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.

Unnecessary hospitalisations and polypharmacy practices in Tajikistan: a health system evaluation for strengthening primary healthcare.

BACKGROUND: Children and pregnant women require multiple contacts with the healthcare system. While most conditions can be managed by primary healthcare (PHC) providers, hospitalisations are common. This health system evaluation in Tajikistan quantifies unnecessary and unnecessarily prolonged hospitalisations and assesses antibiotic and polypharmacy practices. METHODS: Data were retrospectively collected from randomly selected medical records from 15 hospitals. Inclusion criteria were children 2-59 months of age with a primary diagnosis of acute respiratory infection or diarrhoea, or pregnant women with threatened preterm labour, threatened miscarriages, premature rupture of membranes or mild pre-eclampsia, hospitalised between January and September 2021. RESULTS: Among 440 children and 422 pregnant women, unnecessary hospitalisations accounted for 40.5% and 69.2% of hospitalisations, respectively, ranging from 0% to 92.7% across the hospitals. Among necessary hospitalisations, 63.0% and 39.2% were unnecessarily prolonged in children and women, respectively.Prior to admission, 36.8% of children had received antibiotics, in which more than half intramuscularly. During hospitalisation, 92.5% of children and 28.9% of women received antibiotics. Children and women received an average of 5 and 6.5 drugs, respectively; most were not indicated or with no evidence of benefits. CONCLUSIONS: The methodology is applicable across all health systems and can provide important insights on health service use and resource waste. Findings of this assessment in Tajikistan have led to evidence-based decisions and actions from stakeholders and policy makers with the goal of strengthening PHC and improving the management of common diseases in children and pregnant women.

Diagnostic accuracy of multiplex respiratory pathogen panels for influenza or respiratory syncytial virus infections: systematic review and meta-analysis.

Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG respiratory pathogen panels (RPPs)™ (index) against other RPPs (comparator) for detection of RSV and influenza viruses. Studies comparing human clinical respiratory samples tested with the index and at least one comparator test were included. A random-effect latent class meta-analysis was performed to assess the specificity and sensitivity of the index test for RSV and influenza. Risk of bias was assessed using the QUADAS-2 tool and certainty of evidence using GRADE. Ten studies were included. For RSV, predicted sensitivity was 99% (95% credible interval [CrI] 96-100%) and specificity 100% (95% CrI 98-100%). For influenza A and B, predicted sensitivity was 97% (95% CrI 89-100) and 98% (95% CrI 88-100) respectively; specificity 100% (95% CrI 99-100) and 100% (95% CrI 99-100), respectively. Evidence was low certainty. Although index sensitivity and specificity were excellent, comparators' performance varied. Further research with clear patient recruitment strategies could ascertain performance across different populations.Protocol Registration: Prospero CRD42021272062.

Performance of host-response biomarkers to risk-stratify children with pneumonia in Bhutan.

Pneumonia is the leading cause of post-neonatal death amongst children under five years of age; however, there is no simple triage tool to identify children at risk of progressing to severe and fatal disease. Such a tool could assist for early referral and prioritization of care to improve outcomes and enhance allocation of scarce resources. We compared the performance of inflammatory and endothelial activation markers in addition to clinical signs or scoring scales to risk-stratify children hospitalized with pneumonia at the national referral hospital of Bhutan with the goal of predicting clinical outcome. Of 118 children, 31 evolved to a poor prognosis, defined as either mortality, admission in the paediatric intensive care unit, requirement of chest drainage or requirement of more than five days of oxygen therapy. Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) was the best performing biomarker and performed better than clinical parameters. sTREM-1 levels upon admission had good predictive accuracy to identify children with pneumonia at risk of poor prognosis. Our findings confirm that immune and endothelial activation markers could be proactively used at first encounter as risk-stratification and clinical decision-making tools in children with pneumonia; however, further external validation is needed.

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).

Association of Clinical Signs, Host Biomarkers and Etiology With Radiological Pneumonia in Bhutanese Children.

Diagnosing pneumonia and identifying those requiring antibiotherapy remain challenging. Chest radiographs (CXR) are often used as the reference standard. We aimed to describe clinical characteristics, host-response biomarkers and etiology, and assess their relationship to CXR findings in children with pneumonia in Thimphu, Bhutan. Children between 2 and 59 months hospitalized with WHO-defined pneumonia were prospectively enrolled and classified into radiological endpoint and non-endpoint pneumonia. Blood and nasopharyngeal washing were collected for microbiological analyses and plasma levels of 11 host-response biomarkers were measured. Among 149 children with readable CXR, 39 (26.2%) presented with endpoint pneumonia. Identification of respiratory viruses was common, with no significant differences by radiological outcomes. No clinical sign was suggestive of radiological pneumonia, but children with radiological pneumonia presented higher erythrocyte sedimentation rate, C-reactive protein and procalcitonin. Markers of endothelial and immune activation had little accuracy for the reliable identification of radiological pneumonia.

Pediatric Palliative Care Education Model in Low Resource Settings: A Mixed-Methods Evaluation.

CONTEXT: Globally, approximately 21.6 million children need pediatric palliative care (PPC). The greatest burden lies in low- and middle-income countries, where the demand for PPC exceeds available resources. OBJECTIVES: The objective of this study was to assess the impact of a PPC workshop on healthcare providers' self-efficacy, comfort and confidence related to the provision of PPC in a Bhutanese referral-level hospital. METHODS: This mixed-methods study included a one-and-a-half day PPC workshop with surveys administered to participants at three time points (before, immediately after, and six months after the workshop) to evaluate changes in self-efficacy, comfort and confidence. The study was conducted in January 2017 with healthcare providers at the Jigme Dorji Wangchuck National Referral Hospital in Thimphu, Bhutan. RESULTS: Forty-one providers participated in the workshop; 38 completed the post-workshop survey and 27 completed the six months post-workshop survey. Results showed statistically significant increases in comfort levels from pre- to post-workshop surveys across nearly all areas. Qualitative results supported these findings. CONCLUSION: The results of this study suggest that a short, interactive and interdisciplinary workshop, originally designed for the United States setting but adapted to a low resource context, is an effective way to improve providers' self-efficacy, comfort and confidence in the provision of PPC in resource-limited settings.

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.

Prevention of unintentional injuries in children under five years.

We looked at existing recommendations for preventing unintentional injuries in children under five years of age, and we attempted to identify the main sources used as evidence for formulating these recommendations.We conducted a literature search up to the 18th October 2019 by using key terms and manual search in selected sources. We summarized the recommendations and source of the evidence in tables for each of five areas of unintentional injuries: road traffic injuries, drowning, poisoning, thermal injuries, falls.In 2008, the World Health Organization (WHO) published a comprehensive report with strategies for child injury prevention for the European region. More recently, the WHO published several guidance documents focused on one area such as drowning, usually with a global focus. The PrevInfad workgroup (Spanish Association of Primary Care Pediatrics) updated their document on road safety in April 2019, providing recommendations and a summary of the existing evidence. Preventive strategies for injuries in childhood are mainly based on surveillance data and the identification of risk factors. The key strategies for preventing unintentional injuries are a combination of environmental and behaviour modification, that can be achieved through engineering, enforcement and education. Consequently, for this kind of strategies, it is important to evaluate the effectiveness of both the intervention itself, and the way the intervention is advised to parents and caretakers so that there is good compliance of the recommendation.

Newborn pulse oximetry screening for critical congenital heart defects.

We looked at existing recommendations and supporting evidence addressing the effectiveness of pulse oximetry effective for detecting critical congenital heart defects (CCHDs) in newborns. We also looked at the impact of timing of oximetry and the site of testing in the accuracy of screening, and at the potential harms and limitations of pulse oximetry screening,We conducted a literature search up to the 13th of August 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.Current evidence supports consistent accuracy for detection of CCHDs in newborns by pulse oximetry screening in addition to antenatal ultrasonography and clinical examination. Overall, early diagnosis of CCHD with pulse oximetry is judged to be beneficial and cost-effective, and potential harms associated with false-positive tests are not serious, while missing CCHDs and other serious diseases detected by hypoxaemia in absence of pulse oximetry screening can lead to serious consequences. The site of testing (post-ductal versus pre- and post-ductal) had no significant effect on sensitivity nor specificity for detection of CCHDs.

Vision screening in newborns and early childhood.

We looked at existing recommendations and supporting evidence on the effectiveness of screening for visual disorders in newborns and small infants, and in children between six months and five years of age.We conducted a literature search up to the 5th of August 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendations when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported on the accuracy of screening tests for detecting visual alterations; the efficacy of treatment for improving visual acuity, school performance, and quality of life; and potential harms derived from vision screening and treating visual alterations.Although there is little evidence supporting its validity and effectiveness, examining all newborns for congenital cataract and retinoblastoma through the red reflex examination is widely accepted due to the severity of both diseases and the good outcomes reached by early detection and treatment.Overall, there is a moderate certainty of evidence that visual screening in children between three and five years provides a moderate net benefit, as assessed by the US Preventive Services Task Force: vision screening tests are accurate for detecting amblyopia and its risk factors, and their treatment is associated with visual improvement. There is uncertain evidence on whether vision screening in children under three years of age provides net benefits. Among populations with a low prevalence of vision abnormalities, screening the youngest is associated with an increased rate of false positives, leading to unnecessary additional assessment.

Sudden infant death syndrome prevention.

We looked at existing recommendations and supporting evidence for successful strategies to prevent the sudden infant death syndrome (SIDS).We conducted a literature search up to the 14th of December 2020 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.Current evidence supports statistical associations between risk factors and SIDS, but there is globally limited evidence by controlled studies assessing the effect of the social promotion strategies to prevent SIDS through knowledge, attitude and practices, due to obvious ethical reasons. A dramatic decline in SIDS incidence has been observed in many countries after the introduction of "Back to Sleep" campaigns for prevention of SIDS. All infants should be placed to sleep in a safe environment including supine position, a firm surface, no soft objects and loose bedding, no head covering, no overheating, and room-sharing without bed-sharing. Breastfeeding on demand and the use of pacifier during sleep time protect against SIDS and should be recommended. Parents should be advised against the use of tobacco, alcohol and illicit drugs during gestation and after birth.

Supporting recommendations for childhood preventive interventions for primary health care: elaboration of evidence synthesis and lessons learnt.

BACKGROUND: Recommendations to prevent morbidity and mortality in children was a high priority for the editorial group of a WHO pocket book for primary health care in the European region. However, the benefit of preventive interventions is not always clear and recommendations differ across countries and institutions. Here, we summarize the existing recommendations and the most recent evidence on ten selected preventive interventions applied to children under five years to inform this group. In addition, we reflect on the process and challenges of developing these summaries. METHODS: For each intervention, we systematically searched for current recommendations from the WHO, the United States Preventive Services Task Force, the workgroup PrevInfad from the Spanish Association of Primary Care Pediatrics, the Centers of Disease Control and Prevention, and the National Institute for Health and Care Excellence. Then, we systematically searched the sources above and the Cochrane library for relevant systematic reviews. For each topic, we reported the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported. Categorising the ten preventive interventions in three groups allowed narrative comparisons between similar types of interventions and between groups. RESULTS AND DISCUSSION: For the single interventions of providing vitamins D and K and topical fluoride there is overall a high degree of consensus between institutions for the evidence of their effectiveness. For the multiple interventions to prevent sudden infant death syndrome and unintentional injuries consensus was more variable as evidence of effectiveness is harder to ascertain. For the screening interventions the summaries of recommendations and evidence varied too. While institutions generally agreed in recommending for vision screening and against universal screening for language and speech delay and iron deficiency, they had some differences for pulse oximetry and autism. The transparent and independent process shed light upon how institutions use existing evidence in their settings - common and different positions were accounted for and became visible. We also identified gaps and duplications of research. Our approach was a crucial starting point for developing the respective sections in the pocket book.

Vitamin K prophylaxis in newborns.

We looked at existing recommendations and supporting evidence on the effectiveness of vitamin K given after birth in preventing the haemorrhagic disease of the newborn (HDN).We conducted a literature search up to the 10th of December 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.All newborns should receive vitamin K prophylaxis, as it has been proven that oral and intramuscular prophylactic vitamin K given after birth are effective for preventing classical HDN. There are no randomized trials looking at the efficacy of vitamin K supplement on late HDN. There are no randomized trials comparing the oral and intramuscular route of administration of prophylactic vitamin K in newborns. From older trials and surveillance data, it seems that there is no significant difference between the intramuscular and the oral regimens for preventing classical and late HDN, provided that the oral regimen is duly completed. Evidence assessing vitamin K prophylaxis in preterm infants is scarce.

Screening of iron deficiency anaemia in early childhood.

We looked at existing recommendations and supporting evidence on the effectiveness of universal screening of iron deficiency anaemia (IDA) in children under five years of age for improving growth, cognitive function, and psychomotor development. We assessed the accuracy of the screening tests for detecting IDA, the efficacy of existing treatment for children with IDA, and the potential harms associated with screening and treatment.We conducted a literature search up to the 18th of August 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.There is no suitable test for IDA screening that is non-invasive with high accuracy for detecting IDA and there is uncertainty whether IDA in children causes cognitive and psychomotor delays. There is a lack of evidence on the effects of routine screening for IDA in asymptomatic children under five years of age on growth, cognitive and psychomotor development outcomes.Universal screening of IDA in children under five years of age is not recommended by most organisations such as the Spanish Association of Primary Care Paediatrics, the United Kingdom National Screening Committee, and the United States Preventive Services Task Force, but is recommended by the American Academy of Paediatrics. However, selective screening of IDA is recommended in infants and children with risk factors including prematurity, low birth weight, and dietary risk factors.

Screening for autistic spectrum disorder in early childhood.

We looked at existing recommendations and supporting evidence on the effectiveness of screening young children for autistic spectrum disorder (ASD) for improving short- and long-term outcomes.We conducted a literature search up to the 8th of November 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.There are discrepancies among the recommendations given by different institutions on universal screening for ASD in children. Some recommend that all children should be screened with an ASD-specific instrument during well-child visits at ages 18 and 24 months in conjunction with ongoing developmental surveillance and broadband developmental screening; some conclude that the current evidence is insufficient to assess the balance of benefits and harms of screening for ASD in young children for whom no concerns of ASD have been raised by their parents or a clinician; and others recommend against universal screening, but for a screening among children with high risks.There is adequate evidence that ASD screening tools applied to children between 12 and 36 months accurately identify those with ASD. There is some evidence showing benefit of early interventions applied to children with ASD, from children identified with developmental concern by their family, teacher or clinicians. We found no evidence on the effectiveness of interventions applied to children with ASD detected through screening.