Amoxicillin is recommended as first-line antibiotic treatment for community-acquired pneumonia, the leading infectious cause of mortality in children aged less than 5 years. We conducted a ...double-blind, randomized controlled non-inferiority trial comparing 3- to 5-day amoxicillin treatment for non-severe chest-indrawing pneumonia in HIV-negative children aged 2 to 59 months in Malawi. In a secondary analysis, we assessed the frequency of serious adverse events (SAEs) during the trial to evaluate the safety of treatment with amoxicillin. Enrolled children with non-severe chest-indrawing pneumonia were randomized to either 3- or 5-day amoxicillin and followed for 14 days to track clinical outcomes. In addition to evaluation for treatment failure (primary endpoint, day 6), relapse, and study drug adherence, children were assessed for adverse events, including SAEs, which were managed per local standard clinical practice until resolution or stabilization. Between March 2016 and April 2019, 3000 children were enrolled, with male and younger children (aged less than 24 months) demonstrating more SAEs (10.3% for males vs 8.1% for females, p = 0.04; 10.0% for 2-6 months, 10.8% for 7-11 months, 9.7% for 12-23 months and 5.6% for 24-59 months, p = 0.01). The most common SAEs were progression of or recurrent pneumonia (220 SAEs in 217 children), acute gastroenteritis (14 SAEs in 14 children), and fever (8 SAEs in 8 children); however, there were no significant or substantive differences in the percentage of children with pneumonia-related, acute gastroenteritis, or fever SAEs noted between the 3- versus 5-day amoxicillin treatment groups. In our pediatric community-acquired pneumonia trial evaluating amoxicillin treatment, there were relatively few SAEs overall and very few attributed to amoxicillin. Duration of amoxicillin treatment did not impact the frequency of SAEs. We found male and younger children appear to be more vulnerable to SAEs in our trial; however, our data support previous data demonstrating the safety of amoxicillin use in children with pneumonia.Clinical trial registration: ClinicalTrials.gov (NCT02678195).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
IMPORTANCE: Emergency medical services (EMS) commonly perform endotracheal intubation (ETI) or insertion of supraglottic airways, such as the laryngeal tube (LT), on patients with out-of-hospital ...cardiac arrest (OHCA). The optimal method for OHCA advanced airway management is unknown. OBJECTIVE: To compare the effectiveness of a strategy of initial LT insertion vs initial ETI in adults with OHCA. DESIGN, SETTING, AND PARTICIPANTS: Multicenter pragmatic cluster-crossover clinical trial involving EMS agencies from the Resuscitation Outcomes Consortium. The trial included 3004 adults with OHCA and anticipated need for advanced airway management who were enrolled from December 1, 2015, to November 4, 2017. The final date of follow-up was November 10, 2017. INTERVENTIONS: Twenty-seven EMS agencies were randomized in 13 clusters to initial airway management strategy with LT (n = 1505 patients) or ETI (n = 1499 patients), with crossover to the alternate strategy at 3- to 5-month intervals. MAIN OUTCOMES AND MEASURES: The primary outcome was 72-hour survival. Secondary outcomes included return of spontaneous circulation, survival to hospital discharge, favorable neurological status at hospital discharge (Modified Rankin Scale score ≤3), and key adverse events. RESULTS: Among 3004 enrolled patients (median interquartile range age, 64 53-76 years, 1829 60.9% men), 3000 were included in the primary analysis. Rates of initial airway success were 90.3% with LT and 51.6% with ETI. Seventy-two hour survival was 18.3% in the LT group vs 15.4% in the ETI group (adjusted difference, 2.9% 95% CI, 0.2%-5.6%; P = .04). Secondary outcomes in the LT group vs ETI group were return of spontaneous circulation (27.9% vs 24.3%; adjusted difference, 3.6% 95% CI, 0.3%-6.8%; P = .03); hospital survival (10.8% vs 8.1%; adjusted difference, 2.7% 95% CI, 0.6%-4.8%; P = .01); and favorable neurological status at discharge (7.1% vs 5.0%; adjusted difference, 2.1% 95% CI, 0.3%-3.8%; P = .02). There were no significant differences in oropharyngeal or hypopharyngeal injury (0.2% vs 0.3%), airway swelling (1.1% vs 1.0%), or pneumonia or pneumonitis (26.1% vs 22.3%). CONCLUSIONS AND RELEVANCE: Among adults with OHCA, a strategy of initial LT insertion was associated with significantly greater 72-hour survival compared with a strategy of initial ETI. These findings suggest that LT insertion may be considered as an initial airway management strategy in patients with OHCA, but limitations of the pragmatic design, practice setting, and ETI performance characteristics suggest that further research is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02419573
•Comparison of fast-breathing vs chest-indrawing community-acquired pneumonia.•Male and younger children appear more vulnerable to chest-indrawing pneumonia.•Understanding sex-, age-, and ...nutrition-related differences informs interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Out-of-hospital cardiac arrest (OHCA) remains a leading cause of death and a 2010 meta-analysis concluded that outcomes have not improved over several decades. However, guidelines ...have changed to emphasize CPR quality, minimization of interruptions, and standardized post-resuscitation care. We sought to evaluate whether OHCA outcomes have improved over time among agencies participating in the Resuscitation Outcomes Consortium (ROC) cardiac arrest registry (Epistry) and randomized clinical trials (RCTs). Methods Observational cohort study of 47,148 EMS-treated OHCA cases in Epistry from 139 EMS agencies at 10 ROC sites that participated in at least one RCT between 1/1/2006 and 12/31/2010. We reviewed patient, scene, event characteristics, and outcomes of EMS-treated OHCA over time, including subgroups with initial rhythm of pulseless ventricular tachycardia or ventricular fibrillation (VT/VF). Results Mean response interval, median age and male proportion remained similar over time. Unadjusted survival to discharge increased between 2006 and 2010 for treated OHCA (from 8.2% to 10.4%), as well as for subgroups of VT/VF (21.4% to 29.3%) and bystander witnessed VT/VF (23.5% to 30.3%). Compared with 2006, adjusted survival to discharge was significantly higher in 2010 for treated cases (OR = 1.72; 95% CI 1.53, 1.94), VT/VF cases (OR = 1.69; 95% CI 1.45, 1.98) and bystander witnessed VT/VF cases (OR = 1.65; 95% CI 1.36, 2.00). Tests for trend in each subgroup were significant ( p < 0.001). Conclusions ROC-wide survival increased significantly between 2006 and 2010. Additional research efforts are warranted to identify specific factors associated with this improvement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND:Survival following out-of-hospital cardiac arrest (OHCA) with shockable rhythms can be improved with early defibrillation. Although shockable OHCA accounts for only ≈25% of overall ...arrests, ≈60% of public OHCAs are shockable, offering the possibility of restoring thousands of individuals to full recovery with early defibrillation by bystanders. We sought to determine the association of bystander automated external defibrillator use with survival and functional outcomes in shockable observed public OHCA.
