Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Epidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.  The superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.  Our prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates. OBJECTIVES: To assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term. SEARCH METHODS: We searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials. SELECTION CRITERIA: We included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined. DATA COLLECTION AND ANALYSIS: We used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.  The following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women. We used the GRADE system to assess the certainty of evidence associated with our outcome measures. MAIN RESULTS: We included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk. Our results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant. The incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores. WIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses. AUTHORS' CONCLUSIONS: Overall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.

Modifiable Factors Associated With Survival After Out-of-Hospital Cardiac Arrest in the Pan-Asian Resuscitation Outcomes Study.

STUDY OBJECTIVE: The study aims to identify modifiable factors associated with improved out-of-hospital cardiac arrest survival among communities in the Pan-Asian Resuscitation Outcomes Study (PAROS) Clinical Research Network: Japan, Singapore, South Korea, Malaysia, Taiwan, Thailand, and the United Arab Emirates (Dubai). METHODS: This was a prospective, international, multicenter cohort study of out-of-hospital cardiac arrest in the Asia-Pacific. Arrests caused by trauma, patients who were not transported by emergency medical services (EMS), and pediatric out-of-hospital cardiac arrest cases (<18 years) were excluded from the analysis. Modifiable out-of-hospital factors (bystander cardiopulmonary resuscitation [CPR] and defibrillation, out-of-hospital defibrillation, advanced airway, and drug administration) were compared for all out-of-hospital cardiac arrest patients presenting to EMS and participating hospitals. The primary outcome measure was survival to hospital discharge or 30 days of hospitalization (if not discharged). We used multilevel mixed-effects logistic regression models to identify factors independently associated with out-of-hospital cardiac arrest survival, accounting for clustering within each community. RESULTS: Of 66,780 out-of-hospital cardiac arrest cases reported between January 2009 and December 2012, we included 56,765 in the analysis. In the adjusted model, modifiable factors associated with improved out-of-hospital cardiac arrest outcomes included bystander CPR (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.31 to 1.55), response time less than or equal to 8 minutes (OR 1.52; 95% CI 1.35 to 1.71), and out-of-hospital defibrillation (OR 2.31; 95% CI 1.96 to 2.72). Out-of-hospital advanced airway (OR 0.73; 95% CI 0.67 to 0.80) was negatively associated with out-of-hospital cardiac arrest survival. CONCLUSION: In the PAROS cohort, bystander CPR, out-of-hospital defibrillation, and response time less than or equal to 8 minutes were positively associated with increased out-of-hospital cardiac arrest survival, whereas out-of-hospital advanced airway was associated with decreased out-of-hospital cardiac arrest survival. Developing EMS systems should focus on basic life support interventions in out-of-hospital cardiac arrest resuscitation.

Cost-effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria.

UNLABELLED: Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLT-related 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations. CONCLUSION: In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore.

Increasing neurologically intact survival after out-of-hospital cardiac arrest among elderly: Singapore Experience.

Objectives: With more elderly presenting with Out-of-Hospital Cardiac Arrests (OHCAs) globally, neurologically intact survival (NIS) should be the aim of resuscitation. We aimed to study the trend of OHCA amongst elderly in a large Asian registry to identify if age is independently associated with NIS and factors associated with NIS. Methods: All adult OHCAs aged ≥18 years attended by emergency medical services (EMS) from April 2010 to December 2019 in Singapore was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Cases pronounced dead at scene, non-EMS transported, traumatic OHCAs and OHCAs in ambulances were excluded. Patient characteristics and outcomes were compared across four age categories (18-64, 65-79, 80-89, ≥90). Multivariable logistic regression analysis determined the factors associated with NIS. Results: 19,519 eligible cases were analyzed. OHCA incidence increased with age almost doubling in octogenarians (from 312/100,000 in 2011 to 652/100,000 in 2019) and tripling in those ≥90 years (from 458/100,000 in 2011 to 1271/100,000 in 2019). The proportion of patients with NIS improved over time for the 18-64, 65-79- and 80-89-years age groups, with the greatest improvement in the youngest group. NIS decreased with each increasing year of age and minute of response time. NIS increased in the arrests of presumed cardiac etiology, witnessed and bystander CPR. Conclusions: Survival with good outcomes has increased even amongst the elderly. Regardless of age, NIS is possible with good-quality CPR, highlighting its importance. End-of-life planning is a complex yet necessary decision that requires qualitative exploration with elderly, their families and care providers.

Does witness type affect the chance of receiving bystander CPR in out-of-hospital cardiac arrest?

OBJECTIVES: The relationship between the bystander witness type and receipt of bystander CPR (BCPR) is not well understood. Herein we compared BCPR administration between family and non-family witnessed out-of-hospital cardiac arrest (OHCA). BACKGROUND: In many communities, interventions in the past decade have contributed to an increased receipt of BCPR, for example in Singapore from 15% to 60%. However, BCPR rates have plateaued despite sustained and ongoing community-based interventions, which may be related to gaps in education or training for various witness types. The purpose of this study was to investigate the association between witness type and BCPR administration. METHODS: Singapore data from 2010-2020 was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) network registry (n = 25,024). All adult, layperson witnessed, non-traumatic OHCAs were included in this study. RESULTS: Of 10,016 eligible OHCA cases, 6,895 were family witnessed and 3,121 were non-family witnessed. After adjustment for potential confounders, BCPR administration was less likely for non-family witnessed OHCA (OR 0.83, 95% CI 0.75, 0.93). After location stratification, non-family witnessed OHCAs were less likely to receive BCPR in residential settings (OR 0.75, 95% CI 0.66, 0.85). In non-residential settings, there was no statistically significant association between witness type and BCPR administration (OR 1.11, 95% CI 0.88, 1.39). Details regarding witness type and bystander CPR were limited. CONCLUSION: This study found differences in BCPR administration between family and non-family witnessed OHCA cases. Elucidation of witness characteristics may be useful to determine populations that would benefit most from CPR education and training.

