Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Use of Transcranial Doppler for Management of Central Nervous System Infections in Critically Ill Children.

BACKGROUND: The primary objective of this study was to characterize changes in cerebral blood flow measured using transcranial Doppler in children with central nervous system infections. We hypothesized that children with central nervous system infections have abnormal cerebral blood flow, associated with a greater frequency of complications and poor neurological outcome. METHODS: We conducted a single-center, retrospective study of children admitted to the neonatal or pediatric intensive care unit with central nervous system infection and undergoing transcranial Doppler as part of routine care between March 2011 and July 2015. RESULTS: A total of 20 children with central nervous system infection underwent 35 transcranial Dopplers. The mean age was 8.2 ± 6.3 years, including 12 boys and eight girls. The most common infection was meningitis (n = 11, 55%), with the remainder comprising encephalitis (15%), meningoencephalitis (20%), and abscess or empyema (10%). Bacterial (n = 10, 50%) and viral (n = 6) sources were common with only one (5%) fungal infection and three (15%) unknown but presumed viral etiology. The patients underwent transcranial Doppler 4 ± 9 days after intensive care unit admission. Mean cerebral blood flow velocities were overall increased compared with reference values for age (healthy children and critically ill children) mostly because of hyperemia (n = 21, 60%) and vasospasm (6%). Hypoperfusion (cerebral blood flow velocity <1 S.D. of normal value) in at least one vessel was associated with morbidity (intubation, vasoactive medications, neurosurgery, cardiac arrest) (P = 0.04) and mortality (P = 0.03). Two patients had increased intracranial pressure and hyperventilation was safely achieved with transcranial Doppler monitoring to avoid ischemia. Serial transcranial Dopplers were used to guide blood pressure management. CONCLUSIONS: Transcranial Doppler can be used in children with central nervous system infection as a tool to assess cerebral blood flow. In this retrospective study, cerebral hypoperfusion was associated with increased morbidity and mortality. If transcranial Doppler is to guide medical therapy and management of cerebral blood flow in children with central nervous system infections, these results will need to be validated in prospective studies with a more homogenous population of children with encephalitis or meningitis.