METHODS:From 2011 to 2015, the Resuscitation Outcomes Consortium prospectively collected detailed information on all cardiac arrests at 9 regional centers. The exposures were shock administration by a bystander-applied automated external defibrillator in comparison with initial defibrillation by emergency medical services. The primary outcome measure was discharge with normal or near-normal (favorable) functional status defined as a modified Rankin Score ≤2. Survival to hospital discharge was the secondary outcome measure.
RESULTS:Among 49 555 OHCAs, 4115 (8.3%) observed public OHCAs were analyzed, of which 2500 (60.8%) were shockable. A bystander shock was applied in 18.8% of the shockable arrests. Patients shocked by a bystander were significantly more likely to survive to discharge (66.5% versus 43.0%) and be discharged with favorable functional outcome (57.1% versus 32.7%) than patients initially shocked by emergency medical services. After adjusting for known predictors of outcome, the odds ratio associated with a bystander shock was 2.62 (95% confidence interval, 2.07–3.31) for survival to hospital discharge and 2.73 (95% confidence interval, 2.17–3.44) for discharge with favorable functional outcome. The benefit of bystander shock increased progressively as emergency medical services response time became longer.
CONCLUSIONS:Bystander automated external defibrillator use before emergency medical services arrival in shockable observed public OHCA was associated with better survival and functional outcomes. Continued emphasis on public automated external defibrillator utilization programs may further improve outcomes of OHCA.
Point-of-care ultrasound has the potential to help inform assessment, diagnosis, and management of illness in low- and middle-income countries (LMIC). To better understand current ultrasound use, ...barriers and facilitators to use, and perceptions and practices in LMIC, we conducted an anonymous online global survey targeting healthcare providers training and using ultrasound in LMIC. A total of 241 respondents representing 62 countries participated and most were physicians working in publicly-funded urban tertiary hospitals in LMIC. Most had received ultrasound training (78%), reported expertise (65%) and confidence (90%) in ultrasound use, and had access to ultrasound (88%), utilizing ultrasound most commonly for procedures and for evaluations of lungs, heart, and trauma. Access to an ultrasound machine was reported as both the top barrier (17%) and top facilitator (53%); other common barriers included access to education and training, cost, and competition for use and other common facilitators included access to a probe, gel, and electricity, and acceptance by healthcare providers, administrators, and patients. Most (80%) noted ultrasound access was important and 96% agreed that ultrasound improves quality of care and patient outcomes. Improving access to low-cost ultrasound equipment is critical to increasing ultrasound use among those who are trained.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•The utility of clinical assessment every 3 hours in children with pneumonia was evaluated.•Despite frequent assessments, post-discharge treatment failure was not identified.•Reliable parameters for ...risk stratification in childhood pneumonia are needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bystander cardiopulmonary resuscitation (BCPR) improves survival from out-of-hospital cardiac arrest (OHCA), yet BCPR rates remain low. It is unknown whether BCPR delivery disparities exist based on ...victim gender. We measured BCPR rates by gender in private and public environments, hypothesizing that females would be less likely than males to receive BCPR in public settings, with an associated difference in survival to hospital discharge.
We analyzed data from adult, nontraumatic OHCA events within the Resuscitation Outcomes Consortium registry (2011-2015). Using logistic regression, we modeled the likelihood of receiving BCPR by gender, including patient-level variables, stratified by location. A cohort of 19 331 OHCAs was assessed. Mean age was 64±17 years, and 63% (12 225/19 331) were male. Overall, 37% of OHCA victims received bystander CPR. In public locations, 39% (272/694) of females and 45% (1170/2600) of males received BCPR ( P<0.01), whereas in private settings, 35% (2198/6328) of females and 36% (3364/9449) of males received BCPR ( P=NS). Among public OHCAs, males had significantly increased odds of receiving BCPR compared with females (odds ratio, 1.27; 95% CI, 1.05-1.53; P=0.01); this was not the case in the private setting (odds ratio, 0.93; 95% CI, 0.87-1.01; P=NS). Controlling for site, age, and race, BCPR was significantly associated with survival to hospital discharge (odds ratio, 1.69; 95% CI, 1.54-1.85; P<0.01); in this model, males had 29% increased odds of survival compared with females (odds ratio, 1.29; 95% CI, 1.17-1.42; P<0.01).
Males had an increased likelihood of receiving BCPR compared with females in public. BCPR improved survival to discharge, with greater survival among males compared with females.
To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission.
HIV-1 pol sequence data were analyzed to infer the ...local transmission network.
We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions.
HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05).
Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK