Gemma Villanueva

Introduction: Henipaviruses have been identified as priority pathogens by the WHO for research and development. We applied a rapid research needs appraisal (RRNA) review methodology to systematically identify existing henipavirus evidence on clinical characteristics, immune response, transmission, risk factors, medical countermeasures and associated social and behavioural factors, to inform research prioritisation, and strategies to strengthen our preparedness and response for henipaviruses to protect populations and improve outcomes. Method: We searched PubMed, Ovid Embase, Cochrane Library, Epistemonikos from 1974 to 15 May 2025 for studies focused on henipavirus infection including humans or human samples. Two reviewers screened studies and extracted data across predefined research domains without language restrictions. Data were analysed descriptively. Results: Of 106 records included, most focused on Nipah (82.1%, 87/106), followed by Hendra (17.9%, 19/106) and Langya virus (1.9%, 2/106) disease, set in Asia (82.1%, 87/106), Australia (17.9%, 19/106) and Europe (0.9%, 1/106). Most (96.2%, 102/106) were observational, 3.8% (4/106) interventional studies. Adults were included in 76.4% (81/106) studies, children in 32.1% (34/106); pregnant women in 0.9% (1/106). Studies focused on clinical characteristics (n=59), transmission (n=28), risk factors (n=16), social science (n=17), diagnostics (n=14), immune response (n=9), and therapeutics (n=4). Of the four interventional studies, two focused on medical countermeasures, including a non-randomised controlled Nipah ribavirin study and a phase I m102.4 antibody Nipah and Hendra treatment trial in adults. Two were social science studies: one a self-instruction prevention training module, the other a workshop on personal protective equipment. Human vaccine studies were lacking, but nine studies explored attitudes to vaccination of horses against Hendra virus. Conclusion: Our data highlight the limited evidence available and the lack of medical countermeasures for henipaviruses. The gaps in inclusion of high-risk populations (young children, pregnant women) are concerning. Our data show a need to identify effective medical countermeasures, supported by behavioural studies, and to invest in One Health studies to generate evidence to inform strategies to protect societies against the threat of henipaviruses.

Background: Increasing numbers of young people with severe neurological impairment are suffering from gastrointestinal symptoms, which may result in nutritional failure and ultimately death. Gastrointestinal dystonia is a recently described clinical diagnosis amongst patients with severe neurological impairment, and no systematic review of existing evidence currently exists. Aim: To conduct a systematic review of existing evidence for the management of gastrointestinal dystonia in children and young people with severe neurological impairment and palliative care needs. Method: A systematic review assessing pharmacological and non-pharmacological treatments was undertaken using standard Cochrane methodology. We searched Cochrane CENTRAL, MEDLINE, EMBASE, and PsycInfo. All databases were searched from inception, and no language restrictions were used. Results: 1580 references were identified. After abstract screening, 56 references were reviewed at full text, and a case report and case series were identified for inclusion. Low-quality, indirect evidence exists for the management of gastrointestinal dystonia, including symptom management, hydration and nutrition decisions, and end-of-life care. Conclusions: There is a paucity of existing evidence directly relating to gastrointestinal dystonia, but low-quality indirect evidence from studies of children with severe neurological impairment and gastrointestinal symptoms exist, which may begin to inform clinical practice.

Background: Fortification, the addition of essential micronutrients during food processing, reduces mortality and malnutrition. Our objective was to comprehensively synthesize global evidence on the cost-effectiveness (CE) and cost savings of food fortification. Methods: We employed systematic review methodology, PROSPERO registration (CRD42023493795), searching six databases to January 2024. Eligible studies included economic analyses comparing staple food post-harvest micronutrient fortification to no fortification. Quality appraisal used Philips’ modeling framework. We converted incremental cost-effectiveness ratios (ICERs) to 2022 US$; and synthesized the data overall and by micronutrient. For illustration, findings were also categorized by “hypothetical” CE thresholds based on common example percentages of gross domestic product per capita (GDP pc) per country. Findings: After screening 6,425 abstracts, 56 studies in 66 reports were included, reporting >200 analyses. Sixty-three countries were represented, including >40 low- and middle-income economies (LMICs). Most frequent interventions were: vitamin A, folic acid, iron, and iodine added to cereal grains/products (e.g., flours) and condiments (e.g., oils, sugar, salt). Models were heterogeneous and employed various perspectives. Most evaluations (58%; 135/232) had ICERs less than $150 per disability-adjusted life year (DALY) averted (or healthy life year gained). We found 87% (201/232) overall were within a hypothetical CE threshold of “50% GDP pc”. With an example “35% GDP pc” level among LMICs, 84% (190/227) were estimated to be cost-effective; and 71% (37/52) were less than “20% GDP pc” among low-income countries. Additionally, six out of eight cost-utility studies’ ICERs were dominant. Moreover, 47 total unique benefit–cost ratios found benefits outweighed costs, ranging from 1·50:1 to 100·6:1. Interpretation: Food fortification programs are likely cost-effective in the majority of contexts. While cost-effectiveness evaluations are specific to local factors and methodology, this research can assist with evidence-informed decision-making for global health policy and priority setting, particularly in resource-constrained economies. Funding: U.S. Agency for International Development. Research in context: Evidence before this study: Database searches of MEDLINE, Embase, EconLit, and the National Health Service Economic Evaluation Database (NHS EED), from inception to January 2024, were conducted for previous systematic reviews on the economics of food fortification. No language, date, or publication status limits were applied. While the impact of food fortification on health outcomes has been widely studied, we did not find a comprehensive systematic review of the cost-effectiveness of all types of large-scale food fortification. Several smaller systematic reviews and some in-depth narrative reviews have studied the economics of food fortification but their aims were not broad evaluations of its cost-effectiveness as they limited their scope to specific foods or nutrients. Added value of this study: This large systematic review of 56 economic studies reporting over 200 analyses provides a substantially broader synthesis of the economic evidence base of food fortification. Of note, it also spans 63 countries, including >40 low- and middle-income economies (LMICs), thereby augmenting the international research on a system-level intervention for reducing global malnutrition, mortality, and morbidity. We found that food fortification programs are likely cost-effective in the majority of contexts. Overall, across the many diverse economic models, incremental cost-effectiveness ratios (ICERs) for most evaluations (58%; 135/232) were less than $150 per disability-adjusted life year (DALY) averted (or healthy life year gained). As an illustration using a “hypothetical” cost-effectiveness threshold example of ‘35% of gross domestic product (GDP) per capita’ among LMICs, 84% (190/227) of ICERs were estimated to be cost-effective. Additionally, six out of eight cost-utility studies’ (i.e., measuring quality-adjusted life years, QALYs) ICERs were dominant (i.e., fortification was less costly and more effective than the comparator). Moreover, 47 benefit–cost ratios found that food fortification programs’ benefits outweighed the costs (with ranges from 1·50:1 to 100·6:1). Implications of all the available evidence: There are significant policy implications from this research. The decision by policymakers to enact or strengthen food fortification programs in their countries is predicated by many factors, including costs and cost-effectiveness. Synthesizing the evidence of the economic implications of food fortification could translate to improved global advocacy efforts by partners seeking to introduce and scale up food fortification programs. Nutrition for Growth aims to mobilize governments, bilateral agencies, private investors, businesses, civil society, donors, and others to increase and sustain their funding for nutrition actions, especially those that are evidence-based. Through the Global Nutrition Report, such financial commitments are being tracked internationally. The expectation is that this more robust evidence base of the cost-effectiveness of large-scale food fortification will encourage greater investment in initiating and strengthening fortification programs where they are needed. While cost-effectiveness evaluations are specific to local factors and methodology, this research can assist with evidence-informed decision-making for global health policy and priority setting, particularly in resource-constrained economies.

