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.
Introduction. In the attempt to control the spread of the disease and the pandemic, numerous COVID-19 vaccines are in development. A review of the evidence on their efficacy and safety are critical. Methods. A search for trials was done using the COVID-19 Living OVerview of Evidence (L·OVE) platform. We also searched for relevant authorization documents and trial reports for COVID-19 vaccines of the US-Food and Drug Authority (US-FDA), the European Medicines Agency (EMA), the United Kingdom Medicines and Health Products Regulatory Agency (MHRA), and the WHO website. We included studies that fulfilled the following inclusion criteria: population – humans; intervention – COVID-19 vaccines; comparison – control or placebo; outcomes – efficacy and adverse events; methods – phase 3 randomized trials. Two reviewers independently screened the reports, assessed the methodological quality, and extracted the data on the trial characteristics and results on vaccine efficacy and safety. The date of last search was March 11, 2021. Results. Interim results of trials investigating five vaccines were identified and included in the review. All five vaccines demonstrated satisfactory vaccine efficacy (VE) against symptomatic COVID-19 infection among adults in the short term with moderate certainty of evidence: BNT162b2, VE 95% (95% CI 90.3, 97.6); mRNA-1273, VE 93.6% (95% CI 88.6, 96.5); ChAdOx1, VE 66.7% (95% CI 57.4, 74.0), Gam-COVID-Vac, VE 91.1% (95% CI 83.6, 95.1); and Ad26.CoV2.S, VE 67.2% (95% CI 59.3, 73.7). Data on the efficacy against severe COVID-19 infection and asymptomatic COVID-19 infection are still inconclusive, except for Ad26.CoV2.S, which demonstrated good efficacy in preventing moderate and/or severe COVID-19 infection and acceptable protection against asymptomatic COVID-19 infection 28 days after vaccination (moderate certainty of evidence). Efficacy data on preventing death from COVID-19 infection are still inconclusive. Very limited phase 3 trial data is available to inform vaccine efficacy against the different variants of SARS-CoV-2. Vaccination with these five vaccines was associated with higher adverse reactions compared to control. These adverse events, due to reactions to the vaccines, were mild to moderate and of short duration. Available evidence on vaccine efficacy and safety is limited, mainly due to the short follow up and the small sample size of specific populations. Conclusion. BNT162b2, mRNA-1273, ChAdOx1, Gam-COVID-Vac and Ad26.CoV.S vaccines demonstrated satisfactory vaccine efficacy against symptomatic COVID-19 infection among adults in the short term with moderate certainty of evidence. Data on the efficacy against severe COVID-19 infection, asymptomatic COVID-19 infection, and death from COVID-19 infection are still inconclusive. Long-term efficacy and safety data, and data on the efficacy against variant strains of SARS-CoV-2 are still lacking.
Background Prolonged hospitalization leads to poorer health outcomes and consumes limited hospital resources. This study identified factors associated with prolonged length of stay (PLOS) among internal medicine patients admitted in a tertiary government hospital. Methods We reviewed the medical records of 386 adult patients admitted under the primary service of General Internal Medicine at the Philippine General Hospital from January 1 to December 31, 2019. PLOS was defined as at least 14 days for emergency admissions or 3 days for elective admissions. Sociodemographics, clinical characteristics, admission- and hospital system-related factors, disease-specific factors, outcome on the last day of hospitalization, and hospitalization costs were obtained. We determined the proportion with PLOS and reviewed reasons for discharge delays. We conducted multiple logistic regression analyses to assess associations between various factors and PLOS. Results The prevalence of PLOS is 19.17% (95% CI 15.54, 23.42). Positive predictors include being partially dependent on admission (aOR 2.61, 95% CI 0.99, 6.86), more co-managing services (aOR 1.26, 95% CI 1.06, 1.50), and longer duration of intravenous antibiotics (aOR 1.36, 95% CI 1.22, 1.51). The only negative predictor is the need for intravenous antibiotics (aOR 0.14, 95% CI 0.04, 0.54). The most common reason for discharge delays was prolonged treatment. The median hospitalization cost of patients with PLOS was PHP 77,427.20 (IQR 102,596). Conclusions Almost a fifth of emergency admissions and a quarter of elective admissions had PLOS. Addressing factors related to predictors such as functional status on admission, number of co-managing services, and use of intravenous antibiotics can guide clinical and administrative decisions, including careful attention to vulnerable patients and judicious use of resources.
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