmHg were higher for AAs who were male, had higher number of chronic diseases, were on diuretic treatment, and had better medication adherence. Conclusion SPRINT is well poised to examine the effects of SBP targets on clinical outcomes as well as predictors influencing BP control in AAs. PMID:26320890

Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.

PubMed

Rog, David J; Nurmikko, Turo J; Young, Carolyn A

2007-09-01

Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS. The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD (Sativex (R), GW Pharmaceuticals plc, Salisbury, United Kingdom) oromucosal spray in CNP associated with MS. This uncontrolled, open-label trial was an indefinite-duration extension of a previously reported 5-week randomized study in patients with MS and CNP. In the initial trial, patients were randomized to placebo or THC/CBD. Patients were only required to maintain their existing analgesia in the randomized study. In the open-label trial they could vary their other analgesia as required. All patients (placebo and THC/CBD) who completed the randomized trial commenced the open-label follow-up on THC/CBD (27 mg/mL: 25 mg/mL). Patients titrated their dosage, maintaining their existing analgesia. The primary end point of the trial was the number, frequency, and type of adverse events (AEs) reported by patients. Secondary end points included changes from baseline in 11-point numerical rating scale (NRS-11) neuropathic pain score, hematology and clinical chemistry test results, vital signs, trial drug usage, and intoxication visual analogue scale scores. Sixty-six patients were enrolled in the randomized trial; 64 (97%) completed the randomized trial and 63 (95%) entered the open-label extension (race, white, 100%; sex, male, 14 [22%]; mean [SD] age, 49 [8.4] years [range, 27-71 years[). The mean (SD) duration of open-label treatment was 463 (378) days (median, 638 days; range, 3-917 days), with 34 (54%) patients completing >1 year of treatment with THC/CBD and 28 (44%) patients completing the open-label trial with a mean (SD) duration of treatment of 839 (42) days (median, 845 days; range, 701-917 days). Mean NRS-11 pain scores in the final week of the randomized trial were 3.8 in the treatment group and 5.0 in the placebo group. In the 28 (44%) patients who completed the 2-year follow up, the mean (SD) NRS-11 pain score in the final week of treatment was 2.9 (2.0) (range, 0-8.0). Fifty-eight (92%) patients experienced > or =1 treatment-related AE. These AEs were rated by the investigator as mild in 47 (75%) patients, moderate in 49 (78%), and severe in 32 (51%). The most commonly reported AEs were dizziness (27%), nausea (18 %), and feeling intoxicated (11%). Two treatment-related serious AEs (ventricular bigeminy and circulatory collapse) were judged to be treatment-related. Both serious AEs occurred in the same patient and resolved completely following a period of discontinuation. Eleven (17%) patients experienced oral discomfort, 4 persistently. Regular oral examinations revealed that 7 (11%) patients developed white buccal mucosal patches and 2 (3%) developed red buccal mucosal patches; all cases were deemed mild and resolved. Seventeen (25%) patients withdrew due to AEs. The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial. THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment (n = 28). Ninety-two percent of patients experienced an AE, the most common of which were dizziness and nausea. The majority of AEs were deemed to be of mild to moderate severity by the investigators.

Detemir insulin for the treatment of diabetes mellitus in dogs.

PubMed

Fracassi, Federico; Corradini, Sara; Hafner, Michaela; Boretti, Felicitas S; Sieber-Ruckstuhl, Nadia S; Reusch, Claudia E

2015-07-01

To investigate the effects of insulin detemir in dogs with diabetes mellitus. Prospective, uncontrolled clinical trial. 10 client-owned dogs with naturally occurring diabetes mellitus. Dogs were treated with insulin detemir SC every 12 hours for 6 months. Follow-up evaluations were done at 1, 2, 4, 12, and 24 weeks and included evaluation of clinical signs and measurement of blood glucose concentration curves and serum fructosamine concentrations. Insulin detemir administration resulted in a significant decrease in blood glucose and serum fructosamine concentrations at 6 months, compared with pretreatment values. Median insulin dosage at the end of the study was 0.12 U/kg (0.055 U/lb; range, 0.05 to 0.34 U/kg [0.023 to 0.155 U/lb], SC, q 12 h). Hypoglycemia was identified in 22% (10/45) of the blood glucose concentration curves, and 6 episodes of clinical hypoglycemia in 4 dogs were recorded. A subjective improvement in clinical signs was observed in all dogs during the 6-month study period. On the basis of clinical signs and blood glucose concentration curves, efficacy of insulin detemir at the end of the study was considered good in 5 dogs, moderate in 3, and poor in 2. Results suggested that SC injection of insulin detemir every 12 hours may be a viable treatment for diabetes mellitus in dogs. Insulin detemir dosages were lower than reported dosages of other insulin types needed to maintain glycemic control, suggesting that insulin detemir should be used with caution, especially in small dogs.

Teledermatology: quality assessment by user satisfaction and clinical efficiency.

PubMed

Klaz, Itay; Wohl, Yonit; Nathansohn, Nir; Yerushalmi, Nir; Sharvit, Sharon; Kochba, Ilan; Brenner, Sarah

2005-08-01

The Israel Defense Forces implemented a pilot teledermatology service in primary clinics. To assess user satisfaction and clinical short-term effectiveness of a computerized store and forward teledermatology service in urban and rural units. A multi-center prospective uncontrolled cohort pilot trial was conducted for a period of 6 months. Primary care physicians referred patients to a board-certified dermatologist using text email accompanied by digital photographs. Diagnosis, therapy and management were sent back to the referring PCP. Patients were asked to evaluate the level of the CSAFTD service, effect of the service on accessibility to dermatologists, respect for privacy, availability of drugs, health improvement and overall satisfaction. PCPs assessed the quality of the teledermatology consultations they received, the contribution to their knowledge, and their overall satisfaction. Tele-diagnosis alone was possible for 95% (n=413) of 435 CSAFTD referrals; 22% (n=95) of referrals also required face-to-face consultation, Satisfaction with CSAFTD was high among patients in both rural and urban clinics, with significantly higher scores in rural units. Rural patients rated the level of service, accessibility and overall satisfaction higher than did urban patients. PCPs were satisfied with the quality of the service and its contribution to their knowledge. Rural physicians rated level of service and overall satisfaction higher than did urban physicians. Tele-referrals were completed more efficiently than referral for face-to-face appointments. CSAFTD provided efficient, high quality medical service to rural and urban military clinics in the IDF.

Home and Online Management and Evaluation of Blood Pressure (HOME BP) digital intervention for self-management of uncontrolled, essential hypertension: a protocol for the randomised controlled HOME BP trial

PubMed Central

Morton, Katherine; Stuart, Beth; Raftery, James; Bradbury, Katherine; Yao, Guiqing Lily; Zhu, Shihua; Little, Paul; Yardley, Lucy

2016-01-01

Introduction Self-management of hypertension, including self-monitoring and antihypertensive medication titration, lowers blood pressure (BP) at 1 year compared to usual care. The aim of the current trial is to assess the effectiveness of the Home and Online Management and Evaluation of Blood Pressure (HOME BP) intervention for the self-management of hypertension in primary care. Methods and analysis The HOME BP trial will be a randomised controlled trial comparing BP self-management—consisting of the HOME BP online digital intervention with self-monitoring, lifestyle advice and antihypertensive drug titration—with usual care for people with uncontrolled essential hypertension. Eligible patients will be recruited from primary care and randomised to usual care or to self-management using HOME BP. The primary outcome will be the difference in mean systolic BP (mm Hg) at 12-month follow-up between the intervention and control groups adjusting for baseline BP and covariates. Secondary outcomes (also adjusted for baseline and covariates where appropriate) will be differences in mean BP at 6 months and diastolic BP at 12 months; patient enablement; quality of life, and economic analyses including all key resources associated with the intervention and related services, adopting a broad societal perspective to include NHS, social care and patient costs, considered within trial and modelled with a lifetime horizon. Medication beliefs, adherence and changes; self-efficacy; perceived side effects and lifestyle changes will be measured for process analyses. Qualitative analyses will explore patient and healthcare professional experiences of HOME BP to gain insights into the factors affecting acceptability, feasibility and adherence. Ethics and dissemination This study has received NHS ethical approval (REC reference 15/SC/0082). The findings from HOME BP will be disseminated widely through peer-reviewed publications, scientific conferences and workshops. If successful, HOME BP will be directly applicable to UK primary care management of hypertension. Trial registration number ISRCTN13790648; pre-results. PMID:27821598

Anesthesia Preoperative Clinic Referral for Elevated Hba1c Reduces Complication Rate in Diabetic Patients Undergoing Total Joint Arthroplasty.

PubMed

Kallio, Peter J; Nolan, Jenea; Olsen, Amy C; Breakwell, Susan; Topp, Richard; Pagel, Paul S

2015-06-01

Diabetes mellitus (DM) is risk factor for complications after orthopedic surgery. We tested the hypothesis that anesthesia preoperative clinic (APC) referral for elevated glycosylated hemoglobin (HbA1c) reduces complication rate after total joint arthroplasty (TJA). Patients (n = 203) with and without DM were chosen from 1,237 patients undergoing TJA during 2006 - 12. Patients evaluated in the APC had surgery in 2006 - 8 regardless of HbA1c (uncontrolled). Those evaluated between in subsequent two-year intervals were referred to primary care for HbA1c ≥ 10% and ≥ 8%, respectively, to improve DM control before surgery. Complications and mortality were quantified postoperatively and at three, six, and twelve months. Length of stay (LOS) and patients requiring a prolonged LOS (> 5 days) were recorded. Patients (197 men, 6 women) underwent 71, 131, and 1 total hip, knee, and shoulder replacements, respectively. Patients undergoing TJA with uncontrolled HbA1c and those with HbA1c < 10%, but not those with HbA1c < 8%, had a higher incidence of coronary disease and hypercholesterolemia than patients without DM. An increase in complication rate was observed in DM patients with uncontrolled HbA1c versus patients without DM (P < 0.001); the complication rate progressively decreased with tighter HbA1c control. More DM patients with preoperative HbA1c that was uncontrolled or ≥ 10% required prolonged LOS versus those without DM (P < 0.001 and P = 0.0404, respectively). APC referral for elevated HbA1c reduces complication rate and the incidence of prolonged hospitalization during the first year after surgery in diabetics undergoing TJA.

Differences in Paracingulate Connectivity Associated with Epileptiform Discharges and Uncontrolled Seizures in Genetic Generalized Epilepsy

PubMed Central

Kay, Benjamin P; Holland, Scott K; Privitera, Michael D; Szaflarski, Jerzy P

2014-01-01

Summary Objective Patients with genetic generalized epilepsy (GGE) frequently continue to suffer from seizures despite appropriate clinical management. GGE is associated with changes in the resting-state networks modulated by clinical factors such as duration of disease and response to treatment. However, the effect of GSWDs and/or seizures on resting-state functional connectivity (RSFC) is not well understood. Methods We investigated the effects of GSWD frequency (in GGE patients), GGE (patients vs. healthy controls), and seizures (uncontrolled vs. controlled) on RSFC using seed-based voxel correlation in simultaneous EEG and resting-state fMRI (EEG/fMRI) data from 72 GGE patients (23 w/uncontrolled seizures) and 38 healthy controls. We used seeds in paracingulate cortex, thalamus, cerebellum, and posterior cingulate cortex to examine changes in cortical-subcortical resting-state networks and the default mode network (DMN). We excluded from analyses time points surrounding GSWDs to avoid possible contamination of the resting state. Results (1) Higher frequency of GSWDs was associated with an increase in seed-based voxel correlation with cortical and subcortical brain regions associated with executive function, attention, and the DMN, (2) RSFC in patients with GGE, when compared to healthy controls, was increased between paracingulate cortex and anterior, but not posterior, thalamus, and (3) GGE patients with uncontrolled seizures exhibited decreased cereballar RSFC. Significance Our findings in this large sample of patients with GGE (1) demonstrate an effect of interictal GSWDs on resting-state networks, (2) provide evidence that different thalamic nuclei may be affected differently by GGE, and (3) suggest that cerebellum is a modulator of ictogenic circuits. PMID:24447031

Mindfulness-based cognitive therapy for hypochondriasis, or severe health anxiety: a pilot study.

PubMed

Lovas, David A; Barsky, Arthur J

2010-12-01

In spite of the existence of evidence-based treatments for hypochondriasis, or severe health anxiety, recovery rates are low and morbidity is high. Therefore, more treatment options are needed for this prevalent condition. Mindfulness-based cognitive therapy (MBCT) interventions have been gaining research and clinical attention for the treatment of mood, and more recently anxiety disorders. A small, uncontrolled pilot study of an 8-week group MBCT intervention for hypochondriasis was conducted. Ten subjects (five females and five males) with a mean age of 35.6 (range=25-59) recruited from an academic community health network met criteria and completed the study. There were significant improvements in measures of health anxiety, disease-related thoughts, somatic symptoms, and mindfulness at the end of treatment, and these benefits were sustained at 3-month follow-up. Participants evidenced high treatment satisfaction, with no drop-outs or adverse events. These findings provide the basis for a larger, more rigorous, controlled trial of this promising treatment approach. Copyright © 2010 Elsevier Ltd. All rights reserved.

When combination therapy isn't working: emerging therapies for the management of inflammatory bowel disease.

PubMed

Krishnareddy, Suneeta; Swaminath, Arun

2014-02-07

Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.

What Brings You Here? Exploring Why Young Adults Seek Help for Social Anxiety.

PubMed

Hjeltnes, Aslak; Moltu, Christian; Schanche, Elisabeth; Binder, Per-Einar

2016-10-01

Social anxiety disorder typically manifests in young adulthood, but there is an absence of qualitative research on the actual experiences of young adults suffering with this disorder. The aim of the present study was to investigate the lived experiences of 29 Norwegian university students who were seeking professional help for symptoms of social anxiety. We conducted in-depth interviews prior to a clinical trial. The interviews were transcribed and analyzed using a team-based thematic analysis method based on a hermeneutic-phenomenological epistemology. We identified five themes: (a) from being shy to interpreting anxiety as a mental health problem, (b) experiencing emotions as threatening and uncontrollable, (c) encountering loneliness as relationships fall away, (d) hiding the vulnerable self from others, and (e) deciding to face social fears in the future. We relate our findings to existing theory and research, discuss our process of reflexivity, highlight study limitations, and suggest implications for future research. © The Author(s) 2015.

Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies.

PubMed

Gill, Saar

2016-08-01

Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer.

Lupane-type triterpenes and their anti-cancer activities against most common malignant tumors: A review

PubMed Central

Cháirez-Ramírez, MH; Moreno-Jiménez, MR; González-Laredo, RF; Gallegos-Infante, JA; Rocha-Guzmán, Nuria Elizabeth

2016-01-01

In recent times, a great deal of interest has been motivated on plant derived compounds known as nutraceuticals. These compounds exert important beneficial activities that improve people's health status when are consumed regularly, and now they appear as a viable option to explore their possible therapeutic effects against diseases like cancer. Particularly, lupane-type triterpenes have shown great ability to modulate multiple cancer-related signaling pathways and processes, including NF-κB, Wnt/β-catenin, PI3K/Akt, apoptosis, and many other routes related to proliferation or cell death, which are uncontrolled in malignant tumors. These investigations have promoted in vitro and in vivo studies, searching their mechanisms of action; although more research is still needed to prove its potential in human clinical trials. This review focuses on the ability of betulin, betulinic acid and lupeol to show benefits against the most common types of malignant tumors, which are considered a major global threat for public health. PMID:28337107

Cell cycle proteins as promising targets in cancer therapy.

PubMed

Otto, Tobias; Sicinski, Piotr

2017-01-27

Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression (such as cyclin-dependent kinases (CDKs)), as well as checkpoint kinases, Aurora kinases and Polo-like kinases (PLKs). We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors.

Resistant hypertension and hyperaldosteronism.

PubMed

Gonzaga, Carolina C; Calhoun, David A

2008-12-01

Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of >or= 3 antihypertensive medications at effective doses, ideally including a diuretic. Although exact prevalence is unknown, clinical trials suggest that 20% to 30% of study participants are resistant. Hyperaldosteronism, obesity, refractory volume expansion, and obstructive sleep apnea are common findings in resistant hypertension patients. Multiple studies indicate that primary aldosteronism (PA) is common (approximately 20%) in patients with resistant hypertension. Screening for PA is recommended for most patients with resistant hypertension, ideally by measurement of 24-hour urinary aldosterone excretion, or by the plasma aldosterone/plasma renin activity ratio. Successful treatment of resistant hypertension is predicated on improvement of lifestyle factors; accurate diagnosis and treatment of secondary causes of hypertension; and use of effective multidrug regimens. A long-acting diuretic, specifically chlorthalidone, is recommended as part of the treatment regimen. Recent studies demonstrate that mineralocorticoid receptor antagonists provide substantial antihypertensive benefit when added to multidrug regimens, even in patients without demonstrable aldosterone excess.

Treatment of diverticular disease of the colon and prevention of acute diverticulitis: a systematic review.

PubMed

Maconi, Giovanni; Barbara, Giovanni; Bosetti, Cristina; Cuomo, Rosario; Annibale, Bruno

2011-10-01

Diverticular disease of the colon is a common disorder, characterized by recurrent symptoms and complications such as diverticulitis, requiring hospital admissions and surgery. This study aimed to systematically review the evidence for medical therapy of diverticular disease in reducing symptoms and preventing acute diverticulitis. MEDLINE and Embase databases (1966 to February 2010). The studies selected were prospective clinical trials on uncomplicated diverticular disease of the colon. Four investigators independently reviewed articles, extracted data, and assessed study quality according to standardized criteria. The main outcomes measured were improvement in symptoms, complete remission of symptoms, and prevention of acute diverticulitis. We identified 31 studies, including 6 placebo-controlled trials. The methodological quality of these studies was suboptimal. Only 10 trials provided a detailed description of the patient history, 8 assessed symptoms by the use of a validated questionnaire, and 14 appropriately defined inclusion and exclusion criteria. Only one long-term double-blind placebo-controlled study was identified. This reported a significant improvement in symptoms and greater prevalence of symptom-free patients at 1 year with fiber plus rifaximin in comparison with fiber alone. The efficacy of treatment in preventing acute diverticulitis was evaluated in 11 randomized trials. Four trials compared rifaximin plus fiber vs fiber alone and failed to show a significant difference between treatments. However, cumulative data from these trials revealed a significant benefit following rifaximin and fiber (1-year rate of acute diverticulitis: 11/970 (1.1%) vs 20/690 (2.9%); P = .012), but with a number needed to treat of 57, to prevent an attack of acute diverticulitis. : Heterogeneity of the study design, patients' characteristics, regimens and combination of studied treatment, and outcome reporting precluded the pooling of results and limited interpretation. The treatment for diverticular disease relies mainly on data from uncontrolled studies. Treatment showed some evidence of improvement in symptoms, but its role in the prevention of acute diverticulitis remains to be defined.

A systematic review of the clinical presentation, treatment and relapse characteristics of human Plasmodium ovale malaria.

PubMed

Groger, Mirjam; Fischer, Hannah S; Veletzky, Luzia; Lalremruata, Albert; Ramharter, Michael

2017-03-11

Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes. Importantly, the understanding of P. ovale-nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi-largely stems from case reports and case series lacking study designs providing high quality evidence. Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria. The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria. This systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214). P. ovale mono-infection was a strict inclusion criterion. Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria. These articles did not include randomized controlled trials. Five prospective uncontrolled clinical trials were performed on a total of 58 participants. P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays. Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature. There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses. A total of 22 severe cases of P. ovale malaria were published out of which five were fatal. Additionally, two cases of congenital P. ovale malaria were reported. Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations. This systematic review highlights that P. ovale is capable of causing severe disease, severe congenital malaria and may even lead to death. Evidence for relapses in patients with P. ovale malaria adds up to only a handful of cases. Nearly 100 years after P. ovale's first description by Stephens the evidence for the clinical characteristics, relapse potential and optimal treatments for P. ovale malaria is still scarce.

A global study of the unmet need for glycemic control and predictor factors among patients with type 2 diabetes mellitus who have achieved optimal fasting plasma glucose control on basal insulin.

PubMed

Raccah, Denis; Chou, Engels; Colagiuri, Stephen; Gaàl, Zsolt; Lavalle, Fernando; Mkrtumyan, Ashot; Nikonova, Elena; Tentolouris, Nikolaos; Vidal, Josep; Davies, Melanie

2017-03-01

This study used data from different sources to identify the extent of the unmet need for postprandial glycemic control in patients with type 2 diabetes mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia Pacific, the United States, and Latin America. Different levels of evidence were used as available for each country/region, with data extracted from seven randomized controlled trials (RCTs), three clinical trial registries (CTRs), and three electronic medical record (EMR) databases. Glycemic status was categorized as "well controlled" (glycated hemoglobin [HbA 1c ] at target [<7%]), "residual hyperglycemia" (fasting plasma glucose [FPG] but not HbA 1c at target [FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country-specific recommendations]), or "uncontrolled" (both FPG and HbA 1c above target). Predictor factors were identified from the RCT data set using logistic regression analysis. RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1% of patients with T2DM had well-controlled glycemia, residual hyperglycemia, and uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8% to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to 21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of residual hyperglycemia identified from RCT data included high baseline HbA 1c (all countries/regions except Brazil), high baseline FPG (United Kingdom/Japan), longer duration of diabetes (Brazil), and female sex (Europe/Latin America). Irrespective of intrinsic differences between data sources, 24% to 54% of patients with T2DM globally had residual hyperglycemia with HbA 1c not at target, despite achieving FPG control, indicating a significant unmet need for postprandial glycemic control. © 2016 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.

MyAirCoach: the use of home-monitoring and mHealth systems to predict deterioration in asthma control and the occurrence of asthma exacerbations; study protocol of an observational study

PubMed Central

Honkoop, Persijn J; Simpson, Andrew; Bonini, Matteo; Snoeck-Stroband, Jiska B; Meah, Sally; Fan Chung, Kian; Usmani, Omar S; Fowler, Stephen; Sont, Jacob K

2017-01-01

Introduction Asthma is a variable lung condition whereby patients experience periods of controlled and uncontrolled asthma symptoms. Patients who experience prolonged periods of uncontrolled asthma have a higher incidence of exacerbations and increased morbidity and mortality rates. The ability to determine and to predict levels of asthma control and the occurrence of exacerbations is crucial in asthma management. Therefore, we aimed to determine to what extent physiological, behavioural and environmental data, obtained by mobile healthcare (mHealth) and home-monitoring sensors, as well as patient characteristics, can be used to predict episodes of uncontrolled asthma and the onset of asthma exacerbations. Methods and analysis In an 1-year observational study, patients will be provided with mHealth and home-monitoring systems to record daily measurements for the first-month (phase I) and weekly measurements during a follow-up period of 11 months (phase II). Our study population consists of 150 patients, aged ≥18 years, with a clinician's diagnosis of asthma, currently on controller medication, with uncontrolled asthma and/or minimally one exacerbation in the past 12 months. They will be enrolled over three participating centres, including Leiden, London and Manchester. Our main outcomes are the association between physiological, behavioural and environmental data and (1) the loss of asthma control and (2) the occurrence of asthma exacerbations. Ethics This study was approved by the Medical Ethics Committee of the Leiden University Medical Center in the Netherlands and by the NHS ethics service in the UK. Trial registration number NCT02774772. PMID:28119390

Consequences of uncontrolled cooling during sterlet (Acipenser ruthenus) sperm cryopreservation on post-thaw motility and fertilizing ability.

PubMed

Horokhovatskyi, Yevhen; Rodina, Marek; Asyabar, Hadiseh Dadras; Boryshpolets, Sergii; Dzyuba, Borys

2017-06-01

The significant influence of the number and position of fish sperm sample straws in uncontrolled cooling devices on post-thaw spermatozoa parameters, such as motility and fertilizing ability, is presented in this study. The two most popular uncontrolled cooling devices were used in this study: a Styrofoam box setup with a polystyrene floating raft on liquid nitrogen and the dry shipper setup with a straw holder. We tested the effect of different quantities of straws (6 or 60) placed on the polystyrene floating raft and the position of the straws in the holder (on the periphery or in the centre). Using these cooling methods, sperm of 10 male sterlets diluted with methanol containing cryoprotective medium was frozen. All temperature changes were recorded by a thermocouple inside the straw, and the thermogram intervals were analysed. Spermatozoa motility was evaluated by video microscopy with integrated computer-assisted sperm analysis software. Fertilization trials were conducted at a 10 5 spermatozoa/egg ratio. Post-thaw spermatozoa parameters, including the percent of motile spermatozoa, curvilinear velocity, velocity according to the smoothed path, linearity of track, beat-cross frequency and fertilization rate, were significantly decreased in the 60-straw floating raft setup in comparison to all of the other cooling methods. The freezing rate between -10 °C and -30 °C was significantly decreased by up to 18.6 ± 0.61 °C/min for the 60-straw floating raft setup in comparison to the other freezing conditions. Considering the above results, efforts to standardize cryopreservation protocols using uncontrolled cooling devices should take into account the amount of straws subjected to freezing. Copyright © 2017. Published by Elsevier Inc.

Responsibility Attributions for Clients Working with a Counselor, Clinical Psychologist, or Psychiatrist on Various Problems.

ERIC Educational Resources Information Center

Kleinke, Chris L.; Kane, Joseph C.

1998-01-01

Participants in Study 1 rated the appropriateness of four models of responsibility to a man or woman seeking psychotherapy for uncontrolled anger or depression. In Study 2, appropriateness of these models was related to three types of counselor and problems of personal adjustment, anxiety, schizophrenia. Results, clinical implications are…

Comprehensive approach for hypertension control in low-income populations: rationale and study design for the hypertension control program in Argentina.

PubMed

Mills, Katherine T; Rubinstein, Adolfo; Irazola, Vilma; Chen, Jing; Beratarrechea, Andrea; Poggio, Rosana; Dolan, Jacquelyn; Augustovski, Federico; Shi, Lizheng; Krousel-Wood, Marie; Bazzano, Lydia A; He, Jiang

2014-08-01

Although the efficacy and effectiveness of lifestyle modifications and antihypertensive pharmaceutical treatment for the prevention and control of hypertension and concomitant cardiovascular disease have been demonstrated in randomized controlled trials, this scientific knowledge has not been fully applied in the general population, especially in low-income communities. This article summarizes interventions to improve hypertension management and describes the rationale and study design for a cluster randomized trial testing whether a comprehensive intervention program within a national public primary care system will improve hypertension control among uninsured hypertensive men and women and their families. We will recruit 1,890 adults from 18 clinics within a public primary care network in Argentina. Clinic patients with uncontrolled hypertension, their spouses and hypertensive family members will be enrolled. The comprehensive intervention program targets the primary care system through health care provider education, a home-based intervention among patients and their families (home delivery of antihypertensive medication, self-monitoring of blood pressure [BP], health education for medication adherence and lifestyle modification) conducted by community health workers and a mobile health intervention. The primary outcome is net change in systolic BP from baseline to month 18 between intervention and control groups among hypertensive study participants. The secondary outcomes are net change in diastolic BP, BP control and cost-effectiveness of the intervention. This study will generate urgently needed data on effective, practical and sustainable intervention programs aimed at controlling hypertension and concomitant cardiovascular disease in underserved populations in low- and middle-income countries.

The efficacy and adverse effects of in vitro fertilization and embryo transfer.

PubMed

Corabian, P; Hailey, D

1999-01-01

This paper examines the current status of in vitro fertilization and embryo transfer (IVF-ET) as a treatment for various types of infertility. We reviewed studies on the efficacy and safety of IVF-ET and intracytoplasmic sperm injection (ICSI) plus IVF-ET, compared with conventional treatment or no treatment for various infertility diagnoses. Material retrieved included English language publications between 1992 and January 1997 that reported the results of prospective controlled clinical trials, cohort studies, and retrospective comparative studies with large series, and reviews presenting risks, complications, and longer-term health consequences associated with IVF-ET and ICSI. No adequate prospective comparative studies of sufficient power on the use of IVF-ET for specific infertility diagnoses have been reported to date. Most of the published reports concerning results with IVF-ET as a treatment of infertility have been based upon small, uncontrolled studies, with various methodological weaknesses. Reported results are not directly comparable. There are few follow-up data on outcomes after pregnancy is established or on long-term health consequences of the use of IVF-ET on mothers and their babies. IVF-ET has diffused widely without comprehensive assessment of its efficacy and safety. The available evidence supports its use only for severe bilateral tubal occlusion. For other diagnoses of infertility the evidence is limited and does not establish whether IVF-ET is effective. Long-term, well-designed, prospective clinical trials are required to determine when and for what indications IVF-ET is effective and what its health effects are on both mothers and their babies.

Comprehensive Approach for Hypertension Control in Low-income Populations: Rationale and Study Design for the Hypertension Control Program in Argentina (HCPIA)

PubMed Central

Mills, Katherine T.; Rubinstein, Adolfo; Irazola, Vilma; Chen, Jing; Beratarrechea, Andrea; Poggio, Rosana; Dolan, Jacquelyn; Augustovski, Federico; Shi, Lizheng; Krousel-Wood, Marie; Bazzano, Lydia A.; He, Jiang

2014-01-01

Although the efficacy and effectiveness of lifestyle modifications and antihypertensive pharmaceutical treatment for the prevention and control of hypertension and concomitant cardiovascular disease have been demonstrated in randomized controlled trials, this scientific knowledge has not been fully applied in the general population, especially in low-income communities. This paper summarizes interventions to improve hypertension management and describes the rationale and study design for a cluster randomized trial testing whether a comprehensive intervention program within a national public primary care system will improve hypertension control among uninsured hypertensive men and women and their families. We will recruit 1,890 adults from 18 clinics within a public primary care network in Argentina. Clinic patients with uncontrolled hypertension, their spouses and hypertensive family members will be enrolled. The comprehensive intervention program targets the primary care system through health care provider education, a home-based intervention among patients and their families (home delivery of antihypertensive medication, self-monitoring of blood pressure, health education for medication adherence and lifestyle modification) conducted by community health workers, and a mobile health intervention. The primary outcome is net change in systolic blood pressure from baseline to month 18 between intervention and control groups among hypertensive study participants. The secondary outcomes are net change in diastolic blood pressure, blood pressure control, and cost-effectiveness of the intervention. This study will generate urgently needed data on effective, practical, and sustainable intervention programs aimed at controlling hypertension and concomitant cardiovascular disease in underserved populations in low- and middle-income countries. PMID:24978148

Blood pressure after recent stroke: baseline findings from the secondary prevention of small subcortical strokes trial.

PubMed

White, Carole L; Pergola, Pablo E; Szychowski, Jeff M; Talbert, Robert; Cervantes-Arriaga, Amin; Clark, Heather D; Del Brutto, Oscar H; Godoy, Ivan Esteban; Hill, Michael D; Pelegrí, Antoni; Sussman, Craig R; Taylor, Addison A; Valdivia, José; Anderson, Dave C; Conwit, Robin; Benavente, Oscar R

2013-09-01

Hypertension is the most powerful risk factor for stroke. The aim of this study was to characterize baseline blood pressure in participants in the Secondary Prevention of Small Subcortical Strokes trial. For this cross-sectional analysis, participants were categorized by baseline systolic blood pressure (SBP) < 120, 120-139, 140-159, 160-179, and ≥ 180 mm Hg and compared on demographic and clinical characteristics. Predictors of SBP < 140 mm Hg were examined. Mean SBP was 143±19 mm Hg while receiving an average of 1.7 antihypertensive medications; SBP ≥ 140 mm Hg for 53% and ≥ 160 mm Hg for 18% of the 3,020 participants. Higher SBP was associated with a history of hypertension and hypertension for longer duration (both P < 0.0001). Higher SBPs were associated with more extensive white matter disease on magnetic resonance imaging (P < 0.0001). There were significant differences in entry-level SBP when participants were categorized by race and region (both P < 0.0001). Black participants were more likely to have SBP ≥ 140 mm Hg. Multivariable logistic regression showed an independent effect for region with those from Canada more likely (odds ratio = 1.7; 95% confidence interval, 1.29, 2.32) to have SBP < 140 mm Hg compared with participants from United States. In this cohort with symptomatic lacunar stroke, more than half had uncontrolled hypertension at approximately 2.5 months after stroke. Regional, racial, and clinical differences should be considered to improve control and prevent recurrent stroke.

Machine learning of big data in gaining insight into successful treatment of hypertension.

PubMed

Koren, Gideon; Nordon, Galia; Radinsky, Kira; Shalev, Varda

2018-06-01

Despite effective medications, rates of uncontrolled hypertension remain high. Treatment protocols are largely based on randomized trials and meta-analyses of these studies. The objective of this study was to test the utility of machine learning of big data in gaining insight into the treatment of hypertension. We applied machine learning techniques such as decision trees and neural networks, to identify determinants that contribute to the success of hypertension drug treatment on a large set of patients. We also identified concomitant drugs not considered to have antihypertensive activity, which may contribute to lowering blood pressure (BP) control. Higher initial BP predicts lower success rates. Among the medication options and their combinations, treatment with beta blockers appears to be more commonly effective, which is not reflected in contemporary guidelines. Among numerous concomitant drugs taken by hypertensive patients, proton pump inhibitors (PPIs), and HMG CO-A reductase inhibitors (statins) significantly improved the success rate of hypertension. In conclusions, machine learning of big data is a novel method to identify effective antihypertensive therapy and for repurposing medications already on the market for new indications. Our results related to beta blockers, stemming from machine learning of a large and diverse set of big data, in contrast to the much narrower criteria for randomized clinic trials (RCTs), should be corroborated and affirmed by other methods, as they hold potential promise for an old class of drugs which may be presently underutilized. These previously unrecognized effects of PPIs and statins have been very recently identified as effective in lowering BP in preliminary clinical observations, lending credibility to our big data results.

EMPOWER: a randomized trial using community health workers to deliver a lifestyle intervention program in African American women with Type 2 diabetes: design, rationale, and baseline characteristics.

PubMed

Cummings, Doyle M; Lutes, Lesley D; Littlewood, Kerry; Dinatale, Emily; Hambidge, Bertha; Schulman, Kathleen

2013-09-01

African American (AA) women with Type 2 diabetes mellitus (T2DM) in the rural south experience less weight loss and poorer glycemic control in traditional diabetes management programs compared to Caucasians. This paper describes the design, rationale, and baseline characteristics from an innovative community health worker (CHW) delivered intervention program in this population. This prospective trial randomized rural AA women with uncontrolled T2DM (HbA1c ≥ 7.0) to receive a behaviorally-centered, culturally-tailored lifestyle intervention during 16 contacts from a trained AA CHW or 16 approved diabetes educational mailings. Changes from baseline in glycosylated hemoglobin levels (HbA1c), blood pressure (BP), weight, body mass index (BMI), self-reported dietary and physical activity patterns, and psychosocial measures including diabetes distress, empowerment, depression, self-care, medication adherence, and life satisfaction will be assessed at 6- and 12-months. Two hundred AA women (mean age = 53.09 ± 10.89 years) with T2DM from impoverished rural communities were enrolled. Baseline data demonstrated profoundly uncontrolled diabetes of long term duration (mean HbA1c = 9.11 ± 1.82; mean BMI = 37.68 ± 8.20; mean BP = 134.51 ± 20.39/84.19 ± 11.68; 10.5 ± 0.7 years). Self-care behavior assessment revealed poor dietary and medication adherence and sedentary lifestyle. Most psychosocial measures ranged within normal limits. The present sample of AA women from impoverished rural communities exhibited significantly uncontrolled T2DM of long duration with associated obesity and poor lifestyle behaviors. An innovative CHW led lifestyle intervention may lead to more effective strategies for T2DM management in this population. Copyright © 2013 Elsevier Inc. All rights reserved.

Effectiveness of vildagliptin as add-on to metformin monotherapy among uncontrolled type 2 diabetes mellitus patients in a real-world setting.

PubMed

Melzer Cohen, Cheli; Davis, Carla; Shalev, Varda; Chodick, Gabriel

2018-01-01

Vildagliptin is a dipeptidyl peptidase-4 inhibitor commonly used as a dual oral agent with metformin, thiazolidinediones, or sulfonylurea for the treatment of type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with vildagliptin and metformin has been established in randomized controlled trials, but there is little evidence from observational studies. The aims of the present study were to evaluate the effectiveness of vildagliptin as an add-on therapy to metformin in reducing HbA1c and its affects on body weight and blood lipids in a real-life setting. Included in the present retrospective cohort were T2DM patients (n = 345) who were uncontrolled on metformin monotherapy and intensified treatment with vildagliptin. The efficacy of at least 90 days of dual therapy with vildagliptin and metformin in reducing HbA1c levels, as well as changes in blood lipids and body weight, were evaluated. After 180 days (range 90-365 days) from the index date with a mean daily dose of 92 mg vildagliptin, HbA1c was significantly (P < 0.001) reduced by an average of 0.9% (95% confidence interval -1.0%, -0.7%). The absolute reduction in HbA1c was positively associated with baseline HbA1c levels. In addition to HbA1c, a modest but significant (P < 0.05) decrement was also calculated in the patients' body weight and blood lipids. The present analysis of real-world data corroborates the results of previous randomized controlled trials indicating that add-on therapy with vildagliptin in uncontrolled patients on metformin monotherapy is associated with a significant improvement in the control of HbA1c. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Efficacy and safety of lacosamide as first add-on or later adjunctive treatment for uncontrolled partial-onset seizures: A multicentre open-label trial.

PubMed

Zadeh, Wendy Waldman; Escartin, Antonio; Byrnes, William; Tennigkeit, Frank; Borghs, Simon; Li, Ting; Dedeken, Peter; De Backer, Marc

2015-09-01

To evaluate the efficacy and safety of lacosamide administered as either first add-on or later add-on antiepileptic drug (AED) therapy for patients with uncontrolled partial-onset seizures (POS). In this open-label, multicentre trial, patients with POS initiated oral lacosamide (titrated to 400 mg/day) either as add-on to first AED monotherapy, or as later add-on to 1-3 concomitant AEDs after ≥ 2 previous AEDs. The primary efficacy variable was the proportion of patients achieving seizure freedom for the first 12 weeks of the 24-week Maintenance Phase. 456 patients received ≥ 1 dose of lacosamide (96 as first add-on, 360 as later add-on). In the first add-on cohort, 27/72 (37.5%) patients completed 12 weeks treatment and remained seizure-free; 18/68 (26.5%) remained seizure-free after 24 weeks. 64/91 (70.3%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. This was accompanied by a mean 7.1 ± 16.00 point improvement from Baseline in the Quality of Life Inventory in Epilepsy (QOLIE-31-P) total score for 24-week completers, with improvement reported in all subscales. Most common treatment-emergent adverse events (TEAEs) were dizziness (31.3%) and headache (13.5%). In the later add-on cohort, 39/261 (14.9%) and 29/249 (11.6%) patients remained seizure-free after completing 12 and 24 weeks' treatment, respectively. 178/353 (50.4%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. Mean change in QOLIE-31-P total score was 4.8 ± 14.74 points among 24-week completers. Common TEAEs were dizziness (33.6%), somnolence (15.0%) and headache (11.4%). Lacosamide initiated as first add-on treatment was efficacious and well tolerated in patients with uncontrolled POS. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Complementary and alternative medicine for patients with chronic fatigue syndrome: A systematic review

PubMed Central

2011-01-01

Background Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population. Methods Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded. Results A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium. Conclusions The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted. PMID:21982120

Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial.

PubMed

Ducloy-Bouthors, Anne-Sophie; Mignon, Alexandre; Huissoud, Cyril; Grouin, Jean-Marie; Mercier, Frédéric J

2016-08-01

Postpartum haemorrhage (PPH) remains the leading cause for maternal mortality worldwide. Hypofibrinogenaemia has been identified as a major risk factor for progress towards severe PPH. The efficacy of fibrinogen concentrate supplementation in PPH has been shown in various clinical settings but the level of evidence is not sufficient to prove the benefit, evaluate the risks, and determine the value, timing and dose of fibrinogen supplementation in PPH. The FIDEL trial objective is to evaluate the impact of a therapeutic strategy based on the early administration of human fibrinogen concentrate compared to the current practice based on late administration in severe PPH patients requiring second line uterotonics. This is a prospective multicentre, randomised, double-blind, placebo-controlled trial. A total of 412 patients will be randomised if they meet the following criteria: female patients≥18 years old, vaginal delivery, PPH requiring IV administration of prostaglandins (sulprostone) after 20 to 30minutes of oxytocin failure. The participants are assigned to receive either fibrinogen 3g or placebo infusions. The primary endpoint is a composite endpoint defined as the percentage of patients losing at least 4g/dL of Hb, and/or requiring a transfusion of at least 2 units of packed red blood cells, within the 48hours following fibrinogen administration. The purpose of this study is to demonstrate the efficacy and safety of an early fibrinogen concentrate infusion in uncontrolled active PPH. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

The Effectiveness of Online Cognitive Behavioral Treatment in Routine Clinical Practice

PubMed Central

Ruwaard, Jeroen; Lange, Alfred; Schrieken, Bart; Dolan, Conor V.; Emmelkamp, Paul

2012-01-01

Context Randomized controlled trails have identified online cognitive behavioral therapy as an efficacious intervention in the management of common mental health disorders. Objective To assess the effectiveness of online CBT for different mental disorders in routine clinical practice. Design An uncontrolled before-after study, with measurements at baseline, posttest, 6-week follow-up, and 1-year follow-up. Participants & Setting 1500 adult patients (female: 67%; mean age: 40 years) with a GP referral for psychotherapy were treated at a Dutch online mental health clinic for symptoms of depression (n = 413), panic disorder (n = 139), posttraumatic stress (n = 478), or burnout (n = 470). Interventions Manualized, web-based, therapist-assisted CBT, of which the efficacy was previously demonstrated in a series of controlled trials. Standardized duration of treatment varied from 5 weeks (online CBT for Posttraumatic stress) to 16 weeks (online CBT for Depression). Main Outcome Measures Validated self-report questionnaires of specific and general psychopathology, including the Beck Depression Inventory, the Impact of Event Scale, the Panic Disorder Severity Scale-Self Report, the Oldenburg Burnout Inventory, and the Depression Anxiety Stress Scales. Results Treatment adherence was 71% (n = 1071). Study attrition was 21% at posttest, 33% at 6-week FU and 65% at 1-year FU. Mixed-model repeated measures regression identified large short-term reductions in all measures of primary symptoms (d = 1.9±0.2 to d = 1.2±0.2; P<.001), which sustained up to one year after treatment. At posttest, rates of reliable improvement and recovery were 71% and 52% in the completer sample (full sample: 55%/40%). Patient satisfaction was high. Conclusions Results suggest that online therapist-assisted CBT may be as effective in routine practice as it is in clinical trials. Although pre-treatment withdrawal and long-term outcomes require further study, results warrant continued implementation of online CBT. PMID:22792217

Family intervention to control type 2 diabetes: a controlled clinical trial.