Background: Post-exposure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing following health facility outbreaks may control the spread of infection. Aim: This study aimed to assess the impact of testing for SARS-CoV-2 infection on health outcomes during healthcare facility outbreaks. Setting: This review included studies conducted at skilled nursing facilities, a cancer centre, and a geriatric psychiatric facility. Methods: We followed the methods for conducting rapid systematic reviews, searched databases from December 2019 to August 2022, assessed the risk of bias using the modified Newcastle Ottawa scale, and graded the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We pooled the prevalence, mortality, and hospitalisation results as appropriate. Results: Of the 3055 articles from database search, no study was eligible for inclusion as outlined in the protocol. However, eight non-comparative reports (case series) in skilled nursing facilities were included. The pooled prevalence of SARS-CoV-2 infection among residents of care homes and patients were 38% (95% confidence interval [CI] = 25% – 51%; 5 studies, 2044 participants; I2 = 94%, very low certainty evidence) and was 12% (95% CI = 6% – 19%; 5 studies, 2312 participants; I2 = 94%, very low certainty evidence) for exposed healthcare workers. The pooled mortality estimate and hospitalisation rate were 17% and 24%, respectively, (very low certainty evidence). Conclusion: There is no identified evidence for or against testing of people in healthcare facilities where there is ongoing transmission of SARS-CoV-2 infection. Contribution: The evaluation of the effectiveness of testing strategies during SARS-CoV-2 outbreaks need baseline and follow-up data from well-designed before and after studies appropriate for the setting.

Background: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO‐NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).Methods: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.Results: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease‐modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end‐of‐life management.Conclusions: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.

Background: Vaccines may reduce antibiotic use and the development of resistance.Objectives: To provide a comprehensive, up-to-date assessment of the evidence base relating to the effect of vaccines on antibiotic use.Methods: Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and WHO Trials Registry.Study eligibility criteria: Randomised-controlled trials (RCTs) and observational studies published January 1998 to March 2018.Participants: Any population.Interventions: Vaccines versus placebo, no vaccine or another vaccine.Methods: Titles, abstracts, and full-texts were screened independently by two reviewers. Certainty of RCT evidence was assessed using GRADE.Results: 4980 records identified; 895 full-text reports assessed; 96 studies included (24 RCTs, 72 observational). There was high certainty evidence that influenza vaccine reduces days of antibiotic use among healthy adults (1 RCT; n = 4253; rate reduction 28·1% [95% CI 16·0, 38·4]); moderate certainty evidence that influenza vaccines probably reduce antibiotic use in children aged 6 months to 14 years (3 RCTs; n = 610; ratio of means 0·62 [95% CI 0·54, 0·70) and probably reduces community antibiotic use in children aged 3-15 years (1 RCT; n = 10,985 person-seasons; risk ratio 0·68 [95% CI 0·58, 0·83]); moderate certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years (2 RCTs; n = 47,945; rate ratio 0·93 [95% CI 0·87, 0·99]) and reduces illness episodes requiring antibiotics in children aged 12-35 months (1 RCT; n = 264; rate ratio 0·85 [95% CI 0·75, 0·97]). Other RCT evidence was of low or very low certainty, and observational evidence was affected by confounding. Conclusions: The evidence base is poor. Although some vaccines may reduce antibiotic use, collection of high-quality data in future vaccine trials is needed to improve the evidence base. Funding: Wellcome TrustPROSPERO registration: CRD42018103881