Unnecessary hospitalisations and polypharmacy practices in Romania: A health system evaluation for strengthening primary health care.

Background: Children and pregnant women usually have multiple contacts with the health care system. While most conditions can be managed by primary health care (PHC) providers, hospitalisations are nevertheless common and often unjustified. The number of hospitalizations decreased in Romania at the start of the COVID-19 pandemic. While this is likely due to the disruption of health services and public health measures established to limit the spread of COVID-19, it also suggests that a proportion of hospitalisations prior to the pandemic were unnecessary. This healthcare system evaluation in Romania quantified unnecessary and unnecessarily prolonged hospitalisations in children, pregnant women and women hospitalised for delivery, and assessed antibiotic and polypharmacy practices in these groups. Methods: We conducted the healthcare system evaluation in 10 hospitals across the country. We extracted data from medical records of patients hospitalized between 2019 and 2020. In each hospital, we randomly selected 40 medical records for each of the following groups: children 2-59 months of age, pregnant women, and women hospitalised for delivery. Clinical data were compared against WHO standards indicating a need for inpatient treatment or antibiotic therapy. Results: Among 209 children and 349 pregnant women, unnecessary hospitalisations accounted for 57.9% and 56.2% of hospitalisations, respectively. Among necessary hospitalisations, a large proportion was unnecessarily prolonged, including 44.4% (n = 32/72) in children, 23.3% (n = 34/146) in pregnant women, and 45.8% (n = 110/240) in women after delivery. The proportion of unnecessary and unnecessarily prolonged hospitalisations did not differ between the pre-pandemic, the lockdown, and the post-lockdown periods. Antibiotics were prescribed to 53.1% (n = 43/81) of children with diarrhoea, while 50.8% (n = 61/120) of women with caesarean section received an unjustified prolonged course of antibiotics. Children and women were commonly prescribed unnecessary medications. Conclusions: Findings of this evaluation should inform evidence-based decisions and actions for strengthening PHC and the healthcare system structure and improving the management of common diseases in mothers, newborns, and children. The evaluation should be repeated periodically to monitor progress.

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.

BACKGROUND: Respiratory 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. METHODS: In 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). FINDINGS: In 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 in-hospital deaths (6800-28 100), and 45 700 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). INTERPRETATION: RSV 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. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period. METHODS: We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets. RESULTS: 52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041). CONCLUSIONS: Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331834 . Registered on April 2, 2020.

Pneumonia in children admitted to the national referral hospital in Bhutan: A prospective cohort study.

OBJECTIVES: The study aim was to describe the etiological profile and clinical characteristics of pneumonia among children hospitalized in Thimphu, Bhutan. METHODS: This prospective study enrolled children aged 2-59 months admitted to the Jigme Dorji Wangchuck National Referral Hospital with World Health Organization (WHO)-defined clinical pneumonia. Demographic and clinico-radiological data were collected through questionnaires, physical examination, and chest radiography. Blood samples and nasopharyngeal washing were collected for microbiological analysis including culture and molecular methods. RESULTS: From July 2017 to June 2018, 189 children were enrolled, of which 53.4% were infants. Pneumonia-related admissions were less frequent over the winter. Chest radiographies were obtained in 149 children; endpoints included pneumonia in 39 cases (26.2%), other infiltrates in 31 (20.8%), and were normal in 79 children (53.0%). Non-contaminated bacterial growth was detected in 8/152 (5.3%) blood cultures, with only two cases of Streptococcus pneumoniae. Viral detection in upper respiratory secretions was common, with at least one virus detected in 103/115 (89.6%). The three most-commonly isolated viruses were respiratory syncytial virus (52/115; 45.2%), rhinovirus (42/115; 36.5%), and human parainfluenza virus (19/115; 16.5%). A third of patients with viral infections showed mixed infections. Case fatality rate was 3.2% (6/189). CONCLUSION: Respiratory viral infections predominated among this cohort of WHO-defined clinical pneumonia cases, whereas bacterial aetiologies were uncommon, highlighting the epidemiologic transition that Bhutan seems to have reached.