Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?

Antidepressants, in particular newer agents, are among the most widely prescribed medications worldwide with annual sales of billions of dollars. The introduction of these agents in the market has passed through seemingly strict regulatory control. Over a thousand randomized trials have been conducted with antidepressants. Statistically significant benefits have been repeatedly demonstrated and the medical literature is flooded with several hundreds of "positive" trials (both pre-approval and post-approval). However, two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits. A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness. These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied. I discuss how the use of many small randomized trials with clinically non-relevant outcomes, improper interpretation of statistical significance, manipulated study design, biased selection of study populations, short follow-up, and selective and distorted reporting of results has built and nourished a seemingly evidence-based myth on antidepressant effectiveness and how higher evidence standards, with very large long-term trials and careful prospective meta-analyses of individual-level data may reach closer to the truth and clinically useful evidence

Evidence-based de-implementation for contradicted, unproven, and aspiring healthcare practices

Abandoning ineffective medical practices and mitigating the risks of untested practices are important for improving patient health and containing healthcare costs. Historically, this process has relied on the evidence base, societal values, cultural tensions, and political sway, but not necessarily in that order. We propose a conceptual framework to guide and prioritize this process, shifting emphasis toward the principles of evidence-based medicine, acknowledging that evidence may still be misinterpreted or distorted by recalcitrant proponents of entrenched practices and other biases

Retention of Physician Assistants within a Specialty after Completion of a Postgraduate Training Program

Background: The advantages of a specialized training program have led to over 84 postgraduate training programs for Physician Assistants (PAs) covering over 25 specialties. Employee lateral mobility is more prevalent within the PA profession, which allows PA providers to switch between medical specialties. The versatility of PAs promotes higher turnover rates compared to physician counterparts. These high turnover rates can result in increased institutional burden. Postgraduate PA programs provide pre-employment exposure to more in-depth medical training, enabling a well-rounded knowledge base of the PA’s roles and responsibilities, minimizing turnover rates. Purpose: The goal of this survey study is to identify PA graduates’ perceptions of their retention rate, job satisfaction within a given specialty, factors influencing a PA’s decision to change their specialty, and specialty preparation provided by postgraduate training programs and specific educational training. Methods: A mixed method design was utilized to survey both program directors and graduates of PA postgraduate training programs. Results: Of the 398 postgraduate program graduates, 196 (49%) accepted a job within the institution where they trained. Across all postgraduate training programs, 87% of graduates have not changed their specialty since program completion. Ninety-six percent of respondents felt their postgraduate training gave them an accurate preview of employment in their specialty of interest, and all postgraduates would recommend a postgraduate training program to a new PA graduate

A Cost and Power Feasibility Analysis of Quantum Annealing for NextG Cellular Wireless Networks

In order to meet mobile cellular users' ever-increasing data demands, today's 4 G and 5 G wireless networks are designed mainly with the goal of maximizing spectral efficiency. While they have made progress in this regard, controlling the carbon footprint and operational costs of such networks remains a long-standing problem among network designers. This paper takes a long view on this problem, envisioning a NextG scenario where the network leverages quantum annealing for cellular baseband processing. We gather and synthesize insights on power consumption, computational throughput and latency, spectral efficiency, operational cost, and feasibility timelines surrounding quantum annealing technology. Armed with these data, we project the quantitative performance targets future quantum annealing hardware must meet in order to provide a computational and power advantage over CMOS hardware, while matching its whole-network spectral efficiency. Our quantitative analysis predicts that with 82.32 μ s problem latency and 2.68 M qubits, quantum annealing will achieve a spectral efficiency equal to CMOS while reducing power consumption by 41 kW (45% lower) in a Large MIMO base station with 400 MHz bandwidth and 64 antennas, and a 160 kW power reduction (55% lower) using 8.04 M qubits in a CRAN setting with three Large MIMO base stations