PubMed

García-Huidobro, Diego; Bittner, Marcela; Brahm, Paulina; Puschel, Klaus

2011-02-01

Chilean patients with type 2 diabetes mellitus (T2DM) have a low rate of blood sugar control. We studied the effectiveness of a culturally sensitive family oriented intervention designed to improve metabolic control in primary care patients with uncontrolled T2DM. Patients with T2DM from three primary care clinics in Santiago, Chile were randomly selected for inclusion if they had a recent HbA1c ≥7%, were between 18 and 70 years old and lived with a family member. Patients from one clinic received the family oriented intervention; patients from the other two (control) clinics received standard care. The intervention involved family members in care and included family counselling during clinic visits, family meetings and home visits. The primary outcome was HbA1c, measured at 6 and 12 months. A total of 243 patients were enrolled and 209 (86%) completed the study. The intervention was fully administered to only 34% of patients in the intervention clinic. The reduction in the HbA1c from baseline to 12 months was not significantly different between clinics. During the second 6-month period, when the intervention was more intensive, the patients in the intervention clinic significantly improved their HbA1c (P < 0.001) compared to the control patients. A family intervention for the control of T2DM was associated with a significant reduction in HbA1c when the intervention was provided. Incomplete implementation, low statistical power and potential confounding variables between groups could be some of the main factors that explain the lack of difference between clinics in the 12-month period.

Predictability of uncontrollable multifocal seizures - towards new treatment options

NASA Astrophysics Data System (ADS)

Lehnertz, Klaus; Dickten, Henning; Porz, Stephan; Helmstaedter, Christoph; Elger, Christian E.

2016-04-01

Drug-resistant, multifocal, non-resectable epilepsies are among the most difficult epileptic disorders to manage. An approach to control previously uncontrollable seizures in epilepsy patients would consist of identifying seizure precursors in critical brain areas combined with delivering a counteracting influence to prevent seizure generation. Predictability of seizures with acceptable levels of sensitivity and specificity, even in an ambulatory setting, has been repeatedly shown, however, in patients with a single seizure focus only. We did a study to assess feasibility of state-of-the-art, electroencephalogram-based seizure-prediction techniques in patients with uncontrollable multifocal seizures. We obtained significant predictive information about upcoming seizures in more than two thirds of patients. Unexpectedly, the emergence of seizure precursors was confined to non-affected brain areas. Our findings clearly indicate that epileptic networks, spanning lobes and hemispheres, underlie generation of seizures. Our proof-of-concept study is an important milestone towards new therapeutic strategies based on seizure-prediction techniques for clinical practice.

The influence of type 1 and type 2 diabetes on periodontal disease progression: prospective results from the Study of Health in Pomerania (SHIP).

PubMed

Demmer, Ryan T; Holtfreter, Birte; Desvarieux, Moïse; Jacobs, David R; Kerner, Wolfgang; Nauck, Matthias; Völzke, Henry; Kocher, Thomas

2012-10-01

To explore associations between diabetes etiology (type 1 diabetes mellitus [T1DM] vs. T2DM) and glycemic control in the prediction of 5-year periodontal status change. The Study of Health in Pomerania (SHIP) is a population-based stratified sample of German men and women. Healthy participants and those determined to have T2DM arose from the SHIP cohort, and T1DM participants were recruited from diabetes clinics in the catchment area that gave rise to SHIP. Dentate participants (n = 2,626; 53% women; 20-81 years of age) were included. Diabetes was determined via physician diagnosis and/or HbA(1c) ≥6.5% (uncontrolled diabetes >7.0%). Examiners blinded to diabetes status performed random half-mouth periodontal examinations, assessing probing depth (PD) and attachment loss (AL) (four sites/tooth) at baseline and follow-up. Participants were categorized into six groups as follows: 1) diabetes free (n = 2,280), 2) incident T2DM (n = 79), 3) controlled T2DM (n = 80), 4) uncontrolled T2DM (n = 72), 5) controlled T1DM (n = 43), and 6) uncontrolled T1DM (n = 72). In multivariable regressions, mean PD change (ΔMPD), mean AL change (ΔMAL), or incident tooth-loss values were regressed across the aforementioned diabetes categories. Mean (SD) ΔMPD and ΔMAL values among all participants were -0.08 ± 0.5 mm and 0.08 ± 1.03 mm, respectively, and 34% lost one or more teeth. Relative to diabetes-free participants, those with uncontrolled T2DM experienced greater ΔMPD ± SE (P < 0.05), whereas participants with either uncontrolled T1DM or uncontrolled T2DM realized greater ΔMAL (P < 0.05). Uncontrolled T1DM and T2DM were both associated with an increased risk of future tooth loss (P < 0.05). Diabetes control, but not etiology, was associated with future tooth loss and accelerated AL progression.

The PRCI study: design of a randomized clinical trial to evaluate a coping intervention for medical waiting periods used by women undergoing a fertility treatment.

PubMed

Ockhuijsen, Henrietta D L; van den Hoogen, Agnes; Macklon, Nickolas S; Boivin, Jacky

2013-09-03

Many medical situations necessitate a stressful period of waiting for potentially threatening test results. The medical waiting period is often associated with negative anticipatory anxiety and rumination about the outcome of treatment. Few evidence-based self-help coping interventions are available to assist individuals manage these periods. Theory and research suggest that positive reappraisal coping strategies may be particularly useful for this type of unpredictable and uncontrollable stressful context. The objective of this study is to investigate the effects of a Positive Reappraisal Coping Intervention (PRCI) on psychological well-being of women waiting for the outcome of their fertility treatment cycle. In a three-armed randomized controlled trial, the effectiveness of the PRCI will be tested. Consecutive patients undergoing in vitro fertilisation in a Dutch university hospital and meeting selection criteria will be invited to participate. Those who agree will be randomized to one of three experimental groups (N=372). The PRCI Intervention group will receive the intervention that comprises an explanatory leaflet and the 10 statements designed to promote positive reappraisal coping, to be read at least once in the morning, once in the evening. To capture the general impact of PRCI on psychological wellbeing patients will complete questionnaires before the waiting period (pre-intervention), on day ten of the 14-day waiting period (intervention) and six weeks after the start of the waiting period (post-intervention). To capture the specific effects of the PRCI during the waiting period, patients will also be asked to monitor daily their emotions and reactions during the 14-day waiting period. The primary outcome is general anxiety, measured by the Hospital Anxiety and Depression Scale. Secondary outcomes are positive and negative emotions during the waiting period, depression, quality of life, coping and treatment outcome. During recruitment for the RCT it was decided to add a fourth non-randomized group, a PRCI Control group that received the PRCI and completed the questionnaires but did not complete daily monitoring. Positive reappraisal is one of the few ways of coping that has been shown to be associated with increased wellbeing during unpredictable and uncontrollable situations like medical waiting periods. A simple evidence based self-help intervention could facilitate coping during this common medical situation. This RCT study will evaluate the value of a self-help coping intervention designed for medical waiting periods in women undergoing fertility treatment. The study is registered at the Clinical Tials.gov (NCT01701011).

Footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with diabetes: a systematic review.

PubMed

Bus, S A; van Deursen, R W; Armstrong, D G; Lewis, J E A; Caravaggi, C F; Cavanagh, P R

2016-01-01

Footwear and offloading techniques are commonly used in clinical practice for preventing and healing of foot ulcers in persons with diabetes. The goal of this systematic review is to assess the medical scientific literature on this topic to better inform clinical practice about effective treatment. We searched the medical scientific literature indexed in PubMed, EMBASE, CINAHL, and the Cochrane database for original research studies published since 1 May 2006 related to four groups of interventions: (1) casting; (2) footwear; (3) surgical offloading; and (4) other offloading interventions. Primary outcomes were ulcer prevention, ulcer healing, and pressure reduction. We reviewed both controlled and non-controlled studies. Controlled studies were assessed for methodological quality, and extracted key data was presented in evidence and risk of bias tables. Uncontrolled studies were assessed and summarized on a narrative basis. Outcomes are presented and discussed in conjunction with data from our previous systematic review covering the literature from before 1 May 2006. We included two systematic reviews and meta-analyses, 32 randomized controlled trials, 15 other controlled studies, and another 127 non-controlled studies. Several randomized controlled trials with low risk of bias show the efficacy of therapeutic footwear that demonstrates to relief plantar pressure and is worn by the patient, in the prevention of plantar foot ulcer recurrence. Two meta-analyses show non-removable offloading to be more effective than removable offloading for healing plantar neuropathic forefoot ulcers. Due to the limited number of controlled studies, clear evidence on the efficacy of surgical offloading and felted foam is not yet available. Interestingly, surgical offloading seems more effective in preventing than in healing ulcers. A number of controlled and uncontrolled studies show that plantar pressure can be reduced by several conservative and surgical approaches. Sufficient evidence of good quality supports the use of non-removable offloading to heal plantar neuropathic forefoot ulcers and therapeutic footwear with demonstrated pressure relief that is worn by the patient to prevent plantar foot ulcer recurrence. The evidence base to support the use of other offloading interventions is still limited and of variable quality. The evidence for the use of interventions to prevent a first foot ulcer or heal ischemic, infected, non-plantar, or proximal foot ulcers is practically non-existent. High-quality controlled studies are needed in these areas. Copyright © 2015 John Wiley & Sons, Ltd.

Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma: an open phase I/II study with a first assessment of a predictive gene signature

PubMed Central

Grob, Jean-Jacques; Mortier, Laurent; D’Hondt, Lionel; Grange, Florent; Baurain, Jean Francois; Dréno, Brigitte; Lebbe, Céleste; Robert, Caroline; Dompmartin, Anne; Neyns, Bart; Gillet, Marc; Louahed, Jamila; Jarnjak, Silvija; Lehmann, Frédéric F

2017-01-01

Background We assessed safety, immunogenicity and clinical activity of recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) in association with dacarbazine in patients with metastatic melanoma. Methods In this open-label, phase I/II, uncontrolled multicentre trial conducted in Belgium and France, patients with MAGE-A3-positive melanoma received up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with eight doses of dacarbazine. Adverse events (AE) were recorded until 31 days postvaccination, and serious AEs (SAE), until 30 days following the last dose. MAGE-A3-specific antibodies were measured by ELISA. Clinical activity of MAGE-A3 immunotherapeutic was assessed in patients positive/negative for previously identified gene signature (GS) associated with clinical outcome. Results Forty-eight patients were enrolled and treated (32 GS+, 15 GS−, 1 unknown GS status); two patients completed the study. All patients reported AEs, the most common were ‘general disorders and administration site conditions’ (94%). Treatment-related AEs were reported by 85% of patients; the most common was pain at injection site (38%). Sixteen SAEs were reported by 21% of patients; two were considered as treatment related (neutropenia and thrombocytopenia; grade 4). Postdose 4, all patients were seropositive for MAGE-A3-specific antibodies, with a geometric mean titre of 2778.7 ELISA units (EU)/mL (95% CI 1638.3 to 4712.8). One complete and three partial responses were reported (only in GS+ patients). Median overall survival was 11.4 months for GS+ and 5.3 months for GS− patients. Conclusion Although this trial shows poor results compared with the new results with checkpoint inhibitors, it gives an interesting insight in rapidly developing fields like combinations of immunotherapy and chemotherapy, new generation vaccines and the use of gene profile as a predictive marker. Trial registration number NCT00849875. PMID:29177094

Cross-sectional study of patients with type 2 diabetes in OR Tambo district, South Africa

PubMed Central

Yogeswaran, Parimalaranie; Longo-Mbenza, Benjamin; Ter Goon, Daniel; Ajayi, Anthony Idowu

2016-01-01

Objectives South Africa has pledged to the sustainable development goal of promoting good health and well-being to all residents. While this is laudable, paucity of reliable epidemiological data for different regions on diabetes and treatment outcomes may further widen the inequalities of access and quality of healthcare services across the country. This study examines the sociodemographic and clinical determinants of uncontrolled type 2 diabetes mellitus (T2DM) in individuals attending primary healthcare in OR Tambo district, South Africa. Design A cross-sectional analytical study. Setting Primary healthcare setting in OR Tambo district, South Africa. Participants Patients treated for T2DM for 1 or more years (n=327). Primary outcome measure Prevalence of uncontrolled T2DM. Secondary outcome measure Determinants of uncontrolled T2DM (glycosylated haemoglobin (HbA1c) ≥7%). Results Out of the 327 participants, 274 had HbA1c≥7% (83.8%). Female sex (95% CI 1.3 to 4.2), overweight/obesity (95% CI 1.9 to 261.2), elevated low-density lipoprotein cholesterol (95% CI 4.4 to 23.8), sedentary habits (95% CI 7.2 to 61.3), lower monthly income (95% CI 1.3 to 6.5), longer duration of T2DM (95% CI 4.4 to 294.2) and diabetes information from non-health workers (95% CI 1.4 to 7.0) were the significant determinants of uncontrolled T2DM. There was a significant positive correlation of uncontrolled T2DM with increasing duration of T2DM, estimated glomerular filtration rate and body mass index. However, a significant negative correlation exists between monthly income and increasing HbA1c. Conclusions We found a significantly high prevalence (83.8%) of uncontrolled T2DM among the patients, possibly attributable to overweight/obesity, sedentary living, lower income and lack of information on diabetes. Addressing these determinants will require re-engineering of primary healthcare in the district. PMID:27473948

Tablet-Aided BehavioraL intervention EffecT on Self-management skills (TABLETS) for Diabetes.

PubMed

Lynch, Cheryl P; Williams, Joni S; J Ruggiero, Kenneth; G Knapp, Rebecca; Egede, Leonard E

2016-03-22

Multiple randomized controlled trials (RCTs) show that behavioral lifestyle interventions are effective in improving diabetes management and that comprehensive risk factor management improves cardiovascular disease (CVD) outcomes. The role of technology has been gaining strong support as evidence builds of its potential to improve diabetes management; however, evaluation of its impact in minority populations is limited. This study intends to provide early evidence of a theory-driven intervention, Tablet-Aided BehavioraL intervention EffecT on Self-management skills (TABLETS), using real-time videoconferencing for education and skills training. We examine the potential for TABLETS to improve health risk behaviors and reduce CVD risk outcomes among a low-income African American (AA) population with poorly controlled type 2 diabetes. The study is a two-arm, pilot controlled trial that randomizes 30 participants to the TABLETS intervention and 30 participants to a usual care group. Blinded outcome assessments will be completed at baseline, 2.5 months (immediate post-intervention), and 6.5 months (follow-up). The TABLETS intervention consists of culturally tailored telephone-delivered diabetes education and skills training delivered via videoconferencing on tablet devices, with two booster sessions delivered via tablet-based videoconferencing at 3 months and 5 months to stimulate ongoing use of the tablet device with access to intervention materials via videoconferencing slides and a manual of supplementary materials. The primary outcomes are physical activity, diet, medication adherence, and self-monitoring behavior, whereas the secondary outcomes are HbA1c, low-density lipoprotein cholesterol (LDL-C), BP, CVD risk, and quality of life. This study provides a unique opportunity to assess the feasibility and efficacy of a theory-driven, tablet-aided behavioral intervention that utilizes real-time videoconferencing technology for education and skills training on self-management behaviors and quality of life among a high-risk, low-income AA population with an uncontrolled dyad or triad of CVD risk factors (diabetes with or without hypertension or hyperlipidemia). The intervention leverages the use of novel technology for education and skill-building to foster improved diabetes self-management. The findings of this study will inform the process of disseminating the intervention to a broader and larger sample of people and can potentially be refined to align with clinical workflows that target a subsample of patients with poor diabetes self-management. The trial was registered in April 2014 with the United States National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier NCT02128854), available online at: http://clinicaltrials.gov/ct2/show/NCT02128854 .

FORCED NORMALIZATION: Epilepsy and Psychosis Interaction

PubMed Central

Loganathan, Muruga A.; Enja, Manasa

2015-01-01

Forced normalization is the emergence of psychoses following the establishment of seizure control in an uncontrolled epilepsy patient. Two illustrative clinical vignettes are provided about people with epilepsy that was newly controlled and followed by emergence of a psychosis; symptoms appeared only after attaining ictal control. For recognition and differential diagnosis purposes, understanding forced normalization is important in clinical practice. PMID:26155377

Uncontrolled diabetes as a potential risk factor in tibiotalocalcaneal fusion using a retrograde intramedullary nail.

PubMed

Lee, Moses; Choi, Woo Jin; Han, Seung Hwan; Jang, Jinyoung; Lee, Jin Woo

2017-07-22

Tibiotalocalcaneal (TTC) fusion using a retrograde intramedullary (IM) nail is an effective salvage option for terminal-stage hindfoot problems. However, as many patients who receive TTC fusion bear unfavorable medical comorbidities, the risk of nonunion, infection and other complications increases. This study was performed to identify the factors influencing outcomes after TTC fusion using a retrograde IM nail. Between September 2008 and February 2012, 34 consecutive patients received TTC fusion using a retrograde IM nail for limb salvage. All patients had a minimum follow-up of two years. Throughout follow-up, standard ankle radiography was performed along with clinical outcome assessment using a visual analog scale (VAS) for pain, the American Orthopaedic Foot and Ankle Society Ankle-Hind Foot Scale (AOFAS A/H scale) and the Foot and Ankle Outcome Score (FAOS). For the retrospective analysis, demographic factors, preoperative medical status, laboratory markers, and etiology were comprehensively reviewed using medical records. The success of the index operation was determined using clinical and radiological outcomes. Finally, the effect of each factor on failure after the operation was analyzed using univariate logistic regression. In a mean of seven months, 82% (28/34) achieved union, as evaluated by standard radiography. All clinical outcome parameters improved significantly after the operation, including VAS, AOFAS A/H scale, and FAOS (P<0.001). At the last follow-up, five cases of nonunion with less than AOFAS A/H scale of 80 and two cases of below knee amputation due to uncontrolled infection were determined to be failures. None of the factors (etiology, demographics, laboratory markers and medical status) significantly influenced failures. However, uncontrolled DM significantly increased the failure rate with an odds ratio of 10 (P=0.029). TTC fusion with a retrograde intramedullary nail is a successful treatment for complicated hindfoot problems such as traumatic osteoarthritis, Charcot arthropathy and failed TAA. However, it should be used judiciously in patients with uncontrolled DM, as the risk of failure increases. Retrospective cohort study. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Therapist-guided, Internet-based cognitive–behavioural therapy for body dysmorphic disorder (BDD-NET): a feasibility study

PubMed Central

Enander, Jesper; Ivanov, Volen Z; Andersson, Erik; Mataix-Cols, David; Ljótsson, Brjánn; Rück, Christian

2014-01-01

Objectives Cognitive–behavioural therapy (CBT) is an effective treatment for body dysmorphic disorder (BDD). However, most sufferers do not have access to this treatment. One way to increase access to CBT is to administer treatment remotely via the Internet. This study piloted a novel therapist-supported, Internet-based CBT program for BDD (BDD-NET). Design Uncontrolled clinical trial. Participants Patients (N=23) were recruited through self-referral and assessed face to face at a clinic specialising in obsessive–compulsive and related disorders. Suitable patients were offered secure access to BDD-NET. Intervention BDD-NET is a 12-week treatment program based on current psychological models of BDD that includes psychoeducation, functional analysis, cognitive restructuring, exposure and response prevention, and relapse prevention modules. A dedicated therapist provides active guidance and feedback throughout the entire process. Main outcome measure The clinician-administered Yale-Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS). Symptom severity was assessed pretreatment, post-treatment and at the 3-month follow-up. Results BDD-NET was deemed highly acceptable by patients and led to significant improvements on the BDD-YBOCS (p=<0.001) with a large within-group effect size (Cohen's d=2.01, 95% CI 1.05 to 2.97). At post-treatment, 82% of the patients were classified as responders (defined as≥30% improvement on the BDD-YBOCS). These gains were maintained at the 3-month follow-up. Secondary outcome measures of depression, global functioning and quality of life also showed significant improvements with moderate to large effect sizes. On average, therapists spent 10 min per patient per week providing support. Conclusions The results suggest that BDD-NET has the potential to greatly increase access to CBT, at least for low-risk individuals with moderately severe BDD symptoms and reasonably good insight. A randomised controlled trial of BDD-NET is warranted. Trial registration number Clinicaltrials.gov registration ID NCT01850433. PMID:25256187

Behavioral health coaching for rural veterans with diabetes and depression: a patient randomized effectiveness implementation trial.

PubMed

Cully, Jeffrey A; Breland, Jessica Y; Robertson, Suzanne; Utech, Anne E; Hundt, Natalie; Kunik, Mark E; Petersen, Nancy J; Masozera, Nicholas; Rao, Radha; Naik, Aanand D

2014-04-28

Depression and diabetes cause significant burden for patients and the healthcare system and, when co-occurring, result in poorer self-care behaviors and worse glycemic control than for either condition alone. However, the clinical management of these comorbid conditions is complicated by a host of patient, provider, and system-level barriers that are especially problematic for patients in rural locations. Patient-centered medical homes provide an opportunity to integrate mental and physical health care to address the multifaceted needs of complex comorbid conditions. Presently, there is a need to not only develop robust clinical interventions for complex medically ill patients but also to find feasible ways to embed these interventions into the frontlines of existing primary care practices. This randomized controlled trial uses a hybrid effectiveness-implementation design to evaluate the Healthy Outcomes through Patient Empowerment (HOPE) intervention, which seeks to simultaneously address diabetes and depression for rural veterans in Southeast Texas. A total of 242 Veterans with uncontrolled diabetes and comorbid symptoms of depression will be recruited and randomized to either the HOPE intervention or to a usual-care arm. Participants will be evaluated on a host of diabetes and depression-related measures at baseline and 6- and 12-month follow-up. The trial has two primary goals: 1) to examine the effectiveness of the intervention on both physical (diabetes) and emotional health (depression) outcomes and 2) to simultaneously pilot test a multifaceted implementation strategy designed to increase fidelity and utilization of the intervention by coaches interfacing within the primary care setting. This ongoing blended effectiveness-implementation design holds the potential to advance the science and practice of caring for complex medically ill patients within the constraints of a busy patient-centered medical home. Behavioral Activation Therapy for Rural Veterans with Diabetes and Depression: NCT01572389.

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial.

PubMed

Masmiquel, L; Leiter, L A; Vidal, J; Bain, S; Petrie, J; Franek, E; Raz, I; Comlekci, A; Jacob, S; van Gaal, L; Baeres, F M M; Marso, S P; Eriksson, M

2016-02-10

Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

Profile of brivaracetam and its potential in the treatment of epilepsy

PubMed Central

Ferlazzo, Edoardo; Russo, Emilio; Mumoli, Laura; Sueri, Chiara; Gasparini, Sara; Palleria, Caterina; Labate, Angelo; Gambardella, Antonio; De Sarro, Giovambattista; Aguglia, Umberto

2015-01-01

Brivaracetam (BRV) (UCB 34714) is currently under review by the US Food and Drug Administration and European Medicines Agency for approval as an add-on treatment for adult patients with partial seizures. Similar to levetiracetam (LEV), BRV acts as a high-affinity ligand of the synaptic vesicle protein 2A, however, it has been shown to be 10- to 30-fold more potent than LEV. Moreover, BRV does not share the LEV inhibitory activity on the high voltage Ca2+ channels and AMPA receptors, and it has been reported to act as a partial antagonist on neuronal voltage-gated sodium channels. The pharmacokinetic profile of BRV is favorable and linear, and it undergoes an extensive metabolism into inactive compounds, mainly through the hydrolysis of its acetamide group. Furthermore, it does not significantly interact with other antiepileptic drugs and more than 95% is excreted through the urine, with an unchanged fraction of 8%–11%. BRV has a half-life of approximately 8–9 hours and it is usually given twice daily. To date, a wide range of experimental studies have reported the effectiveness of BRV with regards to partial and generalized seizures. In humans, six randomized, placebo-controlled trials and two meta-analyses highlighted the efficacy, or good tolerability, of BRV as an add-on treatment for patients with uncontrolled partial seizures. A wide dose range of BRV has been evaluated in those trials (5–200 mg), but the most suitable for clinical use appears to be 50–100 mg/day. The most common adverse reactions to BRV are mild to moderate, transient, often improve during the course of the treatment, and mainly consist of central nervous system symptoms, such as fatigue, dizziness, and somnolence. The aim of this paper is to critically review the literature data regarding experimental animal models and clinical trials on BRV, and to define its potential usefulness for the clinicians who manage patients with epilepsy. PMID:26664121

Profile of brivaracetam and its potential in the treatment of epilepsy.

PubMed

Ferlazzo, Edoardo; Russo, Emilio; Mumoli, Laura; Sueri, Chiara; Gasparini, Sara; Palleria, Caterina; Labate, Angelo; Gambardella, Antonio; De Sarro, Giovambattista; Aguglia, Umberto

2015-01-01

Brivaracetam (BRV) (UCB 34714) is currently under review by the US Food and Drug Administration and European Medicines Agency for approval as an add-on treatment for adult patients with partial seizures. Similar to levetiracetam (LEV), BRV acts as a high-affinity ligand of the synaptic vesicle protein 2A, however, it has been shown to be 10- to 30-fold more potent than LEV. Moreover, BRV does not share the LEV inhibitory activity on the high voltage Ca(2+) channels and AMPA receptors, and it has been reported to act as a partial antagonist on neuronal voltage-gated sodium channels. The pharmacokinetic profile of BRV is favorable and linear, and it undergoes an extensive metabolism into inactive compounds, mainly through the hydrolysis of its acetamide group. Furthermore, it does not significantly interact with other antiepileptic drugs and more than 95% is excreted through the urine, with an unchanged fraction of 8%-11%. BRV has a half-life of approximately 8-9 hours and it is usually given twice daily. To date, a wide range of experimental studies have reported the effectiveness of BRV with regards to partial and generalized seizures. In humans, six randomized, placebo-controlled trials and two meta-analyses highlighted the efficacy, or good tolerability, of BRV as an add-on treatment for patients with uncontrolled partial seizures. A wide dose range of BRV has been evaluated in those trials (5-200 mg), but the most suitable for clinical use appears to be 50-100 mg/day. The most common adverse reactions to BRV are mild to moderate, transient, often improve during the course of the treatment, and mainly consist of central nervous system symptoms, such as fatigue, dizziness, and somnolence. The aim of this paper is to critically review the literature data regarding experimental animal models and clinical trials on BRV, and to define its potential usefulness for the clinicians who manage patients with epilepsy.

Interventions to improve screening and appropriate referral of patients with cancer for psychosocial distress: systematic review

PubMed Central

Britton, Ben; Baker, Amanda L; Halpin, Sean A; Beck, Alison K; Carter, Gregory; Wratten, Chris; Bauer, Judith; Forbes, Erin; Booth, Debbie

2018-01-01

Objectives The primary aim of the review was to determine the effectiveness of strategies to improve clinician provision of psychosocial distress screening and referral of patients with cancer. Design Systematic review. Data sources Electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) were searched until July 2016. Inclusion criteria Population: adult patients with cancer and clinical staff members. Intervention: any strategy that aimed to improve the rate of routine screening and referral for detected distress of patients with cancer. Comparison: no intervention controls, ‘usual’ practice or alternative interventions. Outcome: (primary) any measure of provision of screening and/or referral for distress, (secondary) psychosocial distress, unintended adverse effects. Design: trials with or without a temporal comparison group, including randomised and non-randomised trials, and uncontrolled pre–post studies. Data extraction and analysis Two review authors independently extracted data. Heterogeneity across studies precluded quantitative assessment via meta-analysis and so a narrative synthesis of the results is presented. Results Five studies met the inclusion criteria. All studies were set in oncology clinics or departments and used multiple implementation strategies. Using the Grades of Recommendation, Assessment, Development and Evaluation, the overall rating of the certainty of the body of evidence reported in this review was assessed as very low. Three studies received a methodological quality rating of weak and two studies received a rating of moderate. Only one of the five studies reported a significant improvement in referrals. Conclusions The review identified five studies of predominantly poor quality examining the effectiveness of strategies to improve the routine implementation of distress screening and referral for patients with cancer. Future research using robust research designs, including randomised assignment, are needed to identify effective support strategies to maximise the potential for successful implementation of distress screening and referral for patients with cancer. PROSPERO registration number CRD42015017518. PMID:29306881

Review of the neurological benefits of phytocannabinoids

PubMed Central

Maroon, Joseph; Bost, Jeff

2018-01-01

Background: Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS. Methods: In 1980, Cunha et al. reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts. Results: Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson's disease, Alzheimer's disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids. Conclusions: In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes. PMID:29770251

Efficacy, safety and risk of augmentation of rotigotine for treating restless legs syndrome.

PubMed

Inoue, Yuichi; Hirata, Koichi; Hayashida, Kenichi; Hattori, Nobutaka; Tomida, Takayuki; Garcia-Borreguero, Diego

2013-01-10

The present study aimed to examine the long-term efficacy and safety of rotigotine treatment for restless legs syndrome (RLS), as well as the rate of clinically significant augmentation, in a 1-year open-label study of Japanese subjects. Japanese patients with RLS who had been treated with rotigotine or placebo in a double-blind trial were enrolled in a 1-year, open-label, uncontrolled extension study and treated with rotigotine at a dose of up to 3 mg/24 h after an 8-week titration phase. Outcomes included International Restless Legs Syndrome Study Group rating scale (IRLS scale), Pittsburgh Sleep Quality Index (PSQI), safety, and investigator-/expert panel-assessed augmentation (including Augmentation Severity Rating Scale). Overall, 185 patients entered the open-label study and 133 completed the study. IRLS and PSQI total scores improved throughout the 52-week treatment period (IRLS, from 23.2±5.1 to 7.8±7.6 and PSQI, from 8.0±3.1 to 5.0±2.9). Treatment-emergent adverse events were mild to moderate in severity, and included application site reactions (52.4%) and nausea (28.6%). Clinically significant augmentation occurred in five patients (2.7%). These results indicate a good long-term efficacy of rotigotine for treating RLS, with a relatively low risk of clinically significant augmentation. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

PubMed

Dahal, Prabin; d'Alessandro, Umberto; Dorsey, Grant; Guerin, Philippe J; Nsanzabana, Christian; Price, Ric N; Sibley, Carol H; Stepniewska, Kasia; Talisuna, Ambrose O

2015-09-07

Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Conversion to eslicarbazepine acetate monotherapy

PubMed Central

French, Jacqueline; Jacobson, Mercedes P.; Pazdera, Ladislav; Gough, Mallory; Cheng, Hailong; Grinnell, Todd; Blum, David

2016-01-01

Objective: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. Methods: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). Results: Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%–26.8%); ESL 1,200 mg = 30.8% (23.0%–40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. Conclusions: Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. Classification of evidence: This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective. PMID:26911639

Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies.

PubMed

Sperling, Michael R; French, Jacqueline; Jacobson, Mercedes P; Pazdera, Ladislav; Gough, Mallory; Cheng, Hailong; Grinnell, Todd; Blum, David

2016-03-22

To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%-26.8%); ESL 1,200 mg = 30.8% (23.0%-40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective. © 2016 American Academy of Neurology.

Distant Healing Of Surgical Wounds: An Exploratory Study

PubMed Central

Schlitz, Marilyn; Hopf, Harriet W.; Eskenazi, Loren; Vieten, Cassandra; Radin, Dean

2012-01-01

Distant healing intention (DHI) is one of the most common complementary and alternative medicine (CAM) healing modalities, but clinical trials to date have provided ambivalent support for its efficacy. One possible reason is that DHI effects may involve variables that are sensitive to unknown, uncontrolled, or uncontrollable factors. To examine two of those potential variables – expectation and belief – the effects of DHI were explored on objective and psychosocial measures associated with surgical wounds in 72 women undergoing plastic surgery. Participants were randomly assigned to one of three groups: blinded and receiving DHI (DH), blinded and not receiving DHI (Control), and knowing that they were receiving DHI (Expectancy). Outcome measures included collagen deposition in a surrogate wound and several self-report measures. DHI was provided by experienced distant healers. No differences in the main measures were observed across the three groups. Participants’ prior belief in the efficacy of DHI was negatively correlated with the status of their mental health at the end of the study (p = 0.04, two-tailed), and healers’ perceptions of the quality of their subjective “contact” with the participants were negatively correlated both with change in mood (p = 0.001) and with collagen deposition (p = 0.04). A post-hoc analysis found that among participants assigned to receive DHI under blinded conditions, those undergoing reconstructive surgery after breast cancer treatment reported significantly better change in mood than those who were undergoing purely elective cosmetic surgery (p = 0.004). If future DHI experiments confirm the post-hoc observations, then some of the ambiguity observed in earlier DHI studies may be attributable to interactions among participants’ and healers’ beliefs, their expectations, and their motivations. PMID:22742672

Efficacy of budesonide/formoterol maintenance and reliever therapy compared with higher-dose budesonide as step-up from low-dose inhaled corticosteroid treatment.

PubMed

Jenkins, Christine R; Eriksson, Göran; Bateman, Eric D; Reddel, Helen K; Sears, Malcolm R; Lindberg, Magnus; O'Byrne, Paul M

2017-04-20

Asthma management may involve a step up in treatment when symptoms are not well controlled. We examined whether budesonide/formoterol maintenance and reliever therapy (MRT) is as effective as higher, fixed-dose budesonide plus as-needed terbutaline in patients requiring step-up from Step 2 treatment (low-dose inhaled corticosteroids), stratified by baseline reliever use. A post-hoc analysis utilized data from three clinical trials of 6-12 months' duration. Patients aged ≥12 years with symptomatic asthma uncontrolled despite Step 2 treatment were included. Severe exacerbation rate, lung function and reliever use were analysed, stratified by baseline reliever use (<1, 1-2 and >2 occasions/day). Overall, 1239 patients were included. Reductions in severe exacerbation rate with budesonide/formoterol MRT versus fixed-dose budesonide were similar across baseline reliever use levels, and were statistically significant in patients using 1-2 (42%, p = 0.01) and >2 (39%, p = 0.02) reliever occasions/day, but not <1 reliever occasion/day (35%, p = 0.11). Both treatments significantly increased mean FEV 1 from baseline; improvements were significantly greater for budesonide/formoterol MRT in all reliever use groups. Reductions in reliever use from baseline were significantly greater with budesonide/formoterol MRT versus fixed-dose budesonide in patients using 1-2 and >2 reliever occasions/day (-0.33 and -0.74 occasions/day, respectively). Treatment benefit with budesonide/formoterol MRT versus higher, fixed-dose budesonide plus short-acting β 2 -agonist was found in Step 2 patients with relatively low reliever use, supporting the proposal that budesonide/formoterol MRT may be useful when asthma is uncontrolled with low-dose inhaled corticosteroid.

Newborn screening for galactosaemia.

PubMed

Lak, Rohollah; Yazdizadeh, Bahareh; Davari, Majid; Nouhi, Mojtaba; Kelishadi, Roya

2017-12-23

Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the review. We were unable to identify any eligible studies for inclusion in this review and hence it is not possible to draw any conclusions based on randomised controlled studies. However, we are aware of uncontrolled studies which support the efficacy of newborn screening for galactosaemia. There are a number of reviews and economic analyses of non-trial literature suggesting that screening is appropriate.

Role of Nutraceuticals in Hypolipidemic Therapy.

PubMed

Barbagallo, Carlo M; Cefalù, Angelo Baldassare; Noto, Davide; Averna, Maurizio R

2015-01-01

Nutraceuticals are food components or active ingredients present in foods and used in therapy. This article analyzes the characteristics of the molecules with a lipid-lowering effect. The different nutraceuticals may have different mechanisms of action: inhibition of cholesterol synthesis primarily through action on the enzyme HMG-CoA reductase (policosanol, polyphenols, garlic and, above all, red yeast rice), increase in LDL receptor activity (berberine), reduction of intestinal cholesterol absorption (garlic, plant sterols, probiotics), and also the ability to interfere with bile metabolism (probiotics, guggul). Based on the different mechanisms of action, some nutraceuticals are then able to enhance the action of statins. Nutraceuticals are often used without relevant evidence: mechanisms of action are not clearly confirmed; most of clinical data are derived from small, uncontrolled studies, and finally, except for fermented red rice, there are no clinical trials which may document the relationship between these interventions and the reduction of clinical events. Therefore, among all nutraceuticals, it is necessary to extrapolate those having a really documentable efficacy. However, these kinds of treatments are usually well-tolerated by patients. Overall, subjects with a middle or low cardiovascular risk are the best indication of nutraceuticals, but they may also be useful for patients experiencing side effects during classical therapies. Finally, in consideration of the additive effect of some nutraceuticals, a combination therapy with classical drugs may improve the achievement of clinical targets. Thus, nutraceuticals may be a helpful alternative in hypolipidemic treatment and, if properly used, might represent a valid strategy of cardiovascular prevention.

Role of Nutraceuticals in Hypolipidemic Therapy

PubMed Central

Barbagallo, Carlo M.; Cefalù, Angelo Baldassare; Noto, Davide; Averna, Maurizio R.

2015-01-01

Nutraceuticals are food components or active ingredients present in foods and used in therapy. This article analyzes the characteristics of the molecules with a lipid-lowering effect. The different nutraceuticals may have different mechanisms of action: inhibition of cholesterol synthesis primarily through action on the enzyme HMG-CoA reductase (policosanol, polyphenols, garlic and, above all, red yeast rice), increase in LDL receptor activity (berberine), reduction of intestinal cholesterol absorption (garlic, plant sterols, probiotics), and also the ability to interfere with bile metabolism (probiotics, guggul). Based on the different mechanisms of action, some nutraceuticals are then able to enhance the action of statins. Nutraceuticals are often used without relevant evidence: mechanisms of action are not clearly confirmed; most of clinical data are derived from small, uncontrolled studies, and finally, except for fermented red rice, there are no clinical trials which may document the relationship between these interventions and the reduction of clinical events. Therefore, among all nutraceuticals, it is necessary to extrapolate those having a really documentable efficacy. However, these kinds of treatments are usually well-tolerated by patients. Overall, subjects with a middle or low cardiovascular risk are the best indication of nutraceuticals, but they may also be useful for patients experiencing side effects during classical therapies. Finally, in consideration of the additive effect of some nutraceuticals, a combination therapy with classical drugs may improve the achievement of clinical targets. Thus, nutraceuticals may be a helpful alternative in hypolipidemic treatment and, if properly used, might represent a valid strategy of cardiovascular prevention. PMID:26664894

Bronchial asthma.

PubMed

Liccardi, Gennaro; Salzillo, Antonello; Sofia, Matteo; D'Amato, Maria; D'Amato, Gennaro

2012-02-01

The aim of this review is to underline the need for an adequate clinical and functional evaluation of respiratory function and asthma control in patients undergoing surgical procedures requiring general anesthesia to obtain useful information for an adequate preoperative pharmacological approach. It has been shown that baseline uncontrolled clinical/functional conditions of airways represent the most important risk factors for perioperative bronchospasm. In nonemergency conditions, asthma patients should undergo clinical/functional assessment at least 1 week before the surgery intervention to obtain, the better feasible control of asthma symptoms in the single patient. Some simple preoperative information given by the patient in preoperative consultation may be sufficient to identify individuals with uncontrolled or poor controlled asthmatic conditions. Spirometric evaluation is essential in individuals with poor control of symptoms, as well as in those patients with uncertain anamnestic data or limited perception of respiratory symptoms, and in those requiring lung resection. A better control of asthma must be considered the 'gold standard' for a patient at 'a reasonable low risk' to develop perioperative/postoperative bronchospasm. International consensus promoted by pulmonologists, anesthesiologists, and allergists might be useful to define a better diagnostic and therapeutic approach.

CSI, optimal control, and accelerometers: Trials and tribulations

NASA Technical Reports Server (NTRS)

Benjamin, Brian J.; Sesak, John R.

1994-01-01

New results concerning optimal design with accelerometers are presented. These results show that the designer must be concerned with the stability properties of two Linear Quadratic Gaussian (LQG) compensators, one of which does not explicitly appear in the closed-loop system dynamics. The new concepts of virtual and implemented compensators are introduced to cope with these subtleties. The virtual compensator appears in the closed-loop system dynamics and the implemented compensator appears in control electronics. The stability of one compensator does not guarantee the stability of the other. For strongly stable (robust) systems, both compensators should be stable. The presence of controlled and uncontrolled modes in the system results in two additional forms of the compensator with corresponding terms that are of like form, but opposite sign, making simultaneous stabilization of both the virtual and implemented compensator difficult. A new design algorithm termed sensor augmentation is developed that aids stabilization of these compensator forms by incorporating a static augmentation term associated with the uncontrolled modes in the design process.

Is mannitol the treatment of choice for patients with ciguatera fish poisoning?

PubMed

Mullins, Michael E; Hoffman, Robert S

2017-11-01

Ciguatera fish poisoning arises primarily from consumption of carnivorous reef fish caught in tropical and sub-tropical waters. Ciguatoxins, a class of tasteless, heat-stable, polycyclic toxins produced by dinoflagellates, accumulate through the food chain and concentrate in various carnivorous fish, such as groupers, barracudas, wrasses, amberjack, kingfishes, and eels. Characteristics of ciguatera fish poisoning include early nausea, vomiting, and diarrhea in the first one to two days post ingestion, followed by the appearance of sensory disturbances. The classic dysaesthesia is cold allodynia, often described as reversal of hot and cold sensation, but a more accurate description is burning pain on exposure to cold. To discuss and appraise the evidence regarding the use of mannitol or other drugs in treating ciguatera framed in the historical context of the last four decades. We searched PubMed and Embase for all years from 1966 to March 31, 2017 with search terms "ciguatera", "mannitol", and "treatment". These searches identified 85 articles, of which 36 were relevant to the review question. We searched Google Scholar to supplement the primary search and reviewed the references of articles for sources overlooked in the original searches. These secondary searches identified another 23 references. We excluded six clinical reports (two case series and four case reports) which did not clearly describe ciguatera or which lacked information on treatment or outcome. Fifty-three clinical articles remained for review. We searched PubMed using "ciguatera" AND "treatment" NOT "mannitol" to better identify reports describing other treatments. The search identified 128 articles, of which nine described specific pharmacological treatments and their outcomes. We combined our findings into a consensus review of the evidence both for and against the use of mannitol or other medications for ciguatera fish poisoning. Early human evidence of effectiveness of mannitol: A 1988 report described an unexpected discovery that intravenous mannitol could rapidly and effectively treat ciguatera fish poisoning. Several other uncontrolled case series and case reports appeared to support the use of mannitol. In 2002, a small randomized, controlled trial reported no significant difference between mannitol and normal saline. Subsequent case reports have cited this study as the reason for or to withhold mannitol. Thus, some controversy exists regarding whether mannitol is useful or not for treating ciguatera fish poisoning. Basic science and animal research on ciguatera and mannitol: In vitro experiments of isolated neurons demonstrate that ciguatoxins produce neuronal edema, open certain sodium channels, block potassium channels, cause uncontrolled and repetitive action potentials after a stimulus. Addition of mannitol decreases the edema and reduces the uncommanded action potentials. However, intraperitoneal injection of ciguatoxin in rats increases neuronal refractory period and slows nerve conduction velocity. Treatment with mannitol fails to correct these effects. Comparative trials of mannitol: Evidence supporting mannitol for ciguatera fish poisoning includes four uncontrolled case series, one prospective, unblinded comparative trial and several case reports. Evidence against mannitol consists of one RCT, which has a small sample size and several potential limitations. Empirical human experience with other treatments: Evidence regarding other treatments consists only of ten case reports and three overlapping case series that describe using amitriptyline, fluoxetine, duloxetine, gabapentin, pregabalin, or tocainide. For each of these, a long duration of treatment appears to be necessary to maintain symptomatic improvement. None of these treatments has been shown to be superior to mannitol. It is reasonable to consider using intravenous mannitol in cases of acute ciguatera fish poisoning. Medications used in other neuropathic syndromes appear to suppress the paresthesiae of persistent ciguatera cases. However, the human evidence is of low quality for all treatments.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial.

