This systematic review aimed to compare the e cacy and tolerability of metformin extended-release (MXR) and the conventional metformin immediate-release (MIR) in adults with type 2 diabetes mellitus (T2DM). PubMed, the Cochrane Library and ClinicalTrials.gov, from database inception to 15 October 2020, and other sources were searched for randomized controlled trials (RCTs) that compared equal daily doses of MXR and MIR in adults with T2DM. Random-effects model meta-analysis were performed to obtain pooled mean difference (MD) of change from baseline for continuous outcomes (glycemic and serum lipid control and anthropometrics) and risk ratio (RR) for dichotomous outcomes (gastrointestinal and serious adverse events). Statistical analysis involving 9 published RCTs with 2609 subjects revealed that MIR was associated with better HbA1c lowering (MD 0.09% [95% con dence interval, 0.02%, 0.017%]) and serum lipid control except LDL-C lowering, while MXR reduced only the cumulative incidence of dyspepsia (RR 0.58 [0.34, 0.98]). MXR and MIR were similar in all other considered outcomes. The use of MXR over MIR among adults with T2DM was associated with statistically worse but likely clinically insigni cant HbA1c lowering, similar plasma glucose lowering, and minimal improvement of metformin intolerance. This information may guide patient-physician discussions in choosing between the two formulations.
Although prevention is vital in managing tumor lysis syndrome (TLS), no study directly compares various regimens. This study compared the effectiveness and safety of urate-lowering agents in preventing TLS. Databases were searched for randomized controlled trials involving adults with hematologic or solid malignancies on chemotherapy or cytoreductive agents given allopurinol, febuxostat, or rasburicase alone or in combination at any dose, form, or frequency published in English by December 2021. Outcomes included laboratory and clinical TLS expressed as relative risks, adverse events as described by authors, and mean serum uric acid (sUA) as mean differences of area under the curve. A network of meta-analysis and post-hoc meta-analysis based on TLS risk using a random-effects model was done using Stata 14.0 and Review Manager 5.3, respectively. Certainty of evidence was assessed using the GRADE approach. Three studies with a total of 633 participants given allopurinol, febuxostat, rasburicase, or rasburicase combined with allopurinol were included. Rasburicase is more effective than allopurinol in preventing laboratory TLS (relative risk: 0.51; 95% confidence interval [CI]: 0.32–0.81) based on moderate quality evidence. No significant differences were observed in clinical TLS. Adverse events were attributable to toxicities of chemotherapy. Rasburicase alone or in combination with allopurinol was better than allopurinol or febuxostat alone in reducing sUA level. Febuxostat is more effective than allopurinol in lowering sUA levels among patients at high-risk of TLS (mean difference −125.75; 95% CI: −223.47 to −28.02). Rasburicase may be the most effective agent in preventing laboratory TLS and maintaining low sUA levels.
This systematic review aimed to compare the efficacy and tolerability of metformin extended-release (MXR) and the conventional metformin immediate-release (MIR) in adults with type 2 diabetes mellitus (T2DM). PubMed, the Cochrane Library and ClinicalTrials.gov, from database inception to 15 October 2020, and other sources were searched for randomized controlled trials (RCTs) that compared equal daily doses of MXR and MIR in adults with T2DM. Random-effects model meta-analysis was performed to obtain pooled mean difference (MD) of change from baseline for continuous outcomes (glycemic and serum lipid control and anthropometrics) and risk ratio (RR) for dichotomous outcomes (gastrointestinal and serious adverse events). Statistical analysis involving 9 published RCTs with 2609 subjects revealed that MIR was associated with better HbA1c lowering (MD 0.09% [95% confidence interval, 0.02%, 0.17%]) and serum lipid control except LDL-C lowering, while MXR reduced only the cumulative incidence of dyspepsia (RR 0.58 [0.34, 0.98]). MXR and MIR were similar in all other considered outcomes. The use of MXR over MIR among adults with T2DM was associated with statistically worse but likely clinically insignificant HbA1c lowering, similar plasma glucose lowering, and minimal improvement of metformin intolerance. This information may guide patient-physician discussions in choosing between the two formulations.
RATIONALE Sepsis is the leading cause of mortality among medical patients in the Philippine General Hospital (PGH). A previous study illustrated variations in sepsis management. The Department of Medicine developed a sepsis pathway based on the Surviving Sepsis Campaign bundles to standardize care and improve outcomes. We determined the coverage and compliance with the pathway, the barriers to compliance and sepsis-related mortality. METHODS This was a single-center mixed methods study on the pilot implementation of the sepsis pathway (April 8 to July 7, 2019) in the medical service areas, i.e. emergency department (ED), medical wards and medical intensive care unit (MICU), of a tertiary level teaching hospital. We tracked all medicine charity admissions with infections to determine coverage. Compliance and patient outcomes were assessed through chart reviews. Focus group discussions and interviews were done to identify barriers to implementing the sepsis bundle. RESULTS Among 296 admissions with infections (49% female, mean age 51.4 years), there were 422 patient-days eligible for pathway coverage but only 199 patient-days (47.16%) were covered. The ED had the highest coverage rate. Overall mortality rate among the admissions was at 39.2%. Among septic patients who were covered, 40% died. Missed cases were associated with increased odds of in-hospital death (adjusted odds ratio [aOR]: 1.42, 95% CI: 1.13 to 1.88) on multivariate analysis. Compliance with recommended diagnostics was high except for lactate and bilirubin. Blood cultures were sent 98% of the time. Only 35% of patients received antibiotics by one hour after activation. Fluids recorded over 6 hours were inadequate (mean 4.77 mL/kg, standard deviation: 2.82 mL/kg). Of 73 patients with hypotension needing fluid resuscitation, only 12 had blood pressure documented 30 minutes post-activation. Stakeholders identified inadequate human and physical resources, hospital policy changes and pathway form construction as barriers to compliance. Fellows, nurses, and students reported lack of orientation on their roles.
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