METHODS: A 5-year retrospective single-center study in all adult patients with SD admitted to a tertiary intensive care unit in Malaysia.
RESULTS: Thirty-nine of 180 (22%) patients with SD died. Twenty-one of 180 (12%) had HLH defined as an HLH probability ≥70% according to histo score (HScore); 9 (43%) died. Similarly, 12 of 31 (39%) fulfilling ≥4 and 7 of 9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and creatinine correlated to fatality (odds ratios [ORs], 2.9, 3.4, 5.8, and 31.9; all P < .0001), as did peak ferritin (OR, 2.5; P = .0028), nadir platelets (OR, 1.9; P = .00068), hepatomegaly (OR, 2.9; P = .012), and increasing age (OR, 1.2; P = .0043). Multivariable logistic regression revealed peak AST (OR, 2.8; P = .0019), peak creatinine (OR, 7.3; P = .0065), and SOFA (Sequential Organ Failure Assessment) score (OR, 1.4; P = .0051) as independent risk factors of death.
CONCLUSIONS: Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multiorgan failure at risk of developing dengue-HLH.
METHODS: We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes.
RESULTS: A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone.
CONCLUSIONS: Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens.
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: Data (2014-2018) from a regional cohort of Asian PHIVA who received at least 6 months of continuous cART were analyzed. Treatment failure was defined according to World Health Organization criteria. Descriptive analyses were used to report treatment failure and subsequent management and evaluate postfailure CD4 count and viral load trends. Kaplan-Meier survival analyses were used to compare the cumulative incidence of death and loss to follow-up (LTFU) by treatment failure status.
RESULTS: A total 3196 PHIVA were included in the analysis with a median follow-up period of 3.0 years, of whom 230 (7.2%) had experienced 292 treatment failure events (161 virologic, 128 immunologic, 11 clinical) at a rate of 3.78 per 100 person-years. Of the 292 treatment failure events, 31 (10.6%) had a subsequent cART switch within 6 months, which resulted in better immunologic and virologic outcomes compared to those who did not switch cART. The 5-year cumulative incidence of death and LTFU following treatment failure was 18.5% compared to 10.1% without treatment failure.
CONCLUSIONS: Improved implementation of virologic monitoring is required to realize the benefits of virologic determination of cART failure. There is a need to address issues related to accessibility to subsequent cART regimens, poor adherence limiting scope to switch regimens, and the role of antiretroviral resistance testing.
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.
STUDY DESIGN: This was an open-label, randomized clinical trial conducted at 14 public hospitals across Malaysia from February to June 2021 among 500 symptomatic, RT-PCR confirmed COVID-19 patients, aged ≥50 years with ≥1 co-morbidity, and hospitalized within first 7 days of illness. Patients were randomized on 1:1 ratio to favipiravir plus standard care or standard care alone. Favipiravir was administered at 1800mg twice-daily on day 1 followed by 800mg twice-daily until day 5. The primary endpoint was rate of clinical progression from non-hypoxia to hypoxia. Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality.
RESULTS: Among 500 patients were randomized (mean age, 62.5 [SD 8.0] years; 258 women [51.6%]; and 251 [50.2%] had COVID-19 pneumonia), 487 (97.4%) patients completed the trial. Clinical progression to hypoxia occurred in 46 (18.4%) patients on favipiravir plus standard care and 37 (14.8%) on standard care alone (OR 1.30; 95%CI, 0.81-2.09; P=.28). All three pre-specified secondary end points were similar between both groups. Mechanical ventilation occurred in 6 (2.4%) vs 5 (2.0%) (OR 1.20; 95%CI, 0.36-4.23; P=.76), ICU admission in 13 (5.2%) vs 12 (4.8%) (OR 1.09; 95%CI, 0.48-2.47; P=.84), and in-hospital mortality in 5 (2.0%) vs 0 (OR 12.54; 95%CI, 0.76- 207.84; P=.08).
CONCLUSIONS: Among COVID-19 patients at high risk of disease progression, early treatment with oral favipiravir did not prevent their disease progression from non-hypoxia to hypoxia.
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: We conducted a nation-wide cross-sectional survey among the general population in Yemen, a low-income conflict country. Participants from all provinces in Yemen were included in the study. We evaluated factors that influence agreement to accept a COVID-19 vaccine and any potential correlation between vaccine hesitancy and lack of access to vaccines.
RESULTS: Overall, 50.1% of the 5329 respondents agreed to accept a COVID-19 vaccine. Only 39.9% of participants agreed that they had access to a COVID-19 vaccine, with females indicating lower access than males. Potential determinants of vaccine acceptance included being male, updating self on the development of vaccines against COVID-19, opinion about severity of COVID-19, anxiety about contracting COVID-19, concerns about the safety of COVID-19 vaccines, and lack of access to vaccines.
CONCLUSIONS: Our results indicate that the immediate threat in Yemen toward achieving population immunity is the severe shortage and lack of access to vaccines, rather than vaccine hesitancy.
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: In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction-confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008.
RESULTS: Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax. Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/microL (interquartile range, 6-222,570 parasites/microL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (p < .002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%-6.6%).
CONCLUSIONS: Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications.