In-hospital Case-fatality Ratios Research Articles

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

BackgroundCOVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. MethodsThis study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. ResultsOf 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). ConclusionApproximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Changes in the global hospitalisation burden of respiratory syncytial virus in young children during the COVID-19 pandemic: a systematic analysis

The COVID-19 pandemic is reported to have affected the epidemiology of respiratory syncytial virus (RSV), which could have important implications for RSV prevention and control strategies. We aimed to assess the hospitalisation burden of RSV-associated acute lower respiratory infection (ALRI) in children younger than 5 years during the pandemic period and the possible changes in RSV epidemiology from a global perspective. We conducted a systematic literature search for studies published between Jan 1, 2020, and June 30, 2022, in MEDLINE, Embase, Global Health, Web of Science, the WHO COVID-19 Research Database, CINAHL, LILACS, OpenGrey, CNKI, WanFang, and CqVip. We included unpublished data on RSV epidemiology shared by international collaborators. Eligible studies reported data on at least one of the following measures for children (aged <5 years) hospitalised with RSV-associated ALRI: hospital admission rates, in-hospital case fatality ratio, and the proportion of hospitalised children requiring supplemental oxygen or requiring mechanical ventilation or admission to intensive care. We used a generalised linear mixed-effects model for data synthesis to measure the changes in the incidence, age distribution, and disease severity of children hospitalised with RSV-associated ALRI during the pandemic, compared with the year 2019. We included 61 studies from 19 countries, of which 14 (23%) studies were from the published literature (4052 identified records) and 47 (77%) were from unpublished datasets. Most (51 [84%]) studies were from high-income countries; nine (15%) were from upper-middle-income countries, one (2%) was from a lower-middle-income country (Kenya), and none were from a low-income country. 15 studies contributed to the estimates of hospitalisation rate and 57 studies contributed to the severity analyses. Compared with 2019, the rates of RSV-associated ALRI hospitalisation in all children (aged 0-60 months) in 2020 decreased by 79·7% (325 000 cases vs 66 000 cases) in high-income countries, 13·8% (581 000 cases vs 501 000 cases) in upper-middle-income countries, and 42·3% (1 378 000 cases vs 795 000 cases) in Kenya. In high-income countries, annualised rates started to rise in 2021, and by March, 2022, had returned to a level similar to 2019 (6·0 cases per 1000 children [95% uncertainty interval 5·4-6·8] in April, 2021, to March, 2022, vs 5·0 cases per 1000 children [3·6-6·8] in 2019). By contrast, in middle-income countries, rates remained lower in the latest period with data available than in 2019 (for upper-middle-income countries, 2·1 cases [0·7-6·1] in April, 2021, to March, 2022, vs 3·4 [1·2-9·7] in 2019; for Kenya, 2·2 cases [1·8-2·7] in 2021 vs 4·1 [3·5-4·7] in 2019). Across all time periods and income regions, hospitalisation rates peaked in younger infants (aged 0 to <3 months) and decreased with increasing age. A significantly higher proportion of children aged 12-24 months were hospitalised with RSV-associated ALRI in high-income and upper-middle-income countries during the pandemic years than in 2019, with odds ratios ranging from 1·30 (95% uncertainty interval 1·07-1·59) to 2·05 (1·66-2·54). No consistent changes in disease severity were observed. The hospitalisation burden of RSV-associated ALRI in children younger than 5 years was significantly reduced during the first year of the COVID-19 pandemic. The rebound in hospitalisation rates to pre-pandemic rates observed in the high-income region but not in the middle-income region by March, 2022, suggests a persistent negative impact of the pandemic on health-care systems and health-care access in the middle-income region. RSV surveillance needs to be established (or re-established) to monitor changes in RSV epidemiology, particularly in low-income and lower-middle-income countries. EU Innovative Medicines Initiative Preparing for RSV Immunisation and Surveillance in Europe (PROMISE), Bill & Melinda Gates Foundation, and WHO.

Prevalence of Antimicrobial Resistance in Gram-Negative Bacteria Bloodstream Infections in Peru and Associated Outcomes: VIRAPERU Study.

Surveillance of antimicrobial resistance among gram-negative bacteria (GNB) is of critical importance, but data for Peru are not available. To fill this gap, a non-interventional hospital-based surveillance study was conducted in 15 hospitals across Peru from July 2017 to October 2019. Consecutive unique blood culture isolates of key GNB (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp.) recovered from hospitalized patients were collected for centralized antimicrobial susceptibility testing, along with linked epidemiological and clinical data. A total of 449 isolates were included in the analysis. Resistance to third-generation cephalosporins (3GCs) was present in 266 (59.2%) GNB isolates. Among E. coli (n = 199), 68.3% showed 3GC resistance (i.e., above the median ratio for low- and middle-income countries in 2020 for this sustainable development goal indicator). Carbapenem resistance was present in 74 (16.5%) GNB isolates, with wide variation among species (0% in E. coli, 11.0% in K. pneumoniae, 37.0% in P. aeruginosa, and 60.8% in Acinetobacter spp. isolates). Co-resistance to carbapenems and colistin was found in seven (1.6%) GNB isolates. Empiric treatment covered the causative GNB in 63.3% of 215 cases. The in-hospital case fatality ratio was 33.3% (92/276). Pseudomonas aeruginosa species and carbapenem resistance were associated with higher risk of in-hospital death. In conclusion, an important proportion of bloodstream infections in Peru are caused by highly resistant GNB and are associated with high in-hospital mortality.

Impact of prior cryptococcal antigen screening on in-hospital mortality in cryptococcal meningitis or fungaemia among HIV-seropositive individuals in South Africa: a cross-sectional observational study

ObjectivesWe investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital. MethodsWe compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/μL and laboratory-confirmed CM/fungaemia from 2017–2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre–COVID-19: before March 2020 vs. COVID-19: after March 2020). ResultsOverall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69–0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47–0.87]; p = 0.005) compared with before (OR, 0.95 [0.76–1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51–0.96]; p = 0.03). DiscussionPrevious CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier.

Adjusting for Case Under-Ascertainment in Estimating RSV Hospitalisation Burden of Older Adults in High-Income Countries: a Systematic Review and Modelling Study.

Previous studies suggest diagnostic testing characteristics (i.e. variations in clinical specimens and diagnostic tests) can contribute to underestimation of RSV disease burden. We aimed to improve the understanding of RSV hospitalisation burden in older adults (aged ≥ 65years) in high-income countries through adjusting for case under-ascertainment. We conducted a systematic review to include data on RSV-associated acute respiratory infection (ARI) hospitalisation burden in older adults in high-income countries. To adjust for case under-ascertainment, we developed a two-step framework that incorporated empirical data on the RSV detection proportion of different clinical specimens and testing approaches as well as their statistical uncertainty. We estimated the unadjusted and adjusted RSV-associated hospitalisation burden through multilevel random-effects meta-analysis. We further explored RSV-associated in-hospital mortality burden. We included 12 studies with eligible RSV hospitalisation burden data. We estimated that pooled unadjusted hospitalisation rate was 157 per 100,000 (95%CI 98-252) for adults aged ≥ 65years; the rate was adjusted to 347 per 100,000 (203-595) after accounting for under-ascertainment. The adjusted rate could be translated into 787,000 (460,000-1,347,000) RSV-associated hospitalisations in high-income countries in 2019, which was about 2.2 times the unadjusted estimate. Stratified analysis by age group showed that the adjusted rate increased with age, from 231 per 100,000 in adults aged 65-74years to 692 per 100,000 in adults aged > 85years. The in-hospital case fatality ratio of RSV was 6.1% (3.3-11.0) and the total RSV-associated in-hospital deaths in high-income countries in 2019 could be between 22,000 and 47,000. This study improves the understanding of RSV-associated hospitalisation burden in older adults and shows that the true RSV-associated hospitalisation burden could be 2.2 times what was reported in existing studies. This study has implications for calculating the benefit of interventions to treat and prevent RSV-associated disease.

COVID-19 in-hospital mortality during the first two pandemic waves, at Helen Joseph Hospital, South Africa.

