Methods: An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014.
Results: The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P < .001) was observed, from 883 viral copies/µL at 1-2 days after symptom onset to 312 viral copies/µL at 3-4 days and 158 viral copies/µL at 5-7 days, before declining to 35 viral copies/µL at ≥8 days. In comparison with RV-A (median VL, 217 copies/µL) and RV-B (median VL, 275 copies/µL), RV-C-infected subjects produced higher VL (505 copies/µL; P < .001). Importantly, higher RV VL (median, 348 copies/µL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P = .017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate.
Conclusions: Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV.
METHODS: We prospectively evaluated children with serologically confirmed Japanese encephalitis over an 8.3-year period. The patients were assessed and their outcomes were graded with a functional outcome score at hospital discharge and at follow-up appointments. We examined how patient outcome at hospital discharge compared with that at long-term follow-up visits, when changes in outcome occurred, and the prognostic indicators of the eventual outcome.
RESULTS: One hundred and eighteen patients were recruited into the study, and 10 (8%) died during the acute phase of illness. At hospital discharge, 44 (41%) of the 108 patients who survived had apparent full recovery; 3 (3%) had mild, 28 (26%) had moderate, and 33 (31%) had severe neurological sequelae. Eighty six of the 108 patients were followed up for a median duration of 52.9 months (range, 0.9-114.9 months). During follow-up, 31 patients experienced improvement, but 15 patients experienced deterioration in their outcome grade. In most cases, assessment during the first 3-6 months after hospital discharge was predictive of the long-term outcome. More than one-half of the patients continued to experience neuropsychological sequelae and behavioral disorders. A combination of poor perfusion, Glasgow coma score < or =8, and > or =2 witnessed seizures predicted a poor long-term outcome with 65% sensitivity and 92% specificity.
CONCLUSIONS: Neurological assessment of Japanese encephalitis survivors at hospital discharge does not predict long-term outcome. Seizures and shock are treatable risk factors for a poor outcome at hospital discharge and at long-term follow-up visits.
METHODS: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence.
RESULTS: Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%-42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%-5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%-8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy.
CONCLUSIONS: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.
METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations.
RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively.
CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
METHODS: PACKNOW was an open-label, randomized, controlled trial of acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen in Malaysian patients aged ≥5 years with knowlesi malaria of any severity. The primary end point was change in creatinine at 72 hours. Secondary end points included longitudinal changes in creatinine in patients with severe malaria or acute kidney injury (AKI), stratified by hemolysis.
RESULTS: During 2016-2018, 396 patients (aged 12-96 years) were randomized to acetaminophen (n = 199) or no acetaminophen (n = 197). Overall, creatinine fell by a mean (standard deviation) 14.9% (18.1) in the acetaminophen arm vs 14.6% (16.0) in the control arm (P = .81). In severe disease, creatinine fell by 31.0% (26.5) in the acetaminophen arm vs 20.4% (21.5) in the control arm (P = .12), and in those with hemolysis by 35.8% (26.7) and 19% (16.6), respectively (P = .07). No difference was seen overall in patients with AKI; however, in those with AKI and hemolysis, creatinine fell by 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .041). Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .041) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .027 and P = .002, respectively).
CONCLUSIONS: Acetaminophen did not improve creatinine among the entire cohort but may improve renal function in patients with severe knowlesi malaria and in those with AKI and hemolysis.
CLINICAL TRIALS REGISTRATION: NCT03056391.
Methods: A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality.
Results: Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBL-producing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL).
Conclusions: A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies.
METHODS: A total of 13 805 non-US-born persons at high risk of TB infection or progression to TB disease were screened for LTBI at 16 clinical sites located across the United States with a tuberculin skin test, QuantiFERON Gold In-Tube test, and T-SPOT.TB test. Bayesian latent class analysis was applied to test results to estimate LTBI prevalence and associated credible intervals (CrIs) for each country or world region of birth.
RESULTS: Among the study population, the estimated LTBI prevalence was 31% (95% CrI, 26%-35%). Country-of-birth-level LTBI prevalence estimates were highest for persons born in Haiti, Peru, Somalia, Ethiopia, Vietnam, and Bhutan, ranging from 42% to 55%. LTBI prevalence estimates were lowest for persons born in Colombia, Malaysia, and Thailand, ranging from 8% to 13%.
CONCLUSIONS: LTBI prevalence in persons born outside the US varies widely by country. These estimates can help target community outreach efforts to the highest-risk groups.
METHODS: We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/μL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/μL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group.
RESULTS: Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63).
CONCLUSIONS: Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined.
CLINICAL TRIALS REGISTRATION: NCT01030211.
METHODS: There were 5 patients, with a median age of 1.75 (range 0.1-6.25) years, a median weight of 10.7 (2.9-21.5) kg, and a median creatinine clearance of 179 (44-384) mL/min/1.73m2, who received intravenous infusions of colistimethate each 8 hours. The median daily dose was 0.21 (0.20-0.21) million international units/kg, equivalent to 6.8 (6.5-6.9) mg of colistin base activity per kg/day. Plasma concentrations of colistimethate and formed colistin were subjected to population pharmacokinetic modeling to explore the patient factors influencing the concentration of colistin.
RESULTS: The median, average, steady-state plasma concentration of colistin (Css,avg) was 0.88 mg/L; individual values ranged widely (0.41-3.50 mg/L), even though all patients received the same body weight-based daily dose. Although the daily doses were ~33% above the upper limit of the FDA- and EMA-recommended dose range, only 2 patients achieved Css,avg ≥2mg/L; the remaining 3 patients had Css,avg <1mg/L. The pharmacokinetic covariate analysis revealed that clearances of colistimethate and colistin were related to creatinine clearance.
CONCLUSIONS: The FDA and EMA dosage recommendations may be suboptimal for many pediatric patients. Renal functioning is an important determinant of dosing in these patients.
METHODS: Sensitive and specific nested polymerase chain reaction was used to identify all Plasmodium species present in (1) blood samples obtained from 960 patients with malaria who were hospitalized in Sarawak, Malaysian Borneo, during 2001-2006; (2) 54 P. malariae archival blood films from 15 districts in Sabah, Malaysian Borneo (during 2003-2005), and 4 districts in Pahang, Peninsular Malaysia (during 2004-2005); and (3) 4 patients whose suspected cause of death was P. knowlesi malaria. For the 4 latter cases, available clinical and laboratory data were reviewed.
RESULTS: P. knowlesi DNA was detected in 266 (27.7%) of 960 of the samples from Sarawak hospitals, 41 (83.7%) of 49 from Sabah, and all 5 from Pahang. Only P. knowlesi DNA was detected in archival blood films from the 4 patients who died. All were hyperparasitemic and developed marked hepatorenal dysfunction.
CONCLUSIONS: Human infection with P. knowlesi, commonly misidentified as the more benign P. malariae, are widely distributed across Malaysian Borneo and extend to Peninsular Malaysia. Because P. knowlesi replicates every 24 h, rapid diagnosis and prompt effective treatment are essential. In the absence of a specific routine diagnostic test for P. knowlesi malaria, we recommend that patients who reside in or have traveled to Southeast Asia and who have received a "P. malariae" hyperparasitemia diagnosis by microscopy receive intensive management as appropriate for severe falciparum malaria.
METHODS: Microscopy-based malaria notification data and polymerase chain reaction (PCR) results were obtained from the Sabah Department of Health and State Public Health Laboratory, respectively, from January 2015 to December 2017. From January 2016 this was complemented by a statewide prospective hospital surveillance study. Databases were matched, and species was determined by PCR, or microscopy if PCR was not available.
RESULTS: A total of 3867 malaria cases were recorded between 2015 and 2017, with PCR performed in 93%. Using PCR results, and microscopy if PCR was unavailable, P. knowlesi accounted for 817 (80%), 677 (88%), and 2030 (98%) malaria cases in 2015, 2016, and 2017, respectively. P. falciparum accounted for 110 (11%), 45 (6%), and 23 (1%) cases and P. vivax accounted for 61 (6%), 17 (2%), and 8 (0.4%) cases, respectively. Of those with P. knowlesi, the median age was 35 (interquartile range: 24-47) years, and 85% were male.
CONCLUSIONS: Malaysia is approaching elimination of the human-only Plasmodium species. However, the ongoing increase in P. knowlesi incidence presents a major challenge to malaria control and warrants increased focus on knowlesi-specific prevention activities. Wider molecular surveillance in surrounding countries is required.