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Journal: Current medical research and opinion


Abstract Background.Dupuytren’s disease (DD) is a fairly prevalent, yet under-recognised disorder of the palmar fascia, resulting in fixed-flexion contractures of joints in the hand. Numerous population-based studies have been conducted in countries around the world, and published prevalence estimates vary widely. Nevertheless, most studies have shown that the prevalence of DD increases with age. Because the global population is aging, the prevalence of DD will also continue to increase. Scope. Patients with DD typically present to a variety of physicians, including generalists and specialists alike. Thus, it is critical that providers have clear guidance on the early recognition of signs and symptoms, comprehensive evaluation of potential risk factors, differential diagnosis and when to refer a patient for treatment. Treatment options range from minimally invasive injections with collagenase to surgery. Findings. Results from a large-scale study of the surgical management of DD in Europe indicate that most DD diagnoses and referrals are made by general practitioners, but there is much inter-country variation. Different patient- and physician-based factors affect diagnosis rates and referral pathways. Different healthcare systems and regulations are also influential. Herein, a simple management algorithm is provided and explained. Conclusion. It is important for generalists to understand the natural history of DD and the potential benefits of early referral and treatment. General practitioners should diagnose and/or refer patients with DD to a specialist as early as possible to optimise disease management and treatment outcomes.

Concepts: Epidemiology, Medical terms, Diagnosis, Physician, Medical diagnosis, Contracture, Dupuytren's contracture, Guillaume Dupuytren


Abstracts Objectives: Docetaxel and paclitaxel show significant clinical activity in metastatic breast cancer(MBC) and have been approved for MBC by the U.S. Food and Drug Administration, but it is still unclear whether paclitaxel-based regimen improves outcomes over docetaxel-based regimen in patients with MBC. We therefore performed a meta-analysis of randomized controlled trials to compare the safety and efficacy of these two regimens in MBC. Methods: We systematically searched for randomized controlled trials that comparing paclitaxel-based with docetaxel-based regimens in patients with MBC in PubMed (up to January 2012), Embase (1980 to January 2012), and the Cochrane databases (up to January 2012). Abstracts presented at the conferences (up to January 2011) were also searched. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by Stata version 12.0 software (Stata Corporation, College Station, TX, USA). Results: Seven eligible trials involving 1694 patients with MBC were selected. Our results showed that paclitaxel-based regimen was comparable to docetaxel-based regimen for MBC patients in terms of OS (HR: 0.87, 95%CI: 0.60-1.27, p=0.48), PFS(HR:0.76, 95%CI:0.58-1.00, p=0.052), TTP(HR: 1.13, 95%CI: 0.81-1.58, p=0.46), and ORR(RR1.01, 95%CI: 0.88-1.15, p=0.92), but less grade 3 or 4 adverse events including anemia(RR:0.64,95%CI:0.44-0.94, p=0.023), neutropenia(RR:0.74,95%CI:0.58-0.93, p=0.011), febrile neutropenia(RR:0.38, 95%CI:0.15-0.96, p=0.041), thrombopenia (RR:0.62, 95%CI: 0.41-0.96, p=0.033), mucositis(RR:0.082,95%CI:0.025-0.27,p=0.000),diarrhea(RR:0.19,95%CI:0.081-0.47,p=0.000) and fatigue(RR:0.43,95%CI:0.20-0.96,p=0.039) were observed in paclitaxel-based regimen. However, limitations of our study needed to be considered when interpreting these results: our study was a meta-analysis of published data, and there was significant heterogeneity among included trials. Potential publication bias might also exist. Conclusion: The present systematic review and meta-analysis demonstrates that both taxanes-based regimens have comparable efficacy for patients with MBC, and paclitaxel-based regimen is associated with less toxicity and better tolerability, especially in older patients and when used in weekly regimens.

Concepts: Cancer, Breast cancer, Evidence-based medicine, Systematic review, Randomized controlled trial, Chemotherapy, Chemotherapy regimens, Meta-analysis


Background: Transthyretin (TTR) amyloidosis is a rare, life-threatening, systemic, autosomal dominant condition occurring in adults, with two main forms: hereditary (associated with TTR gene mutations) and wild-type. Studies indicate considerable heterogeneity in disease presentation, with predominantly polyneuropathic, predominantly cardiac, or mixed phenotypes. Methods: THAOS - the Transthyretin Amyloidosis Outcomes Survey - is the first global, multicenter, longitudinal, observational survey that collects data on the natural history of TTR amyloidosis ( NCT00628745). This paper presents data on signs and symptoms, neurological and cardiac assessments, biomarkers and quality of life in the patients enrolled in THAOS from its inception in December 2007 to September 2011. Results: At the time of this analysis, data were available from 611 symptomatic patients with hereditary TTR amyloidosis, 67 symptomatic patients with wild-type TTR amyloidosis, and 274 currently asymptomatic individuals with a TTR mutation. Nineteen countries were participating in the registry. The largest patient groups came from Portugal (n=453), the USA (n=129), Italy (n=70), and Japan (n=68). Predominant symptom presentation in patients with hereditary TTR amyloidosis differed according to the underlying disease-causing mutation (polyneuropathy for Val30Met, cardiomyopathy for Val122Ile and Leu111Met, and mixed for Glu89Gln). However, each mutation was associated with clear multisystem involvement. Similarly, although cardiomyopathy was predominant in patients with wild-type TTR amyloidosis, many also showed symptoms consistent with neuropathy. Quality of life in patients with hereditary TTR amyloidosis, but not asymptomatic carriers of disease-causing mutations, was severely impaired relative to that of the age-matched general US population. Conclusions: This preliminary analysis highlights the considerable phenotypic heterogeneity for neurological and cardiac manifestations in patients with hereditary and wild-type TTR amyloidosis and the necessity of providing multidisciplinary care. THAOS registry data will help better characterize the diverse presentation and course of TTR amyloidosis worldwide and aid in improving and standardizing diagnosis and treatment.