Generic versus brand-name drugs used in cardiovascular diseases

This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider use

Appendicectomies in Albanians in Greece: outcomes in a highly mobile immigrant patient population

BACKGROUND: Albanian immigrants in Greece comprise a highly mobile population with unknown health care profile. We aimed to assess whether these immigrants were more or less likely to undergo laparotomy for suspected appendicitis with negative findings (negative appendicectomy), by performing a controlled study with individual (1:4) matching. We used data from 6 hospitals in the Greek prefecture of Epirus that is bordering Albania. RESULTS: Among a total of 2027 non-incidental appendicectomies for suspected appendicitis performed in 1994-1999, 30 patients with Albanian names were matched (for age, sex, time of operation and hospital) to 120 patients with Greek names. The odds for a negative appendicectomy were 3.4-fold higher (95% confidence interval [CI], 1.24-9.31, p = 0.02) in Albanian immigrants than in matched Greek-name subjects. The difference was most prominent in men (odds ratio 20.0, 95% CI, 1.41-285, p = 0.02) while it was not formally significant in women (odds ratio 1.56, 95% CI, 0.44-5.48). The odds for perforation were 1.25-fold higher in Albanian-name immigrants than in Greek-name patients (95% CI 0.44- 3.57). CONCLUSIONS: Albanian immigrants in Greece are at high risk for negative appendicectomies. Socioeconomic, cultural and language parameters underlying health care inequalities in highly mobile immigrant populations need better study

Endovenous laser ablation therapy in children: applications and outcomes

BACKGROUND: Endovenous laser ablation is well recognized as the first-line treatment for superficial venous reflux with varicose veins in adults. It is not widely reported and is not an established practice in pediatric patients. OBJECTIVE: To illustrate a variety of pediatric venous conditions in which endovenous laser ablation can be utilized and to demonstrate its feasibility and safety in children. MATERIALS AND METHODS: We conducted a retrospective review of endovenous laser ablation procedures performed between January 2007 and July 2014 at two large pediatric institutions. RESULTS: We included 35 patients (17 males) who underwent endovenous laser ablation to 43 veins. Median age at first treatment was 14 years (range: 3-18 years). Median weight was 56 kg (range: 19-97 kg). Underlying diagnoses were common venous malformation (15), Klippel-Trenaunay syndrome (8), superficial venous reflux with varicose veins (5), verrucous hemangioma-related phlebectasia (4), venous varix (2) and arteriovenous fistula (1). The most common aim of treatment was to facilitate sclerotherapy. Thirty-four patients had treatment in the lower limbs and one patient in an upper limb. Ten of the veins treated with endovenous laser ablation had an additional procedure performed to close the vein. Complications attributable to endovenous laser ablation occurred in two patients (6%). One patient experienced post-procedural pain and one patient developed a temporary sensory nerve injury. Median clinical follow-up was 13 months (range: 28 days-5.7 years). The aim of the treatment was achieved in 29 of the 35 (83%) patients. CONCLUSION: Endovenous laser ablation is technically feasible and safe in children. It can be used in the management of a range of pediatric venous diseases with good outcomes

Sex Differences in the uptake of health care services in persons with disabilities. Identifying barriers to health care access

Background Evidence suggests that disability is more common among vulnerable populations which include women, elderly and children. And people with disabilities face widespread barriers in accessing services in relation to health, education, employment and transport. This study looks at the barriers women with disability face in accessing heath care services. The present study was undertaken in two states of India - Andhra Pradesh (Medak district) and Karnataka (Bidar). This is a descriptive study with a nested case control for comparison of access to health, education and employment status among those with and without disability The study was funded by CBM South Asia Regional Office (SARO) and was technically supported by CBM SARO Aim The main aim of the study was to look into whether women with disability have equitable access to health care in India and if there are disparities in access, the underlying causes and reasons for the same

MYOD-1 in normal colonic mucosa : role as a putative biomarker?

Background DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing. Results We analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio – the latter is also a known risk factor for colon cancer development. Conclusions Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer