Pharmacoepidemiological profile and appropriateness of drug use in paediatric diarrhoea patients: a cross sectional study in western India

Background: The background of the study was to analyze the prescribing pattern and appropriateness of drug treatment of diarrhoea.Methods: Total 194 pediatric patients with diarrhoea (140 admitted at tertiary care centre and 54 patients attended primary health care centre) were included and their demographic details; disease related parameters, drug treatment and adverse drug reactions were recorded. Appropriateness of drug treatment was analyzed using the WHO and Indian Academy of Pediatrics (IAP) guidelines for management of diarrhoea.Results: Most patients (27.32%) were less than 1 year of age and majority 54.64% were males. Most common presenting symptoms was diarrhoea with dehydration (100%) followed by vomiting (60%), fever (54.29%). Stool cultures were carried out only in 22.86% patients at tertiary health care centre while no investigations were carried out at PHC. Average number of drugs prescribed per patient was 8.25 ± 1.3. All the patients were given fluid replacement therapy. 94.29% and 85.19% patients were prescribed antimicrobials at tertiary centre (THC) and PHC respectively. Most common antibiotic used was cephalosporins (82%) followed by aminoglycosides (48.57%) of patients at THC while ofloxacin (82.60%) and metronidazole (17.40%) were commonly used at PHC.  Analgesic/antipyretic was required in 70.71% and 85.19% of patients at THC and PHC respectively. Comparing with the WHO diarrhoea management guidelines and IAP guidelines, only 8 (14.81%) prescriptions were considered as rational. 2.85% patients developed mucocutaneous rash as ADR.Conclusions: Inappropriate prescribing for diarrhoea is highly prevalent in society. Emphasis on proper diagnosis and treatment, education and availability of locally effective guidelines may help in a better and judicious use of drugs in children

Association of Treatment Effects on Early Change in Urine Protein and Treatment Effects on GFR Slope in IgA Nephropathy:An Individual Participant Meta-analysis

Rationale & Objective: An early change in proteinuria is considered a reasonably likely surrogate end point in immunoglobulin A nephropathy (IgAN) and can be used as a basis for accelerated approval of therapies, with verification in a postmarketing confirmatory trial. Glomerular filtration rate (GFR) slope is a recently validated surrogate end point for chronic kidney disease progression and may be considered as the end point used for verification. We undertook a metaanalysis of clinical trials in IgAN to compare treatment effects on change in proteinuria versus change in estimated GFR (eGFR) slope. Study Design: Individual patient-level metaanalysis. Setting & Study Populations: Individual data of 1,037 patients from 12 randomized trials. Selection Criteria for Studies: Randomized trials of IgAN with proteinuria measurements at baseline and 6 (range, 2.5-14) months and at least a further 1 year of follow-up for the clinical outcome. Analytical Approach: For each trial, we estimated the treatment effects on proteinuria and on the eGFR slope, computed as the total slope starting at baseline or the chronic slope starting 3 months after randomization. We used a Bayesian mixed-effects analysis to relate the treatment effects on proteinuria to effects on GFR slope across these studies and developed a prediction model for the treatment effect on the GFR slope based on the effect on proteinuria. Results: Across all studies, treatment effects on proteinuria accurately predicted treatment effects on the total slope at 3 years (median R-2 = 0.88; 95% Bayesian credible interval [BCI], 0.06-1) and on the chronic slope (R-2 = 0.98; 95% BCI, 0.29-1). For future trials, an observed treatment effect of approximately 30% reduction in proteinuria would confer probabilities of at least 90% for nonzero treatment benefits on the total and chronic slopes of eGFR. We obtained similar results for proteinuria at 9 and 12 months and total slope at 2 years. Limitations: Study population restricted to 12 trials of small sample size, leading to wide BCIs. There was heterogeneity among trials with respect to study design and interventions. Conclusions: These results provide new evidence supporting that early reduction in proteinuria can be used as a surrogate end point for studies of chronic kidney disease progression in IgAN

A meta-analysis of GFR slope as a surrogate endpoint for kidney failure

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR

Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression

Background: Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects. Methods: To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable metaregression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects. Results: The mean acute effect across all studies was 20.21 ml/min per 1.73 m2 (95% confidence interval, 20.63 to 0.22) over 3 months, with substantial heterogeneity across interventions (95% coverage interval across studies, 22.50 to 12.08 ml/min per 1.73 m2). We observed negative average acute effects in renin angiotensin system blockade, BP lowering, and sodium-glucose cotransporter 2 inhibitor trials, and positive acute effects in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with a higher mean baseline GFR. Conclusion: The magnitude and consistency of acute GFR effects vary across different interventions, and are larger at higher baseline GFR. Understanding the nature and magnitude of acute effects can help inform the optimal design of randomized clinical trials evaluating disease progression in CKD

A meta-analysis of GFR slope as a surrogate endpoint for kidney failure

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR &lt; 15 ml min−1 per 1.73 m2 or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R2) = 0.97 (95% Bayesian credible interval (BCI) 0.82–1.00)) and moderately associated with those on chronic slope (R2 = 0.55 (95% BCI 0.25–0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression.</p