Do Pleiotropic Effects of Spironolactone in Women with PCOS Make it More than an Anti-androgen? Evidence from a Systematic Review and Meta-analysis.

BACKGROUND: Spironolactone use as a treatment for hirsutism and other dermatological conditions among polycystic ovary syndrome (PCOS) and idiopathic hirsutism shows varied results. OBJECTIVE: This study thus summarizes the entire evidence to better define its impact on Ferriman-Gallwey (FG) score in addition to other derangements associated with PCOS. METHODS: PubMed, Embase, Scopus and bibliographies of relevant articles were searched. Randomized controlled trails (RCTs) investigating the efficacy of spironolactone in PCOS and idiopathic hirsutism were included. Pooled mean difference (MD) was calculated using random effects model and relevant subgroup analysis was done. Potential heterogeneity and publication bias was assessed. RESULTS: Of 1041 retrieved studies, 24 RCTs were included. Spironolactone (100 mg/daily) exhibited a significant reduction in FG score in idiopathic hirsutism compared to finasteride (MD: -2.43; 95% C.I: -3.29, -1.57) and cyproterone acetate (MD: -1.18; 95% C.I: -2.10, -0.26), however, no significant difference was found among PCOS subjects in comparison to flutamide and finasteride. A lower dose of spironolactone (50 mg/day) exhibited no significant difference relative to metformin on FG Score (MD: -0.61; 95% C.I: -1.76, 0.54, I2 = 57%), serum total testosterone (MD: -0.61; 95% C.I: -1.76, 0.54), I2 = 57% and HOMA-IR (MD: 1.03; 95% C.I: -1.22, 3.29), I2 = 60% among PCOS women. The main side effects reported by the studies were menstrual irregularity, mild nausea, vomiting and diarrhea. CONCLUSION: Spironolactone is well tolerated among idiopathic hirsute and PCOS women. The drug significantly improved hirsutism in the former group and shows a positive trend in the latter women, however, displays no effect on FSH, LH, menstrual cyclicity, BMI, and HOMA-IR in PCOS women.

Efficacy and safety of various oral regimens (three oral doses) and schedules (daily v. monthly) of cholecalciferol in North Indian adults with low vitamin D status: evidence from a randomised controlled trial.

Vitamin D (VD) deficiency (serum 25 hydroxy vitamin D (25(OH)D) concentration of < 20 ng/ml), in endemic proportions, demands a supplementation strategy with optimal dosing regimens. A randomised parallel-group, active-controlled trial was conducted among apparently healthy, VD-deficient subjects, aged 18-60 years who received 600 µg/d (Group A), 1000 µg/d (Group B), 2000 µg/d (Group C) and 60 000 µg/month (Group D) of oral cholecalciferol. The intervention was carried in two phases (I and II) of 12 weeks each, with same dose, separated by a washout phase of 12 weeks. Serum 25(OH)D, intact parathyroid hormones (iPTH), Ca, phosphorous (PO4), alkaline phosphatase (ALP) and spot urine Ca/Cr were measured at baseline, 12, 24 and 36 weeks following the intervention, and adverse events were recorded at each occurrence and at 12, 24 and 36 weeks. A statistically significant time-group interaction was found in serum 25(OH)D concentration (P < 0·05). Serum 25(OH)D concentration increased significantly from baseline to 12 weeks (P < 0·05) in all the groups with no change at 24 weeks but further increase at 36 weeks (P < 0·05). At the end of the study, Group C had maximum increment in serum 25(OH)D concentration, while as Groups C and D (95 %, and 90 %) had higher proportion of subjects VD sufficient than Groups A and B (65 % and 78 %) (P < 0·05). No significant time-dose interactions were observed in serum iPTH, Ca, PO4 and ALP or urine Ca/Cr ratio. Three subjects (two in Group C and one in Group D) developed transient hypercalciuria. Supplementation with daily 2000 µg or monthly 60 000 µg of oral cholecalciferol among adults seems optimal and safe.

Comparative short-term efficacy and safety of add-on anti-seizure medications in Dravet syndrome: An indirect treatment comparison.