Concepts: Gene, Mutation, Natural selection, Evolution, Symptom, Phenotype, Windows Registry, Transthyretin


Abstract Objectives. To establish determinants of lipid goal attainment in primary care patients, with particular focus on participation in a disease management program (DMP) on diabetes mellitus (DM) and/or coronary heart disease (CHD), with real-world practical relevance. Methods. The present analysis was based on an observational study in 2359 patients with dyslipidaemia or hypercholesterolemia that were treated with nicotinic acid 1000 mg/ laropiprant 20 mg (Tredaptive * ) 1 or 2 tablets daily. Subgroups were formed by DMP participation (DMP vs. no DMP). A stepwise logistic regression model with backward selection of variables was applied to investigate factors influencing the probability of reaching lipid goals. Follow-up was 23 ± 7 weeks. Results. LDL cholesterol (LDL-C) < 100 mg/dl was achieved by 30.8% in DMP versus 26.8% (no DMP), high density lipoprotein (HDL-C) > 40/50 mg/dl in 61.3% versus 66.1%, and triglycerides (TG) < 150 mg/dl in 28.9% versus 31.7%. On multivariate analysis, age, sex, concomitant high-risk cardiovascular disease, or participation in a DMP appeared to have inconsistent effects on reaching LDL-C, HDL-C and TG goals. Likelihood to reach the LDL-C goal tended to be higher in males, in patients outside DMP, and in patients with DM or CHD, and those treated with the lower extended release nicotinic acid 1000 mg/ laropiprant 20 mg dose. The likelihood of reaching the HDL-C goal was higher in males and in patients without DM or DM+ CHD (no effect of DMP). The likelihood of reaching the TG goals was higher in females, in patients outside DMP, and in patients with DM and/or CHD. Limitations include potential bias due to study design, physician and patient selection, and missing values at follow-up. Conclusion. DMP participation was not associated with overall improved lipid goal attainment. Physicians cannot predict the magnitude of effects of newly initiated lipid modifying therapy based on baseline characteristics of their patients.

Concepts: Cholesterol, Myocardial infarction, Atherosclerosis, Diabetes mellitus, Cardiovascular disease, Low-density lipoprotein, Niacin, High-density lipoprotein


Objective To evaluate the efficacy and safety of the available glucagon-like peptide-1 receptor agonists (GLP-1 RAs), exenatide and liraglutide (marketed as Byetta * and Victoza † , respectively), in first- or second-line pharmacotherapy for type 2 diabetes (T2D), described here as “early use.” Research Design And Methods MEDLINE, EMBASE and Google Scholar databases were queried for clinical trial reports using the terms incretin, GLP-1, exenatide and liraglutide. Relevant articles were those that employed these agents in treatment-naïve patients with T2D and in patients who had failed on metformin monotherapy. Additional targeted searches were conducted on diabetes treatment guidelines and on the range of physiological responses to GLP-1 RAs. Most evidence is level I and II. Results Effective therapy for T2D should be implemented early in the course of this progressive disease. The recently revised 2013 Canadian Diabetes Association (CDA) guidelines now identify the GLP-1 RAs among various injected and oral agents recommended for the management of T2D. Rationale for early use of GLP-1 RAs in T2D management is manifold: these agents offer effective management of hyperglycemia in early-stage T2D, minimal risk of hypoglycemia, weight loss, improvement in multiple non-glycemic cardiovascular risk factors, and potential enhancement of patient adherence to antihyperglycemic treatment. Available data from clinical trials support second-line use of GLP-1 RAs among patients who fail on metformin, as well as first-line use of these agents in a subset of T2D patients. Conclusions The ability to achieve glycemic targets using GLP-1 RAs while simultaneously avoiding hypoglycemia and weight gain could provide substantial reassurance to physicians and patients who might otherwise resist the transition to injected therapies. Exenatide and liraglutide represent appropriate second-line choices for pharmacological treatment of T2D, as indicated in the 2013 CDA guidelines.

Concepts: Pharmacology, Diabetes mellitus type 2, Diabetes mellitus, Obesity, Diabetes, Sulfonylurea, Glucagon-like peptide-1, Exenatide


Abstract Objective: Diagnosis and assessment of response to treatment in acute bronchitis depends on clinical findings. We evaluated published data on the Bronchitis Severity Score (BSS) used to diagnose acute bronchitis and to evaluate the impact of treatment in clinical studies. Methods: We conducted a literature search using PubMed (search terms: acute bronchitis, treatment, score, and BSS; publication date April 2012 or earlier) and asked the manufacturer for relevant publications. Articles were reviewed and relevant studies were classified according to author, study design, measurements made and duration of study, study drug(s), outcome, and statistical significance. Results: The medication most frequently evaluated by the BSS is a herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630). The BSS consistently demonstrated statistically significant differences between active treatments and placebo as well as between different doses of active treatment. The proportion of responders was considerably higher in the EPs 7630 group than in the placebo group. Because of the subjective components of the BSS, inter-individual differences in results may exist. However, the BSS outcome was supported by the results of secondary outcome measures, such as the Integrated Medicine Patient Satisfaction Scale (IMPSS), documenting that patients were more often ‘satisfied’ or ‘very satisfied’ with EPs 7630 than placebo. Conclusions: We recommend further use of the BSS as a reliable and convenient clinical trial tool for selecting and evaluating patients in studies of acute bronchitis. Improvement in the BSS correlates with outcomes reported by these patients.

Concepts: Pharmacology, Cohort study, Clinical trial, Statistics, Statistical significance, Nocebo, Placebo, Statistical hypothesis testing


Abstract BACKGROUND: Vascular dementia (VaD) - a severe form of vascular cognitive impairment - and cognitive decline are associated with hypertension and therefore it seems logical to consider that reducing BP with anti-hypertensive therapy may protect against the development/onset of cognitive function impairment or dementia. SCOPE: This narrative, non-systematic review discusses the available evidence on the potential correlation between the use of anti-hypertensive agents and the risk of VaD and cognitive decline. METHODS: MEDLINE was searched for inclusion of relevant studies. No limitations in time were considered. RESULTS: A consensus on the potential effects of anti-hypertensive treatment in the reduction of VaD and associated cognitive decline has not been reached. A protective effect of anti-hypertensive agents has been observed in a number of studies although it is still unclear if different classes of anti-hypertensive agents have a different effect on the development of VaD. CONCLUSIONS: The protective effect of anti-hypertensive agents appears to depend on the specific drug used - positive effects have been observed with calcium channel blockers (CCBs), such as lercanidipine and nitrenidipine, the combination perindopril-indapamide and telmisartan.

Concepts: Hypertension, Effect, Cognition, Knowledge, Reasoning, Calcium channel blocker, Calcium channel, Binswanger's disease


Abstract Objective Evaluate efficacy of infliximab with response-driven dosing in patients with active RA. Research design and methods: Patients (n=203) with active RA despite methotrexate+etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3mg/kg was infused at Weeks0, 2, 6, 14 and 22 with escalation to 5 or 7mg/kg depending on EULAR response at Week14 and 22. The primary endpoint was EULAR response at Week10. Safety was assessed through Week30. Infliximab levels and antibodies to infliximab (ATI) were measured at Weeks 0, 6, 14 and 26. Clinical trial registration: NCT 00714493, EudraCT 2007-003288-36 Results: Of 197 evaluable patients, 120/77 previously received etanercept/adalimumab. Baseline mean(SD) swollen and tender joint counts: 17.3(10.54) and 30.2(16.89), respectively; mean DAS28-ESR: 6.19(0.981). At Week10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved EULAR response, with a significantly improved DAS28-ESR (mean[SD] change -1.1[1.15]; p<0.001). EULAR response was achieved by 41.7/62.3% of patients previously receiving etanercept/adalimumab (p=0.006). At Week26, 51.8% (95%CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab dose was escalated in 100 patients, 52% achieved EULAR response at Week26. Median serum concentration levels at Week26 showed that dose escalation helped EULAR non-responders achieve levels similar to or higher than the levels seen in responders. ATI were associated with lower serum concentrations of infliximab, consistent with lower efficacy rates among ATI-positive patients. Conclusion: Infliximab, in treat-to-target settings with individual dose escalation, demonstrated significant efficacy at Weeks10 and 26 in patients switched to infliximab after inadequate response to etanercept/adalimumab. The observed efficacy indicated that the switch to infliximab and ability to increase dose in a targeted fashion were beneficial.

Concepts: Rheumatoid arthritis, Rheumatology, Infliximab, Ankylosing spondylitis, Psoriatic arthritis, Etanercept, Adalimumab, Escalation


To examine the contribution of generational epigenetic dysregulation to the inception of obesity and its adiposopathic consequences.

Concepts: Epigenetics, Obesity, Adipose tissue


This meta-analysis compared the median overall survival (mOS) of brentuximab vedotin reported in the pivotal phase 2 study with published results of other therapies for the treatment of relapsed/refractory (R/R) Hodgkin lymphoma (HL) post-autologous stem cell transplant (ASCT).

Concepts: Lymphoma, Hodgkin's lymphoma, Organ transplant