Clinician-identified problems and solutions for delayed diagnosis in primary care: a PRIORITIZE study.

BACKGROUND: Delayed diagnosis in primary care is a common, harmful and costly patient safety incident. Its measurement and monitoring are underdeveloped and underutilised. We created and implemented a novel approach to identify problems leading to and solutions for delayed diagnosis in primary care. METHODS: We developed a novel priority-setting method for patient safety problems and solutions called PRIORITIZE. We invited more than 500 NW London clinicians via an open-ended questionnaire to identify three main problems and solutions relating to delayed diagnosis in primary care. 113 clinicians submitted their suggestions which were thematically grouped and synthesized into a composite list of 33 distinct problems and 27 solutions. A random group of 75 clinicians from the initial cohort scored these and an overall ranking was derived. The agreement between the clinicians' scores was presented using the Average Expert Agreement. RESULTS: The top ranked problems were poor communication between secondary and primary care and the inverse care law, i.e. a mismatch between patients' medical needs and healthcare supply. The highest ranked solutions included: a more rigorous system of communicating abnormal results of investigations to patients, direct hotlines to specialists for GPs to discuss patient problems and better training of primary care clinicians in relevant areas. A priority highlighted throughout the findings is a need to improve communication between clinicians as well as with patients. The highest ranked suggestions had the highest consensus between experts. CONCLUSIONS: The novel method we have developed is highly feasible, informative and scalable, and merits wider exploration with a view of becoming part of a routine pro-active and preventative system for patient safety assessment. Clinicians proposed a range of concrete suggestions with an emphasis on improving communication among clinicians and with patients and better GP training. In their view, delayed diagnosis can be largely prevented with interventions requiring relatively minor investment. Rankings of identified problems and solutions can serve as an aid to policy makers and commissioners of care in prioritization of scarce healthcare resources.

Treatment of infections in young infants in low- and middle-income countries: a systematic review and meta-analysis of frontline health worker diagnosis and antibiotic access.

BACKGROUND: Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription? METHODS AND FINDINGS: We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%-91%) and lower specificity (62%, 95% CI 48%-75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%-88%) and specificity of 69% (95% CI 54%-83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%-34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data. CONCLUSIONS: Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs. REVIEW REGISTRATION: PROSPERO International prospective register of systematic reviews (CRD42013004586). Please see later in the article for the Editors' Summary.

Prevalence and risk factors for long COVID among adults in Scotland using electronic health records: a national, retrospective, observational cohort study.

Background: Long COVID is a debilitating multisystem condition. The objective of this study was to estimate the prevalence of long COVID in the adult population of Scotland, and to identify risk factors associated with its development. Methods: In this national, retrospective, observational cohort study, we analysed electronic health records (EHRs) for all adults (≥18 years) registered with a general medical practice and resident in Scotland between March 1, 2020, and October 26, 2022 (98-99% of the population). We linked data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The operational definition was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2. Possible risk factors for long COVID were identified by stratifying descriptive statistics by long COVID status. Findings: Of 4,676,390 participants, 81,219 (1.7%) were identified as having long COVID. Clinical codes identified the fewest cases (n = 1,092, 0.02%), followed by free text (n = 8,368, 0.2%), sick notes (n = 14,469, 0.3%), and the operational definition (n = 64,193, 1.4%). There was limited overlap in cases identified by the measures; however, temporal trends and patient characteristics were consistent across measures. Compared with the general population, a higher proportion of people with long COVID were female (65.1% versus 50.4%), aged 38-67 (63.7% versus 48.9%), overweight or obese (45.7% versus 29.4%), had one or more comorbidities (52.7% versus 36.0%), were immunosuppressed (6.9% versus 3.2%), shielding (7.9% versus 3.4%), or hospitalised within 28 days of testing positive (8.8% versus 3.3%%), and had tested positive before Omicron became the dominant variant (44.9% versus 35.9%). The operational definition identified long COVID cases with combinations of clinical encounters (from four symptoms, six investigation types, and seven management strategies) recorded in EHRs within 4-26 weeks of a positive SARS-CoV-2 test. These combinations were significantly (p < 0.0001) more prevalent in positive COVID-19 patients than in matched negative controls. In a case-crossover analysis, 16.4% of those identified by the operational definition had similar healthcare patterns recorded before testing positive. Interpretation: The prevalence of long COVID presenting in general practice was estimated to be 0.02-1.7%, depending on the measure used. Due to challenges in diagnosing long COVID and inconsistent recording of information in EHRs, the true prevalence of long COVID is likely to be higher. The operational definition provided a novel approach but relied on a restricted set of symptoms and may misclassify individuals with pre-existing health conditions. Further research is needed to refine and validate this approach. Funding: Chief Scientist Office (Scotland), Medical Research Council, and BREATHE.

Effectiveness of seasonal influenza vaccines in children -- a systematic review and meta-analysis.

AIM: To assess the efficacy and effectiveness of seasonal influenza vaccines in healthy children up to the age of 18 years. METHODS: MedLine, EMBASE, CENTRAL, CINAHL, WHOLIS, LILACS, and Global Health were searched for randomized controlled trials and cohort and case-control studies investigating the efficacy or effectiveness of influenza vaccines in healthy children up to the age of 18 years. The studies were assessed for their quality and data on the outcomes of influenza-like illness, laboratory-confirmed influenza, and hospitalizations were extracted. Seven meta-analyses were performed for different vaccines and different study outcomes. RESULTS: Vaccine efficacy for live vaccines, using random effects model, was as follows: (i) for similar antigen, using per-protocol analysis: 83.4% (78.3%-88.8%); (ii) for similar antigen, using intention to treat analysis: 82.5 (76.7%-88.6%); (iii) for any antigen, using per protocol analysis: 76.4% (68.7%-85.0%); (iv) for any antigen, using intention to treat analysis: 76.7% (68.8%-85.6%). Vaccine efficacy for inactivated vaccines, for similar antigen, using random effects model, was 67.3% (58.2%-77.9%). Vaccine effectiveness against influenza-like illness for live vaccines, using random effects model, was 31.4% (24.8%-39.6%) and using fixed-effect model 44.3% (42.6%-45.9%). Vaccine effectiveness against influenza-like illness for inactivated vaccines, using random effects model, was 32.5% (20.0%-52.9%) and using fixed-effect model 42.6% (38.3%-47.5%). CONCLUSIONS: Influenza vaccines showed high efficacy in children, particularly live vaccines. Effectiveness was lower and the data on hospitalizations were very limited.

Care seeking for neonatal illness in low- and middle-income countries: a systematic review.

BACKGROUND: Despite recent achievements to reduce child mortality, neonatal deaths continue to remain high, accounting for 41% of all deaths in children under five years of age worldwide, of which over 90% occur in low- and middle-income countries (LMICs). Infections are a leading cause of death and limitations in care seeking for ill neonates contribute to high mortality rates. As estimates for care-seeking behaviors in LMICs have not been studied, this review describes care seeking for neonatal illnesses in LMICs, with particular attention to type of care sought. METHODS AND FINDINGS: We conducted a systematic literature review of studies that reported the proportion of caregivers that sought care for ill or suspected ill neonates in LMICs. The initial search yielded 784 studies, of which 22 studies described relevant data from community household surveys, facility-based surveys, and intervention trials. The majority of studies were from South Asia (n = 17/22), set in rural areas (n = 17/22), and published within the last 4 years (n = 18/22). Of the 9,098 neonates who were ill or suspected to be ill, 4,320 caregivers sought some type of care, including care from a health facility (n = 370) or provider (n = 1,813). Care seeking ranged between 10% and 100% among caregivers with a median of 59%. Care seeking from a health care provider yielded a similar range and median, while care seeking at a health care facility ranged between 1% and 100%, with a median of 20%. Care-seeking estimates were limited by the few studies conducted in urban settings and regions other than South Asia. There was a lack of consistency regarding illness, care-seeking, and care provider definitions. CONCLUSIONS: There is a paucity of data regarding newborn care-seeking behaviors; in South Asia, care seeking is low for newborn illness, especially in terms of care sought from health care facilities and medically trained providers. There is a need for representative data to describe care-seeking patterns in different geographic regions and better understand mechanisms to enhance care seeking during this vulnerable time period.