PubMed

Fuchs, Flávio D; Scala, Luiz César N; Vilela-Martin, José F; de Mello, Renato Bandeira; Mosele, Francisca; Whelton, Paul K; Poli-de-Figueiredo, Carlos E; de Alencastro, Paulo Ricardo; E Silva, Ricardo Pereira; Gus, Miguel; Bortolotto, Luiz Aparecido; Schlatter, Rosane; Cesarino, Evandro José; Castro, Iran; Neto, José A Figueiredo; Chaves, Hilton; Steffens, André Avelino; Alves, João Guilherme; Brandão, Andréa Araujo; de Sousa, Marcos R; Jardim, Paulo Cesar; Moreira, Leila B; Franco, Roberto Silva; Gomes, Marco Mota; Neto, Abrahão Afiune; Fuchs, Felipe Costa; Filho, Dario C Sobral; Nóbrega, Antônio C; Nobre, Fernando; Berwanger, Otávio; Fuchs, Sandra C

2016-04-01

To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ± 40.4 versus 16.2 ± 26.7 mg, P = 0.09). Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. NCT00971165.

A weight loss intervention using a commercial mobile application in Latino Americans-Adelgaza Trial.

PubMed

Fukuoka, Yoshimi; Vittinghoff, Eric; Hooper, Julie

2018-02-21

More than half of Latino adults living in the USA are expected to develop type 2 diabetes in their lifetime. Despite the growing interest in smartphone use for weight loss and diabetes prevention, relatively few clinical trials have evaluated the efficacy of mobile app-based interventions in Latino populations. The aim of this study was to evaluate the potential efficacy of an in-person weight loss intervention in conjunction with a commercially available Fitbit app in a Latino sample at risk for type 2 diabetes and explore significant predictors associated with weight loss. After the run-in period, 54 self-identified Latinos with body mass index (BMI) > 24.9 kg/m2 were enrolled in an 8-week uncontrolled pilot study, and received a Fitbit Zip, its app, and two in-person weight loss sessions adapted from the Diabetes Prevention Program. Mean age was 45.3 (SD ± 10.8) years, 61.1% were born in the USA, and mean BMI was 31.4 (SD ± 4.1) kg/m2. Participants lost an average of 3.3 (SD ± 3.4) % of their body weight (p < .0005). We also observed statistically significant reductions in hip and waist circumferences, and systolic and diastolic blood pressure (p < .001). After controlling for demographic factors, use of the mobile app weight diary at least twice a week (p = .01) and change in the International Physical Activity Questionnaire score (p = .03) were associated with change in percent body weight. The intervention showed the potential efficacy of this intervention, which should be formally evaluated in a randomized controlled trial.

Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial.

PubMed

Dreger, Peter; Döhner, Hartmut; Ritgen, Matthias; Böttcher, Sebastian; Busch, Raymonde; Dietrich, Sascha; Bunjes, Donald; Cohen, Sandra; Schubert, Jörg; Hegenbart, Ute; Beelen, Dietrich; Zeis, Matthias; Stadler, Michael; Hasenkamp, Justin; Uharek, Lutz; Scheid, Christof; Humpe, Andreas; Zenz, Thorsten; Winkler, Dirk; Hallek, Michael; Kneba, Michael; Schmitz, Norbert; Stilgenbauer, Stephan

2010-10-07

The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p-). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p-, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.

Designing and evaluating health systems level hypertension control interventions for African-Americans: lessons from a pooled analysis of three cluster randomized trials.

PubMed

Pavlik, Valory N; Chan, Wenyaw; Hyman, David J; Feldman, Penny; Ogedegbe, Gbenga; Schwartz, Joseph E; McDonald, Margaret; Einhorn, Paula; Tobin, Jonathan N

2015-01-01

African-Americans (AAs) have a high prevalence of hypertension and their blood pressure (BP) control on treatment still lags behind other groups. In 2004, NHLBI funded five projects that aimed to evaluate clinically feasible interventions to effect changes in medical care delivery leading to an increased proportion of AA patients with controlled BP. Three of the groups performed a pooled analysis of trial results to determine: 1) the magnitude of the combined intervention effect; and 2) how the pooled results could inform the methodology for future health-system level BP interventions. Using a cluster randomized design, the trials enrolled AAs with uncontrolled hypertension to test interventions targeting a combination of patient and clinician behaviors. The 12-month Systolic BP (SBP) and Diastolic BP (DBP) effects of intervention or control cluster assignment were assessed using mixed effects longitudinal regression modeling. 2,015 patients representing 352 clusters participated across the three trials. Pooled BP slopes followed a quadratic pattern, with an initial decline, followed by a rise toward baseline, and did not differ significantly between intervention and control clusters: SBP linear coefficient = -2.60±0.21 mmHg per month, p<0.001; quadratic coefficient = 0.167± 0.02 mmHg/month, p<0.001; group by time interaction group by time group x linear time coefficient=0.145 ± 0.293, p=0.622; group x quadratic time coefficient= -0.017 ± 0.026, p=0.525). RESULTS were similar for DBP. The individual sites did not have significant intervention effects when analyzed separately. Investigators planning behavioral trials to improve BP control in health systems serving AAs should plan for small effect sizes and employ a "run-in" period in which BP can be expected to improve in both experimental and control clusters.

Patient education and follow-up as an intervention for hypertensive patients discharged from an emergency department: a randomized control trial study protocol.

PubMed

Gleason-Comstock, Julie; Streater, Alicia; Ager, Joel; Goodman, Allen; Brody, Aaron; Kivell, Laura; Paranjpe, Aniruddha; Vickers, Jasmine; Mango, LynnMarie; Dawood, Rachelle; Levy, Phillip

2015-12-21

Persistently elevated blood pressure (BP) is a leading risk factor for cardiovascular disease development, making effective hypertension management an issue of considerable public health importance. Hypertension is particularly prominent among African Americans, who have higher disease prevalence and consistently lower BP control than Whites and Hispanics. Emergency departments (ED) have limited resources for chronic disease management, especially for under-served patients dependent upon the ED for primary care, and are not equipped to conduct follow-up. Kiosk-based patient education has been found to be effective in primary care settings, but little research has been done on the effectiveness of interactive patient education modules as ED enhanced discharge for an under-served urban minority population. Achieving Blood Pressure Control Through Enhanced Discharge (AchieveBP) is a behavioral RCT patient education intervention for patients with a history of hypertension who have uncontrolled BP at ED discharge. The project will recruit up to 200 eligible participants at the ED, primarily African-American, who will be asked to return to a nearby clinical research center for seven, thirty and ninety day visits, with a 180 day follow-up. Consenting participants will be randomized to either an attention-control or kiosk-based interactive patient education intervention. To control for potential medication effects, all participants will be prescribed similar, evidenced-based anti-hypertensive regimens and have their prescription filled onsite at the ED and during visits to the clinic. The primary target endpoint will be success in achieving BP control assessed at 180 days follow-up post-ED discharge. The secondary aim will be to assess the relationship between patient activation and self-care management. The AchieveBP trial will determine whether using interactive patient education delivered through health information technology as ED enhanced discharge with subsequent education sessions at a clinic is an effective strategy for achieving short-term patient management of BP. The project is innovative in that it uses the ED as an initial point of service for kiosk-based health education designed to increase BP self-management. It is anticipated findings from this translational research could also be used as a resource for patient education and follow-up with hypertensive patients in primary care settings. ClinicalTrials.gov. NCT02069015. Registered February 19, 2014.

A Randomized Controlled Dismantling Trial of Post-Workshop Consultation Strategies to Increase Effectiveness and Fidelity to an Evidence-Based Psychotherapy for Posttraumatic Stress Disorder

DTIC Science & Technology

2013-08-01

not eligible for CPT based on the state of research evidence, including those with: current uncontrolled psychotic or bipolar disorder ; substance...among trauma, post-traumatic stress disorder , and health outcomes. Adv Mind Body Med 2004, 20(1):18–29. 10. Kessler RC: Posttraumatic Stress Disorder ...to an evidence-based psychotherapy for Posttraumatic stress disorder Shannon Wiltsey Stirman1, Norman Shields2, Josh Deloriea3, Meredith SH Landy3

Where does the Occluded Artery Trial leave the late open artery hypothesis?

PubMed Central

Lamas, Gervasio A; Hochman, Judith S

2007-01-01

As of April 2007 the early open artery hypothesis is alive and well, but the late open artery hypothesis is adrift. For the foreseeable future, stable patients with persistent occlusion of the infarct artery late after myocardial infarction, and without severe ischaemia or uncontrollable angina, should be managed initially with optimal medical treatment alone, and not with percutaneous coronary intervention. Efforts should focus on establishing reperfusion earlier, including reducing the time to patient presentation. PMID:17933981

Group and multifamily behavioral treatment for obsessive compulsive disorder: a pilot study.

PubMed

Van Noppen, B; Steketee, G; McCorkle, B H; Pato, M

1997-01-01

Recent trends toward managed care in mental health settings require investigation of the efficacy and cost-effectiveness of treatments conducted over shorter time frames or with less therapist involvement. Findings are presented in an uncontrolled trial of two types of group behavioral treatments of OCD: group (GBT) and multifamily (MFBT). Seventeen patients (10 women and 7 men) diagnosed with OCD received a partially manualized GBT delivered by co-therapy teams in three groups of ten 2-hr sessions. Mean interview-based YBOCS scores reduced significantly at posttest and at 1-year follow-up, as did measures of overall functioning on the Sheehan Disability Scale at posttest and follow-up. A second cohort of 19 patients (14 women and 5 men) was treated with MFBT that included spouses/partners and parents in three co-therapy groups. Two groups received ten 2-hr sessions and one received twelve 2-hr sessions. YBOCS scores reduced significantly at posttest and at 1-year follow-up, with corresponding gains in disability scores. Both group treatments showed large effects comparable to those reported for a more intensive individual behavioral treatment. Comparisons of treatments indicated that similar proportions of subjects were reliably changed at posttest and follow-up respectively, but more MFBT than GBT participants were clinically significantly improved. These promising cost effective group treatments remain to be tested in a controlled trial.

The effects of family involvement and practitioner home visits on the control of hypertension.

PubMed Central

Earp, J A; Ory, M G; Strogatz, D S

1982-01-01

The effectiveness of two social support strategies designed to lower hypertensive patients' blood pressure were compared to each other and to a control group (N = 63) receiving routine care in a randomized clinical trial extending over a period of two years. Group 1 (N = 99) received visits and had family members actively participate in their care through home blood pressure monitoring; Group 2 (N = 56) received home visits from nurses and pharmacists. All groups were predominantly Black. After the first year of the trial, the proportion of patients with uncontrolled diastolic blood pressure (greater than or equal to 95mm Hg) had declined significantly for all three groups; no group showed a statistically significant advantage. However, during the last six months of the second year (after visiting had ended), both Groups 1 and 2 demonstrated clear superiority in DBP control over Group 3, achieving borderline statistical significance (p = .07) when multivariable analysis was performed to control for potential confounders. Supplementing routine care with periodic home visits produced an additional 21 per cent of patients with well-controlled DBP, while involving family members plus visits produced a 17 per cent improvement in the percentage of patients with DBP less than 95mm Hg. However, neither support strategy was clearly more effective than the other over time. The efficacy of the interventions is discussed with respect to cost and feasibility of implementation. PMID:7114339

Nutraceuticals for older people: facts, fictions and gaps in knowledge.

PubMed

González-Sarrías, Antonio; Larrosa, Mar; García-Conesa, María Teresa; Tomás-Barberán, Francisco A; Espín, Juan Carlos

2013-08-01

In the last decades nutraceuticals have entered the health market as an easy and attractive means of preventing diseases. These products are of interest for an increasingly health-concerned society and may be especially relevant for preventing or delaying a number of age-related diseases, i.e. arthritis, cancer, metabolic and cardiovascular diseases, osteoporosis, cataracts, brain disorders, etc. Nutraceuticals are marketed in a variety of forms, composition and potential applications which have made their definition ambiguous and their use uncontrolled and poorly funded. Although epidemiological, animal and in vitro studies have given evidence of the potential benefits of some of these nutraceuticals or of their components, definitive proof of their effects in appropriate human clinical trials is still lacking in most cases, more critically among people above 65 years of age. We cover the well-established nutraceuticals (polyvitamins, omega-3 fatty acids, etc.) and will focus on many other 'novel' commercial nutraceuticals where the scientific evidence is more limited (food extracts, polyphenols, carotenoids, etc.). Solid scientific evidence has been reported only for a few nutraceuticals, which have some health claims approved by the European Food Safety Authority (EFSA). Further well-designed trials are needed to improve the current knowledge on the health benefits of nutraceuticals in the elderly. Overall, there are some facts, a lot of fiction and many gaps in the knowledge of nutraceutical benefits. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Group acceptance and commitment therapy (ACT) for bipolar disorder and co-existing anxiety - an open pilot study.

PubMed

Pankowski, Sara; Adler, Mats; Andersson, Gerhard; Lindefors, Nils; Svanborg, Cecilia

2017-03-01

Previous studies have supported acceptance and commitment therapy (ACT) for reducing impairment related to various chronic conditions. ACT may possibly be beneficial for bipolar disorder (BD) with co-existing anxiety, which is associated with a poorer treatment outcome. Efforts are needed to identify suitable psychological interventions for BD and co-existing anxiety. In this open clinical trial, we included 26 patients with BD type 1 or 2 at an outpatient psychiatric unit specializing in affective disorders. The intervention consisted of a 12-session manualized group treatment that included psychoeducation, mindfulness, engaging in values-based behaviour, cognitive defusion, acceptance and relapse prevention modules. Participants completed four self-report questionnaires covering anxiety symptoms (Beck Anxiety Inventory - BAI), depressive symptoms (Beck Depression Inventory - BDI-II), quality of life (Quality of Life Inventory - QOLI) and psychological flexibility (Acceptance and Action Questionnaire - AAQ-2) before, during and after the treatment. At post-treatment, the participants reported significant improvements in all outcome measures, with large effects (Cohen's d between 0.73 and 1.98). The mean reduction in anxiety symptoms was 45%. At post-treatment, 96% of the patients were classified as responders on at least one of the outcome measures. A limitation is that the trial is uncontrolled. The results suggest that ACT has the potential to be an effective treatment for BD patients with co-existing anxiety. Further randomized studies are warranted.

A randomized, controlled trial of virtual reality-graded exposure therapy for post-traumatic stress disorder in active duty service members with combat-related post-traumatic stress disorder.

PubMed

McLay, Robert N; Wood, Dennis P; Webb-Murphy, Jennifer A; Spira, James L; Wiederhold, Mark D; Pyne, Jeffrey M; Wiederhold, Brenda K

2011-04-01

Abstract Virtual reality (VR)-based therapy has emerged as a potentially useful means to treat post-traumatic stress disorder (PTSD), but randomized studies have been lacking for Service Members from Iraq or Afghanistan. This study documents a small, randomized, controlled trial of VR-graded exposure therapy (VR-GET) versus treatment as usual (TAU) for PTSD in Active Duty military personnel with combat-related PTSD. Success was gauged according to whether treatment resulted in a 30 percent or greater improvement in the PTSD symptom severity as assessed by the Clinician Administered PTSD Scale (CAPS) after 10 weeks of treatment. Seven of 10 participants improved by 30 percent or greater while in VR-GET, whereas only 1 of the 9 returning participants in TAU showed similar improvement. This is a clinically and statistically significant result (χ(2) = 6.74, p < 0.01, relative risk 3.2). Participants in VR-GET improved an average of 35 points on the CAPS, whereas those in TAU averaged a 9-point improvement (p < 0.05). The results are limited by small size, lack of blinding, a single therapist, and comparison to a relatively uncontrolled usual care condition, but did show VR-GET to be a safe and effective treatment for combat-related PTSD.

Meta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia

PubMed Central

Freitas, Catarina; Fregni, Felipe; Pascual-Leone, Alvaro

2009-01-01

Background A growing body of evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can alleviate negative and positive symptoms of refractory schizophrenia. However, trials to date have been small and results are mixed. Methods We performed meta-analyses of all prospective studies of the therapeutic application of rTMS in refractory schizophrenia assessing the effects of high-frequency rTMS to the left dorsolateral prefrontal cortex (DLPFC) to treat negative symptoms, and low-frequency rTMS to the left temporo-parietal cortex (TPC) to treat auditory hallucinations (AH) and overall positive symptoms. Results When analyzing controlled (active arms) and uncontrolled studies together, the effect sizes showed significant and moderate effects of rTMS on negative and positive symptoms (based on PANSS-N or SANS, and PANSS-P or SAPS, respectively). However, the analysis for the sham-controlled studies revealed a small non-significant effect size for negative (0.27, p=0.417) and for positive symptoms (0.17, p=0.129). When specifically analyzing AH (based on AHRS, HCS or SAH), the effect size for the sham-controlled studies was large and significant (1.04; p=0.002). Conclusions These meta-analyses support the need for further controlled, larger trials to assess the clinical efficacy of rTMS on negative and positive symptoms of schizophrenia, while suggesting the need for exploration for alternative stimulation protocols. PMID:19138833

What is the best way to manage GERD symptoms in the elderly?

PubMed

Bacak, Brian S; Patel, Mihir; Tweed, Elizabeth; Danis, Peter

2006-03-01

No evidence supports one method over another in managing uncomplicated gastroesophageal reflux disease (GERD) for patients aged >65 years. For those with endoscopically documented esophagitis, proton pump inhibitors (PPIs) relieve symptoms faster than histamine H2 receptor antagonists (H2RAs) (strength of recommendation [SOR]: B, extrapolation from randomized controlled trials [RCTs]). Treating elderly patients with pantoprazole (Protonix) after resolution of acute esophagitis results in fewer relapses than with placebo (SOR: B, double-blind RCT). Limited evidence suggests that such maintenance therapy for prior esophagitis with either H2RAs or PPIs, at half- and full-dose strength, decreases the frequency of relapse (SOR: B, extrapolation from uncontrolled clinical trial). Laparoscopic antireflux surgery for treating symptomatic GERD among elderly patients without paraesophageal hernia reduces esophageal acidity, with no apparent increase in postoperative morbidity or mortality compared with younger patients (SOR: C, nonequivalent before-after study). Upper endoscopy is recommended for elderly patients with alarm symptoms, new-onset GERD, or longstanding disease (SOR: C, expert consensus). Elderly patients are at risk for more severe complications from GERD, and their relative discomfort from the disease process is often less than from comparable pathology for younger patients (SOR: C, expert consensus). Based on safety profiles and success in the general patient population, PPIs as a class are considered first-line treatment for GERD and esophagitis for the elderly (SOR: C, expert consensus).

Chili Peppers, Curcumins, and Prebiotics in Gastrointestinal Health and Disease.

PubMed

Patcharatrakul, Tanisa; Gonlachanvit, Sutep

2016-04-01

There is growing evidence for the role of several natural products as either useful agents or adjuncts in the management of functional GI disorders (FGIDs). In this review, we examine the medical evidence for three such compounds: chili, a culinary spice; curcumin, another spice and active derivative of a root bark; and prebiotics, which are nondigestible food products. Chili may affect the pathogenesis of abdominal pain especially in functional dyspepsia and cause other symptoms. It may have a therapeutic role in FGIDs through desensitization of transient receptor potential vanilloid-1 receptor. Curcumin, the active ingredient of turmeric rhizome, has been shown in several preclinical studies and uncontrolled clinical trials as having effects on gut inflammation, gut permeability and the brain-gut axis, especially in FGIDs. Prebiotics, the non-digestible food ingredients in dietary fiber, may serve as nutrients and selectively stimulate the growth and/or activity of certain colonic bacteria. The net effect of this change on colonic microbiota may lead to the production of acidic metabolites and other compounds that help to reduce the production of toxins and suppress the growth of harmful or disease-causing enteric pathogens. Although some clinical benefit in IBS has been shown, high dose intake of prebiotics may cause more bloating from bacterial fermentation.

Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease

PubMed Central

Lauterbach, Edward C.

2013-01-01

Psychotropics (antipsychotics, mood stabilizers, antidepressants, anxiolytics, etc.) are commonly prescribed to treat Huntington’s disease (HD). In HD preclinical models, while no psychotropic has convincingly affected huntingtin gene, HD modifying gene, or huntingtin protein expression, psychotropic neuroprotective effects include upregulated huntingtin autophagy (lithium), histone acetylation (lithium, valproate, lamotrigine), miR-222 (lithium-plus-valproate), mitochondrial protection (haloperidol, trifluoperazine, imipramine, desipramine, nortriptyline, maprotiline, trazodone, sertraline, venlafaxine, melatonin), neurogenesis (lithium, valproate, fluoxetine, sertraline), and BDNF (lithium, valproate, sertraline) and downregulated AP-1 DNA binding (lithium), p53 (lithium), huntingtin aggregation (antipsychotics, lithium), and apoptosis (trifluoperazine, loxapine, lithium, desipramine, nortriptyline, maprotiline, cyproheptadine, melatonin). In HD live mouse models, delayed disease onset (nortriptyline, melatonin), striatal preservation (haloperidol, tetrabenazine, lithium, sertraline), memory preservation (imipramine, trazodone, fluoxetine, sertraline, venlafaxine), motor improvement (tetrabenazine, lithium, valproate, imipramine, nortriptyline, trazodone, sertraline, venlafaxine), and extended survival (lithium, valproate, sertraline, melatonin) have been documented. Upregulated CREB binding protein (CBP; valproate, dextromethorphan) and downregulated histone deacetylase (HDAC; valproate) await demonstration in HD models. Most preclinical findings await replication and their limitations are reviewed. The most promising findings involve replicated striatal neuroprotection and phenotypic disease modification in transgenic mice for tetrabenazine and for sertraline. Clinical data consist of an uncontrolled lithium case series (n = 3) suggesting non-progression and a primarily negative double-blind, placebo-controlled clinical trial of lamotrigine. PMID:24248060

AB012. Current burden of uncontrolled asthma in the general population: the OPCRD asthma state of the Union study

PubMed Central

Nibber, Anjan; Thomas, Mike; Thomas, Vicky; van Aalderen, Wim; Bleecker, Eugene; Campbell, Jonathan; Roche, Nicolas; Haughney, John; Van Ganse, Eric; Park, Hye-Yun; Rhee, Chin Kook; Skinner, Derek; Chisholm, Alison; van Boven, Job FM; Soriano, Joan B.; Price, David

2016-01-01

Background Questionnaire-based surveys report that uncontrolled asthma is common in Europe, and associated with high healthcare costs. The relationship between treatment step control are less well described. To quantify the asthma burden within routine primary care in the UK, specifically the distribution of asthma control across guideline-recommended management steps and the association between patients’ control and smoking status. Methods Patients were retrospectively identified using the Optimum Patient Care Research Database and prospectively followed-up for at least 1-year. Patients’ routine clinical data and self reports were used to assess GINA control status; clinical records were used to categorise current treatment by GINA management steps and patients’ smoking status. Results A total of 105,018 eligible asthma patients were identified, mean (SD) age 45 (23) years; 55% female; 15% current and 24% ex-smokers. Only 20% of patients were controlled, 59% were partially controlled and 21% were uncontrolled. Control was only weakly correlated to GINA management steps (Spearman’s rho=0.15, P<0.001), 27.5%, 21.5%, 20.3%, 15.1% and 12.1% achieving control across Step 1 to 5, respectively. Similarly, the proportion with uncontrolled asthma rose across higher GINA steps (12.6%, 18.2%, 19.6%, 29.2% and 36.6%). About 13% of patients experienced at least one exacerbation in the 1-year follow-up period. Frequent exacerbations (2 or more per year) were very uncommon at lower treatment steps (step 1 11.6%, step 2 12.8%) but were significantly more common at steps 3 and 4 at 18.8% and 28.2% respectively (P<0.001 for trend with ascending treatment step). Conclusions In this cohort of UK primary care asthma patients, the majority failed to achieve GINA defined control. GINA management step was only weakly correlated with control status, but higher step management was associated with a greater risk of exacerbation.

Efficacy and Safety of Fluticasone Furoate/Vilanterol Compared With Fluticasone Propionate/Salmeterol Combination in Adult and Adolescent Patients With Persistent Asthma

PubMed Central

Bleecker, Eugene R.; Lötvall, Jan; O’Byrne, Paul M.; Bateman, Eric D.; Medley, Hilary; Ellsworth, Anna; Jacques, Loretta; Busse, William W.

2013-01-01

Background: The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on a medium dose of ICS. Methods: In a randomized, double-blind, double-dummy, parallel group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment. Results: Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (341 mL) and FP/SAL (377 mL); the adjusted mean treatment difference was not statistically significant (−37 mL; 95% CI, −88 to 15, P = 0.162). There were no differences between 0- to 4-h serial wmFEV1, trough FEV1, and asthma control and quality-of-life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs and no treatment-related serious adverse events. Conclusions: The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified. Trial registry: ClinicalTrials.gov; No.: NCT01147848; URL: www.clinicaltrials.gov PMID:23846316

DASH for asthma: A pilot study of the DASH diet in not-well-controlled adult asthma⋆

PubMed Central

Ma, Jun; Strub, Peg; Lavori, Phillip W.; Buist, A. Sonia; Camargo, Carlos A.; Nadeau, Kari C.; Wilson, Sandra R.; Xiao, Lan

2014-01-01

This pilot study aims to provide effect size confidence intervals, clinical trial and intervention feasibility data, and procedural materials for a full-scale randomized controlled trial that will determine the efficacy of Dietary Approaches to Stop Hypertension (DASH) as adjunct therapy to standard care for adults with uncontrolled asthma. The DASH diet encompasses foods (e.g., fresh fruit, vegetables, and nuts) and antioxidant nutrients (e.g., vitamins A, C, E, and zinc) with potential benefits for persons with asthma, but it is unknown whether the whole diet is beneficial. Participants (n = 90) will be randomized to receive usual care alone or combined with a DASH intervention consisting of 8 group and 3 individual sessions during the first 3 months, followed by at least monthly phone consultations for another 3 months. Follow-up assessments will occur at 3 and 6 months. The primary outcome measure is the 7-item Juniper Asthma Control Questionnaire, a validated composite measure of daytime and nocturnal symptoms, activity limitations, rescue medication use, and percentage predicted forced expiratory volume in 1 second. We will explore changes in inflammatory markers important to asthma pathophysiology (e.g., fractional exhaled nitric oxide) and their potential to mediate the intervention effect on disease control. We will also conduct pre-specified subgroup analyses by genotype (e.g., polymorphisms on the glutathione S transferase gene) and phenotype (e.g., atopy, obesity). By evaluating a dietary pattern approach to improving asthma control, this study could advance the evidence base for refining clinical guidelines and public health recommendations regarding the role of dietary modifications in asthma management. PMID:23648395

Cell-based interventions to halt autoimmunity in type 1 diabetes mellitus

PubMed Central

Barcala Tabarrozzi, A E; Castro, C N; Dewey, R A; Sogayar, M C; Labriola, L; Perone, M J

2013-01-01

Type 1 diabetes mellitus (T1DM) results from death of insulin-secreting β cells mediated by self-immune cells, and the consequent inability of the body to maintain insulin levels for appropriate glucose homeostasis. Probably initiated by environmental factors, this disease takes place in genetically predisposed individuals. Given the autoimmune nature of T1DM, therapeutics targeting immune cells involved in disease progress have been explored over the last decade. Several high-cost trials have been attempted to prevent and/or reverse T1DM. Although a definitive solution to cure T1DM is not yet available, a large amount of information about its nature and development has contributed greatly to both the improvement of patient's health care and design of new treatments. In this study, we discuss the role of different types of immune cells involved in T1DM pathogenesis and their therapeutic potential as targets and/or modified tools to treat patients. Recently, encouraging results and new approaches to sustain remnant β cell mass and to increase β cell proliferation by different cell-based means have emerged. Results coming from ongoing clinical trials employing cell therapy designed to arrest T1DM will probably proliferate in the next few years. Strategies under consideration include infusion of several types of stem cells, dendritic cells and regulatory T cells, either manipulated genetically ex vivo or non-manipulated. Their use in combination approaches is another therapeutic alternative. Cell-based interventions, without undesirable side effects, directed to block the uncontrollable autoimmune response may become a clinical reality in the next few years for the treatment of patients with T1DM. PMID:23286940

Improvement of Atrophic Acne Scars in Skin of Color Using Topical Synthetic Epidermal Growth Factor (EGF) Serum: A Pilot Study.

PubMed

Stoddard, Marie Alexia; Herrmann, Jennifer; Moy, Lauren; Moy, Ronald

2017-04-01

BACKGROUND: Atrophic scarring in skin of color is a common, permanent, and distressing result of uncontrolled acne vulgaris. Ablative lasers and chemical peels are frequently used to improve the appearance of atrophic scars, primarily through the stimulation of collagen and elastin; however, these treatment modalities are associated with risks, such as dyspigmentation and hypertrophic scarring, especially in patients with darker skin.

OBJECTIVE: We evaluated the efficacy of topically applied synthetic epidermal growth factor (EGF) serum in reducing the appearance of atrophic acne scars in skin of color.

METHODS: A single-center clinical trial was performed on twelve healthy men and women (average age 32.5) with Fitzpatrick Type IV-V skin and evidence of facial grade II-IV atrophic acne scars. Subjects applied topical EGF serum to the full-face twice daily for 12 weeks. Scar improvement was investigated at each visit using an Investigator Global Assessment (IGA), a Goodman grade, clinical photography, and patient self-assessment.

RESULTS: Eleven subjects completed the trial. Compared to baseline, there was an improvement in mean IGA score from 3.36 (SEM = 0.15) to 2.18 (SEM = 0.33). Mean Goodman grade was reduced from 2.73 (SEM = 0.19) to 2.55 (SEM = 0.21). Of the eleven pairs of before and after photographs, nine were correctly chosen as the post-treatment image by a blind investigator. On self-assessment, 81% reported a "good" to "excellent" improvement in their scars compared to baseline (P = 0.004).

CONCLUSION: Topical EGF may improve the appearance of atrophic acne scars in skin of color. Additional, larger studies should be conducted to better characterize improvement.

J Drugs Dermatol. 2017;16(4):322-326.

Design, rationale, and baseline characteristics of a cluster randomized controlled trial of pay for performance for hypertension treatment: study protocol.

PubMed

Petersen, Laura A; Urech, Tracy; Simpson, Kate; Pietz, Kenneth; Hysong, Sylvia J; Profit, Jochen; Conrad, Douglas; Dudley, R Adams; Lutschg, Meghan Z; Petzel, Robert; Woodard, Lechauncy D

2011-10-03

Despite compelling evidence of the benefits of treatment and well-accepted guidelines for treatment, hypertension is controlled in less than one-half of United States citizens. This randomized controlled trial tests whether explicit financial incentives promote the translation of guideline-recommended care for hypertension into clinical practice and improve blood pressure (BP) control in the primary care setting. Using constrained randomization, we assigned 12 Veterans Affairs hospital outpatient clinics to four study arms: physician-level incentive; group-level incentive; combination of physician and group incentives; and no incentives (control). All participants at the hospital (cluster) were assigned to the same study arm. We enrolled 83 full-time primary care physicians and 42 non-physician personnel. The intervention consisted of an educational session about guideline-recommended care for hypertension, five audit and feedback reports, and five disbursements of incentive payments. Incentive payments rewarded participants for chart-documented use of guideline-recommended antihypertensive medications, BP control, and appropriate responses to uncontrolled BP during a prior four-month performance period over the 20-month intervention. To identify potential unintended consequences of the incentives, the study team interviewed study participants, as well as non-participant primary care personnel and leadership at study sites. Chart reviews included data collection on quality measures not related to hypertension. To evaluate the persistence of the effect of the incentives, the study design includes a washout period. We briefly describe the rationale for the interventions being studied, as well as the major design choices. Rigorous research designs such as the one described here are necessary to determine whether performance-based payment arrangements such as financial incentives result in meaningful quality improvements. http://www.clinicaltrials.govNCT00302718.

Detecting Motor Impairment in Early Parkinson's Disease via Natural Typing Interaction With Keyboards: Validation of the neuroQWERTY Approach in an Uncontrolled At-Home Setting.

PubMed

Arroyo-Gallego, Teresa; Ledesma-Carbayo, María J; Butterworth, Ian; Matarazzo, Michele; Montero-Escribano, Paloma; Puertas-Martín, Verónica; Gray, Martha L; Giancardo, Luca; Sánchez-Ferro, Álvaro

2018-03-26

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and one of the most common forms of movement disorder. Although there is no known cure for PD, existing therapies can provide effective symptomatic relief. However, optimal titration is crucial to avoid adverse effects. Today, decision making for PD management is challenging because it relies on subjective clinical evaluations that require a visit to the clinic. This challenge has motivated recent research initiatives to develop tools that can be used by nonspecialists to assess psychomotor impairment. Among these emerging solutions, we recently reported the neuroQWERTY index, a new digital marker able to detect motor impairment in an early PD cohort through the analysis of the key press and release timing data collected during a controlled in-clinic typing task. The aim of this study was to extend the in-clinic implementation to an at-home implementation by validating the applicability of the neuroQWERTY approach in an uncontrolled at-home setting, using the typing data from subjects' natural interaction with their laptop to enable remote and unobtrusive assessment of PD signs. We implemented the data-collection platform and software to enable access and storage of the typing data generated by users while using their computer at home. We recruited a total of 60 participants; of these participants 52 (25 people with Parkinson's and 27 healthy controls) provided enough data to complete the analysis. Finally, to evaluate whether our in-clinic-built algorithm could be used in an uncontrolled at-home setting, we compared its performance on the data collected during the controlled typing task in the clinic and the results of our method using the data passively collected at home. Despite the randomness and sparsity introduced by the uncontrolled setting, our algorithm performed nearly as well in the at-home data (area under the receiver operating characteristic curve [AUC] of 0.76 and sensitivity/specificity of 0.73/0.69) as it did when used to evaluate the in-clinic data (AUC 0.83 and sensitivity/specificity of 0.77/0.72). Moreover, the keystroke metrics presented a strong correlation between the 2 typing settings, which suggests a minimal influence of the in-clinic typing task in users' normal typing. The finding that an algorithm trained on data from an in-clinic setting has comparable performance with that tested on data collected through naturalistic at-home computer use reinforces the hypothesis that subtle differences in motor function can be detected from typing behavior. This work represents another step toward an objective, user-convenient, and quasi-continuous monitoring tool for PD. ©Teresa Arroyo-Gallego, María J Ledesma-Carbayo, Ian Butterworth, Michele Matarazzo, Paloma Montero-Escribano, Verónica Puertas-Martín, Martha L Gray, Luca Giancardo, Álvaro Sánchez-Ferro. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.03.2018.

Prevalence and clinical characteristics of patients with true resistant hypertension in central and Eastern Europe: data from the BP-CARE study.

PubMed

Brambilla, Gianmaria; Bombelli, Michele; Seravalle, Gino; Cifkova, Renata; Laurent, Stephane; Narkiewicz, Krzysztof; Facchetti, Rita; Redon, Josep; Mancia, Giuseppe; Grassi, Guido

2013-10-01

Scanty information is available on the clinical characteristics of resistant hypertension in Central and East European countries. The Blood Pressure (BP) control rate and CArdiovascular Risk profilE (BP-CARE) study allowed us to assess the prevalence and the main clinical features of resistant hypertension in this population. The study was carried out in 1312 treated hypertensive patients living in nine Central and East European countries. Four hundred and twenty-three patients had apparent resistant hypertension, of whom 168 had pseudo-resistant hypertension (noncompliant/white-coat) and 255 were true treatment-resistant hypertension patients (TRH). Clinical BP values in TRH amounted to 157.4±16.9/91.8±10.0 mmHg despite the daily use of 3.6±0.7 drugs. Their 24-h BP values were 149.5±16.5/97.5±9.8 mmHg. Compared to controlled hypertensive patients (n=368) and uncontrolled nonresistant hypertensive patients (n=521), TRH were older with a greater prevalence of women. They showed a higher rate of previous cardiovascular events and a very high cardiovascular risk profile. Estimated glomerular filtration rate was significantly lower in TRH as compared to controlled hypertensive patients and uncontrolled nonresistant hypertensive patients. Overall, target organ damage was more frequently detected in TRH than in controlled hypertensive patients and uncontrolled nonresistant hypertensive patients. The factor most frequently associated with TRH was severity of hypertension followed by age, total cholesterol, BMI and history of heart failure. The present study provides evidence that the prevalence of TRH in Central and East European countries is similar to that found in Western Europe and USA. It also shows the very high cardiovascular risk of TRH and the elevated association of this condition with obesity, renal failure, organ damage and history of cardiovascular events.

Ambulatory blood pressure parameters after canrenone addition to existing treatment regimens with maximum tolerated dose of angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor blockers plus hydrochlorothiazide in uncontrolled hypertensive patients.

PubMed

Guasti, Luigina; Gaudio, Giovanni; Lupi, Alessandro; D'Avino, Marinella; Sala, Carla; Mugellini, Amedeo; Vulpis, Vito; Felis, Salvatore; Sarzani, Riccardo; Vanasia, Massimo; Maffioli, Pamela; Derosa, Giuseppe

2017-01-01

Blockade of the renin-angiotensin-aldosterone system is a cornerstone in cardiovascular disease prevention and hypertension treatment. The relevance of ambulatory blood pressure monitoring (ABPM) has been widely confirmed for both increasing the accuracy of blood pressure (BP) measurements, particularly in pharmacological trials, and focusing on 24 h BP prognostic parameters. The aim of this study was to assess the effects of canrenone addition on ambulatory BP in uncontrolled hypertensive patients already treated with the highest tolerated dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor (AT1R) antagonists plus hydrochlorothiazide (HCT). ABPM was performed at baseline and after 3 months of combination therapy in 158 outpatients with stage 1 or 2 hypertension who were randomized to add canrenone (50 or 100 mg) to the pre-existing therapy with ACE inhibitors or AT1R antagonists plus HCT. Twenty-four-hour systolic and diastolic BPs were considered normalized when the values were <130 and <80 mmHg, respectively. The addition of canrenone was associated with a reduction in systolic and diastolic BPs (24 h and daytime and nighttime; P <0.001), mean arterial pressures ( P <0.001), and pulse pressures ( P <0.01). The Δ 24 h systolic/diastolic BPs were -13.5±11.2/-8±8 mmHg and -16.1±13.5/-11.2±8.3 mmHg (50 and 100 mg/day, respectively). In the 50 mg arm, the 24 h systolic and diastolic BPs were normalized in 67.5% and 74% of the patients, respectively, and in 61.6% and 68.5% of the patients in the 100 mg arm, respectively ( P <0.05; P = not significant for 50 vs 100 mg). The percentage of patients whose nocturnal decrease was >10% with respect to diurnal values did not change during combination therapy. Canrenone addition to ACE inhibitors or AT1R antagonists plus HCT was associated with a significant reduction of 24 h BP and to an increased number of patients meeting 24 h ABPM targets in a clinical setting of uncontrolled stage 1 or 2 hypertension.

Anti-vascular endothelial growth factor for neovascular glaucoma

PubMed Central

Simha, Arathi; Braganza, Andrew; Abraham, Lekha; Samuel, Prasanna; Lindsley, Kristina

2014-01-01

Background Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the formation of abnormal new blood vessels which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG. Objectives To compare the IOP lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of NVG. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 January 2013. Selection criteria We included randomized controlled trials (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG. Data collection and analysis Two authors independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion with a third author. Since no trial met our inclusion criteria, no assessment of risk of bias or meta-analysis was undertaken. Main results No RCTs were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF agents for treating NVG were not included in the review due to the heterogeneity and uncontrolled assignment of adjunct treatments received by the study participants. Authors’ conclusions Currently available evidence is insufficient to evaluate the effectiveness of anti-VEGF treatments, such as intravitreal ranibizumab or bevacizumab, as an adjunct to conventional treatment in lowering IOP in NVG. Well designed RCTs are needed to address this issue, particularly trials that evaluate long-term (at least six months) benefits and risks since the effects of anti-VEGF agents may be short-term only. An RCT comparing anti-VEGF agents with no anti-VEGF agents taking into account the need for co-interventions, such as panretinal photocoagulation (PRP), glaucoma shunt procedures, cyclodestructive procedures, cataract surgery, and deep vitrectomy, could be of use to investigate the additional beneficial effect of anti-VEGF agents in treating NVG. Since decisions for when and which co-interventions should be used are based on clinical criteria, they would not be appropriate for randomization. However, the design of a study on this topic should aim to balance groups by stratification of co-intervention at time of randomization or by enrolling a sufficient number of participants to conduct subgroup analysis by co-interventions (ideally 15 participants per treatment group for each subgroup). Alternatively, the inclusion criteria for a trial could limit participants to those who receive the same co-intervention. PMID:24089293

Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies

PubMed Central

Mameniškienė, Rūta; Quarato, Pier Paolo; Klein, Pavel; Gamage, Jessica; Schiemann, Jimmy; Johnson, Martin E.; Whitesides, John; McDonough, Belinda; Eckhardt, Klaus

2016-01-01

Objective: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. Methods: Data were pooled from patients (aged 16–80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. Results: In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%–29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%–31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%–31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). Conclusions: Adjunctive BRV was effective and generally well tolerated in adults with POS. Classification of evidence: This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures. PMID:27335114

SOLITAIRE™ with the intention for thrombectomy (SWIFT) trial: design of a randomized, controlled, multicenter study comparing the SOLITAIRE™ Flow Restoration device and the MERCI Retriever in acute ischaemic stroke.