there has been significant global variation in Coronavirus Disease (COVID-19) mortality at different time points in the pandemic. Contributing factors include population demographics, comorbidities, health system capacity, prior infection with COVID-19, vaccinations, and viral variants. The study aims to describe COVID-19-related mortality of inpatients at Helen Joseph Hospital (HJH), over 12 months, during the first two waves of the COVID-19 pandemic in South Africa. The primary objectives were to describe the socio-demographic details, clinical characteristics, and hospital outcomes during the first and second waves of COVID-19. This included an assessment of the in-hospital case fatality ratio (CFR) of patients admitted with COVID-19. The secondary objectives were to compare the socio-demographic details, clinical characteristics, and outcomes between the two waves, and to determine risk factors associated with COVID-19-related mortality. this is a retrospective cohort study of all inpatient laboratory-confirmed COVID-19 cases at HJH from 1st May 2020 to 31st April 2021. Data were collected by the National Institute for Communicable Diseases (NICD). Bivariate analysis was performed to describe and compare the socio-demographic characteristics, clinical characteristics, and hospital admission outcomes between the two waves. Multivariate logistic regression was used to determine risk factors for COVID-19-related mortality. overall, 1359 patients were admitted, 595 in wave one, and 764 in wave two. Patients were predominantly male (52.4%), of Black African race (75.1%) with a mean age of 54.6 (standard deviation 15.4) years. The median length of stay was 8 days (interquartile range 5-14 days). In total, 73.2% (995) of patients required oxygen, 5.2% (71) of patients received mechanical ventilation, and 7.1% (96) were admitted to the high care and Intensive Care Unit (ICU). The most common comorbid illnesses were hypertension (36.7%, n=499), diabetes mellitus (26.6%, n=362), Human Immunodeficiency Virus (HIV) (10.8%, n=147), and obesity (11.0%, n=149). The in-hospital CFR during the first wave was 30.4% (181/595) and 25.5% (195/764) (p<0.001) in the second wave, and overall, in-hospital CFR was 27.7% (376/1359). The adjusted odds of death were 79% higher among patients admitted during wave one compared to wave two (aOR=1.79; 95% CI: 1.35-2.38). A one-year increase in age increased the odds of death by 4% (aOR=1.04; 95% CI: 1.03-1.05). The need for oxygen (aOR=2.17, 95%CI: 1.56-3.01) and ventilation (aOR=7.23, 95% CI: 4.02-13.01) were significant risk factors for mortality. prior to the availability of vaccines, COVID-19-related mortality was high and risk factors for mortality were consistent with national and international findings. This study reflects the impact of the pandemic on the South African public sector with limited resources and minimal ICU capacity.

Trends in Cases, Hospitalizations, and Mortality Related to the Omicron BA.4/BA.5 Subvariants in South Africa.

In this study, we compared admission incidence risk and the risk of mortality in the Omicron BA.4/BA.5 wave to previous waves. Data from South Africa's SARS-CoV-2 case linelist, national COVID-19 hospital surveillance system, and Electronic Vaccine Data System were linked and analyzed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100 000 population. In-hospital case fatality ratios (CFRs) during the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves were compared using post-imputation random effect multivariable logistic regression models. The CFR was 25.9% (N = 37 538 of 144 778), 10.9% (N = 6123 of 56 384), and 8.2% (N = 1212 of 14 879) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves, respectively. After adjusting for age, sex, race, comorbidities, health sector, and province, compared with the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR], 1.3; 95% confidence interval [CI]: 1.2-1.4) and Delta wave (aOR, 3.0; 95% CI: 2.8-3.2). Being partially vaccinated (aOR, 0.9; 95% CI: .9-.9), fully vaccinated (aOR, 0.6; 95% CI: .6-.7), and boosted (aOR, 0.4; 95% CI: .4-.5) and having prior laboratory-confirmed infection (aOR, 0.4; 95% CI: .3-.4) were associated with reduced risks of mortality. Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa's first 3 waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.

Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational study

Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines. In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality. From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32-43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0-27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0-40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53-2·48]; p<0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02-1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35-0·64]; p<0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8-15) versus 17 days (13-21) in the comparison group (p=0·0010). In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit. National Institute for Communicable Diseases, a Division of the National Health Laboratory Service. For the Zulu translation of the abstract see Supplementary Materials section.

Clinical severity of COVID-19 in patients admitted to hospital during the omicron wave in South Africa: a retrospective observational study

BackgroundUp to the end of January, 2022, South Africa has had four recognisable COVID-19 pandemic waves, each predominantly dominated by one variant of concern: the ancestral strain with an Asp614Gly mutation during the first wave, the beta variant (B.1.351) during the second wave, the delta variant (B.1.617.2) during the third wave, and lastly, the omicron variant (B.1.1.529) during the fourth wave. We aimed to assess the clinical disease severity of patients admitted to hospital with SARS-CoV-2 infection during the omicron wave and compare the findings with those of the preceding three pandemic waves in South Africa.MethodsWe defined the start and end of each pandemic wave as the crossing of the threshold of weekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases per 100 000 population. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. We compared disease severity across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of the following: acute respiratory distress, receipt of supplemental oxygen or mechanical ventilation, admission to intensive care, or death.FindingsWe analysed 335 219 laboratory-confirmed SARS-CoV-2 hospital admissions with a known outcome, constituting 10·4% of 3 216 179 cases recorded during the four waves. During the omicron wave, 52 038 (8·3%) of 629 617 cases were admitted to hospital, compared with 71 411 (12·9%) of 553 530 in the Asp614Gly wave, 91 843 (12·6%) of 726 772 in the beta wave, and 131 083 (10·0%) of 1 306 260 in the delta wave (p<0·0001). During the omicron wave, 15 421 (33·6%) of 45 927 patients admitted to hospital had severe disease, compared with 36 837 (52·3%) of 70 424 in the Asp614Gly wave, 57 247 (63·4%) of 90 310 in the beta wave, and 81 040 (63·0%) of 128 558 in the delta wave (p<0·0001). The in-hospital case-fatality ratio during the omicron wave was 10·7%, compared with 21·5% during the Asp614Gly wave, 28·8% during the beta wave, and 26·4% during the delta wave (p<0·0001). Compared with those admitted to hospital during the omicron wave, patients admitted during the other three waves had more severe clinical presentations (adjusted odds ratio 2·07 [95% CI 2·01–2·13] in the Asp614Gly wave, 3·59 [3·49–3·70] in the beta wave, and 3·47 [3·38–3·57] in the delta wave).InterpretationThe trend of increasing cases and admissions across South Africa's first three waves shifted in the omicron wave, with a higher and quicker peak but fewer patients admitted to hospital, less clinically severe illness, and a lower case-fatality ratio compared with the preceding three waves. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile, and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and previous infection levels.FundingNational Institute for Communicable Diseases.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis

SummaryBackgroundRespiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0–60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0–60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development.MethodsIn this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0–60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400).FindingsIn addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4–44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9–4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100–49 100), and 101 400 RSV-attributable overall deaths (84 500–125 200) in children aged 0–60 months. In infants aged 0–6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6–9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0–2·0 million), 13 300 RSV-associated acute lower respiratory infection inhospital deaths (6800–28 100), and 45700 RSV-attributable overall deaths (38 400–55 900). 2·0% of deaths in children aged 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0–4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs).InterpretationRSV contributes substantially to morbidity and mortality burden globally in children aged 0–60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0–60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented.FundingEU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Global Disease Burden of Respiratory Syncytial Virus in Preterm Children in 2019: A Systematic Review and Individual Participant Data Meta-Analysis Protocol.

Existing guidelines on respiratory syncytial virus (RSV) prophylaxis differ greatly by gestational age (GA) and other underlying risk factors, highlighting the data gaps in RSV disease burden among preterm infants. We will conduct a systematic review and individual participant data (IPD) meta-analysis of RSV global disease burden among preterm-born children. Three databases, Medline, Embase, and Global Health, will be searched for relevant studies on RSV disease burden for 2019 or before in preterm-born children published between 1 January 1995 and 31 December 2021. IPD will be sought by contacting the investigators identified from published literature and from existing collaboration networks. One-stage and 2-stage random-effects meta-analyses will be used to combine information from IPD and non-IPD studies to produce summary RSV burden estimates of incidence rate, hospital admission rate, and in-hospital case fatality ratio. The framework will be extended to examine subgroup(s) with the most substantial RSV disease burden.

PGI score: prospective validation and correlation with SOFA, SAPS-II, and APACHE-II scores for predicting outcomes in acute aluminum phosphide poisoning.

We recently derived a simplified 3-point PGI score (representing blood pH<7.25, Glasgow coma scale [GCS] score<13, and impaired systolic blood pressure [SBP]<90mm Hg), which accurately predicted in-hospital case fatality ratio (CFR) in acute aluminum phosphide poisoning. The present study aimed to validate the PGI score and compare it with Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment score (SOFA), and Simplified Acute Physiology Score (SAPS) II scores. We performed a prospective cohort study in adult patients with aluminum phosphide ingestion admitted in PGIMER, Chandigarh (India), from April 2013 to August 2014. A univariant analysis detected the association of various baseline variables with CFR. Correlation of the PGI score with SOFA, SAPS-II, and APACHE-II scores was performed using Spearman's correlation (rs , range -1 to +1) and scatter plots. Seventy-six patients were enrolled (mean age, 28.3years; 41 males). CFR was 60.5%. PGI score variables-pH, GCS, and impaired SBP predicted CFR (P-value <0.001). Among patients with a total PGI score of 3 or 2, 100% died, compared with 50% in score 1 and 10.7% in score 0. Baseline PGI, SOFA, SAPS-II, and APACHE-II scores predicted CFR (P-value <0.001). There was a positive correlation between the PGI score and SOFA score (rs , 0.855), SAPS-II score (rs , 0.861), and APACHE-II score (rs , 0.883). The P-value for all rs values was <0.001. The PGI score is a validated toxidrome-specific and simplified risk-stratification tool. Validation in other populations is warranted to confirm its routine use.

Time series analysis of in-hospital maternal case fatality ratio in the postpartum period according to pregnancy risks and route of delivery in the regions of Brazil, 2010-2019.

to analyze in-hospital maternal case fatality ratio in the postpartum period according to pregnancy risks and route of delivery, within the Brazilian National Health System, Brazil and macro-regions, 2010-2019. this was an ecological time-series study, using data from the Hospital Information System; in-hospital maternal case fatality ratio in the postpartum period took into consideration maternal hospitalizations with outcome 'death' over the total number of hospitalizations per year, according to pregnancy risks and route of delivery, in the regions. there were 19,158,167 hospitalizations for childbirth and 5,110 deaths in the period analyzed; maternal case fatality ratio increased from 1.1 (2010) to 1.9 death/10,000 hospitalizations (2019), in usual-risk pregnancies after vaginal deliveries, and decreased from 10.5 (2010) to 7.0 deaths/10,000 hospitalizations (2019) in high-risk pregnancies after cesarean sections; the Midwest region presented the highest and the South region the lowest case fatality ratio for high-risk pregnancies. in-hospital case fatality ratio was higher for high-risk pregnancies, showing differences according to route of delivery and regions.

Epidemiology of SARS-CoV-2 infection and SARS-CoV-2 positive hospital admissions among children in South Africa.

We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and positive admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and whose death was judged SARS-CoV-2 related by attending physician. 315 570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3 548 738 tests and 1.6% of all children in the country. Of children tested, 46 137 (14.6%) were positive. Children made up 2.9% (n =2007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals [CI] 1.08-4.40)] vs female; age <1year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28-18.51)] vs age 1-4years; admission to a public hospital [aOR 5.07(95% 2.01-12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none. Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10years, those in certain provinces and those with underlying conditions should be considered for increased testing and vaccination.

Disease Burden Estimates of Respiratory Syncytial Virus related Acute Respiratory Infections in Adults With Comorbidity: A Systematic Review and Meta-Analysis.

Respiratory syncytial virus related acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in adults with comorbidities. We aimed to identify all studies investigating the disease burden of RSV-ARI in this group. We estimated the incidence, hospitalization rate, and in-hospital case fatality ratio (hCFR) of RSV-ARI in adults with comorbidities based on a systematic review of studies published between January 1996 and March 2020. We also investigated the association between RSV-ARI and any comorbidity in adults. Meta-analyses based on random effects model were carried out. Overall, 20 studies were included. The annual incidence rate of RSV-ARI in adults with any comorbidity was 37.6 (95% confidence interval [CI], 20.1-70.3) per 1000 persons per year in industrialized countries and the seasonal incidence rate was 28.4 (11.4-70.9) per 1000 persons per season. The hCFR in industrialized countries was 11.7% (5.8%-23.4%). There were no studies in developing countries. There were insufficient data to generate the meta-estimate of hospitalization rate. The likelihood of experiencing RSV-ARI for those with any comorbidity compared to those without was estimated to be 4.1 (odds ratio [OR], 1.6-10.4) and 1.1 (OR, 0.6-1.8) from studies using univariable and multivariable analysis respectively. The disease burden of RSV-ARI among adults with comorbidity is substantial with limited data available.

Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis

SummaryBackgroundHuman parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0–5 months, 6–11 months, and 12–59 months of age.MethodsWe did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case–fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570).Findings203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8–28·9) ALRI cases, 725 000 (433 000–1 260 000) ALRI hospital admissions, and 34 400 (16 400–73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0–5 months and 26% for 6–11 months) of the hospital admissions and 66% (42% for infants aged 0–5 months and 24% for 6–11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46–65% for the adjustment for health-care use, 59–77% for patient groups excluded, 54–93% for case definition, 42–93% for sampling strategy, and 67–77% for test methods. Heterogeneity in estimates was found between studies for each outcome.InterpretationWe report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4–14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions.FundingBill & Melinda Gates Foundation.

Factors and Outcomes Related to the Use of Guideline-Recommended Antibiotics in Patients With Neutropenic Fever at the Uganda Cancer Institute.

BackgroundNeutropenic fever (NF) is associated with significant morbidity and mortality for patients receiving cancer treatment in sub-Saharan Africa (sSA). However, the antibiotic management of NF in sub-Saharan Africa has not been well described. We evaluated the timing and selection of antibiotics for patients with NF at the Uganda Cancer Institute (UCI).MethodsWe conducted a retrospective chart review of adults with acute leukemia admitted to UCI from 1 January 2016 to 31 May 2017, who developed NF. For each NF event, we evaluated the association of clinical presentation and demographics with antibiotic selection as well as time to both initial and guideline-recommended antibiotics. We also evaluated the association between ordered antibiotics and the in-hospital case fatality ratio (CFR).ResultsForty-nine NF events occurred among 39 patients. The time to initial antibiotic order was <1 day. Guideline-recommended antibiotics were ordered for 37 (75%) NF events. The median time to guideline-recommended antibiotics was 3 days. Fever at admission, a documented physical examination, and abdominal abnormalities were associated with a shorter time to initial and guideline-recommended antibiotics. The in-hospital CFR was 43%. There was no difference in in-hospital mortality when guideline-recommended antibiotics were ordered as compared to when non-guideline or no antibiotics were ordered (hazard ratio, 0.51 [95% confidence interval {CI}, .10–2.64] and 0.78 [95% CI, .20–2.96], respectively).ConclusionsPatients with acute leukemia and NF had delayed initiation of guideline-recommended antibiotics and a high CFR. Prospective studies are needed to determine optimal NF management in sub-Saharan Africa, including choice of antibiotics and timing of antibiotic initiation.

Trends and outcomes of mechanically ventilated cirrhotic patients in the United States from 2005-2014.

Cirrhotic patients in organ failure are frequently admitted to intensive care units (ICUs) to receive invasive mechanical ventilation (IMV). We evaluated the trends of hospitalizations, in-hospital mortality, hospital costs, and hospital length of stay (LOS) of IMV patients with cirrhosis. We analyzed the United States National Inpatient Sample from 2005-2014. We selected discharges of IMV adult (≥18 years) patients with cirrhosis using the International Classification of Diseases, 9th Edition, Clinical Modification codes. Trends were assessed using linear regression and joinpoint regression. Between 2005 and 2014, there were approximately 9,441,605 hospitalizations of IMV adult patients, of which 4.7% had cirrhosis. There was an increasing trend in the total number of IMV cirrhotic patient hospitalizations (annual percent change [APC] 7.0%, 95% confidence interval [CI] 6.4%; 7.6%, Ptrend < 0.001). The in-hospital case-fatality ratio declined between 2005-2011 (APC -2.9%, 95% CI, -3.4%; -2.4%, Ptrend < 0.001); however, it remained similar between 2011-2014 (Ptrend = 0.58). The total annual hospital costs of all IMV cirrhotic patients increased from approximately $1.2 billion USD in 2005 to $2.7 billion USD in 2014 (Ptrend < 0.001). The mean hospital costs per patient and mean LOS declined between 2005 and 2014 (Ptrend < 0.001 and Ptrend = 0.01 respectively). The total number of hospitalizations and total annual costs of IMV patients with cirrhosis have been increasing over time. However, past hesitancy around admitting cirrhotic patients to the ICU may need to be tempered by the improving mortality trends in this patient population.

Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study

SummaryBackgroundHuman metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.MethodsWe estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus–associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.FindingsIn 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.InterpretationInfants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.FundingBill & Melinda Gates Foundation.

Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study

SummaryBackgroundSeasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.MethodsWe estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.FindingsIn 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1–190·6), 10·1 million influenza-virus-associated ALRI cases (6·8–15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000–1 415 000), 15 300 in-hospital deaths (5800–43 800), and up to 34 800 (13 200–97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.InterpretationA large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries.FundingWHO; Bill & Melinda Gates Foundation.