Efficacy of multi-strain probiotic along with dietary and lifestyle modifications on polycystic ovary syndrome: a randomised, double-blind placebo-controlled study.

PURPOSE: Effect of multi-strain probiotic along with dietary and lifestyle modifications in the management of polycystic ovary syndrome (PCOS) has rarely been reported. We thus aimed to investigate the effect of multi-strain probiotic (Lactobacillus acidophilus UBLA-34, L. rhamnosus UBLR-58, L. reuteri UBLRu-87 (each of 2 billion colony forming units (CFU)); L. plantarum UBLP-40, L. casei UBLC-42, L. fermentum UBLF-31, Bifidobacterium bifidum UBBB-55 (each of 1 billion CFU) and fructo-oligosaccharides (100 mg)) and dietary and lifestyle modifications on restoration of menstrual regularity, weight reduction, metabolic and hormonal profile in women with PCOS. METHODS: A 104 participants (age 18-40 years) were randomly allocated to receive probiotic or placebo capsules for 6 months. Baseline and end line assessment were performed for menstrual cycle regularity, ultrasonography scan for ovaries, total testosterone, dehydroepiandrosterone (DHEAS), insulin, luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, fasting blood sugar (FBS), homeostatic model assessment-insulin resistance (HOMA-IR), weight reduction, waist-/hip circumference (WC, HC), waist to hip ratio (WHR), and body mass index (BMI). Plasma lipopolysaccharide and effect of intervention on quality of life was investigated. Diet and exercise were controlled during the trial. RESULTS: Probiotic supplement along with dietary and lifestyle modifications significantly regularised menstrual cycle (p 0.023), improved levels of total testosterone (p 0.043), WC (p 0.030), WHR (p 0.027) and menstrual domain of quality of life (p 0.034) as compared to placebo. No adverse events related to study were reported. CONCLUSION: Multi-strain probiotic along with dietary and lifestyle modifications were effective in the management of PCOS. TRIAL REGISTRATION: CTRI: CTRI/2016/07/007086, dated 13 July 2016.

Efficacy of Bacopa Monnieri (Brahmi) and Donepezil in Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Double-Blind Parallel Phase 2b Study.

OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia worldwide in the older population. There is no disease-modifying therapy available for AD. The current standard of care drug therapy for AD is cholinesterase inhibitors, including donepezil. Bacopa monnieri or brahmi is used in traditional Indian medicine for memory loss. We conducted a phase 2b randomized controlled trial (RCT) to find out the efficacy of brahmi and donepezil in AD and mild cognitive impairment (MCI). PATIENTS AND METHODS: The study was planned as a 52 week, randomized, double-blind, parallel-group, phase-2 single-center clinical trial comparing the efficacy and safety of Bacopa monnieri (brahmi) 300 mg OD and donepezil 10 mg OD for 12 months in 48 patients with AD and MCI-AD including cognitive and quality of life outcomes. The primary outcome was differences in the change from baseline of the neuropsychological tests [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and postgraduate institute (PGI) memory scale] at 12 months between the intervention group (brahmi) and active comparison group (donepezil). RESULTS: The study was terminated after 3 years and 9 months, after recruiting 34 patients, because of slow recruitment and a high dropout rate. Intention to treat analysis after adjusting for baseline confounders showed no difference in the rate of change in ADAS-Cog score from baseline at any time point, including the last follow-up. There was no difference in the rate of change in PGI Memory scale (PGIMS) at 3, 6, and 9 months. In the last follow-up, there was a significant difference in the change in total PGIMS score between brahmi and donepezil, while there was no difference in individual scores of the PGI memory scale. CONCLUSION: This phase-2 RCT on the efficacy of brahmi vs. donepezil showed no significant difference between them after 1 year of treatment. Larger phase-3 trials, preferably multicentric, are required to find the superiority of brahmi over donepezil.

Neutrophil gelatinase-associated lipocalin: An early biomarker for predicting acute kidney injury and severity in patients with acute pancreatitis.

BACKGROUND AND AIM: Acute kidney injury (AKI) in severe acute pancreatitis (SAP) has a high mortality rate. Traditionally used serum creatinine is an insensitive biomarker for the early detection of AKI. We aimed to study the role of plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL) in predicting AKI and a severe course in patients with acute pancreatitis (AP). METHODS: Consecutive patients of AP who presented within 72 h of symptom onset and age- and gender-matched healthy controls were included. Urinary and serum NGAL levels [enzyme-linked immunosorbent assay (ELISA)] were evaluated within 24 h of and 72 h after admission and once in controls. Urine and serum NGAL levels were correlated with development of AKI, severity, and outcomes of AP. RESULTS: Fifty patients with AP and 30 controls were enrolled. The mean serum and urine NGAL levels in patients on day 1 were significantly higher than the serum and urine NGAL levels in controls (P < 0.001). After excluding patients with AKI on day 1 (n = 10), both serum and urinary NGAL levels on days 1 and 3 were significantly higher in patients who subsequently developed AKI (n = 11) compared to those who did not (n = 29) (P = 0.02, 0.01 and P < 0.001, 0.03). A urinary NGAL level of 221.03 ng/mL on day 1 predicted AKI with a sensitivity and specificity of 82 and 80%, respectively (AUC = 0.9). Mean serum and urinary NGAL levels on day 1 were significantly elevated in patients with SAP compared to those without SAP (P = 0.04 and <0.001). CONCLUSION: NGAL levels in urine and serum can predict severity of AP and development of AKI.

Comparative efficacy and safety of extended-release and instant-release tolterodine in children with neural tube defects having cystometric abnormalities.

AIM: To evaluate the comparative efficacy and safety of extended-release (ER) and instant-release (IR) tolterodine preparations in a pediatric population with neural tube defects having cystometric abnormalities. MATERIALS AND METHODS: Twenty-five patients with neural tube defects and a similar demographic profile underwent a routine hemogram, liver function tests, renal function tests, urine culture, X-ray lumbo-sacral spine, and renal and bladder ultrasound. Vesicoureteric reflux was diagnosed by micturating cystourethrogram under fluoroscopy. Dimercaptosuccinic acid renal scintigraphy was performed to study the presence or absence of renal scars. Patients were treated with tolterodine ER (Group I: 2mg once daily for 21 days) and tolterodine IR (Group II: 2mg twice daily for 21 day) in a cross-over study with a 10-day washout period between administrations. Evaluation was by subjective assessment, visual analog scale, urodynamic assessment and adverse drug reaction monitoring. RESULTS: There was ultrasound evidence of hydroureteronephrosis in 20% of the patients. One patient out of 25 had impaired renal function and eight patients had renal scarring on dimercaptosuccinic acid scans. Both forms of the drug increased the maximum cystometric bladder capacity, decreased detrusor leak pressures and increased compliance compared to pre-therapy levels (P=0.0001). Visual analog scale showed a significant clinical improvement with both ER and IR tolterodine. A significant increase in maximum bladder capacity in the group receiving IR tolterodine as compared to the ER preparation was noted (P=0.0001). The decrease in detrusor leak pressures and improvement in compliance were not significantly different between the groups. No adverse effects of hyperpyrexia, flushing or intolerance to outdoor temperatures, or dryness of mouth were observed in either group. No patient suffered from constipation. CONCLUSION: ER tolterodine 2mg once daily is as effective and well tolerated in children with neurogenic bladder as IR tolterodine 2mg twice a day. The latter was found to be more effective in terms of urodynamic parameters. ER formulation of tolterodine is less expensive and has the advantage of single dosage.