PubMed

Saver, J L; Jahan, R; Levy, E I; Jovin, T G; Baxter, B; Nogueira, R; Clark, W; Budzik, R; Zaidat, O O

2014-07-01

Self-expanding stent retrievers are a promising new device class designed for rapid flow restoration in acute cerebral ischaemia. The SOLITAIRE™ Flow Restoration device (SOLITAIRE) has shown high rates of recanalization in preclinical models and in uncontrolled clinical series. (1) To demonstrate non-inferiority of SOLITAIRE compared with a legally marketed device, the MERCI Retrieval System®; (2) To demonstrate safety, feasibility, and efficacy of SOLITAIRE in subjects requiring mechanical thrombectomy diagnosed with acute ischaemic stroke. DESIGN : Multicenter, randomized, prospective, controlled trial with blinded primary end-point ascertainment. Key entry criteria include: age 22-85; National Institute of Health Stroke Scale (NIHSS) ≥8 and <30; clinical and imaging findings consistent with acute ischaemic stroke; patient ineligible or failed intravenous tissue plasminogen activator; accessible occlusion in M1 or M2 middle cerebral artery, internal carotid artery, basilar artery, or vertebral artery; and patient able to be treated within 8 h of onset. Sites first participate in a roll-in phase, treating two patients with the SOLITAIRE device, before proceeding to the randomized phase. In patients unresponsive to the initially assigned therapy, after the angiographic component of the primary end-point is ascertained (reperfusion with the initial assigned device), rescue therapy with other reperfusion techniques is permitted. The primary efficacy end-point is successful recanalization with the assigned study device (no use of rescue therapy) and with no symptomatic intracranial haemorrhage. Successful recanalization is defined as achieving Thrombolysis In Myocardial Ischemia 2 or 3 flow in all treatable vessels. The primary safety end-point is the incidence of device-related and procedure-related serious adverse events. A major secondary efficacy end-point is time to achieve initial recanalization. Additional secondary end-points include clinical outcomes at 90 days and radiologic haemorrhagic transformation. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma: an open phase I/II study with a first assessment of a predictive gene signature.

PubMed

Grob, Jean-Jacques; Mortier, Laurent; D'Hondt, Lionel; Grange, Florent; Baurain, Jean Francois; Dréno, Brigitte; Lebbe, Céleste; Robert, Caroline; Dompmartin, Anne; Neyns, Bart; Gillet, Marc; Louahed, Jamila; Jarnjak, Silvija; Lehmann, Frédéric F

2017-01-01

We assessed safety, immunogenicity and clinical activity of recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) in association with dacarbazine in patients with metastatic melanoma. In this open-label, phase I/II, uncontrolled multicentre trial conducted in Belgium and France, patients with MAGE-A3-positive melanoma received up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with eight doses of dacarbazine. Adverse events (AE) were recorded until 31 days postvaccination, and serious AEs (SAE), until 30 days following the last dose. MAGE-A3-specific antibodies were measured by ELISA. Clinical activity of MAGE-A3 immunotherapeutic was assessed in patients positive/negative for previously identified gene signature (GS) associated with clinical outcome. Forty-eight patients were enrolled and treated (32 GS+, 15 GS-, 1 unknown GS status); two patients completed the study. All patients reported AEs, the most common were 'general disorders and administration site conditions' (94%). Treatment-related AEs were reported by 85% of patients; the most common was pain at injection site (38%). Sixteen SAEs were reported by 21% of patients; two were considered as treatment related (neutropenia and thrombocytopenia; grade 4). Postdose 4, all patients were seropositive for MAGE-A3-specific antibodies, with a geometric mean titre of 2778.7 ELISA units (EU)/mL (95% CI 1638.3 to 4712.8). One complete and three partial responses were reported (only in GS+ patients). Median overall survival was 11.4 months for GS+ and 5.3 months for GS- patients. Although this trial shows poor results compared with the new results with checkpoint inhibitors, it gives an interesting insight in rapidly developing fields like combinations of immunotherapy and chemotherapy, new generation vaccines and the use of gene profile as a predictive marker. NCT00849875.

Evaluation and Management of the Child with Thyrotoxicosis.

PubMed

Leung, Alexander K C; Leung, Alexander A C

2018-03-26

Uncontrolled thyrotoxicosis, especially in early infancy, may cause irreversible damage to the central nervous system as well as profound effects on the function of many organs. Thyrotoxicosis has multiple etiologies and treatment depends on the underlying etiology. An accurate diagnosis is essential so that appropriate treatment can be initiated without undue delay. To review in depth the evaluation, diagnosis, and treatment of children with thyrotoxicosis. A PubMed search was completed in Clinical Queries using the key terms "thyrotoxicosis" and "hyperthyroidism". The search strategy included meta-analysis, randomized controlled trials, clinical trials, observational studies, and reviews. Patents were searched using the key terms "thyrotoxicosis" and "hyperthyroidism" from www.freepatentsonline.com and www.google.com/patents. Graves' disease accounts for approximately 96% of pediatric cases of thyrotoxicosis. Other causes include Hashitoxicosis, toxic adenoma, toxic multinodular goiter, subacute granulomatous thyroiditis, acute suppurative thyroiditis, pituitary thyroid-stimulating hormone-secreting adenoma, pituitary thyroid hormone resistance, iodine-induced thyrotoxicosis, and drug-induced thyrotoxicosis. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. The underlying cause of thyrotoxicosis should be treated if possible. Treatment options for Graves' disease include antithyroid medications, radioiodine therapy, and surgery. Recent patents related to the management of thyrotoxicosis are discussed. Currently, antithyroid medications are considered to be the initial treatment of choice for Graves' disease in the pediatric age group. Radioactive iodine treatment is generally used for children with poor compliance with antithyroid medications, children not in remission after 1 to 2 years of antithyroid medications, and children with a major adverse effect while receiving an antithyroid medication. Total or near-total thyroidectomy should be considered in children younger than 5 years of age who do not respond to or experience a major adverse effect to antithyroid medications. Surgery should also be considered in those with very large goiter, severe ophthalmopathy, pregnancy, persistent hyperthyroidism in spite of treatment with antithyroid medications and radioactive iodine, and personal preference. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anxiety and depression in asthma patients: impact on asthma control.

PubMed

Vieira, Aline Arlindo; Santoro, Ilka Lopes; Dracoulakis, Samir; Caetano, Lilian Ballini; Fernandes, Ana Luisa Godoy

2011-01-01

There is evidence that asthma is associated with an increase in psychiatric symptoms and mental disorders. This association can make it difficult to achieve asthma control. The purpose of this study was to determine whether the level of asthma control is associated with anxiety and depression. A crosssectional study involving 78 patients with confirmed moderate or severe asthma and under regular treatment at the Asthma Outpatient Clinic of the Federal University of São Paulo Hospital São Paulo, in the city of São Paulo, Brazil. The patients were divided into two groups by asthma control status, as assessed by the asthma control test, and were subsequently compared in terms of demographic, clinical, and spirometric data, as well as scores for asthma quality of life and hospital anxiety/depression. The sample was predominantly female. Of the 78 patients, 49 (63%) were classified as having uncontrolled asthma. The prevalence of anxiety and of anxiety+depression was significantly higher among patients with uncontrolled asthma than among those with controlled asthma (78% and 100%; p = 0.04 and p = 0.02, respectively), whereas there were no differences between the two groups in terms of the prevalence of depression, spirometry results, or quality of life score. In this sample, the prevalence of anxiety symptoms was higher in the patients with uncontrolled asthma than in those with controlled asthma.In the evaluation of asthma patients, the negative impact of mood states ought to be taken into consideration when asthma control strategies are being outlined.

[Control of asthma symptoms and cellular markers of inflammation in induced sputum in children and adolescents with chronic asthma].

PubMed

Ciółkowski, Janusz; Stasiowska, Barbara; Mazurek, Henryk

2009-03-01

After the GINA 2006 publication, asthma therapy is based on control of symptoms. However there are suggestions of monitoring of airway inflammation. Aim of the study was to compare clinical criteria of asthma control with cellular markers of lower airway inflammation in induced sputum in a group of young asthmatics. To assess relationship between sputum eosinophilia, asthma severity and spirometry. A group of 154 young patients with chronic asthma (8-21 years) underwent sputum induction by inhalation of 4,5% saline solution. Sputum induction was effective in 121 patients (78%), and in this group control of clinical symptoms was assessed according to GINA 2006 criteria. Asthma was controlled in 82 subjects (67.8%) and uncontrolled in 39 (32.2%). Patients with controlled asthma had higher FEV1/FVC (79.8 +/- 7.1% vs 74.2 +/- 9.9%; p = 0.004) and MMEF (80.7 +/- 23.0% vs 65.3 +/- 21.8%; p < 0.001) than those with uncontrolled disease, but the average FEV1 (as percent predicted) did not differ between the two groups. Patients with controlled asthma had lower sputum eosinophil count than those with uncontrolled asthma (3.5 +/- 6.3% vs 7.2 +/- 8.7%; p = 0.01), but difference in neutrophil count was borderline (27.3 +/- 15.5% vs 34.5 +/- 21.0%; p = 0.05). High sputum eosinophil count (> 3%) was observed in 24.4% of patients with controlled asthma and in 61.5% with uncontrolled asthma (p < 0.001). Increased sputum neutrophil count was more frequent in a group of uncontrolled asthma (2.4 vs 15.4%; p = 0.022). Mean sputum eosinophil count was lower in patients with mild astma than in patients with moderate-severe disease (3.1 +/- 5.7% vs 7.1% +/- 8.8; p = 0.006). Patients with high sputum eosinophil count had lower FEV1 (89.4 +/- 14.9% vs 94.9 +/- 13.9%; p = 0.047), FEV1/FVC (74.5 +/- 10.1% vs 79.2 +/- 9.3%; p = 0.01) and MMEF (68.7 +/- 23.3% vs 81.7 +/- 23.1%; p = 0.004). In this study of young asthmatics, control of asthma symptoms was observed in 67.8% of patients. However, cellular markers of lower airway inflammation were present in 1/4 of patients with controlled asthma and in 3/4 with uncontrolled disease. Sputum eosinophilia was related to asthma severity. FEV1/FVC and MMEF were more important that FEV1 for estimating control of asthma. Improvement of asthma control scoring is needed as well as availability of simple methods of inflammation monitoring.

Baclofen for alcohol withdrawal.

PubMed

Liu, Jia; Wang, Lu-Ning

2017-08-20

Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4. To assess the efficacy and safety of baclofen for people with AWS. We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. We used standard methodological procedures expected by Cochrane. We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no significant difference in CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low quality evidence), adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence). No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low quality evidence.

Preflight screening techniques for centrifuge-simulated suborbital spaceflight.

PubMed

Pattarini, James M; Blue, Rebecca S; Castleberry, Tarah L; Vanderploeg, James M

2014-12-01

Historically, space has been the venue of the healthy individual. With the advent of commercial spaceflight, we face the novel prospect of routinely exposing spaceflight participants (SPFs) with multiple comorbidities to the space environment. Preflight screening procedures must be developed to identify those individuals at increased risk during flight. We examined the responses of volunteers to centrifuge accelerations mimicking commercial suborbital spaceflight profiles to evaluate how potential SFPs might tolerate such forces. We evaluated our screening process for medical approval of subjects for centrifuge participation for applicability to commercial spaceflight operations. All registered subjects completed a medical questionnaire, physical examination, and electrocardiogram. Subjects with identified concerns including cardiopulmonary disease, hypertension, and diabetes were required to provide documentation of their conditions. There were 335 subjects who registered for the study, 124 who completed all prescreening, and 86 subjects who participated in centrifuge trials. Due to prior medical history, five subjects were disqualified, most commonly for psychiatric reasons or uncontrolled medical conditions. Of the subjects approved, four individuals experienced abnormal physiological responses to centrifuge profiles, including one back strain and three with anxiety reactions. The screening methods used were judged to be sufficient to identify individuals physically capable of tolerating simulated suborbital flight. Improved methods will be needed to identify susceptibility to anxiety reactions. While severe or uncontrolled disease was excluded, many subjects successfully participated in centrifuge trials despite medical histories of disease that are disqualifying under historical spaceflight screening regimes. Such screening techniques are applicable for use in future commercial spaceflight operations.

Targeted gene insertion for molecular medicine.

PubMed

Voigt, Katrin; Izsvák, Zsuzsanna; Ivics, Zoltán

2008-11-01

Genomic insertion of a functional gene together with suitable transcriptional regulatory elements is often required for long-term therapeutical benefit in gene therapy for several genetic diseases. A variety of integrating vectors for gene delivery exist. Some of them exhibit random genomic integration, whereas others have integration preferences based on attributes of the targeted site, such as primary DNA sequence and physical structure of the DNA, or through tethering to certain DNA sequences by host-encoded cellular factors. Uncontrolled genomic insertion bears the risk of the transgene being silenced due to chromosomal position effects, and can lead to genotoxic effects due to mutagenesis of cellular genes. None of the vector systems currently used in either preclinical experiments or clinical trials displays sufficient preferences for target DNA sequences that would ensure appropriate and reliable expression of the transgene and simultaneously prevent hazardous side effects. We review in this paper the advantages and disadvantages of both viral and non-viral gene delivery technologies, discuss mechanisms of target site selection of integrating genetic elements (viruses and transposons), and suggest distinct molecular strategies for targeted gene delivery.

2015 Oman Heart Association guidelines for the management of hypertension : practical recommendations from the Oman Heart Association (OHA).

PubMed

El-Deeb, Mohammed H; Sulaiman, Kadhim J; Al-Riyami, Abdullah A; Mohsin, Nabil; Al-Mukhaini, Mohamed; Al-Lamki, Mohamed; Al-Busaidi, Noor; Al-Salmi, Issa; Al-Lawati, Jawad; Al-Rawahi, Najib; Al-Riyami, Mohamed B; Abdul-Rahman, Said; Al-Hinai, Said; Jaffer, Batool; Al-Wahaebi, Ahmed; Al-Khalili, Hanan; Al-Zadjali, Matllooba

2015-03-01

Hypertension (HTN) is a major independent risk factor for the development of stroke, coronary artery disease (CAD), peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD). HTN is a growing public health problem in Oman, almost certainly the most prevalent modifiable risk factor for cardiovascular disease (CVD). The risk of CVD in patients with HTN can be greatly reduced with lifestyle modifications and effective antihypertensive therapy. Randomized trials have shown that blood pressure (BP) lowering produces rapid reductions in CV risk. Several studies have shown that the majority of the hypertensive patients remain uncontrolled. It is well established that the observed poor control of the disease is not only related to poor adherence to medications, but also to limited awareness and adherence to evidence-based management of hypertension among physicians. Several guidelines for the management of patients with hypertension have been published. However, the aim of this document is to provide the busy physicians in Oman with more concise and direct approach towards implementing these guidelines into clinical practice.

A randomized trial of peer coach and office staff support to reduce coronary heart disease risk in African-Americans with uncontrolled hypertension.

PubMed

Turner, Barbara J; Hollenbeak, Christopher S; Liang, Yuanyuan; Pandit, Kavita; Joseph, Shelly; Weiner, Mark G

2012-10-01

Adopting features of the Chronic Care Model may reduce coronary heart disease risk and blood pressure in vulnerable populations. We evaluated a peer and practice team intervention on reduction in 4-year coronary heart disease risk and systolic blood pressure. A single blind, randomized, controlled trial in two adjacent urban university-affiliated primary care practices. Two hundred eighty African-American subjects aged 40 to 75 with uncontrolled hypertension. Three monthly calls from trained peer patients with well-controlled hypertension and, on alternate months, two practice staff visits to review a personalized 4-year heart disease risk calculator and slide shows about heart disease risks. All subjects received usual physician care and brochures about healthy cooking and heart disease. Change in 4-year coronary heart disease risk (primary) and change in systolic blood pressure, both assessed at 6 months. At baseline, the 136 intervention and 144 control subjects' mean 4-year coronary heart disease risk did not differ (intervention=5.8 % and control=6.4 %, P=0.39), and their mean systolic blood pressure was the same (140.5 mmHg, p=0.83). Endpoint data for coronary heart disease were obtained for 69 % of intervention and 82 % of control subjects. After multiple imputation for missing endpoint data, the reduction in risk among all 280 subjects favored the intervention, but was not statistically significant (difference -0.73 %, 95 % confidence interval: -1.54 % to 0.09 %, p=0.08). Among the 247 subjects with a systolic blood pressure endpoint (85 % of intervention and 91 % of control subjects), more intervention than control subjects achieved a >5 mmHg reduction (61 % versus 45 %, respectively, p=0.01). After multiple imputation, the absolute reduction in systolic blood pressure was also greater for the intervention group (difference -6.47 mmHg, 95 % confidence interval: -10.69 to -2.25, P=0.003). One patient died in each study arm. Peer patient and office-based behavioral support for African-American patients with uncontrolled hypertension did not result in a significantly greater reduction in coronary heart disease risk but did significantly reduce systolic blood pressure.

A Pharmacy Student-Facilitated Interprofessional Diabetes Clinic With the Penobscot Nation.

PubMed

Martin, Sarah Levin; Williams, Evan; Huerth, Benjamin; Robinson, J Daniel

2015-11-05

American Indians/Alaska Natives have a greater increased risk for diabetes than non-Hispanic whites. Lifestyle interventions are effective in preventing and treating diabetes, and an interprofessional approach is important in diabetes management. The Penobscot Nation has a health center with a wide range of services. Our goal with the Nation was to 1) establish an interprofessional, student-facilitated diabetes clinic in the health center; 2) assess the clinic's preliminary impact. Relationship building and problem solving was instrumental in working toward the first goal. A survey was developed to assess satisfaction with the clinic. The clinical outcomes, mean and median values of HbA1c, were calculated at baseline (spring 2013) and were used to establish 2 groups of patients: those with controlled levels (<7%) and those with uncontrolled levels (≥ 7%). HbA1c was reassessed in fall 2013. Changes in HbA1c were calculated and compared using the Wilcoxon signed-rank test. The student-facilitated, interprofessional diabetes clinic has operated for 2 years, and changes are under way. More than 90% of participants reported being well satisfied with the clinic in the first year. Among the group with uncontrolled HbA1c (n = 18), mean HbA1c values declined from 9.3% to 7.6% (P = .004). Among the group with controlled HbA1c (n = 30), 83% were controlled at follow-up. The Penobscot diabetes clinic is evolving to meet the needs of community members, and pharmacy students have an interprofessional practice site well suited for experiential learning.

Comparison of Efficacy Between Endoscopic Cyclophotocoagulation and Alternative Surgeries in Refractory Glaucoma

PubMed Central

Yang, Yangfan; Zhong, Jing; Dun, Zhongjun; Liu, Xiao-an; Yu, Minbin

2015-01-01

Abstract Refractory glaucoma refers to uncontrolled intraocular pressure (IOP) despite anti-glaucoma medication and surgical treatment, which remains a challenge to be treated. The objective of this study is to evaluate and statistically compare the clinical efficacy between endoscopic cyclophotocoagulation (ECP) and alternative surgical techniques in the treatment of refractory glaucoma in this article, as a meta-analysis. Data sources are China Biomedical Database (Sinomed, online version), China National Knowledge Infrastructure (CNKI), Cqvip, Wanfang database, and PubMed. The randomized controlled trial (RCT) and case–control study literatures evaluating the clinical efficacy between ECP and other surgical techniques were searched electronically from public databases. The methodology quality of the retrieved articles was evaluated according to the RCT or case–control study criteria. The success rate of treatment, intraocular pressure (IOP) and visual acuity were statistically compared. RevMan 5.3 software was used for the meta-analysis. In total, 6 relevant control studies were selected in this study with a total sampling of 429 cases (429 eyes), including 204 eyes in the ECP group and 225 in the non-ECP group. Meta-analysis demonstrated that the clinical efficacy did not significantly differ between 2 groups (P > 0.05). Postoperative IOP was dramatically reduced in both groups. However, it was difficult to evaluate the combined influence of ECP and non-ECP therapies upon IOP reduction. In conclusion, ECP and non-ECP treatment yielded almost equivalent clinical efficacy in treating refractory glaucoma. The IOP-lowering degree, safety, and incidence of complications remain to be further elucidated by RCTs with a larger sample size. PMID:26426659

Couple Treatment for Alcohol Use Disorder and Posttraumatic Stress Disorder: Pilot Results From U.S. Military Veterans and Their Partners.

PubMed

Schumm, Jeremiah A; Monson, Candice M; O'Farrell, Timothy J; Gustin, Nancy G; Chard, Kathleen M

2015-06-01

We studied 13 U.S. male military veterans and their female partners who consented to participate in an uncontrolled trial of couple treatment for alcohol use disorder and posttraumatic stress disorder (CTAP). CTAP is a 15-session, manualized therapy, integrating behavioral couples therapy for alcohol use disorder (AUD) with cognitive-behavioral conjoint therapy for posttraumatic stress disorder (PTSD). Due to ineligibility (n = 1) and attrition (n = 3), 9 couples completed the study, and 7 completed 12 or more sessions. There were 8 veterans who showed clinically reliable pre- to posttreatment reduction of PTSD outcomes. There were also significant group-level reductions in clinician-, veteran-, and partner-rated PTSD symptoms (d = 0.94 to 1.71). Most veterans showed clinically reliable reductions in percentage days of heavy drinking. Group-level reduction in veterans' percentage days of heavy drinking was significant (d = 1.01). There were 4 veterans and 3 partners with clinically reliable reductions in depression, and group-level change was significant for veterans (d = 0.93) and partners (d = 1.06). On relationship satisfaction, 3 veterans and 4 partners had reliable improvements, and 2 veterans and 1 partner had reliable deterioration. Group-level findings were nonsignificant for veteran relationship satisfaction (d = 0.26) and for partners (d = 0.52). These findings indicate that CTAP may be a promising intervention for individuals with comorbid PTSD and AUD who have relationship partners. Copyright © 2015 Wiley Periodicals, Inc., A Wiley Company.

Can Chronic Disease Management Programs for Patients with Type 2 Diabetes Reduce Productivity-Related Indirect Costs of the Disease? Evidence from a Randomized Controlled Trial

PubMed Central

Bolin, Jane N.; Ohsfeldt, Robert L.; Phillips, Charles D.; Zhao, Hongwei; Ory, Marcia G.; Forjuoh, Samuel N.

2014-01-01

Abstract The objective was to assess the impacts of diabetes self-management programs on productivity-related indirect costs of the disease. Using an employer's perspective, this study estimated the productivity losses associated with: (1) employee absence on the job, (2) diabetes-related disability, (3) employee presence on the job, and (4) early mortality. Data were obtained from electronic medical records and survey responses of 376 adults aged ≥18 years who were enrolled in a randomized controlled trial of type 2 diabetes self-management programs. All study participants had uncontrolled diabetes and were randomized into one of 4 study arms: personal digital assistant (PDA), chronic disease self-management program (CDSMP), combined PDA and CDSMP, and usual care (UC). The human-capital approach was used to estimate lost productivity resulting from 1, 2, 3, and 4 above, which are summed to obtain total productivity loss. Using robust regression, total productivity loss was modeled as a function of the diabetes self-management programs and other identified demographic and clinical characteristics. Compared to subjects in the UC arm, there were no statistically significant differences in productivity losses among persons undergoing any of the 3 diabetes management interventions. Males were associated with higher productivity losses (+$708/year; P<0.001) and persons with greater than high school education were associated with additional productivity losses (+$758/year; P<0.001). Persons with more than 1 comorbid condition were marginally associated with lower productivity losses (-$326/year; P=0.055). No evidence was found that the chronic disease management programs examined in this trial affect indirect productivity losses. (Population Health Management 2014;17:112–120) PMID:24152055

Efficacy of the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program among patients with mild cognitive impairment: a randomized controlled crossover trial.

PubMed

Han, Ji Won; Son, Kyung Lak; Byun, Hye Jin; Ko, Ji Won; Kim, Kayoung; Hong, Jong Woo; Kim, Tae Hyun; Kim, Ki Woong

2017-06-06

Spaced retrieval training (SRT) is a nonpharmacological intervention for mild cognitive impairment (MCI) and dementia that trains the learning and retention of target information by recalling it over increasingly long intervals. We recently developed the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program as a convenient, self-administered tablet-based SRT program. We also demonstrated the utility of USMART for improving memory in individuals with MCI through an open-label uncontrolled trial. This study had an open-label, single-blind, randomized, controlled, two-period crossover design. Fifty patients with MCI were randomized into USMART-usual care and usual care-USMART treatment sequences. USMART was completed or usual care was provided biweekly over a 4-week treatment period with a 2-week washout period between treatment periods. Primary outcome measures included the Word List Memory Test, Word List Recall Test (WLRT), and Word List Recognition Test. Outcomes were measured at baseline, week 5, and week 11 by raters who were blinded to intervention type. An intention-to-treat analysis and linear mixed modeling were used. Of 50 randomized participants, 41 completed the study (18% dropout rate). The USMART group had larger improvements in WLRT score (effect size = 0.49, p = 0.031) than the usual care group. There were no significant differences in other primary or secondary measures between the USMART and usual care groups. Moreover, no USMART-related adverse events were reported. The 4-week USMART modestly improved information retrieval in older people with MCI, and was well accepted with minimal technical support. ClinicalTrials.gov NCT01688128 . Registered 12 September 2012.

The Development of a Social Networking–Based Relatedness Intervention Among Young, First-Time Blood Donors: Pilot Study

PubMed Central

Frye, Victoria; Duffy, Louisa; France, Janis L; Kessler, Debra A; Rebosa, Mark; Shaz, Beth H; Carlson, Bruce W

2018-01-01

Background Increasing repeat blood donation behavior is a critical public health goal. According to self-determination theory, the process of developing internal motivation to give blood and an associated self-identity as a blood donor may be promoted by feelings of “relatedness” or a connection to other donors, which may be enhanced through social relations and interactions. Objective The purpose of this report it to describe the development and pilot testing of a social networking-based (Facebook) intervention condition designed to increase feelings of relatedness via virtual social interaction and support. Methods To develop the intervention condition content, images, text, polls, and video content were assembled. Ohio University college students (N=127) rated the content (82 images/text) presented by computer in random order using a scale of one to five on various dimensions of relatedness. Mean ratings were calculated and analyses of variance were conducted to assess associations among the dimensions. Based on these results, the relatedness intervention was adapted and evaluated for feasibility, acceptability, and preliminary efficacy among 24 first-time donors, aged 18 to 24 years, in a 30-day pilot trial. Paired t-tests were conducted to examine change over time in relatedness and connectedness. Results The intervention condition that was developed was acceptable and feasible. Results of the uncontrolled, preintervention, and postintervention evaluation revealed that feelings of individual-level relatedness increased significantly after the intervention. Conclusions By promoting first-time blood donor relatedness, our goal is to enhance internal motivation for donating and the integration of the blood donor identity, thus increasing the likelihood of future repeat donation. Trial Registration ClinicalTrials.gov NCT02717338; https://clinicaltrials.gov/ct2/show/NCT02717338 (Archived by WebCite at http://www.webcitation.org/6ymHRBCwu) PMID:29699961

Glycaemic responses in Asian and non-Asian people with type 2 diabetes initiating insulin glargine 100 units/mL: A patient-level pooled analysis of 16 randomised controlled trials.

PubMed

Chan, Juliana C N; Bunnag, Pongamorn; Chan, Siew P; Tan, Iris T I; Tsai, Shih-Tzer; Gao, Ling; Landgraf, Wolfgang

2018-01-01

To compare outcomes between Asian and non-Asian patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetic drugs (OADs) initiating insulin glargine 100 units (U)/mL (Gla-100) in randomised controlled clinical trials. Post hoc analysis of patient-level data (Asian n = 235; non-Asian n = 3351) from 16 trials. At baseline, Asian patients were younger with lower body mass index (BMI), fasting C-peptide, and fasting plasma glucose (FPG) than non-Asian patients (all P < .001). Asian patients had a higher mean glycosylated haemoglobin (HbA1c) at Week 24 and less reduction in HbA1c from baseline (7.4% vs. 7.2%; -1.3% vs. -1.6%, respectively; P = .0001), and were less likely to achieve HbA1c <7.0% (40% vs. 47%; P = .002) than non-Asian patients. Reductions in FPG and rates of hypoglycaemia were similar between Asian and non-Asian patients. Asian patients had less weight gain than non-Asian patients (+1.3 vs. +1.9 kg, respectively, P = .013). In our post hoc meta-analysis, Gla-100 effectively lowers HbA1c and FPG in Asian patients with T2D uncontrolled on OADs with similar incidence of hypoglycaemia and less absolute weight gain compared with non-Asian patients. At a similar FPG reduction, fewer Asian patients achieved HbA1c target <7.0%, suggesting that prandial glucose needs to be addressed. Copyright © 2017. Published by Elsevier B.V.

Sensory re-education after nerve injury of the upper limb: a systematic review.

PubMed

Oud, Tanja; Beelen, Anita; Eijffinger, Elianne; Nollet, Frans

2007-06-01

To systematically review the available evidence for the effectiveness of sensory re-education to improve the sensibility of the hand in patients with a peripheral nerve injury of the upper limb. Studies were identified by an electronic search in the databases MEDLINE, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE, the Cochrane Library, the Physiotherapy Evidence Database (PEDro), and the database of the Dutch National Institute of Allied Health Professions (Doconline) and by screening the reference lists of relevant articles. Two reviewers selected studies that met the following inclusion criteria: all designs except case reports, adults with impaired sensibility of the hand due to a peripheral nerve injury of the upper limb, and sensibility and functional sensibility as outcome measures. The methodological quality of the included studies was independently assessed by two reviewers. A best-evidence synthesis was performed, based on design, methodological quality and significant findings on outcome measures. Seven studies, with sample sizes ranging from 11 to 49, were included in the systematic review and appraised for content. Five of these studies were of poor methodological quality. One uncontrolled study (N = 1 3 ) was considered to be of sufficient methodological quality, and one randomized controlled trial (N = 49) was of high methodological quality. Best-evidence synthesis showed that there is limited evidence for the effectiveness of sensory re-education, provided by a statistically significant improvement in sensibility found in one high-quality randomized controlled trial. There is a need for further well-defined clinical trials to assess the effectiveness of sensory re-education of patients with impaired sensibility of the hand due to a peripheral nerve injury.

Effectiveness of chronic obstructive pulmonary disease-management programs: systematic review and meta-analysis.

PubMed

Peytremann-Bridevaux, Isabelle; Staeger, Philippe; Bridevaux, Pierre-Olivier; Ghali, William A; Burnand, Bernard

2008-05-01

Disease-management programs may enhance the quality of care provided to patients with chronic diseases, such as chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to assess the effectiveness of COPD disease-management programs. We conducted a computerized search of MEDLINE, EMBASE, CINAHL, PsychINFO, and the Cochrane Library (CENTRAL) for studies evaluating interventions meeting our operational definition of disease management: patient education, 2 or more different intervention components, 2 or more health care professionals actively involved in patients' care, and intervention lasting 12 months or more. Programs conducted in hospital only and those targeting patients receiving palliative care were excluded. Two reviewers evaluated 12,749 titles and fully reviewed 139 articles; among these, data from 13 studies were included and extracted. Clinical outcomes considered were all-cause mortality, lung function, exercise capacity (walking distance), health-related quality of life, symptoms, COPD exacerbations, and health care use. A meta-analysis of exercise capacity and all-cause mortality was performed using random-effects models. The studies included were 9 randomized controlled trials, 1 controlled trial, and 3 uncontrolled before-after trials. Results indicate that the disease-management programs studied significantly improved exercise capacity (32.2 m, 95% confidence interval [CI], 4.1-60.3), decreased risk of hospitalization, and moderately improved health-related quality of life. All-cause mortality did not differ between groups (pooled odds ratio 0.84, 95% CI, 0.54-1.40). COPD disease-management programs modestly improved exercise capacity, health-related quality of life, and hospital admissions, but not all-cause mortality. Future studies should explore the specific elements or characteristics of these programs that bring the greatest benefit.

Can chronic disease management programs for patients with type 2 diabetes reduce productivity-related indirect costs of the disease? Evidence from a randomized controlled trial.

PubMed

Adepoju, Omolola E; Bolin, Jane N; Ohsfeldt, Robert L; Phillips, Charles D; Zhao, Hongwei; Ory, Marcia G; Forjuoh, Samuel N

2014-04-01

The objective was to assess the impacts of diabetes self-management programs on productivity-related indirect costs of the disease. Using an employer's perspective, this study estimated the productivity losses associated with: (1) employee absence on the job, (2) diabetes-related disability, (3) employee presence on the job, and (4) early mortality. Data were obtained from electronic medical records and survey responses of 376 adults aged ≥18 years who were enrolled in a randomized controlled trial of type 2 diabetes self-management programs. All study participants had uncontrolled diabetes and were randomized into one of 4 study arms: personal digital assistant (PDA), chronic disease self-management program (CDSMP), combined PDA and CDSMP, and usual care (UC). The human-capital approach was used to estimate lost productivity resulting from 1, 2, 3, and 4 above, which are summed to obtain total productivity loss. Using robust regression, total productivity loss was modeled as a function of the diabetes self-management programs and other identified demographic and clinical characteristics. Compared to subjects in the UC arm, there were no statistically significant differences in productivity losses among persons undergoing any of the 3 diabetes management interventions. Males were associated with higher productivity losses (+$708/year; P<0.001) and persons with greater than high school education were associated with additional productivity losses (+$758/year; P<0.001). Persons with more than 1 comorbid condition were marginally associated with lower productivity losses (-$326/year; P=0.055). No evidence was found that the chronic disease management programs examined in this trial affect indirect productivity losses.

The US Food and Drug Administration's expedited approval programs: Evidentiary standards, regulatory trade-offs, and potential improvements.

PubMed

Wallach, Joshua D; Ross, Joseph S; Naci, Huseyin

2018-06-01

The US Food and Drug Administration has several regulatory programs and pathways to expedite the development and approval of therapeutic agents aimed at treating serious or life-debilitating conditions. A common feature of these programs is the regulatory flexibility, which allows for a customized approval approach that enables market authorization on the basis of less rigorous evidence, in exchange for requiring postmarket evidence generation. An increasing share of therapeutic agents approved by the Food and Drug Administration in recent years are associated with expedited programs. In this article, we provide an overview of the evidentiary standards required by the Food and Drug Administration's expedited development and review programs, summarize the findings of the recent academic literature demonstrating some of the limitations of these programs, and outline potential opportunities to address these limitations. Recent evidence suggests that therapeutic agents in the Food and Drug Administration's expedited programs are approved on the basis of fewer and smaller studies that may lack comparator groups and random allocation, and rather than focusing on clinical outcomes for study endpoints, rely instead on surrogate markers of disease. Once on the market, agents receiving expedited approvals are often quickly incorporated into clinical practice, and evidence generated in the postmarket period may not necessarily address the evidentiary limitations at the time of market entry. Furthermore, not all pathways require additional postmarket studies. Evidence suggests that drugs in expedited approval programs are associated with a greater likelihood that the Food and Drug Administration will take a safety action following market entry. There are several opportunities to improve the timeliness, information value, and validity of the pre- and postmarket studies of therapeutic agents receiving expedited approvals. When use of nonrandomized and uncontrolled studies cannot be avoided prior to market entry, randomized trials should be mandatory in the postmarket period, unless there are strong justifications for not carrying out such studies. In the premarket period, validity of the surrogate markers can be improved by more rigorously evaluating their correlation with patient-relevant clinical outcomes. Opportunities to reduce the duration, complexity, and cost of postmarket randomized trials should not compromise their validity and instead incorporate pragmatic "real-world" design elements. Despite recent enthusiasm for widely using real-world evidence, adaptive designs, and pragmatic trials in the regulatory setting, caution is warranted until large-scale empirical evaluations demonstrate their validity compared to more traditional trial designs.

Cellular replacement therapy for Parkinson's disease--where we are today?

PubMed

Redmond, D Eugene

2002-10-01

The concept of replacing lost dopamine neurons in Parkinson's disease using mesencephalic brain cells from fetal cadavers has been supported by over 20 years of research in animals and over a decade of clinical studies. The ambitious goal of these studies was no less than a molecular and cellular "cure" for Parkinson's disease, other neurodegenerative diseases, and spinal cord injury. Much research has been done in rodents, and a few studies have been done in nonhuman primate models. Early uncontrolled clinical reports were enthusiastic, but the outcome of the first randomized, double blind, controlled study challenged the idea that dopamine replacement cells can cure Parkinson's disease, although there were some significant positive findings. Were the earlier animal studies and clinical reports wrong? Should we give up on the goal? Some aspects of the trial design and implantation methods may have led to lack of effects and to some side effects such as dyskinesias. But a detailed review of clinical neural transplants published to date still suggests that neural transplantation variably reverses some aspects of Parkinson's disease, although differing methods make exact comparisons difficult. While the randomized clinical studies have been in progress, new methods have shown promise for increasing transplant survival and distribution, reconstructing the circuits to provide dopamine to the appropriate targets and with normal regulation. Selected promising new strategies are reviewed that block apoptosis induced by tissue dissection, promote vascularization of grafts, reduce oxidant stress, provide key growth factors, and counteract adverse effects of increased age. New sources of replacement cells and stem cells may provide additional advantages for the future. Full recovery from parkinsonism appears not only to be possible, but a reliable cell replacement treatment may finally be near.

Mental health first aid for eating disorders: pilot evaluation of a training program for the public

PubMed Central

2012-01-01

Background Eating disorders cause significant burden that may be reduced by early and appropriate help-seeking. However, despite the availability of effective treatments, very few individuals with eating disorders seek treatment. Training in mental health first aid is known to be effective in increasing mental health literacy and supportive behaviours, in the social networks of individuals with mental health problems. Increases in these domains are thought to improve the likelihood that effective help is sought. However, the efficacy of mental health first aid for eating disorders has not been evaluated. The aim of this research was to examine whether specific training in mental health first aid for eating disorders was effective in changing knowledge, attitudes and behaviours towards people with eating disorders. Methods A repeated measures, uncontrolled trial was conducted to establish proof of concept and provide guidance on the future design of a randomised controlled trial. Self-report questionnaires, administered at baseline, post-training and 6-month follow-up, assessed the effectiveness of the 4-hour, single session, mental health first aid training. Results 73 participants completed the training and all questionnaires. The training intervention was associated with statistically significant increases in problem recognition and knowledge of appropriate mental health first aid strategies, which were maintained at 6-month follow-up. Sustained significant changes in attitudes and behaviours were less clear. 20 participants reported providing assistance to someone with a suspected eating disorder, seven of whom sought professional help as a result of the first aid interaction. Results provided no evidence of a negative impact on participants or the individuals they provided assistance to. Conclusions This research provides preliminary evidence for the use of training in mental health first aid as a suitable intervention for increasing community knowledge of and support for people with eating disorders to seek appropriate help. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611001181998 PMID:22856517

Online disease management of diabetes: engaging and motivating patients online with enhanced resources-diabetes (EMPOWER-D), a randomized controlled trial.

PubMed

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-05-01

To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational 'nuggets' dispensed electronically by the care team. A1C was the primary outcome variable. Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (-1.32% INT vs -0.66% UC; p<0.001). At 12 months, the differences were not significant (-1.14% INT vs -0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204.

Online disease management of diabetes: Engaging and Motivating Patients Online With Enhanced Resources-Diabetes (EMPOWER-D), a randomized controlled trial

PubMed Central

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-01-01

Objective To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Materials and methods Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational ‘nuggets’ dispensed electronically by the care team. A1C was the primary outcome variable. Results Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (−1.32% INT vs −0.66% UC; p<0.001). At 12 months, the differences were not significant (−1.14% INT vs −0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). Conclusions A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204 PMID:23171659

The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC Trial): study protocol for a randomized controlled trial.

PubMed

Karamat, Fares A; Horjus, Deborah L; Haan, Yentl C; van der Woude, Lisa; Oudman, Inge; van Montfrans, Gert A; Clark, Joseph F; Brewster, Lizzy M

2015-02-22

Despite adequate treatment, up to 30% of treated antihypertensive patients with primary, uncomplicated hypertension remain uncontrolled. We proposed that high intracellular activity of the ATP regenerating enzyme creatine kinase (CK) increases pressor responses and hypertension risk. In line with this, we found that plasma CK activity after rest, a surrogate measure of tissue activity, is the main predictor of blood pressure levels and failure of antihypertensive therapy in the general population. In addition, the creatine analog and competitive oral creatine kinase inhibitor beta-guanidinopropionic acid effectively and safely reduced blood pressure in the spontaneously hypertensive rat. However, to our knowledge there are no human data on the safety of oral supplementation with this substance. Therefore, we will assess the tolerability of beta-guanidinopropionic acid in men, compared to creatine and placebo. This is a randomized, active and placebo controlled, triple blind, double dummy, single center clinical intervention trial in 24 healthy male volunteers, 18 to 50 years old, recruited in the Netherlands. The intervention consists of one week of daily oral administration of beta-guanidinopropionic acid 100 mg, creatine 5 gram, or placebo. The primary outcome is the tolerability of beta-guanidinopropionic acid as a descriptive measure, in an intent-to-treat analysis. Other outcomes include the placebo-adjusted differences with baseline in biochemical and hemodynamic parameters, including plasma markers of muscle tissue damage, urine sodium excretion, resting sitting systolic and diastolic brachial blood pressure, supine systolic and diastolic central blood pressure, pulse wave velocity and augmentation index, heart rate, cardiac contractility, cardiac output, and total peripheral resistance. There is an unfulfilled need for new conservative options to treat resistant hypertension. This study will provide first-in-men data on creatine kinase inhibition as a potential new class of antihypertensive drugs. The Netherlands National Trial Register Trialregister.nl (identifier NTR 4444) , registered 9 March 2014.

"Symptom-based insulin adjustment for glucose normalization" (SIGN) algorithm: a pilot study.

PubMed

Lee, Joyce Yu-Chia; Tsou, Keith; Lim, Jiahui; Koh, Feaizen; Ong, Sooim; Wong, Sabrina

2012-12-01

Lack of self-monitoring of blood glucose (SMBG) records in actual practice settings continues to create therapeutic challenges for clinicians, especially in adjusting insulin therapy. In order to overcome this clinical obstacle, a "Symptom-based Insulin adjustment for Glucose Normalization" (SIGN) algorithm was developed to guide clinicians in caring for patients with uncontrolled type 2 diabetes who have few to no SMBG records. This study examined the clinical outcome and safety of the SIGN algorithm. Glycated hemoglobin (HbA1c), insulin usage, and insulin-related adverse effects of a total of 114 patients with uncontrolled type 2 diabetes who refused to use SMBG or performed SMBG once a day for less than three times per week were studied 3 months prior to the implementation of the algorithm and prospectively at every 3-month interval for a total of 6 months after the algorithm implementation. Patients with type 1 diabetes, nonadherence to diabetes medications, or who were not on insulin therapy at any time during the study period were excluded from this study. Mean HbA1c improved by 0.29% at 3 months (P = 0.015) and 0.41% at 6 months (P = 0.006) after algorithm implementation. A slight increase in HbA1c was observed when the algorithm was not implemented. There were no major hypoglycemic episodes. The number of minor hypoglycemic episodes was minimal with the majority of the cases due to irregular meal habits. The SIGN algorithm appeared to offer a viable and safe approach when managing uncontrolled patients with type 2 diabetes who have few to no SMBG records.