BNT162b2 COVID-19 vaccination uptake, safety, effectiveness and waning in children and young people aged 12-17 years in Scotland.

Background: The two-dose BNT162b2 (Pfizer-BioNTech) vaccine has demonstrated high efficacy against COVID-19 disease in clinical trials of children and young people (CYP). Consequently, we investigated the uptake, safety, effectiveness and waning of the protective effect of the BNT162b2 against symptomatic COVID-19 in CYP aged 12-17 years in Scotland. Methods: The analysis of the vaccine uptake was based on information from the Turas Vaccination Management Tool, inclusive of Mar 1, 2022. Vaccine safety was evaluated using national data on hospital admissions and General Practice (GP) consultations, through a self-controlled case series (SCCS) design, investigating 17 health outcomes of interest. Vaccine effectiveness (VE) against symptomatic COVID-19 disease for Delta and Omicron variants was estimated using a test-negative design (TND) and S-gene status in a prospective cohort study using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. The waning of the VE following each dose of BNT162b2 was assessed using a matching process followed by conditional logistic regression. Findings: Between Aug 6, 2021 and Mar 1, 2022, 75.9% of the 112,609 CYP aged 16-17 years received the first and 49.0% the second COVID-19 vaccine dose. Among 237,681 CYP aged 12-15 years, the uptake was 64.5% and 37.2%, respectively. For 12-17-year-olds, BNT162b2 showed an excellent safety record, with no increase in hospital stays following vaccination for any of the 17 investigated health outcomes. In the 16-17-year-old group, VE against symptomatic COVID-19 during the Delta period was 64.2% (95% confidence interval [CI] 59.2-68.5) at 2-5 weeks after the first dose and 95.6% (77.0-99.1) at 2-5 weeks after the second dose. The respective VEs against symptomatic COVID-19 in the Omicron period were 22.8% (95% CI -6.4-44.0) and 65.5% (95% CI 56.0-73.0). In children aged 12-15 years, VE against symptomatic COVID-19 during the Delta period was 65.4% (95% CI 61.5-68.8) at 2-5 weeks after the first dose, with no observed cases at 2-5 weeks after the second dose. The corresponding VE against symptomatic COVID-19 during the Omicron period were 30.2% (95% CI 18.4-40.3) and 81.2% (95% CI 77.7-84.2). The waning of the protective effect against the symptomatic disease began after five weeks post-first and post-second dose. Interpretation: During the study period, uptake of BNT162b2 in Scotland has covered more than two-thirds of CYP aged 12-17 years with the first dose and about 40% with the second dose. We found no increased likelihood of admission to hospital with a range of health outcomes in the period after vaccination. Vaccination with both doses was associated with a substantial reduction in the risk of COVID-19 symptomatic disease during both the Delta and Omicron periods, but this protection began to wane after five weeks. Funding: UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Chief Scientist's Office of the Scottish Government; Health Data Research UK; National Core Studies - Data and Connectivity.

An evaluation of oxygen systems for treatment of childhood pneumonia.

BACKGROUND: Oxygen therapy is recommended for all of the 1.5 - 2.7 million young children who consult health services with hypoxemic pneumonia each year, and the many more with other serious conditions. However, oxygen supplies are intermittent throughout the developing world. Although oxygen is well established as a treatment for hypoxemic pneumonia, quantitative evidence for its effect is lacking. This review aims to assess the utility of oxygen systems as a method for reducing childhood mortality from pneumonia. METHODS: Aiming to improve priority setting methods, The Child Health and Nutrition Research Initiative (CHNRI) has developed a common framework to score competing interventions into child health. That framework involves the assessment of 12 different criteria upon which interventions can be compared. This report follows the proposed framework, using a semi-systematic literature review and the results of a structured exercise gathering opinion from experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies), to assess and score each criterion as their "collective optimism" towards each, on a scale from 0 to 100%. RESULTS: A rough estimate from an analysis of the literature suggests that global strengthening of oxygen systems could save lives of up to 122,000 children from pneumonia annually. Following 12 CHNRI criteria, the experts expressed very high levels of optimism (over 80%) for answerability, low development cost and low product cost; high levels of optimism (60-80%) for low implementation cost, likelihood of efficacy, deliverability, acceptance to end users and health workers; and moderate levels of optimism (40-60%) for impact on equity, affordability and sustainability. The median estimate of potential effectiveness of oxygen systems to reduce the overall childhood pneumonia mortality was ~20% (interquartile range: 10-35%, min. 0%, max. 50%). However, problems with oxygen systems in terms of affordability, sustainability and impact on equity are noted in both expert opinion scores and on review. CONCLUSION: Oxygen systems are likely to be an effective intervention in combating childhood mortality from pneumonia. However, a number of gaps in the evidence base exist that should be addressed to complete the investment case and research addressing these issues merit greater funding attention.

An evaluation of respiratory administration of measles vaccine for prevention of acute lower respiratory infections in children.

BACKGROUND: Measles was responsible for an estimated 100,000 deaths worldwide in 2008. Despite being a vaccine-preventable disease, measles remains a major cause of morbidity and mortality in young children. Although a safe and effective injectable measles vaccine has been available for over 50 years it has not been possible to achieve the uniformly high levels of coverage (required to achieve measles eradication) in most parts of the developing world. Aerosolised measles vaccines are now under development with the hope of challenging the delivery factors currently limiting the coverage of the existing vaccine. METHODS: We used a modified CHNRI methodology for setting priorities in health research investments to assess the strengths and weaknesses of this emerging intervention to decrease the burden of childhood pneumonia. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging aerosol vaccines against measles relevant to several criteria of interest. Although there are a number of different aerosol vaccine approaches under development, for the purpose of this exercise, all were considered as one intervention. The criteria of interest were: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. RESULTS: The panel of experts expressed mixed feelings about an aerosol measles vaccine. The group expressed low levels of optimism regarding the criteria of likelihood of efficacy and low cost of development (scores around 50%); moderate levels of optimism regarding answerability, low cost of production, low cost of implementation and affordability (score around 60%); and high levels of optimism regarding deliverability, impact on equity and acceptability to health workers and end-users (scores over 80%). Finally, the experts felt that this intervention will have a modest but nevertheless important impact on reduction of burden of disease due to childhood pneumonia (median: 5%, interquartile range 1-15%, minimum 0%, maximum 45%). CONCLUSION: Aerosol measles vaccine is at an advanced stage of development, with evidence of good immunogenicity. This new intervention will be presented as a feasible candidate strategy in the campaign for global elimination of measles. It also presents an unique opportunity to decrease the overall burden of disease due to severe pneumonia in young children.

Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria.

BACKGROUND: Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation. DATA SOURCES/ REVIEW METHODS: A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 years of age in developing countries and its effect on mortality was analyzed. RESULTS: The effect of preventive zinc supplementation on mortality was given in eight trials, while cause specific mortality data was given in five of these eight trials. Zinc supplementation alone was associated with a statistically insignificant 9% (RR = 0.91; 95% CI: 0.82, 1.01) reduction in all cause mortality in the intervention group as compared to controls using a random effect model. The impact on diarrhea-specific mortality of zinc alone was a non-significant 18% reduction (RR = 0.82; 95% CI: 0.64, 1.05) and 15% for pneumonia-specific mortality (RR = 0.85; 95% CI: 0.65, 1.11). The incidence of diarrhea showed a 13% reduction with preventive zinc supplementation (RR = 0.87; 95% CI: 0.81, 0.94) and a 19% reduction in pneumonia morbidity (RR = 0.81; 95% CI: 0.73, 0.90). Keeping in mind the direction of effect of zinc supplementation in reducing diarrhea and pneumonia related morbidity and mortality; we considered all the outcomes for selection of effectiveness estimate for inclusion in the LiST model. After application of the CHERG rules with consideration to quality of evidence and rule # 6, we used the most conservative estimates as a surrogate for mortality. We, therefore, conclude that zinc supplementation in children is associated with a reduction in diarrhea mortality of 13% and pneumonia mortality of 15% for inclusion in the LiST tool. Preventive zinc supplementation had no effect on malaria specific mortality (RR = 0.90; 95% CI: 0.77, 1.06) or incidence of malaria (RR = 0.92; 95 % CI 0.82-1.04). CONCLUSION: Zinc supplementation results in reductions in diarrhea and pneumonia mortality.

