Delivering non-communicable disease interventions to women and children in conflict settings: A systematic review

Background: Non-communicable diseases (NCDs) are the leading cause of death worldwide. In the context of conflict settings, population displacement, disrupted treatment, infrastructure damage and other factors impose serious NCD intervention delivery challenges, but relatively little attention has been paid to addressing these challenges. Here we synthesise the available indexed and grey literature reporting on the delivery of NCD interventions to conflict-affected women and children in low- and middle-income countries (LMICs).Methods: A systematic search in MEDLINE, Embase, CINAHL and PsycINFO databases for indexed articles published between 1 January 1990 and 31 March 2018 was conducted, and publications reporting on NCD intervention delivery to conflict-affected women or children in LMICs were included. A grey literature search of 10 major humanitarian organisation websites for publications dated between 1 January 2013 and 30 November 2018 was also conducted. We extracted and synthesised information on intervention delivery characteristics and delivery barriers and facilitators.Results: Of 27 included publications, most reported on observational research studies, half reported on studies in the Middle East and North Africa region and 80% reported on interventions targeted to refugees. Screening and medication for cardiovascular disease and diabetes were the most commonly reported interventions, with most publications reporting facility-based delivery and very few reporting outreach or community approaches. Doctors were the most frequently reported delivery personnel. No publications reported on intervention coverage or on the effectiveness of interventions among women or children. Limited population access and logistical constraints were key delivery barriers reported, while innovative technology use, training of workforce and multidisciplinary care were reported to have facilitated NCD intervention delivery.Conclusion: Large and persistent gaps in information and evidence make it difficult to recommend effective strategies for improving the reach of quality NCD care among conflict-affected women and children. More rigorous research and reporting on effective strategies for delivering NCD care in conflict contexts is urgently needed

Delivering trauma and rehabilitation interventions to women and children in conflict settings: A systematic review

Background: In recent years, more than 120 million people each year have needed urgent humanitarian assistance and protection. Armed conflict has profoundly negative consequences in communities. Destruction of civilian infrastructure impacts access to basic health services and complicates widespread emergency responses. The number of conflicts occurring is increasing, lasting longer and affecting more people today than a decade ago. The number of children living in conflict zones has been steadily increasing since the year 2000, increasing the need for health services and resources. This review systematically synthesised the indexed and grey literature reporting on the delivery of trauma and rehabilitation interventions for conflict-affected populations.Methods: A systematic search of literature published from 1 January 1990 to 31 March 2018 was conducted across several databases. Eligible publications reported on women and children in low and middle-income countries. Included publications provided information on the delivery of interventions for trauma, sustained injuries or rehabilitation in conflict-affected populations.Results: A total of 81 publications met the inclusion criteria, and were included in our review. Nearly all of the included publications were observational in nature, employing retrospective chart reviews of surgical procedures delivered in a hospital setting to conflict-affected individuals. The majority of publications reported injuries due to explosive devices and remnants of war. Injuries requiring orthopaedic/reconstructive surgeries were the most commonly reported interventions. Barriers to health services centred on the distance and availability from the site of injury to health facilities.Conclusions: Traumatic injuries require an array of medical and surgical interventions, and their effective treatment largely depends on prompt and timely management and referral, with appropriate rehabilitation services and post-treatment follow-up. Further work to evaluate intervention delivery in this domain is needed, particularly among children given their specialised needs, and in different population displacement contexts

Delivering mental health and psychosocial support interventions to women and children in conflict settings: A systematic review

Background: Over 240 million children live in countries affected by conflict or fragility, and such settings are known to be linked to increased psychological distress and risk of mental disorders. While guidelines are in place, high-quality evidence to inform mental health and psychosocial support (MHPSS) interventions in conflict settings is lacking. This systematic review aimed to synthesise existing information on the delivery, coverage and effectiveness of MHPSS for conflict-affected women and children in low-income and middle-income countries (LMICs).Methods: We searched Medline, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Psychological Information Database (PsycINFO)databases for indexed literature published from January 1990 to March 2018. Grey literature was searched on the websites of 10 major humanitarian organisations. Eligible publications reported on an MHPSS intervention delivered to conflict-affected women or children in LMICs. We extracted and synthesised information on intervention delivery characteristics, including delivery site and personnel involved, as well as delivery barriers and facilitators, and we tabulated reported intervention coverage and effectiveness data.Results: The search yielded 37 854 unique records, of which 157 were included in the review. Most publications were situated in Sub-Saharan Africa (n=65) and Middle East and North Africa (n=36), and many reported on observational research studies (n=57) or were non-research reports (n=53). Almost half described MHPSS interventions targeted at children and adolescents (n=68). Psychosocial support was the most frequently reported intervention delivered, followed by training interventions and screening for referral or treatment. Only 19 publications reported on MHPSS intervention coverage or effectiveness.Discussion: Despite the growing literature, more efforts are needed to further establish and better document MHPSS intervention research and practice in conflict settings. Multisectoral collaboration and better use of existing social support networks are encouraged to increase reach and sustainability of MHPSS interventions