PURPOSE: Although cannabidiol and fenfluramine have been recently approved by the US Food and Drug Administration (FDA) for seizures in children with Dravet syndrome (DS), the comparative efficacy and safety of these and stiripentol as an add-on therapy for DS has not been evaluated in head-to-head trials. The current study aimed to assess the comparative efficacy and safety of add-on anti-seizure medications in DS. METHODS: PubMed and EMBASE database search and a manual search was done using keywords; "antiepileptic", "Dravet syndrome" and "antiseizure". The primary efficacy outcome was ≥50% reduction in convulsive seizure frequency from baseline while the safety outcome was treatment-emergent adverse events (TEAEs). Frequentist approach were used for combining direct and indirect evidence and network plots prepared. The drugs were ranked based on p-scores obtained using the surface under the cumulative ranking (SUCRA). Heterogeneity across studies was calculated by I2 statistic and Q test. RESULTS: Five randomized controlled trials (RCTs) with 565 patients with DS (2-20 years) who received placebo or any of the three active interventions (stiripentol, cannabidiol, and fenfluramine) were included. Compared with placebo, all the three drugs were associated with a significant reduction in convulsive seizure frequency from baseline. Stiripentol had the highest probability ranking for ≥50% reduction in convulsive seizure frequency from baseline [OR: 20.2; 95% CI: 2.1-198.0] and for occurrence of any treatment emergent adverse events (TEAEs) [OR:53.9; 95% CI: 1.4 to 2079.8] followed by fenfluramine and cannabidiol. However, for serious TEAEs, the ranking order was stiripentol followed by cannabidiol and fenfluramine. The trial on stiripentol had limited sample size explaining the wide confidence intervals for the comparative outcomes. CONCLUSION: In this indirect comparison, fenfluramine and stiripentol hadd comparable efficacy but fenfluramine appeareded to be safer in terms of less frequent serious TEAEs. Cannabidiol had relatively lower efficacy and was associated with serious TEAEs. A head-to-head trial between stiripentol, cannabidiol and fenfluramine is the need of the hour.

Psychosocial morbidity profile in a community based sample of low back pain patients.

Low back pain (LBP) is a major health concern and is closely associated with psychosocial morbidity and diminished Health-related quality of life (HRQoL). This is minimally investigated in community-based samples of developing nations like India. This study is aimed to specifically investigate the exposure-outcome associations between LBP and burden of disability (Modified Oswestry questionnaire (MODQ)), psychological morbidities (Depression, Anxiety and Stress Scale (DASS-21)), and HRQoL (Short Form -12 version 2 (SF12V2). A Cross-sectional study using a community-based sample of LBP positive population was conducted. The range of treatment options sought was also collected. Chi-square tests and independent t-test were used to analyze the data. Of 1531 recruited participants, 871(57%) were identified as LBP positive of whom 60% were females. Mean (SD) of age and pain intensity of LBP patients was 33 (11) years and numeric rating scale4.2 (2.6) respectively. Two-third reported minimal/moderate disability. Mean (SD) scores of depression 11.87 (4.05), anxiety (8.32), stress 13.7 (5.98), physical and mental summary scores of SF-12v2 were 47.9 (7.4) and 42.2 (10.4). A multitude of remedial options was sought for the ailment. LBP causes significant disability and psychological morbidity among affected population. This may adversely affect their HRQoL and subsequently productivity. Acupuncture was a preferred treatment sought by Indian LBP patients.

Relative Efficacy and Safety of Pharmacotherapeutic Interventions for Diabetic Peripheral Neuropathy: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a most common devitalizing complication of diabetes mellitus, which is primarily characterized by sensory loss, paresthesia, prickling, pain, or allodynia. OBJECTIVES: To evaluate the relative efficacy and safety of the interventions used in the DPN pain management and rank their order. STUDY DESIGN: A systematic review and Bayesian network meta-analysis (NMA). METHODS: Randomized, controlled trials were identified through a comprehensive, systematic literature exploration, primarily utilizing the PubMed, EMBASE, Ovid, and Cochrane Library databases. The efficacy and safety outcomes consist of the proportion of patients reporting either 30% or 50% pain reduction and overall withdrawal or withdrawal due to adverse drug events, respectively. Effect estimates from Bayesian NMA were presented as odds ratio (OR) with 95% credible intervals (CrI). Heterogeneity and convergence were assessed by using I2 and deviation information criteria. The risk of bias was evaluated by using Pedro Scale. RESULTS: A total of 3,246 potentially relevant trials were identified and screened, finally 43 trials consisting of 7,877 randomized patients met the inclusion criteria. Statistically significant treatment difference for 50% pain reduction was reported for duloxetine vs. placebo (OR: 2.50; CrI: 1.62-3.91), mirogabalin vs. placebo (OR: 3.25; CrI: 1.16-9.35), pregabalin vs. placebo (OR: 2.33; CrI: 1.69-3.27), duloxetine vs. carbamazepine (OR: 3.37; CrI: 1.07-10.90), mirogabalin vs. carbamazepine (OR: 4.39; CrI: 1.01-19.63), mirogabalin vs. lamotrigine (OR: 4.05: CrI: 1.07-15.77), pregabalin vs. lamotrigine (OR: 2.90, CrI: 1.19-7.22) and pregabalin vs. nortriptyline (OR: 4.10, CrI: 1.13-5.28). Nortriptyline reported the highest possibility of achieving 30% and 50% pain reduction. Sodium valproate and benztropine reported the highest probability of total withdrawals and withdrawals due to adverse drug events, respectively. LIMITATION: The different follow-up time of the included studies can result in the variation of intended results. CONCLUSION: Nortriptyline reported the advantage relative to other drugs in achieving 30% and 50% pain reduction from the baseline. Gabapentin reported a significance of 50% pain reduction relative to placebo.