An evaluation of emerging vaccines for childhood meningococcal disease.

BACKGROUND: Meningococcal meningitis is a major cause of disease worldwide, with frequent epidemics particularly affecting an area of sub-Saharan Africa known as the "meningitis belt". Neisseria meningitidis group A (MenA) is responsible for major epidemics in Africa. Recently W-135 has emerged as an important pathogen. Currently, the strategy for control of such outbreaks is emergency use of meningococcal (MC) polysaccharide vaccines, but these have a limited ability to induce herd immunity and elicit an adequate immune response in infant and young children. In recent times initiatives have been taken to introduce meningococcal conjugate vaccine in these African countries. Currently there are two different types of MC conjugate vaccines at late stages of development covering serogroup A and W-135: a multivalent MC conjugate vaccine against serogroup A,C,Y and W-135; and a monovalent conjugate vaccine against serogroup A. We aimed to perform a structured assessment of these emerging meningococcal vaccines as a means of reducing global meningococcal disease burden among children under 5 years of age. METHODS: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In the first stage we systematically reviewed the literature related to emerging MC vaccines relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. RESULTS: For MenA conjugate vaccine the experts showed very high level of optimism (~ 90% or more) for 7 out of the 12 criteria. The experts felt that the likelihood of efficacy on meningitis was very high (~ 90%). Deliverability, acceptability to health workers, end users and the effect on equity were all seen as highly likely (~ 90%). In terms of the maximum potential impact on meningitis disease burden, the median potential effectiveness of the vaccines in reduction of overall meningitis mortality was estimated to be 20%; (interquartile range 20-40% and min. 8%, max 50 %). For the multivalent meningococcal vaccines the experts had similar optimism for most of the 12 CHNRI criteria with slightly lower optimism in answerability and low development cost criteria. The main concern was expressed over the cost of product, its affordability and cost of implementation. CONCLUSIONS: With increasing recognition of the burden of meningococcal meningitis, especially during epidemics in Africa, it is vitally important that strategies are taken to reduce the morbidity and mortality attributable to this disease. Improved MC vaccines are a promising investment that could substantially contribute to reduction of child meningitis mortality world-wide.

An evaluation of emerging vaccines for childhood pneumococcal pneumonia.

BACKGROUND: Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP) or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA) vaccine offering protection for all serotypes. METHODS: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. RESULTS: The experts expressed very high level of optimism (over 80%) that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9 relevant CHNRI criteria. The median potential effectiveness of conjugate SP vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 25% (interquartile range 20-38%, min. 15%, max 45%). For low cost, cross-protective common protein vaccines for SP the experts expressed concerns over answerability (72%) and the level of development costs (50%), while the scores for all other criteria were over 80%. The median potential effectiveness of common protein vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 30% (interquartile range 26-40%, min. 20%, max 45%). CONCLUSIONS: Improved SP vaccines are a very promising investment that could substantially contribute to reduction of child mortality world-wide.

Analysis of public engagement with ten major global health topics on a social network profile and a newspaper website.

BACKGROUND: Efforts in global health and development have broad political support and substantial financial commitment from most governments. However, this support could be greater if global health issues featured more prominently in the public debate. It has proven quite difficult to make global health issues attractive for viewing and engaging with, as compared to other forms of entertainment or public debates in the media. METHODS: Within the Massive Open Online Course "Survival: The Story of Global Health", we created 10 educational videos on major global health topics. Between August 1 and September 30, 2017, we posted each episode with a brief background text on the Facebook profile of the narrator, who had an average of 450 friends and further 800 followers throughout the period of study. We studied the interaction of Facebook friends and followers with each posted video, tracing the number of their "likes", "shares" and "comments". Moreover, a popular Croatian online newspaper portal with about 250 000 daily viewers shared three of these stories after they were posted on Facebook and views, shares and comments were monitored. We recorded the effect on the number of YouTube views of the featured videos. RESULTS: The 10 posts received between 65 and 274 "likes" on the Facebook profile and between 2 and 124 shares, receiving between 0 and 17 comments. The three episodes that were shared by the online newspaper portal were further shared between 164 and 2820 times, receiving between 8 and 111 comments from the general public. The effect of these two promotion channels on YouTube viewership resulted in between 107 and 9784 views of the 10 featured videos, with the number of "likes" received on YouTube ranging between 0 and 43. The video that raised the most attention and shares was the one on the history of pandemics, which also had the highest number of shares on YouTube (n=69), followed by the video on human evolution (n = 14). Topics of non-communicable diseases, ageing and dying, and the future of humanity were also popular, while the topics more specific to global health raised less interest - ie, maternal and child mortality, major infectious diseases, international organizations, inequality and equity, and the UN Millennium Development Goals. CONCLUSION: Our study showed that the interest in "core" global health topics was, as a rule, lower than in the topics which have a more general appeal - such as pandemic threat, human origins, ageing and dying. If we aim to increase public interest in global health topics, a feasible strategy would be to adjust the language and presentation used to be of more appeal to popular culture. Linking promotional materials to other popular topics that are dominating the public debate or capturing their interest could prove to be a successful strategy to achieve this.

A systematic analysis of online public engagement with 10 videos on major global health topics involving 229 459 global online viewers.

BACKGROUND: Online interest in issues specific to global health outside of times of pandemics or other crises is rather limited. To achieve long term global health goals, public support and engagement needs to be fostered on a continual basis. Strategies for capturing the attention of the general public online for the persisting problems outside of emergency situations are poorly defined. There are only a few isolated examples of success. In this study we explored the engagement of the viewers with different global health topics that were provided on public and privately advertised YouTube channels. METHODS: We developed the Massive Open Online Course "Survival: The Story of Global Health", consisting of 10 educational videos on major global health topics. We conducted two experiments in two separate samples of viewers. The first was based on posting videos on a YouTube channel between August 30 and September 30, 2017 and collecting analytics on the viewership. By June 30, 2019 this approach attracted 41 305 viewers. The second experiment was more controlled and conducted on a private YouTube channel and the videos were advertised to reach a high number of viewers. This attracted 188 154 viewers and we collected data on viewers' behaviour using YouTube Analytics. We investigated the nature of engagement, which was defined by 22 different parameters. RESULTS: In the first experiment, there were clear differences in all measured parameters of engagement based on the topic of the video. Episodes on pandemics (14 594 views) and human evolution (10 761 views) were clear outliers, while the remaining 8 episodes received between 1110 and 3197 views. In the second experiment, there were several clear differences between the 10 videos in the parameters analysed through YouTube Analytics. Episode 2 on maternal and child health had the highest view rate (18.90%), followed by Episode 7 on international organisations in global health (16.83%). At the bottom of the rank were Episode 6 on ageing and dying (view rate of 13.83%) and Episode 5 on non-communicable diseases (view rate 14.59%). CONCLUSIONS: We determined that 5 main interdependent factors contributed to the success or failure of our global health videos: Responsive content, timing, contribution to public debate, emotional valency and endorsement from an authentic scientific voice with a strong public profile. Several of these factors are also recognised as important in marketing research which may indicate the value of such techniques for use in a global health context. In order to communicate long term sustainable solutions to complex issues in a capricious media landscape focused on transient issues the global health community needs to embrace novel marketing approaches.

Effective approaches to public engagement with global health topics.

BACKGROUND: "Public engagement" in science is a term that covers a broad spectrum of activities undertaken by the scientific community. The precise definitions are constantly evolving to incorporate new means of engagement, facilitated by emerging technologies. Global health research is amenable to community engagement and popularization, but it is difficult to know which strategies work best to attract considerable attention from the public. METHODS: This is a review of the articles and documents that address the question of public engagement with topics in medical sciences, particularly in global health. Semantic searches were conducted using Google Scholar rather than indexed databases due to poor indexing of the topic. More than 1000 titles were screened and 48 articles were retained as most useful. It then moves to a more specific topic of the online public engagement in global health. RESULTS: The review presents the attempts to define public engagement in science and its general importance, particularly in the field of global health. Examples of the latter include tobacco use, vaccination, and maternal and child health. In reviewing effective approaches to public engagement in global health through online video campaigns, it studies the examples of crowdfunding, USAID's First Public Engagement Campaign, World Health Organization's Social Media Campaigns and the impact of Global Health Media Project. CONCLUSIONS: This review reveals three key gaps in the understanding of determinants of effective online public engagement in global health. The mixed results of traditional mass media campaigns in global health emphasise the calls for more research on message content. A framework for effective message content would help in both raising awareness of key issues and creating behaviour change in the general public. Moreover, it is surprising to find no formal research on what constitutes effective video content in global health. Finally, few studies considered important metrics to track in social media campaigns. There is a clear need to investigate which video features are effective in global health online public engagement. Success will be defined through key video marketing metrics and tracked in order to isolate effective content features.

Primary health care: making Alma-Ata a reality.

The principles agreed at Alma-Ata 30 years ago apply just as much now as they did then. "Health for all" by the year 2000 was not achieved, and the Millennium Development Goals (MDGs) for 2015 will not be met in most low-income countries without substantial acceleration of primary health care. Factors have included insufficient political prioritisation of health, structural adjustment policies, poor governance, population growth, inadequate health systems, and scarce research and assessment on primary health care. We propose the following priorities for revitalising primary health care. Health-service infrastructure, including human resources and essential drugs, needs strengthening, and user fees should be removed for primary health-care services to improve use. A continuum of care for maternal, newborn, and child health services, including family planning, is needed. Evidence-based, integrated packages of community and primary curative and preventive care should be adapted to country contexts, assessed, and scaled up. Community participation and community health workers linked to strengthened primary-care facilities and first-referral services are needed. Furthermore, intersectoral action linking health and development is necessary, including that for better water, sanitation, nutrition, food security, and HIV control. Chronic diseases, mental health, and child development should be addressed. Progress should be measured and accountability assured. We prioritise research questions and suggest actions and measures for stakeholders both locally and globally, which are required to revitalise primary health care.

Research priorities to reduce global mortality from newborn infections by 2015.

BACKGROUND: Newborn infections are responsible for approximately one-third of the estimated 4.0 million neonatal deaths that occur globally every year. Appropriately targeted research is required to guide investment in effective interventions, especially in low resource settings. Setting global priorities for research to address neonatal infections is essential and urgent. METHODS: The Department of Child and Adolescent Health and Development of the World Health Organization (WHO/CAH) applied the Child Health and Nutrition Research Initiative (CHNRI) priority-setting methodology to identify and stimulate research most likely to reduce global newborn infection-related mortality by 2015. Technical experts were invited by WHO/CAH to systematically list and then use standard methods to score research questions according to their likelihood to (i) be answered in an ethical way, (ii) lead to (or improve) effective interventions, (iii) be deliverable, affordable, and sustainable, (iv) maximize death burden reduction, and (v) have an equitable effect in the population. The scores were then weighted according to the values provided by a wide group of stakeholders from the global research priority-setting network. FINDINGS: On a 100-point scale, the final priority scores for 69 research questions ranged from 39 to 83. Most of the 15 research questions that received the highest scores were in the domain of health systems and policy research to address barriers affecting existing cost-effective interventions. The priority questions focused on promotion of home care practices to prevent newborn infections and approaches to increase coverage and quality of management of newborn infections in health facilities as well as in the community. While community-based intervention research is receiving some current investment, rigorous evaluation and cost analysis is almost entirely lacking for research on facility-based interventions and quality improvement. INTERPRETATION: Given the lack of progress in improving newborn survival despite the existence of effective interventions, it is not surprising that of the top ranked research priorities in this article the majority are in the domain of health systems and policy research. We urge funding agencies and investigators to invest in these research priorities to accelerate reduction of neonatal deaths, particularly those due to infections.

Setting priorities for global mental health research.