Prevalence of true therapeutic inertia in blood pressure control in an academic chronic kidney disease clinic.

PubMed

Desai, Nayan; Madhavankutty Saraswathy, Vishnupriya; Hunter, Krystal; McFadden, Christopher

2013-06-01

Therapeutic inertia (TI) in blood pressure (BP) control has been traditionally defined as failure to initiate or intensify therapy when treatment goals are not met. The fallacy with this definition is that TI may be overestimated because it includes hypertensive patients deliberately uncontrolled. This is a retrospective chart review study that evaluated physicians' response to an uncontrolled clinic BP reading in a population of patients with stage 3 to 5 chronic kidney disease (CKD) and hypertension. Of 429 patients screened, 166 had controlled BP and 263 did not. Of these 263 patients, 115 patients had no clear reason documented for the absence of changes in medication regimen. This population was defined as cases with true TI. In the remaining 148 patients, the medication regimen was changed in 81 patients. In the rest of the patients, there was a reason documented for not changing the medication regimen. The prevalence of true TI rate (defined as percentage of uncontrolled hypertension as a result of physician inaccountability) in our study was 44% as compared with 69% if the traditional TI definition is applied. Thus, we conclude that the prevalence of TI in the literature overestimates the rate of true TI as it does not account for physician decision making. The current definition of TI in BP control needs to be revised, as it underestimates a provider's care to improve BP control and is misleading. The TI definition should include some mechanism to account for interventions beyond medication titration. © 2013 Wiley Periodicals, Inc.

Risk factors and predictors of uncontrolled hyperglycemia and diabetic ketoacidosis in children and adolescents with type 1 diabetes mellitus in Jeddah, western Saudi Arabia.

PubMed

Sayed, Mohamed Hesham; Hegazi, Moustafa Abdelaal; Abdulwahed, Khairyah; Moussa, Khairya; El-Deek, Basem Salama; Gabel, Hala; Ragheb, Rana

2017-02-01

Little is known about levels of glycemic control and risk factors for uncontrolled hyperglycemia in Saudi children with type 1 diabetes mellitus (T1DM). The aim of the present study was to identify levels of glycemic control, risk factors and predictors of uncontrolled hyperglycemia (HG) and diabetic ketoacidosis (DKA) in children with T1DM. A retrospective study was performed on Saudi children and adolescents with confirmed T1DM who were followed at the Pediatric Endocrinology Clinic of the Maternity and Children Hospital, Jeddah, from 2000 to 2014. Data collection included all possible factors that may be associated with uncontrolled T1DM. Patients were classified according to American Diabetes Association guidelines for target HbA1c levels per age group. Comparisons were made between well-controlled (WC) patients, HG patients, and DKA patients. Calculation of odds ratios and logistic regression allowed for estimation of the role of each risk factor in uncontrolled T1DM. Only 31.2 % of children and adolescents with T1DM were well controlled. Better glycemic control was associated with age < 6 years, urban residence, and T1DM duration <5 years. Glycemic control was not affected by gender, insulin therapy, or comorbidities. The most significant independent predictors of hyperglycemia and DKA were poor compliance with a healthy lifestyle (adjusted hazards ratio [AHR] 28.94; 95 % confidence interval [CI] 8.37-100.04) and an excess intake of sweets (AHR 3.31; 95 % CI 1.54-7.11). The most significant independent predictor for poor glycemic control (particularly DKA rather than hyperglycemia) in Saudi children and adolescents was poor compliance with a healthy lifestyle with an excessive intake of sweets. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

A Systematic Review of Antimicrobial Stewardship Interventions in the Emergency Department.

PubMed

Losier, Mia; Ramsey, Tasha D; Wilby, Kyle John; Black, Emily K

2017-09-01

To improve antimicrobial utilization, development and implementation of antimicrobial stewardship programs in the emergency department (ED) has been recommended. The primary objective of this review was to characterize antimicrobial stewardship (AMS) in the ED and to identify interventions that improve patient outcomes or process of care and/or reduce consequences of antimicrobial use. This study was completed as a systematic review. The following databases were searched from inception through November, 2016: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Web of Science. Randomized controlled trials, nonrandomized controlled trials, controlled and uncontrolled before-and-after studies, interrupted time series studies, and repeated-measures studies evaluating AMS interventions in the ED were included in the review. Studies published in languages other than English were excluded. A total of 43 studies meeting inclusion criteria were identified from our search. Patient or provider education and guideline or clinical pathway implementation were the most commonly reported interventions. Few studies reported on audit and feedback, and no study evaluated preauthorization. Impact of interventions showed variable results. Where identified, benefits of AMS interventions primarily included improvement in delivery of care or a decrease in antimicrobial utilization; however, most studies were rated as having unclear or high risk of bias. AMS interventions in the ED may improve patient care. However, the optimal combination of interventions is unclear. Additional studies with more rigorous design evaluating core components of AMS programs, including prospective audit and feedback are needed.

Mechanical CPR: Who? When? How?

PubMed

Poole, Kurtis; Couper, Keith; Smyth, Michael A; Yeung, Joyce; Perkins, Gavin D

2018-05-29

In cardiac arrest, high quality cardiopulmonary resuscitation (CPR) is a key determinant of patient survival. However, delivery of effective chest compressions is often inconsistent, subject to fatigue and practically challenging.Mechanical CPR devices provide an automated way to deliver high-quality CPR. However, large randomised controlled trials of the routine use of mechanical devices in the out-of-hospital setting have found no evidence of improved patient outcome in patients treated with mechanical CPR, compared with manual CPR. The limited data on use during in-hospital cardiac arrest provides preliminary data supporting use of mechanical devices, but this needs to be robustly tested in randomised controlled trials.In situations where high-quality manual chest compressions cannot be safely delivered, the use of a mechanical device may be a reasonable clinical approach. Examples of such situations include ambulance transportation, primary percutaneous coronary intervention, as a bridge to extracorporeal CPR and to facilitate uncontrolled organ donation after circulatory death.The precise time point during a cardiac arrest at which to deploy a mechanical device is uncertain, particularly in patients presenting in a shockable rhythm. The deployment process requires interruptions in chest compression, which may be harmful if the pause is prolonged. It is recommended that use of mechanical devices should occur only in systems where quality assurance mechanisms are in place to monitor and manage pauses associated with deployment.In summary, mechanical CPR devices may provide a useful adjunct to standard treatment in specific situations, but current evidence does not support their routine use.

Adapting Interpersonal Psychotherapy for Older Adults at Risk for Suicide

PubMed Central

Heisel, Marnin J.; Talbot, Nancy L.; King, Deborah A.; Tu, Xin M.; Duberstein, Paul R.

2014-01-01

Objective To pilot a psychological intervention adapted for older adults at-risk for suicide. Design A focused, uncontrolled, pre-to-post-treatment psychotherapy trial. All eligible participants were offered the study intervention. Setting Outpatient mental healthcare provided in the psychiatry department of an academic medical center in a mid-sized Canadian city. Participants Seventeen English-speaking adults 60 years or older, at- risk for suicide by virtue of current suicide ideation, death ideation, and/or recent self-injury. Intervention A 16-session course of Interpersonal Psychotherapy (IPT) adapted for older adults at-risk for suicide who were receiving medication and/or other standard psychiatric treatment for underlying mood disorders. Measurements Participants completed a demographics form, screens for cognitive impairment and alcohol misuse, a semi-structured diagnostic interview, and measures of primary (suicide ideation and death ideation), and secondary study outcomes (depressive symptom severity; social adjustment and support; psychological well-being), and psychotherapy process measures. Results Participants experienced significant reductions in suicide ideation, death ideation, and depressive symptom severity, and significant improvement in perceived meaning in life, social adjustment, perceived social support, and other psychological well-being variables. Conclusions Study participants experienced enhanced psychological well-being and reduced symptoms of depression and suicide ideation over the course of IPT adapted for older adults at-risk for suicide. Larger, controlled trials are needed to further evaluate the impact of this novel intervention and to test methods for translating and integrating focused interventions into standard clinical care with at-risk older adults. PMID:24840611

A comparison of different antibiotic regimens for the treatment of infective endocarditis.

PubMed

Martí-Carvajal, Arturo J; Dayer, Mark; Conterno, Lucieni O; Gonzalez Garay, Alejandro G; Martí-Amarista, Cristina Elena; Simancas-Racines, Daniel

2016-04-19

Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but their use is not standardised, due to the differences in presentation, populations affected and the wide variety of micro-organisms that can be responsible. To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE Classic and EMBASE, LILACS, CINAHL and the Conference Proceedings Citation Index on 30 April 2015. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. We included randomised controlled trials assessing the effects of antibiotic regimens for treating possible infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. Three review authors independently performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of studies. We described the included studies narratively. Four small randomised controlled trials involving 728 allocated/224 analysed participants met our inclusion criteria. These trials had a high risk of bias. Drug companies sponsored two of the trials. We were unable to pool the data due to the heterogeneity in outcome definitions and the different antibiotics used.The included trials compared the following antibiotic schedules. The first trial compared quinolone (levofloxacin) plus standard treatment (anti-staphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin) and rifampicin) versus standard treatment alone reporting uncertain effects on all-cause mortality (8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; RR 1.12, 95% CI 0.49 to 2.56, very low quality evidence). The second trial compared daptomycin versus low-dose gentamicin plus an anti-staphylococcal penicillin (nafcillin, oxacillin or flucloxacillin) or vancomycin. This showed uncertain effects in terms of cure rates (9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus anti-staphylococcal penicillin or vancomycin, RR 0.89 95% CI 0.42 to 1.89; very low quality evidence). The third trial compared cloxacillin plus gentamicin with a glycopeptide (vancomycin or teicoplanin) plus gentamicin. In participants receiving gentamycin plus glycopeptide only 13/23 (56%) were cured versus 11/11 (100%) receiving cloxacillin plus gentamicin (RR 0.59, 95% CI 0.40 to 0.85; very low quality evidence). The fourth trial compared ceftriaxone plus gentamicin versus ceftriaxone alone and found no conclusive differences in terms of cure (15/34 (44%) with ceftriaxone plus gentamicin versus 21/33 (64%) with ceftriaxone alone, RR 0.69, 95% CI 0.44 to 1.10; very low quality evidence).The trials reported adverse events, need for cardiac surgical interventions, uncontrolled infection and relapse of endocarditis and found no conclusive differences between comparison groups (very low quality evidence). No trials assessed septic emboli or quality of life. Limited and very low quality evidence suggested that there were no conclusive differences between antibiotic regimens in terms of cure rates or other relevant clinical outcomes. However, because of the very low quality evidence, this needs confirmation. The conclusion of this Cochrane review was based on randomised controlled trials with high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for treatment of infective endocarditis.

Impact of Distress Reduction on Behavioral Correlates and A1C in African American Women with Uncontrolled Type 2 Diabetes: Results from EMPOWER.

PubMed

Cummings, Doyle M; Lutes, Lesley D; Littlewood, Kerry; Solar, Chelsey; Hambidge, Bertha; Gatlin, Peggy

2017-01-01

Symptoms of emotional distress related to diabetes have been associated with inadequate self-care behaviors, medication non-adherence, and poor glycemic control that may predispose patients to premature death. African American women, in whom diabetes is more common and social support is often insufficient, may be at particularly high risk. The objective of this study was to examine the impact of lowering diabetes-related emotional distress on glycemic control and associated behavioral correlates in rural African American women with uncontrolled type 2 diabetes (T2D). Post-hoc analysis of prospective, randomized, controlled trial. Rural communities in the southeastern United States. 129 rural middle-aged African American women with uncontrolled type 2 diabetes (T2D)(A1C ≥ 7.0). Diabetes-related distress. Changes from baseline to 12-month follow-up in diabetes-related distress, and associated changes in medication adherence, self-care activities, self-efficacy, and glycemic control (A1C). Patients with a reduction in diabetes-related distress (n=79) had significantly greater improvement in A1C, medication adherence, self-care activities, and self-efficacy compared with those in whom diabetes distress worsened or was unchanged (n=50). Changes in distress were also significantly and inversely correlated with improvements in medication adherence, self-care activities, and self-efficacy. Among rural African American women, reductions in diabetes-related distress may be associated with lower A1C and improvements in self-efficacy, self-care behaviors, and medication adherence.

Practice Level Costs of Office-Based Hypertension Performance Improvement: The Heart Healthy Lenoir Study.

PubMed

Primary care practice leaders who consider engaging in quality improvement (QI) need to understand the practice level costs incurred when asking staff to take on new tasks. The Heart Healthy Lenoir study is a prospective cohort trial in which QI methods were used to enhance hypertension (HTN) care and reduce racial disparities in blood pressure control in small rural primary care practices in North Carolina. As part of this effort, we performed an activity-based costing analysis to describe the costs incurred to develop, implement, and maintain key tasks.We interviewed 20 practice stakeholders and phone-based health coaches during 2012-2014. We calculated the time invested by individuals to perform each task within each study phase and applied national hourly wages to generate cost estimates. Our descriptive analyses focus on four of the most widely used practices. Activities included time to abstract HTN control data, participate in project meetings, identify patients with uncontrolled HTN, create standardized work, and provide additional health coaching for patients with uncontrolled HTN. Despite practice and staffing differences, the developmental phase costs were similar, ranging from $879 to $1,417. Implementation costs varied more widely as practices took different approaches to identifying patients with uncontrolled HTN. Practice-specific phone health coaching costs ranged from $19,508 to more than $38,000. This study adds to the growing literature regarding practice level costs of engaging in systems change. Understanding these costs and balancing them against practice incentives may be helpful as stakeholders make decisions regarding HTN QI.

Klebsiella pneumoniae liver abscess in diabetic patients: association of glycemic control with the clinical characteristics

PubMed Central

2013-01-01

Background Klebsiella pneumoniae liver abscess (KPLA) has been reported with increasing frequency in East Asian countries in the past 3 decades, especially in Taiwan and Korea. Diabetes is a well-known risk factor for KPLA and highly associated with septic metastatic complications from KPLA. We investigated the association of glycemic control in diabetic patients with the clinical characteristics of KPLA in Taiwan. Methods Adult diabetic patients with KPLA were identified retrospectively in a medical center from January 2007 to January 2012. Clinical characteristics were compared among patients with different levels of current hemoglobin A1c (HbA1c). Risk factors for metastatic infection from KPLA were analyzed. Results Patients with uncontrolled glycemia (HbA1c ≥ 7%) were significantly younger than those with controlled glycemia (HbA1c < 7%). Patients with uncontrolled glycemia had the trend to have a higher rate of gas-forming liver abscess, cryptogenic liver abscess, and metastatic infection than those with controlled glycemia. Cryptogenic liver abscess and metastatic infection were more common in the poor glycemic control group (HbA1c value >; 10%) after adjustment with age. HbA1c level and abscess < 5 cm were independent risk factors for metastatic complications from KPLA. Conclusions Glycemic control in diabetic patients played an essential role in the clinical characteristics of KPLA, especially in metastatic complications from KPLA. PMID:23363608

Suppression of TIM-1 predicates clinical efficacy of sublingual immunotherapy for allergic rhinitis in children.

PubMed

Lin, Zhibin; Zhou, Lifeng; Luo, Xi; Xia, Wentong; Chen, Dehua; Xu, Rui; Wang, Jie; Luo, Renzhong; Xu, Geng; Li, Huabin

2013-08-01

To evaluate the clinical efficacy of sublingual immunotherapy (SLIT) with house-dust mite (HDM) extract and to examine the change of biomarkers (TIM-1, IL-5 and IL-10) after 6-month SLIT in children with allergic rhinitis (AR). One hundred and sixteen HDM-sensitized children with persistent AR were enrolled to assess the clinical efficacy of SLIT by determining the individual nasal symptom score (INSS) and total nasal symptom scores (TNSS) after 6-month SLIT. Moreover, the mRNA expression of TIM-1, IL-5 and IL-10 in peripheral blood mononuclear cells (PBMCs) was examined in 16 well-controlled and 12 uncontrolled AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). After 6-month SLIT, both TNSS and INSS scores were significantly decreased compared with the baseline value (p < 0.01). The rates for well-controlled, partly controlled and uncontrolled children were 43.1%, 32.8% and 24.1%, respectively. Accordingly, the mRNA levels of TIM-1 and IL-5 decreased significantly and IL-10 mRNA level increased significantly compared with the baseline value in well-controlled children (p < 0.05). Our findings suggest SLIT with HDM extract is effective and safe for AR children and TIM-1 may be considered as an indicator for evaluating the clinical efficacy of SLIT. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Hyperglycemic crisis.

PubMed

Van Ness-Otunnu, Ronald; Hack, Jason B

2013-11-01

Hyperglycemic crisis is a metabolic emergency associated with uncontrolled diabetes mellitus that may result in significant morbidity or death. Acute interventions are required to manage hypovolemia, acidemia, hyperglycemia, electrolyte abnormalities, and precipitating causes. Despite advances in the prevention and management of diabetes, its prevalence and associated health care costs continue to increase worldwide. Hyperglycemic crisis typically requires critical care management and hospitalization and contributes to global health expenditures. Diagnostic and resolution criteria and management strategies for diabetic ketoacidosis and hyperosmolar hyperglycemic crisis are provided. A discussion of prevalence, mortality, pathophysiology, risk factors, clinical presentation, differential diagnosis, evaluation, and management considerations for hyperglycemic crisis are included. Emergency physicians confront the most severe sequelae of uncontrolled diabetes and provide crucial, life-saving management. With ongoing efforts from diabetes societies to incorporate the latest clinical research to refine treatment guidelines, management and outcomes of hyperglycemic crisis in the emergency department continue to improve. We provide an overview of the evaluation and treatment of hyperglycemic crisis and offer a concise, targeted management algorithm to aid the practicing emergency physician. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical heterogeneity of diffuse large B cell lymphoma following failure of front-line immunochemotherapy.

PubMed

Farooq, Umar; Maurer, Matthew J; Thompson, Carrie A; Thanarajasingam, Gita; Inwards, David J; Micallef, Ivana; Macon, William; Syrbu, Sergei; Lin, Tasha; Lin, Yi; Ansell, Stephen M; Nowakowski, Grzegorz S; Habermann, Thomas M; Cerhan, James R; Link, Brian K

2017-10-01

This study aimed to describe the patterns of care and outcomes of diffuse large B cell lymphoma (DLBCL) after failure of front line anthracycline-based immunochemotherapy (IC). Patients with newly diagnosed lymphoma were prospectively enrolled in Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellzence. All DLBCL and primary mediastinal B-cell lymphoma (PMBL) patients treated with front-line anthracycline-based IC were followed for relapse. Patients with relapse on follow-up and subsequently retreated were included in this analysis. 1039 patients received anthracycline-based IC between 2002 and 2012, of which 244 relapsed and were subsequently retreated. Across all therapies, overall survival at 4 years (OS4) from relapse was 28% and 103 patients ultimately underwent autologous haematopoietic cell transplant (autoHCT) with OS4 from autoHCT of 51%. Patients relapsing after 12 months from initial diagnosis had OS4 of 47% but those with a transient or no response to initial therapy had OS4 of only 13%. Outcomes of relapsed or refractory DLBCL differ substantially when categorized by response to initial therapy, timing of relapse and opportunity to undergo autoHCT. The design and interpretation of uncontrolled trials should account for this heterogeneity in patients with relapsed DLBCL. © 2017 John Wiley & Sons Ltd.

A Randomized, Controlled Trial of a Shared Panel Management Program for Small Practices.

PubMed

Bishop, Tara F; Ryan, Andrew M; Chen, Melinda A; Mendelsohn, Jayme; Gottlieb, Daniel; Shih, Sarah; Desai, Priya; Wolff, Elizabeth A; Casalino, Lawrence P

2016-10-01

To determine whether a shared panel management program was effective at improving quality of care for patients with uncontrolled chronic disease. Data were extracted from electronic health records. Randomized controlled trial of a panel management program initiated by New York City Department of Health and Mental Hygiene. Patients from 20 practices with an uncontrolled chronic disease and a lapse in care were assigned to the intervention (a phone call requesting that the patient schedule a physician appointment) or usual care. Outcomes were visits to physician practices, body mass index measurement, blood pressure measurement and control, use of antithrombotics, and low-density lipoprotein measurement and control. Panel managers were able to successfully speak with 1,676 patients (14.7 percent of the intervention group). There were no significant differences in outcomes between the intervention and usual care groups. Successfully contacted patients were more likely to have an office visit within 1 year of randomization (45.6 percent [95 percent CI: 22.8, 26.9] vs. 38.1 percent [95 percent CI: 36.8, 39.3]) and more likely to be on antithrombotics (24.4 percent [95 percent CI: 17.7, 31.0]) versus those in the usual care group (17.0 percent [95 percent CI: 13.9, 20.0]) but had no other difference in quality. A shared, low-intensity panel management program run by a city health department did not improve quality of care for patients with chronic illnesses and lapses in care. © Health Research and Educational Trust.

The impact of second generation antipsychotics on insight in schizophrenia: Results from 14 randomized, placebo controlled trials.

PubMed

Mattila, Taina; Koeter, Maarten; Wohlfarth, Tamar; Storosum, Jitschak; van den Brink, Wim; Derks, Eske; Leufkens, Hubertus; Denys, Damiaan

2017-01-01

Despite the negative impact of lack of insight on the prognosis, general functioning and treatment adherence, the effect of antipsychotic medication on insight has been investigated only in small samples and uncontrolled studies. In this study we examine whether previously reported effects of antipsychotics on insight from uncontrolled studies can be confirmed in a database including 14 randomized, double-blind, placebo-controlled trials. The database contained placebo-controlled RCTs of five second-generation antipsychotics (SGAs: olanzapine, paliperidone, quetiapine, risperidone and sertindole) and included a total of 4243 patients with schizophrenia. Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS) at baseline and at six weeks. Overall, SGA treatment resulted in a significantly larger improvement in insight than placebo (0.43 points versus 0.15 points; Hedge׳s g 0.23; p<0.001). However this difference in improvement in insight was largely explained by improvement in other symptoms. In the initial analysis, one of the compounds was significantly less effective in improving insight than the other SGAs, but this difference no longer persisted when improvement in other symptoms was taken into account. The effect of SGAs on improvement in insight was not moderated by geographic region, illness duration or drop-out. The present study showed that SGA treatment of patients with schizophrenia is associated with improved insight, but that this improvement is associated with SGA induced improvements in other symptoms, though the causal relationship may not be established. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Environmental interventions to reduce fear of crime: systematic review of effectiveness.

PubMed

Lorenc, Theo; Petticrew, Mark; Whitehead, Margaret; Neary, David; Clayton, Stephen; Wright, Kath; Thomson, Hilary; Cummins, Steven; Sowden, Amanda; Renton, Adrian

2013-05-12

Fear of crime is associated with negative health and wellbeing outcomes, and may mediate some impacts of the built environment on public health. A range of environmental interventions have been hypothesized to reduce the fear of crime. This review aimed to synthesize the literature on the effectiveness of interventions in the built environment to reduce the fear of crime. Systematic review methodology, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance, was used. Studies of environmental interventions which reported a fear of crime outcome and used any prospective evaluation design (randomized controlled trial (RCT), trial or uncontrolled before-and-after study) were included. Eighteen databases were searched. The Hamilton tool was used to assess quality. A narrative synthesis of findings was undertaken. A total of 47 studies were included, 22 controlled and 25 uncontrolled, with total sample sizes ranging from n = 52 to approximately n = 23,000. Thirty-six studies were conducted in the UK, ten studies in the USA and one study in the Netherlands. The quality of the evidence overall is low. There are some indications that home security improvements and non-crime-related environmental improvements may be effective for some fear of crime outcomes. There is little evidence that the following reduce fear of crime: street lighting improvements, closed-circuit television (CCTV), multi-component environmental crime prevention programs or regeneration programs. There is some evidence for the effectiveness of specific environmental interventions in reducing some indicators of fear of crime, but more attention to the context and possible confounders is needed in future evaluations of complex social interventions such as these.

Acceptability and feasibility of the 'DASH for Asthma' intervention in a randomized controlled trial pilot study.

PubMed

Blonstein, Andrea C; Lv, Nan; Camargo, Carlos A; Wilson, Sandra R; Buist, A Sonia; Rosas, Lisa G; Strub, Peg; Ma, Jun

2016-08-01

'DASH for Asthma' (n 90) was a 6-month randomized controlled trial that demonstrated potential benefits of a DASH (Dietary Approaches to Stop Hypertension) behavioural intervention for improving diet quality and asthma control by comparing intervention to usual care in adults with uncontrolled asthma. The present study examined acceptability and feasibility of the intervention from the perspective of intervention participants and lifestyle coaches. Grounded in Social Cognitive Theory, the 3-month intensive stage, including three individual and eight group sessions, focused on diet modifications and behavioural self-regulation. The 3-month maintenance stage contained telephone consultations. Participants and lifestyle coaches completed surveys including 5-point Likert scales and open-ended questions. We analysed data using descriptive and inductive content analyses. Forty-six intervention participants (survey response rate was 65-72 %) and two lifestyle coaches. Participants and lifestyle coaches were highly satisfied (all mean ratings >4) with individual and group sessions. Participants identified mastery of knowledge and skills (awareness, goal setting, self-monitoring, problem solving), social learning (class members sharing experiences and ideas) and good coaching skills (reflective listening, empathy, motivational counselling) as important contributors to self-efficacy and programme satisfaction. Participants also valued personalized feedback received in individual sessions. Lifestyle coaches viewed participant engagement as a facilitator to effective sessions. Finally, participants and lifestyle coaches identified food tasting as beneficial for observational learning and facilitation of participant engagement. High class attendance and self-monitoring rate also reflected the high engagement among participants. The DASH behavioural intervention was feasible and highly acceptable to participants with uncontrolled asthma and lifestyle coaches.

Guided internet-administered self-help to reduce symptoms of anxiety and depression among adolescents and young adults diagnosed with cancer during adolescence (U-CARE: YoungCan): a study protocol for a feasibility trial.

PubMed

Ander, Malin; Wikman, Anna; Ljótsson, Brjánn; Grönqvist, Helena; Ljungman, Gustaf; Woodford, Joanne; Lindahl Norberg, Annika; von Essen, Louise

2017-01-27

A subgroup of adolescents and young adults diagnosed with cancer during adolescence reports elevated levels of anxiety and depressive symptoms and unmet needs for psychological support. Evidence-based psychological treatments tailored for this population are lacking. This protocol describes a feasibility study of a guided-internet-administered self-help programme (YoungCan) primarily targeting symptoms of anxiety and depression among young persons diagnosed with cancer during adolescence and of the planned study procedures for a future controlled trial. The study is an uncontrolled feasibility trial with a pre-post and 3-month follow-up design. Potential participants aged 15-25 years, diagnosed with cancer during adolescence, will be identified via the Swedish Childhood Cancer Registry. 30 participants will be included. Participants will receive YoungCan, a 12-week therapist-guided, internet-administered self-help programme consisting primarily of cognitive-behavioural therapy organised into individually assigned modules targeting depressive symptoms, worry and anxiety, body dissatisfaction and post-traumatic stress. Interactive peer support and psychoeducative functions are also available. Feasibility outcomes include: recruitment and eligibility criteria; data collection; attrition; resources needed to complete the study and programme; safety procedures; participants' and therapists' adherence to the programme; and participants' acceptability of the programme and study methodology. Additionally, mechanisms of impact will be explored and data regarding symptoms of anxiety, depression, post-traumatic stress, body dissatisfaction, reactions to social interactions, quality of life, axis I diagnoses according to the Mini International Neuropsychiatric Interview and healthcare service use will be collected. Exploratory analyses of changes in targeted outcomes will be conducted. This feasibility protocol was approved by the Regional Ethical Review Board in Uppsala, Sweden (ref: 2016/210). Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences. ISRCTN97835363. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Diabetes and cardiovascular disease interventions by community pharmacists: a systematic review.

PubMed

Evans, Charity D; Watson, Erin; Eurich, Dean T; Taylor, Jeff G; Yakiwchuk, Erin M; Shevchuk, Yvonne M; Remillard, Alfred; Blackburn, David

2011-05-01

To systematically review and assess the quality of studies evaluating community pharmacist interventions for preventing or managing diabetes or cardiovascular disease (CVD) and/or their major risk factors. A comprehensive literature search was performed using MEDLINE (1950-February 2011), EMBASE (1980-February 2011), International Pharmaceutical Abstracts (1970-February 2011), Cumulative Index to Nursing and Allied Health Literature (1982-June 2007), and Cochrane Central Register of Controlled Trials (1898-February 2011). Search terms included: community pharmacy(ies), community pharmacist(s), cardiovascular, diabetes, and intervention. The grey literature was searched using the ProQuest Dissertations and Theses, Theses Canada, and OAlster databases. Articles published in English or French with all study designs were considered for the review. Studies were included if they contained interventions designed to reduce the incidence, risk, or mortality of CVD or diabetes; affect clinical indicators of CVD or diabetes mellitus (including hypertension, dyslipidemia, or hemoglobin A(1c)); and/or improve adherence to treatment strategies. Only studies involving interventions carried out primarily by pharmacists in community pharmacy settings were included. Study quality was assessed using a checklist validated for both randomized and nonrandomized studies. A total of 4142 studies were initially identified, with 40 meeting our inclusion criteria. Eleven studies were randomized controlled trials, 4 were cluster randomized trials, and 2 studies had randomized before-after designs. The remaining studies were controlled before-after (n = 2), cohort (n = 4), and uncontrolled before-after (n = 17) designs. Interventions focused on diabetes (n = 12), hypertension (n = 9), medication adherence (n = 9), lipids (n = 5), evidence-based medication initiation or optimization (n = 3), risk factor prediction scores (n = 1), and body mass index (n = 1). All studies contained interventions focused at the patient level and the majority of studies (34/40) involved interventions directed at both the physician and patient. No specific intervention emerged as superior, and study quality was generally poor, making it difficult to determine the true effect of the interventions. Poor study quality, time-intensive interventions, and unproven clinical significance warrant the need for further high-quality studies of community pharmacist interventions for preventing or managing diabetes or CVD and/or their major risk factors.

Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials.

PubMed

Shear, Neil H; Paul, Carle; Blauvelt, Andrew; Gooderham, Melinda; Leonardi, Craig; Reich, Kristian; Ohtsuki, Mamitaro; Pangallo, Beth; Xu, Wen; Ball, Susan; Ridenour, Terri; Torisu-Itakura, Hitoe; Agada, Noah; Mallbris, Lotus

2018-02-01

BACKGROUND: Injection-site reactions (ISRs) are reported with biologic therapies. The objective of this study was to comprehensively characterize ISRs among moderate-to-severe psoriasis patients treated with ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A.

METHODS: ISRs are presented from UNCOVER-1, UNCOVER-2, and UNCOVER-3 (12 weeks) and all ixekizumab-exposed patients in 11 controlled and uncontrolled trials (156 weeks).

RESULTS: At week 12, reported ISR frequency with 80 mg ixekizumab every 2 weeks (IXE Q2W, 16.8%) was comparable with etanercept twice weekly (16.4%); both were significantly higher than placebo (3.3%). With IXE Q2W, ISRs were mild (12.3%), moderate (3.9%), or severe (0.7%), typically reported in the first 2 weeks (median onset, 6.6 days), and most commonly characterized as nonspecified, erythema, and pain. Generally, erythema onset was delayed, whereas pain occurred around drug administration. Discontinuation from ixekizumab due to ISRs (0.4%) occurred in the first 12 weeks. After 2 weeks, ISR frequency decreased and remained stable (≤4.2%) through week 156. No ISR-related serious adverse events were reported in ixekizumab-treated patients. ISR data were solicited if patients reported injection-associated events. Since nonspecified ISR was the most commonly reported term, specific types might be underreported.

CONCLUSIONS: ISRs have been reported with ixekizumab during clinical trials. These reactions are typically tolerable, manageable, and decrease over time.

Clinicaltrials.gov: NCT01474512 (UNCOVER-1); NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3); NCT01777191 (UNCOVER-A); NCT01624233 (UNCOVER-J); NCT01107457 (I1F-MC-RHAJ); NCT02561806 (I1F-MC-RHBS); NCT02387801 (I1F-US-RHBO);NCT02513550 (I1F-MC-RHBP); NCT02634801 (I1F-EW-RHBZ)

J Drugs Dermatol. 2018;17(2):200-206.

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Real-life efficacy and safety of omalizumab in Portuguese patients with persistent uncontrolled asthma.

PubMed

Pereira Barbosa, M; Bugalho de Almeida, A; Pereira, C; Chen, C-W; Georgiou, P; Peachey, G

2015-01-01

The real life effectiveness, safety and the use of omalizumab for Portuguese patients with uncontrolled persistent allergic asthma are not sufficiently well known. The objective of this report was to make an evaluation, in a post-marketing, non-interventional, observational registry, of the Portuguese population included in the eXpeRience study. The methods used in this report are the same as the global eXpeRience ones, applied to a Portuguese sub-population. Patients with uncontrolled allergic asthma who had started omalizumab within the previous 15 weeks were enrolled and received omalizumab add-on therapy for 24 months. The physicians' global evaluation of treatment effectiveness (GETE), asthma symptoms and control (ACT score), quality of life (mini-AQLQ score), exacerbations, and serious adverse events (SAE) were reported. Of the 943 patients recruited in the eXpeRience registry, 62 patients were from Portugal. 62.1% of them were observed to be responders with good/excellent GETE assessment at Week 16. Clinically meaningful improvements in asthma control (ACT score) and quality of life (mini-AQLQ score) were observed with omalizumab therapy at Months 12 (mean change: +7.7 [n=35]; +2.1 [n=20], respectively) and 24 (mean change: +7.0 [n=26]; +2.7 [n=13], respectively). Asthma symptoms and rescue medication usage were reduced to ≤1 day/week at Month 24 from a baseline of ≥3.5 days/week. The proportion of patients with no clinically significant exacerbations increased from 6.5% during pre-treatment (n=62) to 50% at Month 12 (n=54) and 60% at Month 24 (n=45). The findings from the Portugal subpopulation of eXpeRience registry confirm that omalizumab add-on therapy is efficacious and well tolerated in the management of uncontrolled persistent allergic asthma. Another pertinent issue is the fact that the Portuguese subpopulation response is similar to the international population average of the study. Copyright © 2014 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

EXERCISE, MANUAL THERAPY AND POSTURAL RE-EDUCATION FOR UNCONTROLLED EAR TWITCHING AND RELATED IMPAIRMENTS AFTER WHIPLASH INJURY: A CASE REPORT.

PubMed

Flanders, Kelsey; Feldner, Heather

2017-10-01

Whiplash Associated Disorders and the interventions used to remediate them are well documented in physical therapy literature. However, specific interventions for spasms of the neck musculature that also involve constant ear twitching have yet to be addressed. The purpose of this case report is twofold. First, to describe comprehensive physical therapy management and outcomes for a subject with uncontrolled ear twitching and related musculoskeletal impairments, and second, to discuss the physical therapist's approach to evidence-based care when faced with a paucity of literature addressing physical therapy interventions for subjects with uncontrolled ear twitching. The subject was a 14-year-old female who sustained a right anterolateral whiplash injury when struck in the head by a volleyball seven months prior to physical therapy. Beginning five months after that injury, she experienced uncontrolled and constant superior/inferior movement of her right ear (hereafter described in this report as a twitch) in addition to facial and cervical pain from her initial injury. She was unable to participate in high school athletics due to her pain. A multimodal treatment approach including exercise, manual therapy, and postural reeducation was utilized during the subject's episode of care. After eight treatment sessions, the subjects's cervical range of motion and upper extremity strength improved. The reported frequency of ear twitching decreased, as did reports of neck and shoulder pain. In addition, her Neck Disability Index improved from a score of 22, indicating moderate disability, to 9, indicating mild disability and she was able to return to sport activity. With limited research to direct intervention, clinical reasoning was utilized to formulate an effective therapeutic intervention. A combination of manual therapy, exercise, and postural reeducation intervention was effective for this subject and could assist in guiding interventions for similarly unique clinical presentations in the future. Further research is needed to examine the etiology of ear twitching caused by muscle spasm and to develop additional evidence-based interventions for Whiplash Associated Disorders. Level 4.

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability.

PubMed

Szulc, P; Naylor, K; Hoyle, N R; Eastell, R; Leary, E T

2017-09-01

The National Bone Health Alliance (NBHA) recommends standardized sample handling and patient preparation for C-terminal telopeptide of type I collagen (CTX-I) and N-terminal propeptide of type I procollagen (PINP) measurements to reduce pre-analytical variability. Controllable and uncontrollable patient-related factors are reviewed to facilitate interpretation and minimize pre-analytical variability. The IOF and the International Federation of Clinical Chemistry (IFCC) Bone Marker Standards Working Group have identified PINP and CTX-I in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA Bone Turnover Marker Project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

Movement - uncontrolled or slow

MedlinePlus

Dystonia; Involuntary slow and twisting movements; Choreoathetosis; Leg and arm movements - uncontrollable; Arm and leg movements - uncontrollable; Slow involuntary movements of large muscle groups; Athetoid movements

Task shifting in the management of hypertension in Kinshasa, Democratic Republic of Congo: a cross-sectional study.

PubMed

Lulebo, Aimée M; Kaba, Didine K; Atake, Silvestre E-H; Mapatano, Mala A; Mafuta, Eric M; Mampunza, Julien M; Coppieters, Yves

2017-12-04

The Democratic Republic of the Congo (DRC) is characterized by a high prevalence of hypertension (HTN) and a high proportion of uncontrolled HTN, which is indicative of poor HTN management. Effective management of HTN in the African region is challenging due to limited resources, particularly human resources for health. To address the shortage of health workers, the World Health Organization (WHO) recommends task shifting for better disease management and treatment. Although task shifting from doctors to nurses is being implemented in the DRC, there are no studies, to the best of our knowledge, that document the association between task shifting and HTN control. The aim of this study was to investigate the association between task shifting and HTN control in Kinshasa, DRC. We conducted a cross-sectional study in Kinshasa from December 2015 to January 2016 in five general referral hospitals (GRHs) and nine health centers (HCs). A total of 260 hypertensive patients participated in the study. Sociodemographic, clinical, health care costs and perceived health care quality assessment data were collected using a structured questionnaire. To examine the association between task shifting and HTN control, we assessed differences between GRH and HC patients using bivariate and multivariate analyses. Almost half the patients were female (53.1%), patients' mean age was 59.5 ± 11.4 years. Over three-fourths of patients had uncontrolled HTN. There was no significant difference in the proportion of GRH and HC patients with uncontrolled HTN (76.2% vs 77.7%, p = 0.771). Uncontrolled HTN was associated with co-morbidity (OR = 10.3; 95% CI: 3.8-28.3) and the type of antihypertensive drug used (OR = 4.6; 95% CI: 1.3-16.1). The mean healthcare costs in the GRHs were significantly higher than costs in the HCs (US$ 34.2 ± US$3.34 versus US$ 7.7 ± US$ 0.6, respectively). Uncontrolled HTN was not associated with the type of health facility. This finding suggests that the management of HTN at primary healthcare level might be just as effective as at secondary level. However, the high proportion of patients with uncontrolled HTN underscores the need for HTN management guidelines at all healthcare levels.

Cluster Analysis on Longitudinal Data of Patients with Adult-Onset Asthma.

PubMed

Ilmarinen, Pinja; Tuomisto, Leena E; Niemelä, Onni; Tommola, Minna; Haanpää, Jussi; Kankaanranta, Hannu

Previous cluster analyses on asthma are based on cross-sectional data. To identify phenotypes of adult-onset asthma by using data from baseline (diagnostic) and 12-year follow-up visits. The Seinäjoki Adult Asthma Study is a 12-year follow-up study of patients with new-onset adult asthma. K-means cluster analysis was performed by using variables from baseline and follow-up visits on 171 patients to identify phenotypes. Five clusters were identified. Patients in cluster 1 (n = 38) were predominantly nonatopic males with moderate smoking history at baseline. At follow-up, 40% of these patients had developed persistent obstruction but the number of patients with uncontrolled asthma (5%) and rhinitis (10%) was the lowest. Cluster 2 (n = 19) was characterized by older men with heavy smoking history, poor lung function, and persistent obstruction at baseline. At follow-up, these patients were mostly uncontrolled (84%) despite daily use of inhaled corticosteroid (ICS) with add-on therapy. Cluster 3 (n = 50) consisted mostly of nonsmoking females with good lung function at diagnosis/follow-up and well-controlled/partially controlled asthma at follow-up. Cluster 4 (n = 25) had obese and symptomatic patients at baseline/follow-up. At follow-up, these patients had several comorbidities (40% psychiatric disease) and were treated daily with ICS and add-on therapy. Patients in cluster 5 (n = 39) were mostly atopic and had the earliest onset of asthma, the highest blood eosinophils, and FEV 1 reversibility at diagnosis. At follow-up, these patients used the lowest ICS dose but 56% were well controlled. Results can be used to predict outcomes of patients with adult-onset asthma and to aid in development of personalized therapy (NCT02733016 at ClinicalTrials.gov). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis.