A systematic review of economic evaluations of treatment regimens in multiple myeloma.

BACKGROUND: The expansion of advanced expensive therapeutic innovations for Multiple Myeloma (MM) led to increased disclosure of economic evaluations. The present analysis systematically reviewed and appraised the reporting quality of economic evaluations in MM. METHODOLOGY: A comprehensive literature search in Ovid, MEDLINE(R), PubMed, and Cochrane libraries was conducted for studies published in the past decade. Two independent authors performed study selection and data extraction in a standardized form. Study methodological quality assessment was performed using 10-item Drummond's tool. RESULTS: Of potentially eligible 1150 retrieved studies, 17 met eligibility criteria. Six evaluations (35%) were in newly diagnosed MM and 11 (65%) in relapse refractory (RR) MM. Nine studies (53%) embraced the payer's perspective, five (29%) adopted health care system, one (6%) societal and two did not report. Six (35%) employed partitioned survival model, 4(24%) discrete event simulation, 4(24%) Markov model and 2(12%) used decision tree model. The methodological quality has improved significantly; 16 (94%) studies comprehended a well-defined question by affirming the analysis perspective and examined both costs and outcomes while 13 (71%) provided a comprehensive description of competing alternatives. CONCLUSION: The addition of novel drugs to the treatment armamentarium of MM is considerably cost-effective. The evaluations became more frequent, methodological quality has improved in the last decade.

Prevalence and Impact of Low Back Pain in a Community-Based Population in Northern India.

BACKGROUND: Low back pain (LBP) ranks first for disability and sixth for overall burden on world health, with an annual approximate cost of $135 billion. There are limited data on the prevalence and risk factors for LBP in developing countries, such as India. OBJECTIVES: To assess the prevalence, pain intensity, and quality of life (QOL) associated with LBP in northern India. STUDY DESIGN: Cross-sectional study. SETTINGS: Northern states of India. METHODS: Adult population of different strata of the community were interviewed. Lifetime, point, 1-year, and age standardized lifetime prevalence with 95% confidence intervals (CI) and QOL, and pain intensity using the Numeric Rating Scale (NRS-11) were determined. Binary logistic regression test was conducted to determine the predictors of LBP prevalence; odds ratio (OR) with 95% CI are presented. Significance level was set at P <= 0.05. RESULTS: A total of 1,531 patients were interviewed of whom 48% were men and mean (standard deviation [SD]) age was 32 (10) years. Lifetime, point, 1-year, and age standardized lifetime prevalence (95% CI) were 57% (54%-59%), 32% (30%-34%), 48% (46%-51%), and 59% (56%-62%), respectively. Average (SD) NRS-11 was 4.2 (2.6). Significant impact of LBP on sleep (24%), depression/psychological problems (24%), and social life (28%) were observed. Women (OR, 2.23; 95% CI, 1.80-2.77; P < 0.05), walking/lifting activity (OR, 1.362; 95% CI, 1.097-1.692; P < 0.05), and increasing age (OR, 1.03; 95% CI, 1.02-1.04; P < 0.05) were most significant positive predictors of LBP. LIMITATIONS: The progression of LBP could not be assessed in the enrolled patients. CONCLUSIONS: LBP is highly prevalent in India, adversely affecting QOL in respondents. This calls for action by health officials to plan prevention, education, and management programs in the society. KEY WORDS: Low back pain, pain intensity, prevalence, incidence, quality of life.