OBJECTIVE: To set investment priorities in global mental health research and to propose a more rational use of funds in this under-resourced and under-investigated area. METHODS: Members of the Lancet Mental Health Group systematically listed and scored research investment options on four broad classes of disorders: schizophrenia and other major psychotic disorders, major depressive disorder and other common mental disorders, alcohol abuse and other substance abuse disorders, and the broad class of child and adolescent mental disorders. Using the priority-setting approach of the Child Health and Nutrition Research Initiative, the group listed various research questions and evaluated them using the criteria of answerability, effectiveness, deliverability, equity and potential impact on persisting burden of mental health disorders. Scores were then weighted according to the system of values expressed by a larger group of stakeholders. FINDINGS: The research questions that scored highest were related to health policy and systems research, where and how to deliver existing cost-effective interventions in a low-resource context, and epidemiological research on the broad categories of child and adolescent mental disorders or those pertaining to alcohol and drug abuse questions. The questions that scored lowest related to the development of new interventions and new drugs or pharmacological agents, vaccines or other technologies. CONCLUSION: In the context of global mental health and with a time frame of the next 10 years, it would be best to fill critical knowledge gaps by investing in research into health policy and systems, epidemiology and improved delivery of cost-effective interventions.

Directing diarrhoeal disease research towards disease-burden reduction.

Despite gains in controlling mortality relating to diarrhoeal disease, the burden of disease remains unacceptably high. To refocus health research to target disease-burden reduction as the goal of research in child health, the Child Health and Nutrition Research Initiative developed a systematic strategy to rank health research options. This priority-setting exercise included listing of 46 competitive research options in diarrhoeal disease and their critical and quantitative appraisal by 10 experts based on five criteria for research that reflect the ability of the research to be translated into interventions and achieved disease-burden reduction. These criteria included the answerability of the research questions; the efficacy and effectiveness of the intervention resulting from the research; the maximal potential for disease-burden reduction of the interventions derived from the research; the affordability, deliverability, and sustainability of the intervention supported by the research; and the overall effect of the research-derived intervention on equity. Experts scored each research option independently to delineate the best investments for diarrhoeal disease control in the developing world to reduce the burden of disease by 2015. Priority scores obtained for health policy and systems research obtained eight of the top 10 rankings in overall scores, indicating that current investments in health research are significantly different from those estimated to be the most effective in reducing the global burden of diarrhoeal disease by 2015.

Agreeing on global research priorities for medication safety: an international prioritisation exercise.

OBJECTIVES: Medication errors continue to contribute substantially to global morbidity and mortality. In the context of the recent launch of the World Health Organization's (WHO) Third Global Patient Safety Challenge: Medication Without Harm, we sought to establish agreement on research priorities for medication safety. METHODS: We undertook a consensus prioritisation exercise using an approach developed by the Child Health and Nutrition Research Initiative. Based on a combination of productivity and citations, we identified leading researchers in patient and medication safety and invited them to participate. We also extended the invitation to a further pool of experts from the WHO Global Patient Safety Network. All experts independently generated research ideas, which they then independently scored based on the criteria of: answerability, effectiveness, innovativeness, implementation, burden reduction and equity. An overall Research Priority Score and Average Expert Agreement were calculated for each research question. FINDINGS: 131 experts submitted 333 research ideas, and 42 experts then scored the proposed research questions. The top prioritised research areas were: (1) deploying and scaling technology to enhance medication safety; (2) developing guidelines and standard operating procedures for high-risk patients, medications and contexts; (3) score-based approaches to predicting high-risk patients and situations; (4) interventions to increase patient medication literacy; (5) focused training courses for health professionals; and (6) universally applicable pictograms to avoid medication-related harm. Whilst there was a focus on promoting patient education and involvement across resource settings, priorities identified in high-resource settings centred on the optimisation of existing systems through technology. In low- and middle-resource settings, priorities focused on identifying systemic issues contributing to high-risk situations. CONCLUSIONS: WHO now plans to work with global, regional and national research funding agencies to catalyse the investment needed to enable teams to pursue these research priorities in medication safety across high-, middle- and low-resource country settings.