PubMed

Terrin, Gianluca; Conte, Francesca; Oncel, Mehmet Yekta; Scipione, Antonella; McNamara, Patrick J; Simons, Sinno; Sinha, Rahul; Erdeve, Omer; Tekgunduz, Kadir S; Dogan, Mustafa; Kessel, Irena; Hammerman, Cathy; Nadir, E; Yurttutan, Sadik; Jasani, Bonny; Alan, Serdar; Manguso, Francesco; De Curtis, Mario

2016-03-01

We performed a systematic review and meta-analysis of all the available evidence to assess the efficacy and safety of paracetamol for the treatment of patent ductus arteriosus (PDA) in neonates, and to explore the effects of clinical variables on the risk of closure. MEDLINE, Scopus and ISI Web of Knowledge databases, using the following medical subject headings and terms: paracetamol, acetaminophen and patent ductus arteriosus. Electronic and manual screening of conference abstracts from international meetings of relevant organisations. Manual search of the reference lists of all eligible articles. Studies comparing paracetamol versus ibuprofen, indomethacin, placebo or no intervention for the treatment of PDA. Data regarding efficacy and safety were collected and analysed. Sixteen studies were included: 2 randomised controlled trials (RCTs) and 14 uncontrolled studies. Quality of selected studies is poor. A meta-analysis of RCTs does not demonstrate any difference in the risk of ductal closure (Mantel-Haenszel model, RR 1.07, 95% CI 0.87 to 1.33 and RR 1.03, 95% CI 0.92 to 1.16, after 3 and 6 days of treatment, respectively). Proportion meta-analysis of uncontrolled studies demonstrates a pooled ductal closure rate of 49% (95% CI 29% to 69%) and 76% (95% CI 61% to 88%) after 3 and 6 days of treatment with paracetamol, respectively. Safety profiles of paracetamol and ibuprofen are similar. Efficacy and safety of paracetamol appear to be comparable with those of ibuprofen. These results should be interpreted with caution, taking into account the non-optimal quality of the studies analysed and the limited number of neonates treated with paracetamol so far. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Efficacy and economic analysis of Ex-PRESS implantation versus trabeculectomy in uncontrolled glaucoma: a systematic review and Meta-analysis

PubMed Central

Wang, Ling; Sha, Fang; Guo, Da-Dong; Bi, Hong-Sheng; Si, Jun-Kang; Du, Yu-Xiang; Tang, Kai

2016-01-01

AIM To systematically review the current evidence based on the efficacy and cost of Ex-PRESS implantation and trabeculectomy (Trab) for uncontrolled glaucoma. METHODS Clinical trials were identified by electronic databases (PubMed, EMBASE, ISI Web of science and Cochrane library), and data, such as intraocular pressure (IOP), the complete and qualified success rate, the postoperative complications and the cost, were exacted from these relevant studies. Weighted mean difference (WMD), odds ratio (OR) and 95% confidence intervals (CIs) were calculated and were pooled using a random-effects model. RESULTS Eleven relevant publications and two abstracts met the inclusion criteria. The efficacy of Ex-PRESS was similar to that of Trab in the percentage of IOP reduction (IOPR %) at 1, 2y (WMD: -2.01; 95% CI: -7.92-3.90; P=0.50 and WMD: 2.89; 95% CI: -8.05-13.83; P=0.60, respectively). Ex-PRESS possessed a significant higher complete and qualified success rate (OR: 1.59; 95% CI: 1.07-2.35; P=0.02 and OR: 1.74; 95% CI: 1.06-2.86; P=0.03, respectively). Moreover, Ex-PRESS exerted a significantly lower frequency of hypotony and hyphema than Trab (OR: 0.39; 95% CI: 0.21-0.72; P=0.003 and OR: 0.27; 95% CI: 0.10-0.69; P=0.003, respectively). However, there was no consistent result on the cost between the two groups according to the previous three studies. CONCLUSION Both Trab and Ex-PRESS have equivalent efficacy in lowering IOP, yet Ex-PRESS had a lower risk of hypotony and hyphema than Trab. Nevertheless, whether the cost of Ex-PRESS was less than that of Trab should be further investigated to ensure evidence-based conclusion in the long run. PMID:26949622

[Features of Clinical Register of Chinese Medicine and Pharmacy Based on ClinicalTrials.gov. (USA)].

PubMed

Lu, Peng-fei; Liao, Xing; Xie, Yan-ming; Wang, Zhi-guo

2015-11-01

In recent 10 years, clinical trials of Chinese medicine and pharmacy (cMP) at clinicalTrials.gov.(USA) are gradually increasing. In order to analyze features of CMP clinical register, ClinicalTrials.gov register database were comprehensively retrieved in this study. Included clinical trials were input one item after another using EXCEL. A final of 348 CMP clinical trials were included. Results showed that China occupied the first place in CMP clinical register, followed by USA. CMP clinical trials, sponsored mainly by colleges/universities and hospitals, mostly covered interventional studies on evaluating safety/effectiveness of CMP. The proportions of studies, sponsored by mainland China and companies, recruitment trials and multi-center clinical trials in interventional trials were increasing. The proportions of studies sponsored by Hong Kong and Taiwan, research completed trials, unclear research status, phase III clinical trials, and published research trials in interventional trials were decreasing. Published ratios of CMP clinical trials were quite low. There were more missing types and higher proportions in trial register information.

Longitudinal Study of Left Ventricular Mass Growth: Comparative Study of Clinic and Ambulatory Systolic Blood Pressure in Chronic Kidney Disease.

PubMed

Agarwal, Rajiv

2016-04-01

Left ventricular (LV) hypertrophy is an established cardiovascular risk factor, yet little is known about its trajectory in people with chronic kidney disease. The goal of this prospective research study was to describe the trajectory of LV mass index, its relationship with blood pressure (BP), and specifically to compare the relationship of BP measured in the clinic and 24-hour ambulatory BP monitoring with LV mass index. Among 274 veterans with chronic kidney disease followed for over ≤ 4 years, the rate of growth of log LV mass index was inversely related to baseline LV mass index; it was rapid in the first 2 years, and plateaued subsequently. Systolic BP also significantly increased, but linearly, 1.7 mm Hg/y by clinic measurements and 1.8 mm Hg/y by 24-hour ambulatory BP. Cross-sectional and longitudinal associations of both clinic BP and 24-hour ambulatory BP with LV mass index were similar; both BP recording methods were associated with LV mass index and its growth over time. Controlled hypertension, masked uncontrolled hypertension, and uncontrolled hypertension categories had increasing LV mass index when diagnosed by 24-hour ambulatory and awake BP (P<0.05 for linear trend) but not sleep BP. After accounting for clinic BP both at baseline and longitudinally, LV mass index among individuals was additionally predicted by the difference in sleep systolic BP and clinic systolic BP (P=0.032). In conclusion, among people with chronic kidney disease, the growth of LV mass index is rapid. Research-grade clinic BP is useful to assess LV mass index and its growth over time. © 2016 American Heart Association, Inc.

[Initial clinical experience with radiofrequency-guided percutaneous vertebral augmentation in the treatment of vertebral compression fractures].

PubMed

Marosfoi, Miklós; Kulcsár, Zsolt; Berentei, Zsolt; Gubucz, István; Szikora, István

2011-07-30

Percutaenous Vertebroplasty (PVP) is effective in alleviating pain and facilitating early mobilization following vertebral compression fractures. The relatively high risk of extravertebral leakage due to uncontrolled delivery of low viscosity bone cement is an inherent limitation of the technique. The aim of this research is to investigate the ability of controlled cement delivery in decreasing the rate of such complications by applying radiofrequency heating to regulate cement viscosity. Thirty two vetebrae were treated in 28 patients as part of an Ethics Committee approved multicenter clinical trial using RadioFreqency assisted Percutaenous Vertebral Augmentation (RF-PVA) technique. This technique is injecting low viscosity polymethylmethacrylate (PMMA) bone cement using a pressure controlled hydraulic pump and applying radiofrequency heating to increase cement viscosity prior to entering the vertebral body. All patients were screened for any cement leakage by X-ray and CT scan. The intensity of pain was recorded on a Visual Analog Scale (VAS) and the level of physical activity on the Oswestry Disability Index (ODI) prior to, one day, one month and three months following procedure. All procedures were technically successful. There were no clinical complication, intraspinal or intraforaminal cement leakage. In nine cases (29%) a small amount of PMMA entered the intervertebral space through the broken end plate. Intensity of pain by VAS was reduced from a mean of 7.0 to 2.5 and physical inactivity dropped on the ODI from 52% to 23% three months following treatment. In this small series controlled cement injection using RF-PVA was capable of preventing clinically hazardous extravertebral cement leakage while achieving outcomes similar to that of conventional vertebroplasty.

Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients.

PubMed

Ribeiro, Camila Ferrari; Souza, Fernanda Homem de Mello de; Jordão, Juliana Merheb; Haendchen, Letícia Cortes; Mesquita, Lismary; Schmitt, Juliano Vilaverde; Faucz, Luciana Lisboa

2012-01-01

Actinic cheilitis, a common disease caused by chronic solar exposure and tobacco use, is considered a premalignant lesion with potential to develop into squamous cell carcinoma. Some of the available treatments are invasive, have unaesthetic results and require multiple sessions. To assess the efficacy of a therapy and its cosmetic results. In this uncontrolled clinical trial a single photodynamic therapy (PDT) session using 16% methyl-aminolevulinate was performed on actinic cheilitis of the lower lip. A standardized questionnaire was applied in order to assess the clinical improvement from the patients' point of view and the satisfaction with the treatment. Anatomopathological evaluation was performed before the treatment and two months afterwards. The sample was composed of 19 patients (10 males and 9 females), phototypes I to III, with average age of 62 years. Main adverse effects were: sudden pain, scabs, herpes flare-up, and edema. The average score of pain during the procedure was 5,8+2,9. At the final assessment the patients reported improvement of 80% and satisfaction of 85% (p<0.01). Anatomopathological analysis showed a significant decrease of dysplasia (p=0.03) in spite of its presence in 84% of cases. There was no significant correlation between the level of dysplasia with either the subjective impression of clinical improvement (p=0.82) or with the patients' final satisfaction (p=0.96). PDT is effective in the treatment of actinic cheilitis, but it is associated with a significant level of pain. Due to the persistence of dysplasia, more research needs to be done in order to define the ideal number of sessions for the effective treatment of these lesions.

Introduction to pseudobulbar affect: setting the stage for recognition and familiarity with this challenging disorder.

PubMed

Demler, Tammie Lee

2017-12-01

Pseudobulbar affect (PBA), despite its prevalence and distinctive symptoms, is widely underrecognized and undertreated. It is characterized by uncontrollable laughing or crying that can occur in an exaggerated manner or inappropriately to a given situation or stimuli. PBA is thought to center around preexisting neurological conditions, which include Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, traumatic brain injury, and stroke. The PBA Registry Series trial was created to measure the prevalence of PBA among patients with these underlying neurological conditions. Through greater awareness, recognition, and diagnosis, treatment for patients with PBA can be improved.

Impact of an Electronic Monitoring Intervention to Improve Adherence to Inhaled Medication in Patients with Asthma and Chronic Obstructive Pulmonary Disease: Study Protocol for a Randomized Controlled Trial

PubMed Central

Dieterle, Thomas; Dürr, Selina; Arnet, Isabelle; Hersberger, Kurt E; Leuppi, Jörg D

2017-01-01

Background Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among patients with asthma and chronic obstructive pulmonary disease (COPD) is high and patients are frequently hospitalized due to exacerbations. Reasons for uncontrolled diseases are manifold, but are often associated with poor inhalation technique and non-adherence to the prescribed treatment plan. This causes substantial mortality, morbidity, and costs to the healthcare system. In this respect, the study of causes for non-adherence and the development of measures to increase and maintain treatment adherence in chronic diseases is of major clinical importance. Objective The primary objective of this study is to investigate the impact of using specific, validated electronic devices on adherence to inhaled medication in patients with chronic obstructive lung diseases such as asthma and COPD. Furthermore, it aims to assess the impact of a reminder and close supervision of the course of disease and quality of life. Methods In this ongoing prospective, single-blind, randomized controlled study, adherence to inhaled medication is analyzed over a 6-month period in at least 154 in- and outpatients with asthma or COPD who have experienced at least 1 exacerbation during the last year. Adherence is measured using electronic data capture devices, which save the date and time of each inhalative device actuation and transfer these data daily via a wireless connection to a Web-based database. Patients are randomly assigned to either the intervention or the control group. The clinical intervention consists of an automated and personal reminder. The intervention group receives an audio reminder and support calls in case medication has not been taken as prescribed or if rescue medication is used more frequently than pre-specified in the study protocol. During the study, participants are assessed every 2 months in the form of clinical visits. Results Recruitment started in January 2014. To date, a total of 169 patients have been recruited. Follow-up assessments are still ongoing. The study will be concluded in the first quarter of 2017. Data analysis will take place during 2017. Conclusions Few studies have investigated medication adherence in patients with chronic obstructive lung diseases. With this prospective study design and the use of state-of-the-art devices for measuring adherence, we expect scientifically relevant and clinically meaningful results that will have a substantial and positive impact on the provision of healthcare in chronically ill patients suffering from asthma or COPD. Trial Registration ClinicalTrials.gov: NCT02386722; https://clinicaltrials.gov/ct2/show/NCT02386722 (Archived by WebCite at http://www.webcitation.org/6oJq1fel0) PMID:29061556

Targeted therapy for localized non-small-cell lung cancer: a review

PubMed Central

Paleiron, Nicolas; Bylicki, Olivier; André, Michel; Rivière, Emilie; Grassin, Frederic; Robinet, Gilles; Chouaïd, Christos

2016-01-01

Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations) is a major challenge. PMID:27462164

Pimecrolimus 1% cream for the treatment of discoid lupus erythematosus.

PubMed

Tlacuilo-Parra, A; Guevara-Gutiérrez, E; Gutiérrez-Murillo, F; Soto-Ortiz, A; Barba-Gómez, F; Hernández-Torres, M; Salazar-Páramo, M

2005-12-01

To determine the safety and efficacy of pimecrolimus cream on lesions of discoid lupus erythematosus. In an open-label phase II trial, patients with discoid lupus were treated with pimecrolimus 1% cream twice daily for 8 weeks. We assessed skin involvement with a clinical severity score, quality of life, patient improvement and toxicity. The changes were documented by skin biopsy at baseline and at the end of treatment. Ten patients with a mean age of 34 +/- 17 yr and disease duration of 3 yr (range 1-8) were studied; 90% were female and 40% had received prior topical or systemic therapy without response. In all patients, improvement of skin damage was observed after therapy. A significant decrease of 52% was observed in the mean +/- s.d. clinical severity score, from 6.1 +/- 1.4 before treatment to 2.9 +/- 1.5 after treatment (P = 0.005). Quality of life score (0 = no effect, 100 = maximum effect on quality of life) showed a mean improvement of 46%, from 42.8 +/- 23.1 before to 23 +/- 16.5 after treatment (P = 0.008). According to the patients' assessment of the response to treatment, 50% qualified as marked improvement, 40% moderate and 10% slight improvement. The treatment was well tolerated; adverse reactions consisted of minimal erythema and pruritus, which resolved without any further action. Our data suggest that pimecrolimus cream for discoid lupus erythematosus seems to be a safe and clinically effective option. However, this was an open and uncontrolled study, and double-blind, placebo-controlled studies are needed.

Persistent Outpatient Hypertension Is Independently Associated with Spinal Cord Dysfunction and Imaging Characteristics of Spinal Cord Damage among Patients with Cervical Spondylosis.

PubMed

Kalb, Samuel; Zaidi, Hasan A; Ribas-Nijkerk, Juan C; Sindhwani, Maughan K; Clark, Justin C; Martirosyan, Nikolay L; Theodore, Nicholas

2015-08-01

Hypertension and cervical spondylosis are diseases of the adult population that are approaching near pandemic proportions. However, the interactions between these two disease processes are poorly understood. We set out to determine the associations among systemic hypertension, clinical status, and imaging findings of spinal cord damage for patients with cervical stenosis. A retrospective chart review was performed on patients with symptomatic cervical stenosis related to degenerative disease and divided on the basis of outpatient blood pressure control (normal <140/<90 mm Hg). Sagittal T2-weighted magnetic resonance imaging (MRI) of the cervical spine was analyzed to determine the degree of maximal canal stenosis (MCS; %), surface area of increased signal intensity (ISI; cm(2)), and signal intensity ratio (SIR). Functional status was evaluated using the modified Japanese Orthopaedic Association (mJOA) scale and the Nurick scale. One hundred twenty-two patients were identified (64 hypertensive, 58 nonhypertensive). Likelihood of ISI was higher in hypertensive patients (P < 0.05). Average ISI was significantly higher in patients with uncontrolled blood pressure (P = 0.02) despite MCS being identical between the two groups. The mJOA and Nurick scores were worse for patients with systemic hypertension (P < 0.02). Diabetes mellitus and smoking history did not affect these findings. Persistent hypertension in outpatients is associated with worsened clinical status and increased markers of spinal cord damage on MRI. Perioperative management of blood pressure may serve to improve clinical outcomes. Larger prospective trials are necessary to further validate these findings. Copyright © 2015 Elsevier Inc. All rights reserved.

Post-marketing observational program of the effectiveness of fluvoxamine for the treatment of depression in patients with neurological disorders: the FRIENDS study.

PubMed

Yahno, Nikolay N; Fedotova, Anastasia V

2017-01-01

In a prospective, non-blinded, uncontrolled, multicenter, post-marketing, observational study (FRIENDS; NCT02043197), fluvoxamine (50-300 mg/day for 90 days) was effective for the treatment of depression in 299 adult patients (age ≥18 years) with neurological disorders at baseline. The therapeutic effect of fluvoxamine was measured by means of changes in the Hospital Anxiety and Depression Scale depression and anxiety scores (HADS-D and HADS-A, respectively), global severity of illness, and clinical condition (measured using the Clinical Global Improvement [CGI] scale). The mean HADS-D subscale score at baseline in the per-protocol cohort (n=296) was 11.7±3.1 points and the corresponding mean HADS-A score was 12.6±3.2. Significant ( P <0.0001) improvements in both scores were recorded during fluvoxamine treatment and later follow-up. Most patients (>85%) recorded reductions versus baseline in both indices. In the CGI-based assessment, most evaluated patients (>200) experienced moderate to very substantial clinical improvement, with no or limited side effects. Significant improvements were also recorded in the exploratory outcomes of sleep quality, assessed using the Insomnia Severity Index, and cognitive function, assessed using the Montreal Cognitive Assessment ( P <0.0001 vs baseline for both). No death or serious adverse drug reactions were reported during the study. The results of this observational study affirm that fluvoxamine is effective and well tolerated for the treatment of depression in the context of neurological disorders. The effects on the exploratory endpoints of this research merit evaluation in controlled trials.

Prevalence of poor glycemic and blood pressure control and pattern of drug use among primary health-care outpatients in Al Ahsa Saudi Arabia

PubMed Central

Emeka, Promise M.; Mukalaf, Ahmed Al; Helal, Hussien Al; Khan, Tahir M.; Almukalf, Mishial A.

2017-01-01

Objectives: To assess drug use pattern and the effect on glycemic and blood pressure (BP) control in type 2 diabetes mellitus (T2DM) and hypertensive patients. Furthermore, to evaluate the duration of drug use and antecedence in diagnosis. Methodology: A cross-sectional study design, comprising interview/questionnaire targeting outpatients attending primary health centers in Al Ahsa was adopted. During the interview, their fasting blood glucose, weight, and height were measured, along with their BP. Time and duration of drug use were recorded. The history, sociodemographic data and the presence of any other disease conditions were also documented. Results: The highest number of uncontrolled BP and poor glycemic control was among the age group of 45 and 49 years. Significant number of the patients (92.9%) had body mass index >30 kg/m2. The prevalence of developing hypertension before T2DM among participants was 59.9%. A significant number (84%) had uncontrolled hypertension, and 67.3% had uncontrolled T2DM. Drug use pattern revealed single or combinations according to clinical guidelines initially but did not follow through in meeting targets. Majority received angiotensin converting enzyme inhibitors, amlodipine or atenolol for BP control and metformin for T2DM. Patients diagnosed between 1 and 5 years displayed significant poor glycemic and BP control. Significantly, most patients appeared to have been on same prescriptions for a longer time without review. Conclusion: Poor glycemic and BP controls observed in this study could be due to deficient treatment strategy among others. Patients were, however, not adequately managed in line with prescribed clinical guidelines. PMID:28936150

Inpatient Management of Diabetes Mellitus among Noncritically Ill Patients at University Hospital of Puerto Rico.

PubMed

Allende-Vigo, Myriam Zaydee; González-Rosario, Rafael A; González, Loida; Sánchez, Viviana; Vega, Mónica A; Alvarado, Milliette; Ramón, Raul O

2014-05-01

To describe the state of glycemic control in noncritically ill diabetic patients admitted to the Puerto Rico University Hospital and adherence to current standard of care guidelines for the treatment of diabetes. This was a retrospective study of patients admitted to a general medicine ward with diabetes mellitus as a secondary diagnosis. Clinical data for the first 5 days and the last 24 hours of hospitalization were analyzed. A total of 147 noncritically ill diabetic patients were evaluated. The rates of hyperglycemia (blood glucose ≥180 mg/dL) and hypoglycemia (blood glucose <70 mg/dL) were 56.7 and 2.8%, respectively. Nearly 60% of patients were hyperglycemic during the first 24 hours of hospitalization (mean random blood glucose, 226.5 mg/dL), and 54.2% were hyperglycemic during the last 24 hours of hospitalization (mean random blood glucose, 196.51 mg/dL). The mean random last glucose value before discharge was 189.6 mg/dL. Most patients were treated with subcutaneous insulin, with basal insulin alone (60%) used as the most common regimen. The proportion of patients classified as uncontrolled receiving basal-bolus therapy increased from 54.3% on day 1 to 60% on day 5, with 40% continuing to receive only basal insulin. Most of the uncontrolled patients had their insulin dose increased (70.1%); however, a substantial proportion had no change (23.7%) or even a decrease (6.2%) in their insulin dose. The management of hospitalized diabetic patients is suboptimal, probably due to clinical inertia, manifested by absence of appropriate modification of insulin regimen and intensification of dose in uncontrolled diabetic patients. A comprehensive educational diabetes management program, along with standardized insulin orders, should be implemented to improve the care of these patients.

Protective Role of Cytotoxic T Lymphocytes in Filovirus Hemorrhagic Fever

PubMed Central

Warfield, Kelly Lyn; Olinger, Gene Garrard

2011-01-01

Infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, Marburg (MARV), and Ebola virus (EBOV), leaves the host with a short timeframe in which to mouse a protective immune response. In lethal cases, uncontrolled viral replication and virus-induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. Vaccination studies in animals have demonstrated an association of IgG and neutralizing antibody responses against the protective glycoprotein antigen with survival from lethal challenge. More recently, studies in animal models of filovirus hemorrhagic fever have established that induction of a strong filovirus-specific cytotoxic T lymphocyte (CTL) response can facilitate complete viral clearance. In this review, we describe assays used to discover CTL responses after vaccination or live filovirus infection in both animal models and human clinical trials. Unfortunately, little data regarding CTL responses have been collected from infected human survivors, primarily due to the low frequency of disease and the inability to perform these studies in the field. Advancements in assays and technologies may allow these studies to occur during future outbreaks. PMID:22253531

The syndrome of pseudotumour cerebri and idiopathic intracranial hypertension.

PubMed

Fraser, Clare; Plant, Gordon T

2011-02-01

Idiopathic intracranial hypertension (IIH) is a condition in which raised intracranial pressure is associated with a high body mass index, and in those societies in which the prevalence of obesity is increasing the disorder is of increasing importance. It is one cause of the syndrome of pseudotumour cerebri but the cause and the link with a rise in body weight are not understood. Furthermore the treatment of the more severe, sight-threatening cases is controversial. A major theme in recent years has been an attempt to identify the underlying mechanism of IIH. Some theories - such as the dural sinus stenosis theory - seem to ignore the relationship with weight gain; others have proposed a direct link between obesity and raised intracranial pressure through a specific fat distribution in the body; others through the production of lipokines; and yet others have suggested a converse causation with raised intracranial pressure giving rise to obesity. Uncontrolled case series continue to demonstrate the success of interventions such as cerebrospinal fluid diversion procedures, venous sinus stenting and bariatric surgery but there are no level 1 clinical trials. Interest in IIH is increasing and currently generating numerous studies but there is no consensus view on either cause or management.

Adapting Interpersonal Psychotherapy for Older Adults at Risk for Suicide: Preliminary Findings

PubMed Central

Heisel, Marnin J.; Duberstein, Paul R.; Talbot, Nancy L.; King, Deborah A.; Tu, Xin M.

2010-01-01

We report preliminary findings of the first ever study testing a 16-week course of Interpersonal Psychotherapy (IPT) modified for older outpatients at elevated risk for suicide. Participants were referred from inpatient and outpatient medicine and mental health services. Psychotherapy sessions took place in a therapist’s office in a teaching hospital. Twelve adults 60 years or older (M=70.5, SD=6.1) with current thoughts of suicide (suicide ideation) or a wish to die (death ideation) or with recent self-injurious behavior were recruited into weekly sessions of IPT; one was subsequently excluded due to severe cognitive impairment. Participants completed measures of suicide ideation, death ideation, and depressive symptom severity at pre-treatment, mid-treatment, post-treatment, and at 3-month follow-up periods, and measures of therapeutic process variables. Preliminary findings of this uncontrolled pre-post-treatment study support the feasibility of recruiting and retaining older adults at-risk for suicide into psychotherapy research and suggest that adapted IPT is tolerable and safe. Findings indicate a substantial reduction in participant suicide ideation, death ideation, and depressive symptoms; controlled trials are needed to further evaluate these findings. We discuss implications for clinical care with at-risk older adults. PMID:20574546

G2 accumulation and melanin overproduction in malignant melanocytes treated with a new nitrosourea.

PubMed

Buchdahl, C; Papon, J; Communal, Y; Bourges, M; Madelmont, J C

1998-12-01

Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea), a new anticancer chloroethylnitrosourea (CENU) is being tested in a phase II clinical trial of disseminated melanoma. The antitumour effect of this drug is mainly due to DNA damage in malignant melanocytes. Recently, we have shown that this damage can induce apoptosis in some melanoma cell lines. In others, apoptosis is not clearly observed, although there is a strong cytostatic effect. In this paper, we have characterized the cytological effect of cystemustine on murine malignant melanocytes (B16 cell line) which are resistant to apoptosis induced by this CENU. The results show that 3 days after cystemustine treatment, these melanocytes had accumulated in phase G2 of the cell cycle. There was then a strong morphological modification during a long cytostatic phase up to 30 days after treatment. During this cytostatic phase, there was uncontrolled DNA synthesis and marked swelling. Also, tyrosinase activity, melanin content and the number of mature melanosomes were greatly increased. These results suggest that when malignant melanocytes are not able to undergo apoptosis after treatment with CENU, they accumulate in G2 and this is followed by enhancement of melanogenesis.

Direct and indirect effectiveness of influenza vaccination delivered to children at school preceding an epidemic caused by 3 new influenza virus variants.

PubMed

Glezen, W Paul; Gaglani, Manjusha J; Kozinetz, Claudia A; Piedra, Pedro A

2010-12-01

Influenza is an uncontrolled epidemic disease that is vaccine preventable. New recommendations for universal immunization present a challenge to the implementation of vaccine delivery. This field trial examines the effectiveness of school-based clinics for vaccine delivery before an epidemic caused by 3 new influenza virus variants not contained in the vaccine. Live attenuated influenza vaccine (LAIV) was offered to eligible children in elementary schools of eastern Bell County, Texas. Age-specific rates of medically attended acute respiratory illness for health plan members at the intervention site were compared with those for members at comparison sites during the epidemic, defined by viral surveillance at all sites. Almost 48% of children in elementary schools were vaccinated. Significant herd protection attributed to LAIV was detected for all age groups except 12-17-year-old students, who were not offered free vaccine. Approximately 2500 medical encounters were prevented at the intervention site. Inactivated vaccine provided marginal protection against the epidemic viruses. LAIV delivered to elementary-school children before an epidemic caused by 3 new variant influenza viruses generated significant cross-protection for the recipients and indirect (herd) protection for the community.

Efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose: Results of a randomized controlled trial.

PubMed

Göke, R; Eschenbach, P; Dütting, E D

2015-06-01

This study compared the efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose (FPG) as single-pill combinations (SPCs) with metformin. The randomized crossover, open-label, active-controlled study design assessed the FPG-lowering abilities of a vildagliptin/metformin (50/1000 mg twice daily) SPC compared with a sitagliptin/metformin (50/1000 mg twice daily) SPC after 2 weeks of treatment in 99 type 2 diabetes patients uncontrolled by stable metformin therapy (1000-2000 mg/day). The change in FPG from baseline to day 14 was significantly greater (P < 0.02, Wilcoxon) with vildagliptin [-21.9 mg/dL (SD 27.0)] than with sitagliptin [-14.5 mg/dL (SD 23.0)]. After 14 days of treatment, the mean FPG was 137.8 mg/dL (SD 28.5) with vildagliptin and 140.1mg/dL (SD 26.5) with sitagliptin (P < 0.05, Wilcoxon). Both of these DPP-4 inhibitors, given as SPCs twice daily with metformin, lowered FPG after 14 days of treatment. However, vildagliptin produced a significantly greater reduction in FPG vs baseline compared with sitagliptin, which may translate into clinical relevance. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Innovation to motivation--pilot study of a mobile phone intervention to increase physical activity among sedentary women.

PubMed

Fukuoka, Yoshimi; Vittinghoff, Eric; Jong, So Son; Haskell, William

2010-01-01

This uncontrolled pilot study assessed changes in pedometer-measured step counts and self-reported physical activity during a 3-week mobile phone-based intervention. We also explored whether age, BMI, and psychosocial factors were associated with changes in step counts. Forty-one sedentary adult women in San Francisco, California were asked to report their pedometer steps using a study-supplied mobile phone from June to September 2008. In the second and third weeks, daily prompts delivered by the mobile phone encouraged participants to increase steps by 20% from the previous week. Mean age was 48 years. Average daily total steps increased by approximately 800 or 15% over three weeks (p<0.001). Lower BMI, no antidepressant use, and lower self-reported health status were associated with higher step counts at baseline. Improvements in self-reported will-power were associated with increases in step counts (p<0.001). Neither age (p=0.55) nor BMI (p=0.13) was significantly associated with changes in activity over the 3 weeks. The intervention appeared to motivate sedentary women to increase their physical activity. A randomized controlled clinical trial is warranted and feasible. Copyright © 2010 Elsevier Inc. All rights reserved.

The Role of Patient Navigation on Colorectal Cancer Screening Completion and Education: a Review of the Literature.

PubMed

Sunny, Ajeesh; Rustveld, Luis

2018-04-01

Although the general assumption is that patient navigation helps patients adhere to CRC screening recommendations, concrete evidence for its effectiveness is still currently under investigation. The present literature review was conducted to explore effectiveness of patient navigation and education on colorectal cancer (CRC) screening completion in medically underserved populations. Data collection included PubMed, Google Scholar, and Cochrane reviews searches. Study inclusion criteria included randomized controlled trials and prospective investigations that included an intervention and control group. Case series, brief communications, commentaries, case reports, and uncontrolled studies were excluded. Twenty-seven of the 36 studies screened for relevance were selected for inclusion. Most studies explored the utility of lay and clinic-based patient navigation. Others implemented interventions that included tailored messaging, and culturally and linguistically appropriate outreach and education efforts to meet CRC screening needs of medically underserved individuals. More recent studies have begun to conduct cost-effectiveness analyses of patient navigation programs that impacted CRC screening and completion. Peer-reviewed publications consistently indicate a positive impact of patient navigation programs on CRC screening completion, as well have provided preliminary evidence for their cost-effectiveness.

Pharmacological management of dermatomyositis.

PubMed

Griger, Zoltán; Nagy-Vincze, Melinda; Dankó, Katalin

2017-10-01

Dermatomyositis is a rare heterogeneous systemic autoimmune disease with multiple organ involvement which can result in significant disability and mortality. Despite the lack of placebo-controlled trials, glucocorticoids are considered to be the mainstay of initial management. Treatment strategies are mainly based on uncontrolled studies, evidence based guidelines for treatments do not exist. Areas covered: This review provides an overview of the currently available pharmacological treatments in the field of dermatomyositis including conventional immunosuppressants, biologics and topical agents. The role of antibodies in different treatment responses of dermatomyositis related clinicoserological syndromes is also discussed. A PubMed search was performed in order to find relevant literature for this review. Expert commentary: Early recognition and intervention is essential to ameliorate disease outcome. Determination of antibodies provide a useful key in diagnosis, clinical manifestations, malignancy, prognosis, and treatment response and may lead to wider acceptance of personalized medicine. Corticosteroids with adjunctive steroid-sparing immunosuppressive therapies are recommended to treat disease activity, prevent mortality, and reduce long-term disability. Combinations of second-line therapies or newer third-line therapies are used in severe, refractory, or corticosteroid-dependent diseases. Further research is required to assess the role of new therapies.

Psychotherapy for compulsive buying disorder: a systematic review.

PubMed

Lourenço Leite, Priscilla; Pereira, Valeska Martinho; Nardi, Antônio Egidio; Silva, Adriana Cardoso

2014-11-30

Based on a literature review, the purpose is to identify the main therapeutic approaches for the compulsive buying disorder, a present time disorder characterized by excessive and uncontrollable concerns or behaviors related to buying or expenses, which may lead to adverse consequences. The systematic review was carried out by searching the electronic scientific bases Medline/Pubmed, ISI, PsycInfo. The search was comprised of full-text articles, written in Portuguese and English, with no time limit or restrictions on the type of study and sample. A total of 1659 references were found and, by the end, 23 articles were selected for this review. From the articles found, it was determined that, although there are case studies and clinical trials underlining the effectiveness of the treatment for compulsive buying, only those studies with a focus on the cognitive-behavioral therapy approach make evident the successful response to the treatment. The publication of new studies on the etiology and epidemiology of the disorder is necessary, in order to establish new forms of treatment and to verify the effectiveness and response of the Brazilian population to the existing protocols. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Metabolic Management during Critical Illness: Glycemic Control in the ICU.

PubMed

Honiden, Shyoko; Inzucchi, Silvio E

2015-12-01

Hyperglycemia is a commonly encountered metabolic derangement in the ICU. Important cellular pathways, such as those related to oxidant stress, immunity, and cellular homeostasis, can become deranged with prolonged and uncontrolled hyperglycemia. There is additionally a complex interplay between nutritional status, ambient glucose concentrations, and protein catabolism. While the nuances of glucose management in the ICU have been debated, results from landmark studies support the notion that for most critically ill patients moderate glycemic control is appropriate, as reflected by recent guidelines. Beyond the target population and optimal glucose range, additional factors such as hypoglycemia and glucose variability are important metrics to follow. In this regard, new technologies such as continuous glucose sensors may help alleviate the risks associated with such glucose fluctuations in the ICU. In this review, we will explore the impact of hyperglycemia upon critical cellular pathways and how nutrition provided in the ICU affects blood glucose. Additionally, important clinical trials to date will be summarized. A practical and comprehensive approach to glucose management in the ICU will be outlined, touching upon important issues such as glucose variability, target population, and hypoglycemia. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inhibition of FLT3 Expression by Green Tea Catechins in FLT3 Mutated-AML Cells

PubMed Central

Ly, Bui Thi Kim; Chi, Hoang Thanh; Yamagishi, Makoto; Kano, Yasuhiko; Hara, Yukihiko; Nakano, Kazumi; Sato, Yuko; Watanabe, Toshiki

2013-01-01

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by a block in differentiation and uncontrolled proliferation. FLT3 is a commonly mutated gene found in AML patients. In clinical trials, the presence of a FLT3-ITD mutation significantly correlates with an increased risk of relapse and dismal overall survival. Therefore, activated FLT3 is a promising molecular target for AML therapies. In this study, we have shown that green tea polyphenols including (−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), and (−)-epicatechin-3-gallate (ECG) suppress the proliferation of AML cells. Interestingly, EGCG, EGC and ECG showed the inhibition of FLT3 expression in cell lines harboring FLT3 mutations. In the THP-1 cells harboring FLT3 wild-type, EGCG showed the suppression of cell proliferation but did not suppress the expression of FLT3 even at the concentration that suppress 100% cell proliferation. Moreover, EGCG-, EGC-and ECG-treated cells showed the suppression of MAPK, AKT and STAT5 phosphorylation. Altogether, we suggest that green tea polyphenols could serve as reagents for treatment or prevention of leukemia harboring FLT3 mutations. PMID:23840454

Small molecule inhibition of fibroblast growth factor receptors in cancer.

PubMed

Liang, Guang; Chen, Gaozhi; Wei, Xiaoyan; Zhao, Yunjie; Li, Xiaokun

2013-10-01

Fibroblast growth factors (FGFs) signal through FGF receptors (FGFRs), which are a sub-family of the superfamily of receptor tyrosine kinases, to regulate human development and metabolism. Uncontrolled FGF signaling is responsible for diverse array of developmental disorders, most notably skeletal syndromes due to FGFR gain-of-function mutations. Studies in the last few years have provided significant evidence for the importance of FGF signaling in the pathogenesis of diverse cancers, including endometrial and bladder cancers. FGFs are both potent mitogenic and angiogenic factors and can contribute to carcinogenesis by stimulating cell proliferation and tumor angiogenesis. Gene knockout and pharmacological inhibition of FGFRs in in vivo and in vitro models validate FGFRs as a target for cancer treatment. Considerable efforts are being expended to develop specific, small-molecule inhibitors for treating FGFR-driven cancers. Recent reviews on the FGF/FGFR system have focused primarily on signaling, pathophysiology, and functions in cancer. In this article, we review the key roles of FGFR in cancer, provide an update on the status of clinical trials with small-molecule FGFR inhibitors, and discuss how the current structural data on FGFR kinases guide the design and characterization of new FGFR inhibitors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mass drug administration for malaria

PubMed Central

Poirot, Eugenie; Skarbinski, Jacek; Sinclair, David; Kachur, S Patrick; Slutsker, Laurence; Hwang, Jimee

2013-01-01

Background Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission. Objectives To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings. Selection criteria Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded. Data collection and analysis Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach. Main results Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity (≤5%) Within the first month post-MDA, a single uncontrolled before-and-after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence). In addition, one cluster-randomized trial evaluating MDA in a low endemic setting reported zero episodes of parasitaemia at baseline, and throughout five months of follow-up in both the control and intervention arms (one study, very low quality evidence). Areas of moderate endemicity (6-39%) Within the first month post-MDA, the prevalence of parasitaemia was much lower in three non-randomized controlled studies from Kenya and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate quality evidence), and in three uncontrolled before-and-after studies conducted between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality evidence). The longest follow-up in these settings was four to six months. At this time point, the prevalence of parasitaemia remained substantially lower than controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to 0.33, two studies, low quality evidence). In contrast, the two uncontrolled before-and-after studies found mixed results: one found no difference and one found a substantially higher prevalence compared to baseline (not pooled, two studies, very low quality evidence). Areas of high endemicity (≥40%) Within the first month post-MDA, the single cluster-randomized trial from the Gambia in 1999 found no significant difference in parasite prevalence (one study, low quality evidence). However, prevalence was much lower during the MDA programmes in three non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95% CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to 0.49, four studies,low quality evidence). Four trials reported changes in prevalence beyond three months. In the Gambia, the single cluster-randomized trial found no difference at five months (one trial, moderate quality evidence). The three uncontrolled before-and-after studies had mixed findings with large studies from Palestine and Cambodia showing sustained reductions at four months and 12 months, respectively, and a small study from Malaysia showing no difference after four to six months of follow-up (three studies,low quality evidence). 8-aminoquinolines We found no studies directly comparing MDA regimens that included 8-aminoquinolines with regimens that did not. In a crude subgroup analysis with a limited number of studies, we were unable to detect any evidence of additional benefit of primaquine in moderate- and high-transmission settings. Plasmodium species In studies that reported species-specific outcomes, the same interventions resulted in a larger impact on Plasmodium falciparum compared to P. vivax. Authors' conclusions MDA appears to reduce substantially the initial risk of malaria parasitaemia. However, few studies showed sustained impact beyond six months post-MDA, and those that did were conducted on small islands or in highland settings. To assess whether there is an impact of MDA on malaria transmission in the longer term requires more quasi experimental studies with the intention of elimination, especially in low- and moderate-transmission settings. These studies need to address any long-term outcomes, any potential barriers for community uptake, and contribution to the development of drug resistance. PLAIN LANGUAGE SUMMARY Administration of antimalarial drugs to whole populations Malaria is the most important mosquito-borne disease caused by a parasite, accounting for an estimated 660,000 deaths annually. Fortunately, malaria is both preventable and treatable. Several malaria control tools currently exist, and new and innovative approaches are continually under development. The administration of drugs against malaria to whole populations, termed mass drug administration (MDA), was a component of many malaria elimination programmes in the 1950s, and is once again attracting interest as a malaria elimination tool. As a consequence, it is important to review the currently available literature in order to assess the potential for this strategy to reduce malaria burden and transmission, and to identify gaps in our understanding. This review assessed the impact of MDA on several malaria-specific outcome measures. Thirty-two studies were included in this review, from sites in Asia, Africa, Europe and the Americas. The review found that although MDA can reduce the initial risk of malaria-specific outcomes, these reductions are often not sustained. However, a few studies conducted on small islands or in highland areas did show sustained impact more than six months after MDA. Adverse events were inadequately addressed in most studies. Notable severe drug reactions, including haemolysis, haemoglobinuria, severe anaemia and death, were reported with 8-aminoquinoline plus schizonticide drug co-administration, while severe skin reactions were reported with sulphadoxine-pyrimethamine plus artesunate plus primaquine. Assessing the true impact of MDA programmes can be a challenge due to the heterogeneity of the study methods employed. Nonetheless, this review can help guide future antimalarial MDA interventions and their evaluation. PMID:24318836

Clinical and Economic Burden of Elevated Blood Eosinophils in Patients With and Without Uncontrolled Asthma.

PubMed

Casciano, Julian; Krishnan, Jerry; Dotiwala, Zenobia; Li, Chenghui; Sun, Shawn X

2017-01-01

The European Respiratory Society and American Thoracic Society (ERS/ATS) published guidelines in 2014 for the evaluation and treatment of asthma. These guidelines draw attention to management of patients with asthma that remains uncontrolled despite therapy. One phenotypic characteristic of therapy-resistant asthma is eosinophil elevation. It is important to better understand the burden of care gaps in this patient subgroup in order to support improved treatment strategies in the future. To quantify the economic burden of asthma patients with and without peripheral blood eosinophil elevation. A retrospective cohort study was conducted using data from patients aged 12 years or older with a diagnosis of asthma using electronic health records of over 2 million patients between 2004-2010. Patients with a diagnosis of chronic obstructive pulmonary disease, Churg Strauss syndrome/Wegener's granulomatosis, eosinophilia, cystic/pulmonary fibrosis, allergic bronchopulmonary aspergillosis, or lung cancer in the 12-month period before the date of asthma diagnosis were excluded. Patients with asthma were followed for 12 months after their initial asthma diagnosis to identify those with controlled versus uncontrolled asthma based on ERS/ATS criteria. Patients with at least 1 peripheral blood eosinophil test result of ≥ 400 cells/µL were classified as those with elevated eosinophils. Total annual paid-claim cost was compared by eosinophil levels within the controlled and uncontrolled asthma subgroups. Costs were adjusted to 2015 U.S. dollars. Patients were stratified by control level, and generalized linear modeling regressions were used to assess the magnitude of increase in cost of the elevated eosinophil group. A total of 2,701 patients were included in the study, of which 17% had uncontrolled asthma and 21% had elevated eosinophils. The mean total annual cost of patients with uncontrolled asthma was more than 2 times the cost of those with controlled asthma ($18,341 vs. $8,670, P < 0.001). Patients with uncontrolled asthma in the elevated eosinophil group had almost double the total cost ($28,644 vs. $14,188, P = 0.008) compared with those with blood eosinophil levels in a normal range. Similarly, patients classified as those with controlled asthma in the elevated eosinophil group had almost twice the average costs as those without elevated eosinophils ($14,754 vs. $7,203, P < 0.001). Uncontrolled asthma with elevated eosinophils had 4 times greater hospital admissions and over 4 times higher total costs than controlled asthma without elevated eosinophils. Among patients with uncontrolled asthma, patients with elevated eosinophils had a 53% increase in mean cost ($17,723 vs. $11,581, P < 0.001) compared with patients without elevated eosinophils. Among patients with controlled asthma, patients with elevated eosinophils had a 62% increase in mean cost ($8,897 vs. $5,486, P < 0.001) compared with patients without elevated eosinophils. Elevated peripheral blood eosinophil level is associated with higher cost irrespective of disease control status. This study was funded by Teva Pharmaceuticals. Dotiwala and Casciano report consulting and writing fees from Teva Pharmaceuticals for work on this study. Sun is an employee and stockholder of Teva Pharmaceuticals. Li reports consulting fees from eMAX Health. All authors contributed to study design. Dotiwala took the lead in data collection, along with the other authors, and data interpretation was performed primarily by Krishnan, Sun, and Li, along with Casciano and Dotiwala. The manuscript was written by Casciano, Dotiwala, and Li, along with Sun and Krishnan, and revised by Casciano, Dotiwala, Sun, and Li, with assistance from Krishnan.

Current status of registry of vaccine clinical trials conducted by Korean investigators in ClinicalTrials.gov, database of US National Institutes of Health.

PubMed

Cho, Jahyang; Kim, Bo Bae; Bae, Chong-Woo; Cha, Sung-Ho

2013-01-01

PubMed is not only includes international medical journals but also has a registration site for the ongoing clinical trials, such as ClinicalTrials.gov, under the supervision of US National Institutes of Health. We analyzed current status of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. As of October 2012, there are total of 72 trials found on registry of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. These trials were analyzed and classified by conditions of vaccine clinical trials, biologicals or drugs used in vaccine clinical trials, status of proceeding research, and list of sponsor and collaborators. Total 72 trials of vaccine clinical trials conducted by Korean investigators are classified by groups of infection (64 trials), cancer (4 trials), and others (4 trials). Infections group shown are as follows: poliomyelitis, pertussis, diphtheria, tetanus, and Haemophilus influenzae type b (10), influenza (9), human papillomavirus infection (8), pneumococcal vaccine (6), herpes zoster (4), smallpox (4), hepatitis B (4), etc. One trial of each in lung cancer, breast cancer, prostate cancer, and colorectal cancer are shown in cancer group. One trial of each in Crohn's disease, ulcerative colitis, renal failure, and rheumatoid arthritis are shown in other group. Vaccine clinical trials conducted by Korean investigators in ClinicalTrial.gov reflects the current status of Korean research on vaccine clinical trials at the international level and can indicate research progress. It is hoped that this aids the development of future vaccine clinical trials in Korea.

Automaticity in Anxiety Disorders and Major Depressive Disorder

PubMed Central

Teachman, Bethany A.; Joormann, Jutta; Steinman, Shari; Gotlib, Ian H.

2012-01-01

In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is not sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation. PMID:22858684

Perceived self-control of seizures in patients with uncontrolled partial epilepsy.

PubMed

Lee, Sang-Ahm; No, Young-Joo

2005-03-01

Many patients with epilepsy have warning symptoms prior to seizure onset, and some of these individuals report the ability to abort or prevent these seizures. We investigated the clinical characteristics of perceived self-control of seizures in 174 patients with uncontrolled partial epilepsy. The warning symptoms were categorized as premonitory (prodrome) and as initial symptoms of simple partial seizure onset, depending on the relationship between the warning events and the ensuing seizures. About 50% of the patients with simple partial seizure onset and about 70% of those with prodrome or premonitory symptoms reported that they could abort or prevent their seizures by various self-developed techniques. Patients who attempted to abort or prevent their seizures reported success rates as high as 80%. The proportion of patients with secondary generalized seizures was significantly lower in patients who tried to abort their seizures than in those who did not (p<0.05). The ability to prevent seizures was significantly higher in patients with brain lesions on MRI than in those without lesions (p<0.05). These results suggest that spontaneously developed methods are helpful in controlling seizures in some patients with uncontrolled partial epilepsy and that the potential success of self-control methods may be influenced by structural abnormalities on brain MRI.

Healthcare utilization and costs in adults with stable and uncontrolled epilepsy.

PubMed

Cramer, Joyce A; Wang, Zhixiao J; Chang, Eunice; Powers, Annette; Copher, Ronda; Cherepanov, Dasha; Broder, Michael S

2014-02-01

Despite the availability of numerous antiepileptic drugs (AEDs), some epilepsies remain resistant to treatment. We compared utilization and costs in patients with uncontrolled epilepsy to those with stable epilepsy. Claims data (2007-2009) were used to identify adults with epilepsy requiring additional AED therapy (having uncontrolled epilepsy) and those not requiring additional AED therapy (having stable epilepsy). The date in 2008 on which an additional AED was started was the index date for patients with uncontrolled epilepsy, and a randomly selected date was used for patients with stable epilepsy, whose AED use was unchanged in the preceding year. In the postindex year, all pharmacy and medical claims were used to estimate overall utilization and costs; claims with epilepsy in any diagnosis field were used to estimate epilepsy-related outcomes. Outcomes were adjusted using multivariate analyses. We identified 1536 patients with uncontrolled epilepsy and 8571 patients with stable epilepsy (mean age: 42.8years; female: 48%). Patients with uncontrolled epilepsy had higher comorbidity rates (p<.02). A greater proportion of patients with uncontrolled epilepsy had ≥1 hospitalization or emergency department visit (p<.001). Patients with uncontrolled epilepsy had a greater mean length of hospital stay and more physician office visits (p<.034). After adjustment, the odds of hospitalization (OR: 1.8, any diagnosis; 2.2, epilepsy-related) and emergency department visit (OR: 1.6, any diagnosis; 1.9, epilepsy-related) were greater for patients with uncontrolled epilepsy. Annual overall ($23,238 vs. $13,839) and epilepsy-related ($12,399 vs. $5511) costs were higher in patients with uncontrolled epilepsy and remained higher after adjustment (p<.001). Patients with uncontrolled epilepsy use more services and incur higher costs compared with those with stable epilepsy. Epilepsy-related costs accounted for <50% of the total costs, suggesting that comorbid conditions and/or underidentification of utilization may substantially contribute to costs. © 2013.

46 CFR 32.63-5 - Barge hull classifications-B/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the uncontrolled release of the cargo to the waterways and/or atmosphere. (2) Type II barge hull... measures to preclude uncontrolled release to the atmosphere, but whose uncontrolled release to the...

46 CFR 32.63-5 - Barge hull classifications-B/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the uncontrolled release of the cargo to the waterways and/or atmosphere. (2) Type II barge hull... measures to preclude uncontrolled release to the atmosphere, but whose uncontrolled release to the...

Direct costs of asthma in Brazil: a comparison between controlled and uncontrolled asthmatic patients.

PubMed

Santos, L A; Oliveira, M A; Faresin, S M; Santoro, I L; Fernandes, A L G

2007-07-01

Asthma is a common chronic illness that imposes a heavy burden on all aspects of the patient's life, including personal and health care cost expenditures. To analyze the direct cost associated to uncontrolled asthma patients, a cross-sectional study was conducted to determine costs related to patients with uncontrolled and controlled asthma. Uncontrolled patient was defined by daytime symptoms more than twice a week or nocturnal symptoms during two consecutive nights or any limitations of activities, or need for relief rescue medication more than twice a week, and an ACQ score less than 2 points. A questionnaire about direct cost stratification in health services, including emergency room visits, hospitalization, ambulatory visits, and asthma medications prescribed, was applied. Ninety asthma patients were enrolled (45 uncontrolled/45 controlled). Uncontrolled asthmatics accounted for higher health care expenditures than controlled patients, US$125.45 and US$15.58, respectively [emergency room visits (US$39.15 vs US$2.70) and hospitalization (US$86.30 vs US$12.88)], per patient over 6 months. The costs with medications in the last month for patients with mild, moderate and severe asthma were US$1.60, 9.60, and 25.00 in the uncontrolled patients, respectively, and US$6.50, 19.00 and 49.00 in the controlled patients. In view of the small proportion of uncontrolled subjects receiving regular maintenance medication (22.2%) and their lack of resources, providing free medication for uncontrolled patients might be a cost-effective strategy for the public health system.

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

PubMed

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants <18 years old) conducted in South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

Surgical Treatment of Epilepsy

PubMed Central

Miller, John W.; Hakimian, Shahin

2013-01-01

Purpose of Review: This article outlines indications for neurosurgical treatment of epilepsy, describes the presurgical workup, summarizes surgical approaches, and details expected risks and benefits. Recent Findings: There is class I evidence for the efficacy of temporal lobectomy in treating intractable seizures, and accumulating documentation that successful surgical treatment reverses much of the disability, morbidity, and excess mortality of chronic epilepsy. Summary: Chronic, uncontrolled focal epilepsy causes progressive disability and increased mortality, but these can be reversed with seizure control. Vigorous efforts to stop seizures are warranted. If two well-chosen and tolerated medication trials do not achieve seizure control, an early workup for epilepsy surgery should be arranged. If this workup definitively identifies the brain region from which the seizures arise, and this region can be removed with a low risk of disabling neurologic deficits, neurosurgery will have a much better chance of stopping seizures than further medication trials. PMID:23739107

The safety and efficacy of the administration of recombinant activated factor VII in major surgery and trauma patients.

PubMed

Wilson, Stephen J; Bellamy, Mark C; Giannoudis, Peter V

2005-05-01

Recombinant activated Factor VII (rFVIIa) has been successfully used in the treatment of haemophilia A and B with associated inhibitors for some years. Activated Factor VII binds to activated platelets independently of tissue factor. The resulting stimulation of an exaggerated early thrombin burst at sites of vascular injury makes it an attractive potential treatment for massive, uncontrolled bleeding associated with surgery and trauma. This article describes the evidence relating to surgery and trauma. The lack of large, controlled trials of rFVIIa means that a definitive recommendation regarding its use cannot be made at present. However, in the context of clearly defined protocols and balanced treatment strategies, rFVIIa may have a role in traumatic bleeding. Large scale, randomised controlled trials in trauma are required, as is further work on the safety profile of rFVIIa with an independent international safety monitoring committee.

Polycystic Ovary Syndrome: Effect and Mechanisms of Acupuncture for Ovulation Induction

PubMed Central

Johansson, Julia; Stener-Victorin, Elisabet

2013-01-01

Polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, is characterized by the coexistence of hyperandrogenism, ovulatory dysfunction, and polycystic ovaries (PCO). PCOS also represents the largest part of female oligoovulatory infertility, and the management of ovulatory and menstrual dysfunction, comprises a third of the high costs of PCOS treatment. Current pharmacological and surgical treatments for reproductive symptoms are effective, however, associated with negative side effects, such as cardiovascular complications and multiple pregnancies. For menstrual irregularities and ovulation induction in women with PCOS, acupuncture has indicated beneficial effects. This review will focus on the results from randomized controlled acupuncture trials for regulation of menstrual dysfunction and for inducing ovulation in women with PCOS although there are uncontrolled trials with nonetheless interesting results. Animal experimental studies will be further discussed when they can provide a more mechanistic explanatory view. PMID:24073009

Conducting clinical trials in Singapore.

PubMed

Woo, K T

1999-04-01

All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

Resuscitation with lactated ringer's does not increase inflammatory response in a Swine model of uncontrolled hemorrhagic shock.

PubMed

Watters, Jennifer M; Brundage, Susan I; Todd, S Rob; Zautke, Nathan A; Stefater, J A; Lam, J C; Muller, Patrick J; Malinoski, Darren; Schreiber, Martin A

2004-09-01

Lactated Ringer's (LR) and normal saline (NS) are widely and interchangeably used for resuscitation of trauma victims. Studies show LR to be superior to NS in the physiologic response to resuscitation. Recent in vitro studies demonstrate equivalent effects of LR and NS on leukocytes. We aimed to determine whether LR resuscitation would produce an equivalent inflammatory response compared with normal saline (NS) resuscitation in a clinically relevant swine model of uncontrolled hemorrhagic shock. Thirty-two swine were randomized. Control animals (n = 6) were sacrificed following induction of anesthesia for baseline data. Sham animals (n = 6) underwent laparotomy and 2 h of anesthesia. Uncontrolled hemorrhagic shock animals (n = 10/group) underwent laparotomy, grade V liver injury, and blinded resuscitation with LR or NS to maintain baseline blood pressure for 1.5 h before sacrifice. Lung was harvested, and tissue mRNA levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-alpha) were determined using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR). Sections of lung were processed and examined for neutrophils sequestered within the alveolar walls. Cytokine analysis showed no difference in IL-6 gene transcription in any group (P = 0.99). Resuscitated swine had elevated G-CSF and TNF-alpha gene transcription, but LR and NS groups were not different from each other (P= 0.96 and 0.10, respectively). Both resuscitation groups had significantly more alveolar neutrophils present than controls (P < 0.01) and shams (P < 0.05) but were not different from one another (P= 0.83). LR and NS resuscitation have equivalent effects on indices of inflammation in the lungs in our model of uncontrolled hemorrhagic shock.

Clinical lung transplantation from uncontrolled non-heart-beating donors revisited.

PubMed

Gomez-de-Antonio, David; Campo-Cañaveral, Jose Luis; Crowley, Silvana; Valdivia, Daniel; Cordoba, Mar; Moradiellos, Javier; Naranjo, Jose Manual; Ussetti, Piedad; Varela, Andrés

2012-04-01

The aim of our study is to review and update the long-term results from our previously published series of lung transplantation in uncontrolled non-heart-beating donors (NHBDs). A prospective collection of data was undertaken from all lung transplants performed among uncontrolled NHBDs between 2002 and December 2009. The statistical analysis was performed using SPSS software and survival was estimated using the Kaplan-Meier method. Twenty-nine lung transplants were performed. Mean total ischemic times for the first and second lung were 575 minutes (SD 115.6) and 701 minutes (SD 111.3), respectively. Primary graft dysfunction (PGD) G1, G2 and G3 occurred in 5 cases (17%), 5 cases (17%) and 11 cases (38%), respectively. Overall hospital mortality rate was 17% (5 patients). Statistical analysis revealed a statistically significant association of mortality with ischemic times and with PGD. In terms of overall survival, 3-month, 1-year, 2-year and 5-year survival rates were 78%, 68%, 57% and 51%, respectively, and the conditional survival rates in those who survived the first 3 months were 86%, 72% and 65%, respectively. The cumulative incidence of bronchiolitis obliterans syndrome (BOS) was 11%, 35% and 45% at 1, 3 and 5 years, respectively. Lung transplantation from uncontrolled non-heart-beating donors shows acceptable results for both mid- and long-term survival and BOS; however, the higher rates of PGD and its impact on early mortality must make us more demanding with respect to the acceptance criteria and methods of evaluation used with these donors. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Is There a Clinically Meaningful Change in the Blood Pressure of Osteoarthritis Patients with Comorbid Hypertension During the Course of Balneotherapy?

PubMed Central

Hayta, Emrullah; Yılmaz, Mehmet Birhan; Yayıkçı, İlker; Özer, Zafer; Şahin, Özlem

2015-01-01

Background: Balneotherapy (BT) is a treatment modality that uses the physical and chemical effects of water, including thermomineral, acratothermal, and acratopegal waters. It has many effects on cardiovascular system. Aim: The aim of the study is to investigate the effects of 3-week BT on blood pressure of osteoarthritis (OA) patients with no hypertension (HT), and controlled or uncontrolled HT. Materials and Methods: The OA patients (n = 270) were divided into three groups: No HT, controlled HT, and uncontrolled HT. All the groups received BT in the facilities of our university hospital at the same time every day (10:00-11:30 AM) for 10 min per day, 5 days per week, for a total duration of 15 days in a 3-week period. Systolic and diastolic blood pressures and pulse rates were measured before and after BT on daily basis. Results: Overall, (1) the pulse rates of study groups measured after BT were significantly increased compared to before BT; (2) the systolic blood pressures of study groups measured before and after BT were found as comparable; and (3) the diastolic blood pressures of no HT and controlled HT groups measured before and after BT were not statistically significant (P > 0.05); however, in the uncontrolled HT group, the diastolic blood pressure showed a decreasing trend after BT (P < 0.05). Conclusions: In patients with OA, BT can be safely used without resulting in any meaningful changes in systolic and diastolic blood pressures in patients with normal and controlled HT but a decrease in diastolic blood pressure of patients with uncontrolled HT. This may be an advantage in OA patients having HT as comorbid disease. PMID:26713300

The effect of patient race and blood pressure control on patient-physician communication.

PubMed

Cené, Crystal W; Roter, Debra; Carson, Kathryn A; Miller, Edgar R; Cooper, Lisa A

2009-09-01

Racial disparities in hypertension control contribute to higher rates of cardiovascular mortality among blacks. Patient-physician communication quality is associated with better health outcomes, including blood pressure (BP) control. Both race/ethnicity and BP control may adversely affect communication. To determine whether being black and having poor BP control interact to adversely affect patient-physician communication more than either condition alone, a situation referred to as "double jeopardy." Cross-sectional study of enrollment data from a randomized controlled trial of interventions to enhance patient adherence to therapy for hypertension. Participants included 226 hypertensive patients and 39 physicians from 15 primary care practices in Baltimore, MD. Communication behaviors and visit length from coding of audiotapes. After controlling for patient and physician characteristics, blacks with uncontrolled BP have shorter visits (B = -3.9 min, p < 0.01) with less biomedical (B = -24.0, p = 0.05), psychosocial (B = -19.4, p < 0.01), and rapport-building (B = -19.5, p = 0.01) statements than whites with controlled BP. Of all communication outcomes, blacks with uncontrolled BP are only in "double jeopardy" for a patient positive affect-coders give them lower ratings than all other patients. Blacks with controlled BP also experience shorter visits and less communication with physicians than whites with controlled BP. There are no significant communication differences between the visits of whites with uncontrolled versus controlled BP. This study reveals that patient race is associated with the quality of patient-physician communication to a greater extent than BP control. Interventions that improve patient-physician communication should be tested as a strategy to reduce racial disparities in hypertension care and outcomes.

Baroreflex activation therapy in patients with prior renal denervation.

PubMed

Wallbach, Manuel; Halbach, Marcel; Reuter, Hannes; Passauer, Jens; Lüders, Stephan; Böhning, Enrico; Zenker, Dieter; Müller, Gerhard A; Wachter, Rolf; Koziolek, Michael J

2016-08-01

Both baroreflex activation therapy (BAT) and renal denervation modulate sympathetic activity. The aim of this study was to systematically investigate whether additive modulation of autonomic nervous system by BAT lowers blood pressure (BP) in patients who still suffer from uncontrolled resistant hypertension despite prior renal denervation. From 2012 to January 2015, patients treated with BAT for uncontrolled resistant hypertension, who prior received renal denervation were consecutively analyzed in four German centers for hypertension. Analyses of office BP, 24-h ambulatory BP, central hemodynamics, parameters of renal function were performed. A total of 28 patients, who underwent renal denervation at least 5 months before and still suffer from uncontrolled BP, were subsequently treated with BAT. The office SBP decreased from 182 ± 28 to 163 ± 27 mmHg (P < 0.01) with a responder rate of 68% (office SBP reduction ≥10 mmHg) at month 6, whereas the number of prescribed antihypertensive drug classes remained unchanged (6.2 ± 1.5 vs. 6.0 ± 1.7, P = 0.30). Serum creatinine, estimated glomerular filtration rate and cystatin C remained stable (P = 1.00, P = 0.41 and P = 0.22, respectively), whereas albuminuria was significantly reduced by a median of -29% (P = 0.02). Central SBP (-15 ± 24 mmHg, P = 0.047) and end systolic pressure (-14 ± 20 mmHg, P = 0.03) were significantly reduced. The present data demonstrate that BAT may exert BP-lowering as well as antiproteinuric effects in patients with prior renal denervation. However, precise evaluation of BAT effects in patients with prior renal denervation will need randomized controlled trials using sham procedures.

Apparent and true resistant hypertension: definition, prevalence and outcomes

PubMed Central

Judd, E; Calhoun, DA

2014-01-01

Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of ≥3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires ≥4 agents to achieve control, has received more attention with increased efforts to improve BP control rates and the emergence of device-based therapies for hypertension. This classically defined resistant group consists of patients with true resistant hypertension, controlled resistant hypertension and pseudo-resistant hypertension. In studies where pseudo-resistant hypertension cannot be excluded (for example, 24-h ambulatory BP not obtained), the term apparent resistant hypertension has been used to identify ‘apparent’ lack of control on ≥3 medications. Large, well-designed studies have recently reported the prevalence of resistant hypertension. Pooling prevalence data from these studies and others within North America and Europe with a combined sample size of >600 000 hypertensive participants, the prevalence of resistant hypertension is 14.8% of treated hypertensive patients and 12.5% of all hypertensives. However, the prevalence of true resistant hypertension, defined as uncontrolled both by office and 24-h ambulatory BP monitoring with confirmed medication adherence, may be more meaningful in terms of identifying risk and estimating benefit from newer therapies like renal denervation. Rates of cardiovascular events and mortality follow mean 24-h ambulatory BPs in patients with resistant hypertension, and true resistant hypertension represents the highest risk. The prevalence of true resistant hypertension has not been directly measured in large trials; however, combined data from smaller studies suggest that true resistant hypertension is present in half of the patients with resistant hypertension who are uncontrolled in the office. Our pooled analysis shows prevalence rates of 10.1% and 7.9% for uncontrolled resistant hypertension among individuals treated for hypertension and all hypertensive individuals, respectively. PMID:24430707

Safety of a condom uterine balloon tamponade (ESM-UBT) device for uncontrolled primary postpartum hemorrhage among facilities in Kenya and Sierra Leone.

PubMed

Ramanathan, Aparna; Eckardt, Melody J; Nelson, Brett D; Guha, Moytrayee; Oguttu, Monica; Altawil, Zaid; Burke, Thomas

2018-05-15

Postpartum hemorrhage is the leading cause of maternal mortality in low- and middle-income countries. While evidence on uterine balloon tamponade efficacy for severe hemorrhage is encouraging, little is known about safety of this intervention. The objective of this study was to evaluate the safety of an ultra-low-cost uterine balloon tamponade package (named ESM-UBT) for facility-based management of uncontrolled postpartum hemorrhage (PPH) in Kenya and Sierra Leone. Data were collected on complications/adverse events in all women who had an ESM-UBT device placed among 92 facilities in Sierra Leone and Kenya, between September 2012 and December 2015, as part of a multi-country study. Three expert maternal health investigator physicians analyzed each complication/adverse event and developed consensus on whether there was a potential causal relationship associated with use of the ESM-UBT device. Adverse events/complications specifically investigated included death, hysterectomy, uterine rupture, perineal or cervical injury, serious or minor infection, and latex allergy/anaphylaxis. Of the 201 women treated with an ESM-UBT device in Kenya and Sierra Leone, 189 (94.0%) survived. Six-week or longer follow-up was recorded in 156 of the 189 (82.5%). A causal relationship between use of an ESM-UBT device and one death, three perineal injuries and one case of mild endometritis could not be completely excluded. Three experts found a potential association between these injuries and an ESM-UBT device highly unlikely. The ESM-UBT device appears safe for use in women with uncontrolled PPH. Trial registration was not completed as data was collected as a quality assurance measure for the ESM-UBT kit.

Systems analysis and improvement to optimize pMTCT (SAIA): a cluster randomized trial

PubMed Central

2014-01-01

Background Despite significant increases in global health investment and the availability of low-cost, efficacious interventions to prevent mother-to-child HIV transmission (pMTCT) in low- and middle-income countries with high HIV burden, the translation of scientific advances into effective delivery strategies has been slow, uneven and incomplete. As a result, pediatric HIV infection remains largely uncontrolled. A five-step, facility-level systems analysis and improvement intervention (SAIA) was designed to maximize effectiveness of pMTCT service provision by improving understanding of inefficiencies (step one: cascade analysis), guiding identification and prioritization of low-cost workflow modifications (step two: value stream mapping), and iteratively testing and redesigning these modifications (steps three through five). This protocol describes the SAIA intervention and methods to evaluate the intervention’s impact on reducing drop-offs along the pMTCT cascade. Methods This study employs a two-arm, longitudinal cluster randomized trial design. The unit of randomization is the health facility. A total of 90 facilities were identified in Côte d’Ivoire, Kenya and Mozambique (30 per country). A subset was randomly selected and assigned to intervention and comparison arms, stratified by country and service volume, resulting in 18 intervention and 18 comparison facilities across all three countries, with six intervention and six comparison facilities per country. The SAIA intervention will be implemented for six months in the 18 intervention facilities. Primary trial outcomes are designed to assess improvements in the pMTCT service cascade, and include the percentage of pregnant women being tested for HIV at the first antenatal care visit, the percentage of HIV-infected pregnant women receiving adequate prophylaxis or combination antiretroviral therapy in pregnancy, and the percentage of newborns exposed to HIV in pregnancy receiving an HIV diagnosis eight weeks postpartum. The Consolidated Framework for Implementation Research (CFIR) will guide collection and analysis of qualitative data on implementation process. Discussion This study is a pragmatic trial that has the potential benefit of improving maternal and infant outcomes by reducing drop-offs along the pMTCT cascade. The SAIA intervention is designed to provide simple tools to guide decision-making for pMTCT program staff at the facility level, and to identify low cost, contextually appropriate pMTCT improvement strategies. Trial registration ClinicalTrials.gov NCT02023658 PMID:24885976

Mepolizumab for Treating Severe Eosinophilic Asthma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

PubMed

Bermejo, Iñigo; Stevenson, Matt; Cooper, Katy; Harnan, Sue; Hamilton, Jean; Clowes, Mark; Carroll, Christopher; Harrison, Tim; Saha, Shironjit

2018-02-01

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company (GlaxoSmithKline) that manufactures mepolizumab (Nucala ® ) to submit evidence on the clinical and cost effectiveness of mepolizumab for the treatment of severe eosinophilic asthma. The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent evidence review group (ERG). The ERG produced a review of the evidence for the clinical and cost effectiveness of mepolizumab as add-on to standard of care (SoC) compared with SoC and omalizumab, based upon the company's submission to NICE. The clinical-effectiveness evidence in the company's submission was based predominantly on three randomised controlled trials (DREAM, MENSA and SIRIUS) comparing add-on mepolizumab with placebo plus SoC. The relevant population was defined in terms of degree of asthma severity (four or more exacerbations in the previous year and/or dependency on maintenance oral corticosteroids [mOCS]) and degree of eosinophilia (a blood eosinophil count of ≥ 300 cells/µl in the previous year) based on post hoc subgroup analyses of the pivotal trials. Other subpopulations were considered throughout the appraisal, defined by different eosinophil measurements, number of exacerbations and dependency (or lack thereof) on mOCS. Statistically significant reductions in clinically significant exacerbations were observed in patients receiving mepolizumab compared with SoC meta-analysed across MENSA and DREAM in the modified intention-to-treat (ITT) population (rate ratio [RR] 0.51; 95% confidence interval [CI] 0.42-0.62) as well as in the relevant population (RR 0.47; 95% CI 0.36-0.62). In terms of quality of life, differences on the St. George's Respiratory Questionnaire in MENSA for add-on subcutaneous mepolizumab 100 mg vs. placebo were 7 and 7.5 units in the modified ITT and relevant populations, respectively. A number of issues in the clinical evidence base warrant caution in its interpretation. The ERG noted that the definition of SoC used in the trials differed from that in clinical practice, where patients with severe uncontrolled asthma start treatment with a mOCS. The company's economic post-consultation analysis incorporating a confidential patient access scheme (PAS) estimated that the incremental cost-effectiveness ratio (ICER) for add-on mepolizumab compared with SoC was £27,418 per quality-adjusted life-year (QALY) gained in the relevant population if patients stopped mepolizumab after 1 year unless (1) the number of exacerbations decreased at least 50% or (2) a reduction in corticosteroids dose was achieved whilst maintaining asthma control. The ERG applied an age adjustment to all utilities and corrected the post-continuation assessment utilities, which resulted in an ICER for add-on mepolizumab compared with SoC of £29,163 per QALY gained. The ERG noted that this ICER was not robust for patients who continued treatment due to a corticosteroid dose reduction where exacerbations had decreased by less than 50%, because corticosteroid dose reduction was not allowed in the main trial in which the evidence was gathered (MENSA). The NICE appraisal committee (AC) concluded that add-on mepolizumab could be recommended as an option for treating severe refractory eosinophilic asthma in adults for the relevant population when the stopping rule suggested by the company was applied. The AC also concluded that the comparison between mepolizumab and omalizumab was not clinically relevant or methodologically robust.

The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

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

Higginson, Daniel S., E-mail: daniel.higginson@gmail.com; Chen, Ronald C.; Tracton, Gregg

2012-11-01

Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods andmore » Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1.54; P=.022) remained significant. Conclusions: Patients with bulky central disease, bronchial/vascular compression, and/or pulmonary symptoms exhibited worse overall survival after first-line, platinum-based chemotherapy. A subset of these patients may be studied to determine whether early, planned palliative thoracic radiation could also be of benefit.« less

A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs.

PubMed

Mauri, Laura; Kario, Kazuomi; Basile, Jan; Daemen, Joost; Davies, Justin; Kirtane, Ajay J; Mahfoud, Felix; Schmieder, Roland E; Weber, Michael; Nanto, Shinsuke; Azizi, Michel

2018-01-01

Catheter-based renal denervation is a new approach to treat hypertension via modulation of the renal sympathetic nerves. Although nonrandomized and small, open-label randomized studies resulted in significant reductions in office blood pressure 6months after renal denervation with monopolar radiofrequency catheters, the first prospective, randomized, sham-controlled study (Symplicity HTN-3) failed to meet its blood pressure efficacy end point. New clinical trials with new catheters have since been designed to address the limitations of earlier studies. Accordingly, the RADIANCE-HTN and REQUIRE studies are multicenter, blinded, randomized, sham-controlled trials designed to assess the blood pressure-lowering efficacy of the ultrasound-based renal denervation system (Paradise) in patients with established hypertension either on or off antihypertensive medications, is designed to evaluate patients in 2 cohorts-SOLO and TRIO, in the United States and Europe. The SOLO cohort includes patients with essential hypertension, at low cardiovascular risk, and either controlled on 1 to 2 antihypertensive medications or uncontrolled on 0 to 2 antihypertensive medications. Patients undergo a 4-week medication washout period before randomization to renal denervation (treatment) or renal angiogram (sham). The TRIO cohort includes patients with hypertension resistant to at least 3 antihypertensive drugs including a diuretic. Patients will be stabilized on a single-pill, triple-antihypertensive-drug combination for 4weeks before randomization to treatment or sham. Reduction in daytime ambulatory systolic blood pressure (primary end point) will be assessed at 2months in both cohorts. A predefined medication escalation protocol, as needed for blood pressure control, is implemented between 2 and 6months in both cohorts by a study staff member blinded to the randomization process. At 6months, daytime ambulatory blood pressure and antihypertensive treatment score will be assessed. REQUIRE is designed to evaluate patients with resistant hypertension on standard of care medication in Japan and Korea. Reduction in 24-hour ambulatory systolic blood pressure will be assessed at 3months (primary end point). Both studies are enrolling patients, and their results are expected in 2018. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of carpal tunnel syndrome with polarized polychromatic noncoherent light (Bioptron light): a preliminary, prospective, open clinical trial.

PubMed

Stasinopoulos, D; Stasinopoulos, I; Johnson, M I

2005-04-01

Our aim was to assess the efficacy of polarized polychromatic noncoherent light (Bioptron light) in the treatment of idiopathic carpal tunnel syndrome. Carpal tunnel syndrome is the most common compression neuropathy, but no satisfactory conservative treatment is available at present. An uncontrolled experimental study was conducted in patients who visited our clinic from mid-2001 to mid-2002. A total of 25 patients (22 women and three men) with unilateral idiopathic carpal tunnel syndrome, mild to moderate nocturnal pain, and paraesthesia lasting >3 months participated in the study. The average age of the patients was 47.4 years and the average duration of patients' symptoms was 5.2 months. Polarized polychromatic noncoherent light (Bioptron light) was administered perpendicular to the carpal tunnel area. The irradiation time for each session was 6 min at an operating distance of 5-10 cm from the carpal tunnel area, three times weekly for 4 weeks. Outcome measures used were the participants' global assessments of nocturnal pain and paraesthesia, respectively, at 4 weeks and 6 months. At 4 weeks, two patients (8%) had no change in nocturnal pain, six (24%) were in slightly less nocturnal pain, 12 (48%) were much better in regard to nocturnal pain and five (20%) were pain-free. At 6 months, three patients (12%) were slightly better in regard to nocturnal pain, 13 (52%) were much better regarding nocturnal pain, and nine patients (36%) were pain-free. At 4 weeks, four patients (16%) had no change in paraesthesia, five (20%) were slightly better, 13 patients (52%) were much better, and three patients (12%) were without paraesthesia. At 6 months, two patients (8%) had no change in paraesthesia, two (8%) were slightly better, 14 (56%) were much better, and seven (28%) were without paraesthesia. Nocturnal pain and paraesthesia associated with idiopathic carpal tunnel syndrome improved during polarized polychromatic noncoherent light (Bioptron light) treatment. Controlled clinical trials are needed to establish the absolute and relative effectiveness of this intervention.

The effectiveness of culturally tailored video narratives on medication understanding and use self-efficacy among stroke patients: A randomized controlled trial study protocol.

PubMed

Appalasamy, Jamuna Rani; Tha, Kyi Kyi; Quek, Kia Fatt; Ramaiah, Siva Seeta; Joseph, Joyce Pauline; Md Zain, Anuar Zaini

2018-06-01

A substantial number of the world's population appears to end with moderate to severe long-term disability after stroke. Persistent uncontrolled stroke risk factor leads to unpredicted recurrent stroke event. The increasing prevalence of stroke across ages in Malaysia has led to the adaptation of medication therapy adherence clinic (MTAC) framework. The stroke care unit has limited patient education resources especially for patients with medication understanding and use self-efficacy. Nevertheless, only a handful of studies have probed into the effectiveness of video narrative at stroke care centers. This is a behavioral randomized controlled trial of patient education intervention with video narratives for patients with stroke lacking medication understanding and use self-efficacy. The study will recruit up to 200 eligible stroke patients at the neurology tertiary outpatient clinic, whereby they will be requested to return for follow-up approximately 3 months once for up to 12 months. Consenting patients will be randomized to either standard patient education care or intervention with video narratives. The researchers will ensure control of potential confounding factors, as well as unbiased treatment review with prescribed medications only obtained onsite. The primary analysis outcomes will reflect the variances in medication understanding and use self-efficacy scores, as well as the associated factors, such as retention of knowledge, belief and perception changes, whereas stroke risk factor control, for example, self-monitoring and quality of life, will be the secondary outcomes. The study should be able to determine if video narrative can induce a positive behavioral change towards stroke risk factor control via enhanced medication understanding and use self-efficacy. This intervention is innovative as it combines health belief, motivation, and role model concept to trigger self-efficacy in maintaining healthy behaviors and better disease management. ACTRN (12618000174280).

The Role of Melatonin in the Treatment of Primary Headache Disorders

PubMed Central

Gelfand, Amy A.; Goadsby, Peter J.

2016-01-01

Objective To provide a summary of knowledge about the use of melatonin in the treatment of primary headache disorders. Background Melatonin is secreted by the pineal gland; its production is regulated by the hypothalamus and increases during periods of darkness. Methods We undertook a narrative review of the literature on the role of melatonin in the treatment of primary headache disorders. Results There are randomized placebo-controlled trials examining melatonin for preventive treatment of migraine and cluster headache. For cluster headache, melatonin 10 mg was superior to placebo. For migraine, a randomized placebo-controlled trial of melatonin 3 mg (immediate release) was positive, though an underpowered trial of melatonin 2 mg (sustained release) was negative. Uncontrolled studies, case series, and case reports cover melatonin’s role in treating tension-type headache, hypnic headache, hemicrania continua, SUNCT/SUNA and primary stabbing headache. Conclusions Melatonin may be effective in treating several primary headache disorders, particularly cluster headache and migraine. Future research should focus on elucidating the underlying mechanisms of benefit of melatonin in different headache disorders, as well as clarifying optimal dosing and formulation. PMID:27316772

Do prophylactic antibiotics in gynecologic surgery prevent postoperative inflammatory complications? A systematic review.

PubMed

Boesch, Cedric Emanuel; Pronk, Roderick Franziskus; Medved, Fabian; Hentschel, Pascal; Schaller, Hans-Eberhard; Umek, Wolfgang

2017-06-01

The aim of this study was to systematically review the literature on antibiotic prophylaxis in gynaecologic surgeries to prevent inflammatory complications after gynaecological operations. The study was carried out as a systematic review. Only randomised controlled trials of women undergoing gynaecological surgery were included. The Medline and the Cochrane library databases were searched from 1966 to 2016. The trials must have investigated an antibiotic intervention to prevent an inflammatory complication after gynaecological surgery. Trials were excluded if they were not randomised, uncontrolled or included obstetrical surgery. Prophylactic antibiotics prevent inflammatory complications after gynaecological surgery. Prophylactic antibiotics are more effective in surgery requiring access to the peritoneal cavity or the vagina. Cefotetan appears to be more capable in preventing the overall inflammatory complication rate than cefoxitin or cefazolin. No benefit has been shown for the combination of antibiotics as prophylaxis. No difference has been shown between the long-term and short-term use of antibiotics. There is no need for the primary use of an anaerobic antibacterial agent. Antibiotics help to prevent postoperative inflammatory complications after major gynecologic surgeries.

Environmental interventions to reduce fear of crime: systematic review of effectiveness

PubMed Central

2013-01-01

Background Fear of crime is associated with negative health and wellbeing outcomes, and may mediate some impacts of the built environment on public health. A range of environmental interventions have been hypothesized to reduce the fear of crime. Methods This review aimed to synthesize the literature on the effectiveness of interventions in the built environment to reduce the fear of crime. Systematic review methodology, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance, was used. Studies of environmental interventions which reported a fear of crime outcome and used any prospective evaluation design (randomized controlled trial (RCT), trial or uncontrolled before-and-after study) were included. Eighteen databases were searched. The Hamilton tool was used to assess quality. A narrative synthesis of findings was undertaken. Results A total of 47 studies were included, 22 controlled and 25 uncontrolled, with total sample sizes ranging from n = 52 to approximately n = 23,000. Thirty-six studies were conducted in the UK, ten studies in the USA and one study in the Netherlands. The quality of the evidence overall is low. There are some indications that home security improvements and non-crime-related environmental improvements may be effective for some fear of crime outcomes. There is little evidence that the following reduce fear of crime: street lighting improvements, closed-circuit television (CCTV), multi-component environmental crime prevention programs or regeneration programs. Conclusions There is some evidence for the effectiveness of specific environmental interventions in reducing some indicators of fear of crime, but more attention to the context and possible confounders is needed in future evaluations of complex social interventions such as these. PMID:23663285

Renal sympathetic denervation for resistant hypertension.

PubMed

Froeschl, Michael; Hadziomerovic, Adnan; Ruzicka, Marcel

2013-05-01

Resistant hypertension is an increasingly prevalent health problem associated with important adverse cardiovascular outcomes. The pathophysiology that underlies this condition involves increased function of both the sympathetic nervous system and the renin-angiotensin II-aldosterone system. A crucial link between these 2 systems is the web of sympathetic fibres that course within the adventitia of the renal arteries. These nerves can be targeted by applying radiofrequency energy from the lumen of the renal arteries to renal artery walls (percutaneous renal sympathetic denervation [RSD]), an approach that has attracted great interest. This paper critically reviews the evidence supporting the use of RSD. Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data. Some of these concerns are being addressed in the ongoing Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN-3) trial. The first percutaneous RSD system was approved by Health Canada in the spring of 2012. But until more and better-quality data are available, this procedure should generally be reserved for those patients whose resistant hypertension is truly uncontrolled. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Electronic communications and home blood pressure monitoring (e-BP) study: design, delivery, and evaluation framework.

PubMed

Green, Beverly B; Ralston, James D; Fishman, Paul A; Catz, Sheryl L; Cook, Andrea; Carlson, Jim; Tyll, Lynda; Carrell, David; Thompson, Robert S

2008-05-01

Randomized controlled trials have provided unequivocal evidence that treatment of hypertension decreases mortality and major disability from cardiovascular disease; however, blood pressure remains inadequately treated in most affected individuals. This large gap continues despite the facts that more than 90% of adults with hypertension have health insurance, and hypertension is the leading cause of visits to the doctor. New approaches are needed to improve hypertension care. The Electronic Communications and Home Blood Pressure Monitoring (e-BP) study is a three-arm randomized controlled trial designed to determine whether care based on the Chronic Care Model and delivered over the Internet improves hypertension care. The primary study outcomes are systolic, diastolic, and blood pressure control; secondary outcomes are medication adherence, patient self-efficacy, satisfaction and quality of life, and healthcare utilization and costs. Hypertensive patients receiving care at Group Health medical centers are eligible if they have uncontrolled blood pressure on two screening visits and access to the Web and an e-mail address. Study participants are randomly assigned to three intervention groups: (a) usual care; (b) home blood pressure monitoring receipt and proficiency training on its use and the Group Health secure patient website (with secure e-mail access to their healthcare provider, access to a shared medical record, prescription refill and other services); or (c) this plus pharmacist care management (collaborative care management between the patient, the pharmacist, and the patient's physician via a secure patient website and the electronic medical record). We will determine whether a new model of patient-centered care that leverages Web communications, self-monitoring, and collaborative care management improves hypertension control. If this model proves successful and cost-effective, similar interventions could be used to improve the care of large numbers of patients with uncontrolled hypertension.

Lixisenatide Therapy in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Antidiabetic Treatment: The GetGoal-O Randomized Trial.