Delivering infectious disease interventions to women and children in conflict settings: A systematic review

Background: Conflict has played a role in the large-scale deterioration of health systems in low-income and middle-income countries (LMICs) and increased risk of infections and outbreaks. This systematic review aimed to synthesise the literature on mechanisms of delivery for a range of infectious disease-related interventions provided to conflict-affected women, children and adolescents.Methods: We searched Medline, Embase, CINAHL and PsychINFO databases for literature published in English from January 1990 to March 2018. Eligible publications reported on conflict-affected neonates, children, adolescents or women in LMICs who received an infectious disease intervention. We extracted and synthesised information on delivery characteristics, including delivery site and personnel involved, as well as barriers and facilitators, and we tabulated reported intervention coverage and effectiveness data.Results: A majority of the 194 eligible publications reported on intervention delivery in sub-Saharan Africa. Vaccines for measles and polio were the most commonly reported interventions, followed by malaria treatment. Over two-thirds of reported interventions were delivered in camp settings for displaced families. The use of clinics as a delivery site was reported across all intervention types, but outreach and community-based delivery were also reported for many interventions. Key barriers to service delivery included restricted access to target populations; conversely, adopting social mobilisation strategies and collaborating with community figures were reported as facilitating intervention delivery. Few publications reported on intervention coverage, mostly reporting variable coverage for vaccines, and fewer reported on intervention effectiveness, mostly for malaria treatment regimens.Conclusions: Despite an increased focus on health outcomes in humanitarian crises, our review highlights important gaps in the literature on intervention delivery among specific subpopulations and geographies. This indicates a need for more rigorous research and reporting on effective strategies for delivering infectious disease interventions in different conflict contexts

Delivering water, sanitation and hygiene interventions to women and children in conflict settings: A systematic review

Background: Access to safe water and sanitation facilities and the adoption of effective hygiene practices are fundamental to reducing maternal and child morbidity and mortality globally. In armed conflict settings, inadequate water, sanitation and hygiene (WASH) infrastructure poses major health risks for women and children. This review aimed to synthesise the existing information on WASH interventions being delivered to women and children in conflict settings in low-income and middle-income countries (LMICs) and to identify the personnel, sites and platforms being used to deliver such interventions.Methods: We conducted a systematic search for publications indexed in four databases, and grey literature was searched through the websites of humanitarian agencies and organisations. Eligible publications reported WASH interventions delivered to conflict-affected women or children. We extracted and synthesised information on intervention delivery characteristics, as well as barriers and facilitators.Results: We identified 58 eligible publications reporting on the delivery of WASH interventions, mostly in Sub-Saharan Africa. Non-Governmental Organization (NGO)/United Nations (UN) agency staff were reported to be involved in delivering interventions in 62% of publications, with the most commonly reported delivery site being community spaces (50%). Only one publication reported quantitative data on intervention effectiveness among women or children.Discussion: This review revealed gaps in the current evidence on WASH intervention delivery in conflict settings. Little information is available on the delivery of water treatment or environmental hygiene interventions, or about the sites and personnel used to deliver WASH interventions. Limited quantitative data on WASH intervention coverage or effectiveness with respect to women or children are important gaps, as multiple factors can affect how WASH services are accessed differently by women and men, and the hygiene needs of adolescent girls and boys differ; these factors must be taken into account when delivering interventions in conflict settings

Delivery of sexual and reproductive health interventions in conflict settings: A systematic review

Background: It is essential to provide comprehensive sexual and reproductive health (SRH) interventions to women affected by armed conflict, but there is a lack of evidence on effective approaches to delivering such interventions in conflict settings. This review synthesised the available literature on SRH intervention delivery in conflict settings to inform potential priorities for further research and additional guidance development.Methods: We searched MEDLINE, Embase, CINAHL and PsycINFO databases using terms related to conflict, women and children, and SRH. We searched websites of 10 humanitarian organisations for relevant grey literature. Publications reporting on conflict-affected populations in low-income and middle-income countries and describing an SRH intervention delivered during or within 5 years after the end of a conflict were included. Information on population, intervention and delivery characteristics were extracted and narratively synthesised. Quantitative data on intervention coverage and effectiveness were tabulated, but no meta-analysis was undertaken.Results: 110 publications met our eligibility criteria. Most focused on sub-Saharan Africa and displaced populations based in camps. Reported interventions targeted family planning, HIV/STIs, gender-based violence and general SRH. Most interventions were delivered in hospitals and clinics by doctors and nurses. Delivery barriers included security, population movement and lack of skilled health staff. Multistakeholder collaboration, community engagement and use of community and outreach workers were delivery facilitators. Reporting of intervention coverage or effectiveness data was limited.Discussion: There is limited relevant literature on adolescents or out-of-camp populations and few publications reported on the use of existing guidance such as the Minimal Initial Services Package. More interventions for gender-based violence were reported in the grey than the indexed literature, suggesting limited formal research in this area. Engaging affected communities and using community-based sites and personnel are important, but more research is needed on how best to reach underserved populations and to implement community-based approaches.Prospero registration number: CRD42019125221

Delivering maternal and neonatal health interventions in conflict settings: A systematic review

Background: While much progress was made throughout the Millennium Development Goals era in reducing maternal and neonatal mortality, both remain unacceptably high, especially in areas affected by humanitarian crises. While valuable guidance on interventions to improve maternal and neonatal health in both non-crisis and crisis settings exists, guidance on how best to deliver these interventions in crisis settings, and especially in conflict settings, is still limited. This systematic review aimed to synthesise the available literature on the delivery on maternal and neonatal health interventions in conflict settings.Methods: We searched MEDLINE, Embase, CINAHL and PsycINFO databases using terms related to conflict, women and children, and maternal and neonatal health. We searched websites of 10 humanitarian organisations for relevant grey literature. Publications reporting on conflict-affected populations in low-income and middle-income countries and describing a maternal or neonatal health intervention delivered during or within 5 years after the end of a conflict were included. Information on population, intervention, and delivery characteristics were extracted and narratively synthesised. Quantitative data on intervention coverage and effectiveness were tabulated but no meta-analysis was undertaken.Results: 115 publications met our eligibility criteria. Intervention delivery was most frequently reported in the sub-Saharan Africa region, and most publications focused on displaced populations based in camps. Reported maternal interventions targeted antenatal, obstetric and postnatal care; neonatal interventions focused mostly on essential newborn care. Most interventions were delivered in hospitals and clinics, by doctors and nurses, and were mostly delivered through non-governmental organisations or the existing healthcare system. Delivery barriers included insecurity, lack of resources and lack of skilled health staff. Multi-stakeholder collaboration, the introduction of new technology or systems innovations, and staff training were delivery facilitators. Reporting of intervention coverage or effectiveness data was limited.Discussion: The relevant existing literature focuses mostly on maternal health especially around the antenatal period. There is still limited literature on postnatal care in conflict settings and even less on newborn care. In crisis settings, as much as in non-crisis settings, there is a need to focus on the first day of birth for both maternal and neonatal health. There is also a need to do more research on how best to involve community members in the delivery of maternal and neonatal health interventions.Prospero registration number: CRD42019125221

Initial Public Offerings and the Firm Location

The firm geographic location matters in IPOs because investors have a strong preference for newly issued local stocks and provide abnormal demand in local offerings. Using equity holdings data for more than 53,000 households, we show the probability to participate to the stock market and the proportion of the equity wealth is abnormally increasing with the volume of the IPOs inside the investor region. Upon nearly the universe of the 167,515 going public and private domestic manufacturing firms, we provide consistent evidence that the isolated private firms have higher probability to go public, larger IPO underpricing cross-sectional average and volatility, and less pronounced long-run under-performance. Similar but opposite evidence holds for the local concentration of the investor wealth. These effects are economically relevant and robust to local delistings, IPO market timing, agglomeration economies, firm location endogeneity, self-selection bias, and information asymmetries, among others. Findings suggest IPO waves have a strong geographic component, highlight that underwriters significantly under-estimate the local demand component thus leaving unexpected money on the table, and support state-contingent but constant investor propensity for risk

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population