PubMed

Meneilly, Graydon S; Roy-Duval, Christine; Alawi, Hasan; Dailey, George; Bellido, Diego; Trescoli, Carlos; Manrique Hurtado, Helard; Guo, Hailing; Pilorget, Valerie; Perfetti, Riccardo; Simpson, Hamish

2017-04-01

To evaluate the efficacy and safety of lixisenatide versus placebo on glycemic control in older patients with type 2 diabetes uncontrolled on their current antidiabetic treatment. In this phase III, double-blind, randomized, placebo-controlled, two-arm, parallel-group, multicenter trial, patients aged ≥70 years were randomized to receive once-daily lixisenatide 20 μg or placebo before breakfast concomitantly with their existing antidiabetic therapy (including insulin) for 24 weeks. Patients at risk for malnutrition or with moderate to severe cognitive impairment were excluded. The primary end point was absolute change in HbA 1c from baseline to week 24. Secondary end points included change from baseline to week 24 in 2-h postprandial plasma glucose (PPG) and body weight. A total of 350 patients were randomized. HbA 1c decreased substantially with lixisenatide (-0.57% [6.2 mmol/mol]) compared with placebo (+0.06% [0.7 mmol/mol]) from baseline to week 24 ( P < 0.0001). Mean reduction in 2-h PPG was significantly greater with lixisenatide (-5.12 mmol/L) than with placebo (-0.07 mmol/L; P < 0.0001). A greater decrease in body weight was observed with lixisenatide (-1.47 kg) versus placebo (-0.16 kg; P < 0.0001). The safety profile of lixisenatide in this older population, including rates of nausea and vomiting, was consistent with that observed in other lixisenatide studies. Hypoglycemia was reported in 17.6% of patients with lixisenatide versus 10.3% with placebo. In nonfrail older patients uncontrolled on their current antidiabetic treatment, lixisenatide was superior to placebo in HbA 1c reduction and in targeting postprandial hyperglycemia, with no unexpected safety findings. © 2017 by the American Diabetes Association.

A Laparoscopic Swine Model of Noncompressible Torso Hemorrhage

DTIC Science & Technology

2014-01-01

Various porcine models of hemorrhage have been developed for civilian and military trauma research. However, the predominant contemporary models lack...significant predictors of mortality. CONCLUSION: This study describes a model of NCTH that reflects clinically relevant physiology in trauma and...uncontrolled hemorrhage. In addition, it quantitatively assesses the role of the swine contractile spleen in the described model. (J Trauma Acute Care Surg

Facial nerve paralysis: A case report of rare complication in uncontrolled diabetic patient with mucormycosis

PubMed Central

Shekar, Vandana; Sikander, Jeelani; Rangdhol, Vishwanath; Naidu, Madhulika

2015-01-01

Mucormycosis is a rare opportunistic aggressive and fatal infection caused by mucor fungus. Seven types of mucormycosis are identified based on the extension and involvement of the lesion, of which the rhino orbital mucormycosis is most common in the head and neck region. Although it is widely spread in nature, clinical cases are rare and observed only in immunocompromised patients and patients with uncontrolled diabetes mellitus. Early symptoms include fever, nasal ulceration or necrosis, periorbital edema or facial swelling, paresthesia and reduced vision. Involvement of cranial nerves although not common, facial nerve palsy is a rare finding. The infection may spread through cribriform plate to the brain resulting in extensive cerebellar infarctions. Timely diagnosis and early recognition of the signs and symptoms, correction of underlying medical disorders, and aggressive medical and surgical intervention are necessary for successful therapeutic outcome. PMID:25810669

A randomized controlled trial of exercise therapy for dizziness and vertigo in primary care.

PubMed Central

Yardley, L; Beech, S; Zander, L; Evans, T; Weinman, J

1998-01-01

BACKGROUND: 'Vestibular rehabilitation' (VR) is an increasingly popular treatment option for patients with persistent dizziness. Previous clinical trials have only evaluated the effects of specialist therapy programmes in small, selective, or uncontrolled patient samples. AIM: To determine the benefits of VR compared with standard medical care, using a brief intervention for dizzy patients in primary care. METHOD: Adults consulting their general practitioner (GP) with dizziness or vertigo were randomly assigned to treatment or control groups. Patients in both groups received the same evaluation at baseline, six-week follow-up, and six-month follow-up, comprising examination of nystagmus, postural control, and movement-provoked dizziness, and a questionnaire assessment of subjective status, symptoms, handicap, anxiety, and depression. At baseline and six weeks later, the treatment group also received an individualized 30-minute therapy session, in which they were taught head, eye, and body exercises designed to promote vestibular compensation and enhance skill and confidence in balance. RESULTS: The treatment group (n = 67) improved on all measures, whereas the control group (n = 76) showed no improvement, resulting in a significant difference between the two groups on physical indices of balance and subjective indices of symptoms and distress. Odds ratios for improvement in treated patients relative to untreated patients were 3.1:1 at six weeks (95% CI = 1.4-6.8) and 3.8:1 at six months (95% CI = 1.6-8.7). CONCLUSION: VR is a simple, inexpensive, and beneficial treatment, and may be an appropriate first stage of management for many dizzy patients in primary care. PMID:9667087

Time-intensive cognitive behaviour therapy for obsessive-compulsive disorder: A case series and matched comparison group.

PubMed

Oldfield, Victoria B; Salkovskis, Paul M; Taylor, Tracey

2011-03-01

A time-intensive format may be both useful and effective for the delivery of cognitive behaviour therapy (CBT) for obsessive-compulsive disorder (OCD). Intensive treatments also offer a pragmatic alternative to in-patient admission for those in a geographically remote location. Published studies of intensive treatment include pioneering exposure-response prevention (ERP) trials that emphasized the requirement for high-intensity treatment; more recently several studies have used treatment protocols with a heavy emphasis on ERP. This study compares intensive versus standard weekly treatment format following the integrated formulation-driven CBT approach widely used in UK adult mental health settings. An analysis of patients undertaking intensive CBT using a matched comparison group of those who undertook weekly CBT for OCD. Twenty-two adult patients undertook intensive format treatment (matched with a weekly group for age, gender, and initial symptoms). A range of self-report measures were examined at the end of treatment and at a 3-month follow-up. Significant treatment effects were found on a range of self-report measures; both conditions were found to be equally effective at the end of treatment and at 3-month follow-up. Uncontrolled effect sizes show that the intensive treatment was comparable to other trials of CBT for OCD. An intensive treatment format for the delivery of CBT for OCD was found to be as effective as weekly treatment. This is consistent with the recommendations from the National Institute for Clinical Excellence guidelines. This study adds to the growing literature on the effectiveness of intensive format treatment. ©2010 The British Psychological Society.

Vitamin D supplementation has no major effect on pain or pain behavior in bedridden geriatric patients with advanced dementia.

PubMed

Björkman, Mikko; Sorva, Antti; Tilvis, Reijo

2008-08-01

In a few, earlier, uncontrolled trials, alleviation of chronic pain has been documented by vitamin D supplementation. This randomized double-blind placebo controlled trial addressed the association between pain and vitamin D deficiency and the effects of vitamin D supplementation on pain in institutionalized aged patients. 216 long-term care patients were enrolled in Helsinki, Finland. Pain was assessed by three tools: Resident Assessment Instrument (RAI), Discomfort Behavior Scale, and Pain Assessment in Advanced Dementia Scale. Scores for Cognitive Performance Scale (CPS) and other clinical assessments were also collected from the RAI-database. Levels of 25-hydroxyvitamin D (25- OHD) and parathyroid hormone were also determined. Patients in pain (n=202) were randomized into three treatment groups, each receiving 0, 400, or 1200 IU cholecalciferol per day, respectively. Assessments were repeated after six-month vitamin D supplementation. Patients were aged (84.5+/-7.5 yrs), demented (CPS= 4.9+/-1.4, range 1-6), and chronically bedridden. Pain was present in 38.4% to 83.8% of patients depending on assessment tool. Low 25-OHD levels (<50 nmol/L) were very common (98.1%). However, vitamin D deficiency was not associated with pain or pain behavior. The supplementation resulted in a marked increase in 25-OHD levels. However, neither prevalence of painlessness nor pain scores changed significantly after vitamin D supplementation. We were not able either to show an association between vitamin D deficiency and pain or to observe alleviation of pain by vitamin D supplementation. The independent role of vitamin D in the etiology of pain remains controversial.

Adapting interpersonal psychotherapy for older adults at risk for suicide.

PubMed

Heisel, Marnin J; Talbot, Nancy L; King, Deborah A; Tu, Xin M; Duberstein, Paul R

2015-01-01

To pilot a psychological intervention adapted for older adults at risk for suicide. A focused, uncontrolled, pre-to-post-treatment psychotherapy trial. All eligible participants were offered the study intervention. Outpatient mental health care provided in the psychiatry department of an academic medical center in a mid-sized Canadian city. Seventeen English-speaking adults 60 years or older, at risk for suicide by virtue of current suicide ideation, death ideation, and/or recent self-injury. A 16-session course of Interpersonal Psychotherapy (IPT) adapted for older adults at risk for suicide who were receiving medication and/or other standard psychiatric treatment for underlying mood disorders. Participants completed a demographics form, screens for cognitive impairment and alcohol misuse, a semi-structured diagnostic interview, and measures of primary (suicide ideation and death ideation) and secondary study outcomes (depressive symptom severity, social adjustment and support, psychological well-being), and psychotherapy process measures. Participants experienced significant reductions in suicide ideation, death ideation, and depressive symptom severity, and significant improvement in perceived meaning in life, social adjustment, perceived social support, and other psychological well-being variables. Study participants experienced enhanced psychological well-being and reduced symptoms of depression and suicide ideation over the course of IPT adapted for older adults at risk for suicide. Larger, controlled trials are needed to further evaluate the impact of this novel intervention and to test methods for translating and integrating focused interventions into standard clinical care with at-risk older adults. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Treatment options for rheumatoid arthritis: celecoxib, leflunomide, etanercept, and infliximab.

PubMed

Luong, B T; Chong, B S; Lowder, D M

2000-06-01

To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). A MEDLINE search (1966-January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. All controlled and uncontrolled trials were reviewed. Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.

Novel Therapies in Light Chain Amyloidosis.

PubMed

Milani, Paolo; Merlini, Giampaolo; Palladini, Giovanni

2018-05-01

Light chain (AL) amyloidosis is the most common form of amyloidosis involving the kidney. It is characterized by albuminuria, progressing to overt nephrotic syndrome and eventually end-stage renal failure if diagnosed late or ineffectively treated, and in most cases by concomitant heart involvement. Cardiac amyloidosis is the main determinant of survival, whereas the risk of dialysis is predicted by baseline proteinuria and glomerular filtration rate, and by response to therapy. The backbone of treatment is chemotherapy targeting the underlying plasma cell clone, that needs to be risk-adapted due to the frailty of patients with AL amyloidosis who have cardiac and/or multiorgan involvement. Low-risk patients (∼20%) can be considered for autologous stem cell transplantation that can be preceded by induction and/or followed by consolidation with bortezomib-based regimens. Bortezomib combined with alkylators, such as melphalan, preferred in patients harboring t(11;14), or cyclophosphamide, is used in most intermediate-risk patients, and with cautious dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents, such as pomalidomide, ixazomib, and daratumumab, prove effective in the relapsed/refractory setting, and are being moved to upfront therapy in clinical trials. Novel approaches based on small molecules interfering with the amyloidogenic process and on antibodies targeting the amyloid deposits gave promising results in preliminary uncontrolled studies, are being tested in controlled trials, and will likely prove powerful complements to chemotherapy. Finally, improvements in the understanding of the molecular mechanisms of organ damage are unveiling novel potential treatment targets, moving toward a cure for this dreadful disease.

Improving blood pressure control: increase the dose of diuretic or switch to a fixed-dose angiotensin receptor blocker/diuretic? the valsartan hydrochlorothiazide diuretic for initial control and titration to achieve optimal therapeutic effect (Val-DICTATE) trial.

PubMed

White, William B; Calhoun, David A; Samuel, Rita; Taylor, Addison A; Zappe, Dion H; Purkayastha, Das

2008-06-01

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.

Searching for cures: Inner-city and rural patients' awareness and perceptions of cancer clinical trials.

PubMed

Geana, Mugur; Erba, Joseph; Krebill, Hope; Doolittle, Gary; Madhusudhana, Sheshadri; Qasem, Abdulraheem; Malomo, Nikki; Sharp, Denise

2017-03-01

Fewer than 5% of cancer patients participate in clinical trials, making it challenging to test new therapies or interventions for cancer. Even within that small number, patients living in inner-city and rural areas are underrepresented in clinical trials. This study explores cancer patients' awareness and perceptions of cancer clinical trials, as well as their perceptions of patient-provider interactions related to discussing cancer clinical trials in order to improve accrual in cancer clinical trials. Interviews with 66 former and current in inner-city and rural cancer patients revealed a lack of awareness and understanding about clinical trials, as well as misconceptions about what clinical trials entail. Findings also revealed that commercials and television shows play a prominent role in forming inner-city and rural patients' attitudes and/or misconceptions about clinical trials. However, rural patients were more likely to hold unfavorable views about clinical trials than inner-city patients. Patient-provider discussions emerged as being crucial for increasing awareness of clinical trials among patients and recruiting them to trials. Findings from this study will inform communication strategies to enhance recruitment to cancer clinical trials by increasing awareness and countering misconceptions about clinical trials.

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

PubMed

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

2014-07-01

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

A systematic review of training programmes for recruiters to randomised controlled trials.

PubMed

Townsend, Daisy; Mills, Nicola; Savović, Jelena; Donovan, Jenny L

2015-09-28

Recruitment to randomised controlled trials (RCTs) is often difficult. Clinician related factors have been implicated as important reasons for low rates of recruitment. Clinicians (doctors and other health professionals) can experience discomfort with some underlying principles of RCTs and experience difficulties in conveying them positively to potential trial participants. Recruiter training has been suggested to address identified problems but a synthesis of this research is lacking. The aim of our study was to systematically review the available evidence on training interventions for recruiters to randomised trials. Studies that evaluated training programmes for trial recruiters were included. Those that provided only general communication training not linked to RCT recruitment were excluded. Data extraction and quality assessment were completed by two reviewers independently, with a third author where necessary. Seventeen studies of 9615 potentially eligible titles and abstracts were included in the review: three randomised controlled studies, two non-randomised controlled studies, nine uncontrolled pre-test/post-test studies, two qualitative studies, and a post-training questionnaire survey. Most studies were of moderate or weak quality. Training programmes were mostly set within cancer trials, and usually consisted of workshops with a mix of health professionals over one or two consecutive days covering generic and trial specific issues. Recruiter training programmes were well received and some increased recruiters' self-confidence in communicating key RCT concepts to patients. There was, however, little evidence that this training increased actual recruitment rates or patient understanding, satisfaction, or levels of informed consent. There is a need to develop recruiter training programmes that can lead to improved recruitment and informed consent in randomised trials.

Patient Navigation As a Model to Increase Participation of African Americans in Cancer Clinical Trials.

PubMed

Fouad, Mona N; Acemgil, Aras; Bae, Sejong; Forero, Andres; Lisovicz, Nedra; Martin, Michelle Y; Oates, Gabriela R; Partridge, Edward E; Vickers, Selwyn M

2016-06-01

Less than 10% of patients enrolled in clinical trials are minorities. The patient navigation model has been used to improve access to medical care but has not been evaluated as a tool to increase the participation of minorities in clinical trials. The Increasing Minority Participation in Clinical Trials project used patient navigators (PNs) to enhance the recruitment of African Americans for and their retention in therapeutic cancer clinical trials in a National Cancer Institute-designated comprehensive cancer center. Lay individuals were hired and trained to serve as PNs for clinical trials. African American patients potentially eligible for clinical trials were identified through chart review or referrals by clinic nurses, physicians, and social workers. PNs provided two levels of services: education about clinical trials and tailored support for patients who enrolled in clinical trials. Between 2007 and 2014, 424 African American patients with cancer were referred to the Increasing Minority Participation in Clinical Trials project. Of those eligible for a clinical trial (N = 378), 304 (80.4%) enrolled in a trial and 272 (72%) consented to receive patient navigation support. Of those receiving patient navigation support, 74.5% completed the trial, compared with 37.5% of those not receiving patient navigation support. The difference in retention rates between the two groups was statistically significant (P < .001). Participation of African Americans in therapeutic cancer clinical trials increased from 9% to 16%. Patient navigation for clinical trials successfully retained African Americans in therapeutic trials compared with non-patient navigation trial participation. The model holds promise as a strategy to reduce disparities in cancer clinical trial participation. Future studies should evaluate it with racial/ethnic minorities across cancer centers. Copyright © 2016 by American Society of Clinical Oncology.

Modeling posttraumatic growth among cancer patients: The roles of social support, appraisals, and adaptive coping.

PubMed

Cao, Weidan; Qi, Xiaona; Cai, Deborah A; Han, Xuanye

2018-01-01

The purpose of the study was to build a model to explain the relationships between social support, uncontrollability appraisal, adaptive coping, and posttraumatic growth (PTG) among cancer patients in China. The participants who were cancer patients in a cancer hospital in China filled out a survey. The final sample size was 201. Structural equation modeling was used to build a model explaining PTG. Structural equation modeling results indicated that higher levels of social support predicted higher levels of adaptive coping, higher levels of uncontrollability appraisal predicted lower levels of adaptive coping, and higher levels of adaptive coping predicted higher levels of PTG. Moreover, adaptive coping was a mediator between social support and growth, as well as a mediator between uncontrollability and growth. The direct effects of social support and uncontrollability on PTG were insignificant. The model demonstrated the relationships between social support, uncontrollability appraisal, adaptive coping, and PTG. It could be concluded that uncontrollability appraisal was a required but not sufficient condition for PTG. Neither social support nor uncontrollability appraisal had direct influence on PTG. However, social support and uncontrollability might indirectly influence PTG, through adaptive coping. It implies that both internal factors (eg, cognitive appraisal and coping) and external factors (eg, social support) are required in order for growth to happen. Copyright © 2017 John Wiley & Sons, Ltd.

Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery.

PubMed

Coppola, Antonio; Windyga, Jerzy; Tufano, Antonella; Yeung, Cindy; Di Minno, Matteo Nicola Dario

2015-02-09

In people with haemophilia or other congenital bleeding disorders undergoing surgical interventions, haemostatic treatment is needed in order to correct the underlying coagulation abnormalities and minimise the bleeding risk. This treatment varies according to the specific haemostatic defect, its severity and the type of surgical procedure. The aim of treatment is to ensure adequate haemostatic coverage for as long as the bleeding risk persists and until wound healing is complete. To assess the effectiveness and safety of different haemostatic regimens (type, dose and duration, modality of administration and target haemostatic levels) administered in people with haemophilia or other congenital bleeding disorders for preventing bleeding complications during and after surgical procedures. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the last search: 20 November 2014. Randomised and quasi-randomised controlled trials comparing any hemostatic treatment regimen to no treatment or to another active regimen in children and adults with haemophilia or other congenital bleeding disorders undergoing any surgical intervention. Two authors independently assessed trials (eligibility and risks of bias) and extracted data. Meta-analyses were performed on available and relevant data. Of the 16 identified trials, four (112 participants) were eligible for inclusion.Two trials evaluated 59 people with haemophilia A and B undergoing 63 dental extractions. Trials compared the use of a different type (tranexamic acid or epsilon-aminocaproic acid) and regimen of antifibrinolytic agents as haemostatic support to the initial replacement treatment. Neither trial specifically addressed mortality (one of this review's primary outcomes); however, in the frame of safety assessments, no fatal adverse events were reported. The second primary outcome of blood loss was assessed after surgery and these trials showed the reduction of blood loss and requirement of post-operative replacement treatment in people receiving antifibrinolytic agents compared with placebo. The remaining primary outcome of need for re-intervention was not reported by either trial.Two trials reported on 53 people with haemophilia A and B with inhibitors treated with different regimens of recombinant activated factor VII (rFVIIa) for haemostatic coverage of 33 major and 20 minor surgical interventions. Neither of the included trials specifically addressed any of the review's primary outcomes (mortality, blood loss and need for re-intervention). In one trial a high-dose rFVIIa regimen (90 μg/kg) was compared with a low-dose regimen (35 μg/kg); the higher dose showed increased haemostatic efficacy, in particular in major surgery, with shorter duration of treatment, similar total dose of rFVIIa administered and similar safety levels. In the second trial, bolus infusion and continuous infusion of rFVIIa were compared, showing similar haemostatic efficacy, duration of treatment and safety. There is insufficient evidence from randomised controlled trials to assess the most effective and safe haemostatic treatment to prevent bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgical procedures. Ideally large, adequately powered, and well-designed randomised controlled trials would be needed, in particular to address the cost-effectiveness of such demanding treatments in the light of the increasing present economic constraints, and to explore the new challenge of ageing patients with haemophilia or other congenital bleeding disorders. However, performing such trials is always a complex task in this setting and presently does not appear to be a clinical and research priority. Indeed, major and minor surgeries are effectively and safely performed in these individuals in clinical practice, with the numerous national and international recommendations and guidelines providing regimens for treatment in this setting mainly based on data from observational, uncontrolled studies.

Review of the registration of clinical trials in UMIN-CTR from 2 June 2005 to 1 June 2010 - focus on Japan domestic, academic clinical trials

PubMed Central

2013-01-01

Background Established on 1 June 2005, the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) is the largest clinical trial registry in Japan, and joined the World Health Organization (WHO) registry network in October 2008. Our aim was to understand the registration trend and overall characteristics of Japan domestic, academic (non-industry-funded) clinical trials, which constitute the main body of registrations in UMIN-CTR. In addition, we aimed to investigate the accessibility of clinical trials in UMIN-CTR to people worldwide, as well as the accessibility of clinical trials conducted in Japan but registered abroad to Japanese people in the Japanese language. Methods We obtained the data for registrations in UMIN-CTR from the UMIN Center, and extracted Japan domestic, academic clinical trials to analyze their registration trend and overall characteristics. We also investigated how many of the trials registered in UMIN-CTR could be accessed from the International Clinical Trials Registry Platform (ICTRP). Finally, we searched ClinicalTrials.gov for all clinical trials conducted in Japan and investigated how many of them were also registered in Japanese registries. All of the above analyses included clinical trials registered from 2 June 2005 to 1 June 2010. Results During the period examined, the registration trend showed an obvious peak around September 2005 and rapid growth from April 2009. Of the registered trials, 46.4% adopted a single-arm design, 34.5% used an active control, only 10.9% were disclosed before trial commencement, and 90.0% did not publish any results. Overall, 3,063 of 3,064 clinical trials registered in UMIN-CTR could be accessed from ICTRP. Only 8.7% of all clinical trials conducted in Japan and registered in ClinicalTrials.gov were also registered in Japanese registries. Conclusions The International Committee of Medical Journal Editors (ICMJE) announcements about clinical trial registration and the Ethical Guidelines for Clinical Research published by the Japanese government are considered to have promoted clinical trial registration in UMIN-CTR. However, problems associated with trial design, retrospective registration, and publication of trial results need to be addressed in future. Almost all clinical trials registered in UMIN-CTR are accessible to people worldwide through ICTRP. However, many trials conducted in Japan but registered abroad cannot be accessed from Japanese registries in Japanese. PMID:24124926

Sick Day Management in Children and Adolescents with Type 1 Diabetes.

PubMed

Choudhary, Abha

2016-06-01

Diabetic Ketoacidosis (DKA) has high morbidity and mortality and can be prevented. It is extremely important to give clear guidance to patients and families on how to manage diabetes during intercurrent illnesses to avoid complications of ketoacidosis, dehydration,uncontrolled or symptomatic hyperglycemia and hypoglycemia. This descriptive review of clinical cases and management guidelines for sick days in children and adolescents with diabetes is provided as a resource for physicians who may take calls from parents of sick children with diabetes or manage these children in a clinic, emergency room or hospital setting.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be laid down on the quality of trials being conducted in order to provide justice in the name of EBP. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians' Patient Care Decisions.

PubMed

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians.

Electronic nicotine delivery systems: a research agenda.

PubMed

Etter, Jean-François; Bullen, Chris; Flouris, Andreas D; Laugesen, Murray; Eissenberg, Thomas

2011-05-01

Electronic nicotine delivery systems (ENDS, also called electronic cigarettes or e-cigarettes) are marketed to deliver nicotine and sometimes other substances by inhalation. Some tobacco smokers report that they used ENDS as a smoking cessation aid. Whether sold as tobacco products or drug delivery devices, these products need to be regulated, and thus far, across countries and states, there has been a wide range of regulatory responses ranging from no regulation to complete bans. The empirical basis for these regulatory decisions is uncertain, and more research on ENDS must be conducted in order to ensure that the decisions of regulators, health care providers and consumers are based on science. However, there is a dearth of scientific research on these products, including safety, abuse liability and efficacy for smoking cessation. The authors, who cover a broad range of scientific expertise, from basic science to public health, suggest research priorities for non-clinical, clinical and public health studies. They conclude that the first priority is to characterize the safety profile of these products, including in long-term users. If these products are demonstrated to be safe, their efficacy as smoking cessation aids should then be tested in appropriately designed trials. Until these studies are conducted, continued marketing constitutes an uncontrolled experiment and the primary outcome measure, poorly assessed, is user health. Potentially, this research effort, contributing to the safety and efficacy of new smoking cessation devices and to the withdrawal of dangerous products, could save many lives.

Electronic nicotine delivery systems: a research agenda

PubMed Central

Etter, Jean-François; Bullen, Chris; Flouris, Andreas D; Laugesen, Murray; Eissenberg, Thomas

2011-01-01

Electronic nicotine delivery systems (ENDS, also called electronic cigarettes or e-cigarettes) are marketed to deliver nicotine and sometimes other substances by inhalation. Some tobacco smokers report that they used ENDS as a smoking cessation aid. Whether sold as tobacco products or drug delivery devices, these products need to be regulated, and thus far, across countries and states, there has been a wide range of regulatory responses ranging from no regulation to complete bans. The empirical basis for these regulatory decisions is uncertain, and more research on ENDS must be conducted in order to ensure that the decisions of regulators, health care providers and consumers are based on science. However, there is a dearth of scientific research on these products, including safety, abuse liability and efficacy for smoking cessation. The authors, who cover a broad range of scientific expertise, from basic science to public health, suggest research priorities for non-clinical, clinical and public health studies. They conclude that the first priority is to characterize the safety profile of these products, including in long-term users. If these products are demonstrated to be safe, their efficacy as smoking cessation aids should then be tested in appropriately designed trials. Until these studies are conducted, continued marketing constitutes an uncontrolled experiment and the primary outcome measure, poorly assessed, is user health. Potentially, this research effort, contributing to the safety and efficacy of new smoking cessation devices and to the withdrawal of dangerous products, could save many lives. PMID:21415064

How Safe Is Ginger Rhizome for Decreasing Nausea and Vomiting in Women during Early Pregnancy?

PubMed Central

Stanisiere, Julien; Mousset, Pierre-Yves; Lafay, Sophie

2018-01-01

Ginger, Zingiber officinale Roscoe, is increasingly consumed as a food or in food supplements. It is also recognized as a popular nonpharmacological treatment for nausea and vomiting of pregnancy (NVP). However, its consumption is not recommended by all countries for pregnant women. Study results are heterogeneous and conclusions are not persuasive enough to permit heath care professionals to recommend ginger safely. Some drugs are also contraindicated, leaving pregnant women with NVP with few solutions. We conducted a review to assess effectiveness and safety of ginger consumption during early pregnancy. Systematic literature searches were conducted on Medline (via Pubmed) until the end of December 2017. For the evaluation of efficacy, only double-blind, randomized, controlled trials were included. For the evaluation of the safety, controlled, uncontrolled, and pre-clinical studies were included in the review. Concerning toxicity, none can be extrapolated to humans from in vitro results. In vivo studies do not identify any major toxicities. Concerning efficacy and safety, a total of 15 studies and 3 prospective clinical studies have been studied. For 1 g of fresh ginger root per day for four days, results show a significant decrease in nausea and vomiting and no risk for the mother or her future baby. The available evidence suggests that ginger is a safe and effective treatment for NVP. However, beyond the ginger quantity needed to be effective, ginger quality is important from the perspective of safety. PMID:29614764

Hearing Tests on Mobile Devices: Evaluation of the Reference Sound Level by Means of Biological Calibration.

PubMed

Masalski, Marcin; Kipiński, Lech; Grysiński, Tomasz; Kręcicki, Tomasz

2016-05-30

Hearing tests carried out in home setting by means of mobile devices require previous calibration of the reference sound level. Mobile devices with bundled headphones create a possibility of applying the predefined level for a particular model as an alternative to calibrating each device separately. The objective of this study was to determine the reference sound level for sets composed of a mobile device and bundled headphones. Reference sound levels for Android-based mobile devices were determined using an open access mobile phone app by means of biological calibration, that is, in relation to the normal-hearing threshold. The examinations were conducted in 2 groups: an uncontrolled and a controlled one. In the uncontrolled group, the fully automated self-measurements were carried out in home conditions by 18- to 35-year-old subjects, without prior hearing problems, recruited online. Calibration was conducted as a preliminary step in preparation for further examination. In the controlled group, audiologist-assisted examinations were performed in a sound booth, on normal-hearing subjects verified through pure-tone audiometry, recruited offline from among the workers and patients of the clinic. In both the groups, the reference sound levels were determined on a subject's mobile device using the Bekesy audiometry. The reference sound levels were compared between the groups. Intramodel and intermodel analyses were carried out as well. In the uncontrolled group, 8988 calibrations were conducted on 8620 different devices representing 2040 models. In the controlled group, 158 calibrations (test and retest) were conducted on 79 devices representing 50 models. Result analysis was performed for 10 most frequently used models in both the groups. The difference in reference sound levels between uncontrolled and controlled groups was 1.50 dB (SD 4.42). The mean SD of the reference sound level determined for devices within the same model was 4.03 dB (95% CI 3.93-4.11). Statistically significant differences were found across models. Reference sound levels determined in the uncontrolled group are comparable to the values obtained in the controlled group. This validates the use of biological calibration in the uncontrolled group for determining the predefined reference sound level for new devices. Moreover, due to a relatively small deviation of the reference sound level for devices of the same model, it is feasible to conduct hearing screening on devices calibrated with the predefined reference sound level.

76 FR 16240 - Mandatory Reliability Standards for Interconnection Reliability Operating Limits

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-23

... Standards. The Reliability Standards were designed to prevent instability, uncontrolled separation, or... designed to prevent instability, uncontrolled separation, or cascading outages that adversely impact the... instability, uncontrolled separation, or cascading outages. See NERC Glossary, available at http://www.nerc...

[Psychostimulants for late life depression].

PubMed

Delsalle, P; Schuster, J-P; von Gunten, A; Limosin, F

2017-11-28

The use of psychostimulants in the treatment of depressive disorders is receiving renewed interest. Recent publications suggest a particular interest of psychostimulants in the treatment of depression in the elderly. The aim of this article is to review the literature on the role of psychostimulants in the treatment of depression in older adults. The literature review focused on efficacy and tolerability studies of psychostimulants in the treatment of depression for the elderly that were published between 1980 and 2016. The only inclusion criterion applied was an average age of the sample studied greater than or equal to 60 years. Overall, 12 trials were selected: 3 controlled trials and 9 uncontrolled trials. Of the 3 controlled trials, one compared parallel groups and the other two were cross-tests. Among the psychostimulants, methylphenidate was the most studied molecule. The trials demonstrate an efficacy of this molecule in particular as an add-on therapy in old-age depression but for the most part with a level of proof that remains insufficient. The small size of the samples and the methodological limitations of the studies obviate the possibility of extracting definitive conclusions concerning the place of psychostimulants in the treatment of depression in the elderly. Further studies are required in particular in the treatment of resistant depressive episodes. Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

An Ontology-based Architecture for Integration of Clinical Trials Management Applications

PubMed Central

Shankar, Ravi D.; Martins, Susana B.; O’Connor, Martin; Parrish, David B.; Das, Amar K.

2007-01-01

Management of complex clinical trials involves coordinated-use of a myriad of software applications by trial personnel. The applications typically use distinct knowledge representations and generate enormous amount of information during the course of a trial. It becomes vital that the applications exchange trial semantics in order for efficient management of the trials and subsequent analysis of clinical trial data. Existing model-based frameworks do not address the requirements of semantic integration of heterogeneous applications. We have built an ontology-based architecture to support interoperation of clinical trial software applications. Central to our approach is a suite of clinical trial ontologies, which we call Epoch, that define the vocabulary and semantics necessary to represent information on clinical trials. We are continuing to demonstrate and validate our approach with different clinical trials management applications and with growing number of clinical trials. PMID:18693919

Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

PubMed

Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo

2015-02-01

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; P<0.0001) in the nonresistant cohort and by 8.76 mm Hg (95% confidence interval, 4.83-12.70; P<0.0001) in the resistant cohort. Using metaregression, the falls were larger in trials that did not use ambulatory blood pressure monitoring as an inclusion criterion (z=2.84; P=0.0045), in those with higher baseline blood pressures (z=-0.3; P=0.0001), and in those where the patients were prescribed a continuous background of antihypertensives (z=-2.72; P=0.0065). The nontrivial magnitude of these apparent blood pressure reductions with perfectly ineffective intervention (placebo) illustrates that efficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design. © 2014 American Heart Association, Inc.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov.

PubMed

Chen, Junchao; Huang, Jihan; Li, Jordan V; Lv, Yinghua; He, Yingchun; Zheng, Qingshan

2017-01-01

The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov

PubMed Central

Huang, Jihan; Li, Jordan V.; Lv, Yinghua; He, Yingchun

2017-01-01

Objective The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. Methods We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Results Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. Conclusion This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM. PMID:29138646

Factors associated with reporting results for pulmonary clinical trials in ClinicalTrials.gov.

PubMed

Riley, Isaretta L; Boulware, L Ebony; Sun, Jie-Lena; Chiswell, Karen; Que, Loretta G; Kraft, Monica; Todd, Jamie L; Palmer, Scott M; Anderson, Monique L

2018-02-01

Background/aims The Food and Drug Administration Amendments Act mandates that applicable clinical trials report basic summary results to the ClinicalTrials.gov database within 1 year of trial completion or termination. We aimed to determine the proportion of pulmonary trials reporting basic summary results to ClinicalTrials.gov and assess factors associated with reporting. Methods We identified pulmonary clinical trials subject to the Food and Drug Administration Amendments Act (called highly likely applicable clinical trials) that were completed or terminated between 2008 and 2012 and reported results by September 2013. We estimated the cumulative percentage of applicable clinical trials reporting results by pulmonary disease category. Multivariable Cox regression modeling identified characteristics independently associated with results reporting. Results Of 1450 pulmonary highly likely applicable clinical trials, 380 (26%) examined respiratory neoplasms, 238 (16%) asthma, 175 (12%) chronic obstructive pulmonary disease, and 657 (45%) other respiratory diseases. Most (75%) were pharmaceutical highly likely applicable clinical trials and 71% were industry-funded. Approximately 15% of highly likely applicable clinical trials reported results within 1 year of trial completion, while 55% reported results over the 5-year study period. Earlier phase highly likely applicable clinical trials were less likely to report results compared to phase 4 highly likely applicable clinical trials (phases 1/2 and 2 (adjusted hazard ratio 0.41 (95% confidence interval: 0.31-0.54)), phases 2/3 and 3 (adjusted hazard ratio 0.55 (95% confidence interval: 0.42-0.72)) and phase not applicable (adjusted hazard ratio 0.43 (95% confidence interval: 0.29-0.63)). Pulmonary highly likely applicable clinical trials without Food and Drug Administration oversight were less likely to report results compared with those with oversight (adjusted hazard ratio 0.65 (95% confidence interval: 0.51-0.83)). Conclusion A total of 15% of pulmonary clinical highly likely applicable clinical trials report basic summary results to ClinicalTrials.gov within 1 year of trial completion. Strategies to improve reporting are needed within the pulmonary community.

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

PubMed

Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

2012-05-02

Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

Stability of steady hand force production explored across spaces and methods of analysis.

PubMed

de Freitas, Paulo B; Freitas, Sandra M S F; Lewis, Mechelle M; Huang, Xuemei; Latash, Mark L

2018-06-01

We used the framework of the uncontrolled manifold (UCM) hypothesis and explored the reliability of several outcome variables across different spaces of analysis during a very simple four-finger accurate force production task. Fourteen healthy, young adults performed the accurate force production task with each hand on 3 days. Small spatial finger perturbations were generated by the "inverse piano" device three times per trial (lifting the fingers 1 cm/0.5 s and lowering them). The data were analyzed using the following main methods: (1) computation of indices of the structure of inter-trial variance and motor equivalence in the space of finger forces and finger modes, and (2) analysis of referent coordinates and apparent stiffness values for the hand. Maximal voluntary force and the index of enslaving (unintentional finger force production) showed good to excellent reliability. Strong synergies stabilizing total force were reflected in both structure of variance and motor equivalence indices. Variance within the UCM and the index of motor equivalent motion dropped over the trial duration and showed good to excellent reliability. Variance orthogonal to the UCM and the index of non-motor equivalent motion dropped over the 3 days and showed poor to moderate reliability. Referent coordinate and apparent stiffness indices co-varied strongly and both showed good reliability. In contrast, the computed index of force stabilization showed poor reliability. The findings are interpreted within the scheme of neural control with referent coordinates involving the hierarchy of two basic commands, the r-command and c-command. The data suggest natural drifts in the finger force space, particularly within the UCM. We interpret these drifts as reflections of a trade-off between stability and optimization of action. The implications of these findings for the UCM framework and future clinical applications are explored in the discussion. Indices of the structure of variance and motor equivalence show good reliability and can be recommended for applied studies.

Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

PubMed

Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

2015-01-01

In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

Hypertension Control in Adults With Diabetes Mellitus and Recurrent Cardiovascular Events: Global Results From the Trial Evaluating Cardiovascular Outcomes With Sitagliptin.

PubMed

Navar, Ann Marie; Gallup, Dianne S; Lokhnygina, Yuliya; Green, Jennifer B; McGuire, Darren K; Armstrong, Paul W; Buse, John B; Engel, Samuel S; Lachin, John M; Standl, Eberhard; Van de Werf, Frans; Holman, Rury R; Peterson, Eric D

2017-11-01

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function. © 2017 American Heart Association, Inc.

Mental health first aid for eating disorders: pilot evaluation of a training program for the public.

PubMed

Hart, Laura M; Jorm, Anthony F; Paxton, Susan J

2012-08-02

Eating disorders cause significant burden that may be reduced by early and appropriate help-seeking. However, despite the availability of effective treatments, very few individuals with eating disorders seek treatment. Training in mental health first aid is known to be effective in increasing mental health literacy and supportive behaviours, in the social networks of individuals with mental health problems. Increases in these domains are thought to improve the likelihood that effective help is sought. However, the efficacy of mental health first aid for eating disorders has not been evaluated. The aim of this research was to examine whether specific training in mental health first aid for eating disorders was effective in changing knowledge, attitudes and behaviours towards people with eating disorders. A repeated measures, uncontrolled trial was conducted to establish proof of concept and provide guidance on the future design of a randomised controlled trial. Self-report questionnaires, administered at baseline, post-training and 6-month follow-up, assessed the effectiveness of the 4-hour, single session, mental health first aid training. 73 participants completed the training and all questionnaires. The training intervention was associated with statistically significant increases in problem recognition and knowledge of appropriate mental health first aid strategies, which were maintained at 6-month follow-up. Sustained significant changes in attitudes and behaviours were less clear. 20 participants reported providing assistance to someone with a suspected eating disorder, seven of whom sought professional help as a result of the first aid interaction. Results provided no evidence of a negative impact on participants or the individuals they provided assistance to. This research provides preliminary evidence for the use of training in mental health first aid as a suitable intervention for increasing community knowledge of and support for people with eating disorders to seek appropriate help. Australian New Zealand Clinical Trials Registry ACTRN12611001181998.

Vegetarian diets and glycemic control in diabetes: a systematic review and meta-analysis.

PubMed

Yokoyama, Yoko; Barnard, Neal D; Levin, Susan M; Watanabe, Mitsuhiro

2014-10-01

Previous studies have suggested an association between vegetarian diets and improvements in glycemic control in diabetes, although this relationship is not well established. No meta-analysis of these studies has been performed. To conduct a systematic review and meta-analysis of controlled clinical trials examining the association between vegetarian diets and glycemic control in type 2 diabetes. The electronic databases Medline, Web of Science, Excerpta Medica Database (EMBASE), and Cochrane Central Register of Controlled Trials were searched for articles published in any language through December 9, 2013. The following criteria were used for study inclusion: (I) age of participants >20 years; (II) vegetarian diet as intervention; (III) mean difference in hemoglobin A1c (HbA1c) and/or fasting blood glucose levels used as outcomes; and (IV) controlled trials, duration ≥4 weeks. Exclusion criteria were: (I) not an original investigation; (II) duplicate samples; (III) diabetes other than type 2; (IV) multiple interventions; and (V) uncontrolled studies. The data collected included study design, baseline population characteristics, dietary data, and outcomes. Data were pooled using a random-effects model. Differences in HbA1c and fasting blood glucose levels associated with vegetarian diets were assessed. Of 477 studies identified, six met the inclusion criteria (n=255, mean age 42.5 years). Consumption of vegetarian diets was associated with a significant reduction in HbA1c [-0.39 percentage point; 95% confidence interval (CI), -0.62 to -0.15; P=0.001; I(2)=3.0; P for heterogeneity =0.389], and a non-significant reduction in fasting blood glucose concentration (-0.36 mmol/L; 95% CI, -1.04 to 0.32; P=0.301; I(2)=0; P for heterogeneity =0.710), compared with consumption of comparator diets. Consumption of vegetarian diets is associated with improved glycemic control in type 2 diabetes. PROSPERO registration number is CRD42013004370.

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians’ Patient Care Decisions

PubMed Central

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians. PMID:28269867

What Are Clinical Trials? | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn Javascript on. Feature: Clinical Trials What Are Clinical Trials? Past Issues / Fall 2010 Table of Contents ... conducted all the time. The Different Phases of Clinical Trials Clinical trials related to drugs are classified ...

ClinicalTrials.gov Turns 10! | NIH MedlinePlus the Magazine

MedlinePlus

... please turn Javascript on. Feature: Clinical Trials ClinicalTrials.gov Turns 10! Past Issues / Fall 2010 Table of ... and whom to contact for more information. ClinicalTrials.gov's Helpful Features ClinicalTrials.gov has many helpful consumer ...

Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial

PubMed Central

Pérez-Bárcena, Jon; Llompart-Pou, Juan A; Homar, Javier; Abadal, Josep M; Raurich, Joan M; Frontera, Guillem; Brell, Marta; Ibáñez, Javier; Ibáñez, Jordi

2008-01-01

Introduction Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. Methods This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation ≤ 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. Results A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis – undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital – thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. Conclusions Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups. Trial Registration (Trial registration: US Clinical Trials registry NCT00622570.) PMID:18759980