Nationwide Alcohol-related visits In Singapore's Emergency departments (NAISE): A retrospective population-level study from 2007 to 2016.

INTRODUCTION: Excessive alcohol consumption is associated with increased morbidity and mortality, and its societal impact is substantial. The Nationwide Alcohol-related visits In Singapore Emergency departments study aims to characterise trends in ED visits involving acute and chronic alcohol consumption between 2007 and 2016. METHODS: Data from the Singapore Ministry of Health, comprising all ED visits in Singapore from 2007 to 2016, were used. The data were aggregated by year and analysed for changes in prevalence and rates of ED visits for acute and chronic alcohol consumption, broken down by age, gender and ethnicity. RESULTS: Over the study period, the number of ED visits involving alcohol consumption increased 98.3%, from 2236 in 2007 to 4433 in 2016. During the same period, the rate per 100 000 population increased 62.4% from 48.7 to 79.1, and total ED-related costs rose by 140%, from 528 680 to 1 269 638 SGD. The increase in alcohol-related visits rates and costs was higher than non-alcohol-related visits rates and costs, which increased by 12.1% and 115% respectively. While trends in acute and chronic alcohol-related ED visits stayed stable amongst women, they rose substantially in men. Older men aged 50-69 show the highest rates and rate of increase for both acute and chronic alcohol-related ED visits. DISCUSSION AND CONCLUSIONS: Alcohol-related visits contributed disproportionately to the increasing number of ED visits in Singapore between 2007 and 2016. Older men form the demographic with the highest rates and increase in rates of alcohol-related ED visits and form a potential group for targeted intervention.

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.

Delivering nutrition interventions to women and children in conflict settings: a systematic review.

BACKGROUND: Low/middle-income countries (LMICs) face triple burden of malnutrition associated with infectious diseases, and non-communicable diseases. This review aims to synthesise the available data on the delivery, coverage, and effectiveness of the nutrition programmes for conflict affected women and children living in LMICs. METHODS: We searched MEDLINE, Embase, CINAHL, and PsycINFO databases and grey literature using terms related to conflict, population, and nutrition. We searched studies on women and children receiving nutrition-specific interventions during or within five years of a conflict in LMICs. We extracted information on population, intervention, and delivery characteristics, as well as delivery barriers and facilitators. Data on intervention coverage and effectiveness were tabulated, but no meta-analysis was conducted. RESULTS: Ninety-one pubblications met our inclusion criteria. Nearly half of the publications (n=43) included population of sub-Saharan Africa (n=31) followed by Middle East and North African region. Most publications (n=58) reported on interventions targeting children under 5 years of age, and pregnant and lactating women (n=27). General food distribution (n=34), micronutrient supplementation (n=27) and nutrition assessment (n=26) were the most frequently reported interventions, with most reporting on intervention delivery to refugee populations in camp settings (n=63) and using community-based approaches. Only eight studies reported on coverage and effectiveness of intervention. Key delivery facilitators included community advocacy and social mobilisation, effective monitoring and the integration of nutrition, and other sectoral interventions and services, and barriers included insufficient resources, nutritional commodity shortages, security concerns, poor reporting, limited cooperation, and difficulty accessing and following-up of beneficiaries. DISCUSSION: Despite the focus on nutrition in conflict settings, our review highlights important information gaps. Moreover, there is very little information on coverage or effectiveness of nutrition interventions; more rigorous evaluation of effectiveness and delivery approaches is needed, including outside of camps and for preventive as well as curative nutrition interventions. PROSPERO REGISTRATION NUMBER: CRD42019125221.

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 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. PROSPERO registration number: CRD42019125221.

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. PROSPERO REGISTRATION NUMBER: CRD42019125221.

Delivering infectious disease interventions to women and children in conflict settings: a systematic reviefw.

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. PROSPERO REGISTRATION NUMBER: CRD42019125221.

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. PROSPERO registration number: CRD42019125221.

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. PROSPERO REGISTRATION NUMBER: CRD42019125221.

Effect of known history of heart disease on survival outcomes after out-of-hospital cardiac arrests.

OBJECTIVE: We aimed to investigate the effect of known heart disease on post-out-of-hospital cardiac arrest (OHCA) survival outcomes, and its association with factors influencing survival. METHODS: This was an observational, retrospective study involving an OHCA database from seven Asian countries in 2009-2012. Heart disease was defined as a documented diagnosis of coronary artery disease or congenital heart disease. Patients with non-traumatic arrests for whom resuscitation was attempted and with known medical histories were included. Differences in demographics, arrest characteristics and survival between patients with and without known heart disease were analysed. Multivariate logistic regression was performed to identify factors influencing survival to discharge. RESULTS: Of 19 044 eligible patients, 5687 had known heart disease. They were older (77 vs 72 years) and had more comorbidities like diabetes (40.9 vs 21.8%), hypertension (60.6 vs 36.0%) and previous stroke (15.2 vs 10.1%). However, they were not more likely to receive bystander cardiopulmonary resuscitation (P = 0.205) or automated external defibrillation (P = 0.980). On univariate analysis, known heart disease was associated with increased survival (unadjusted odds ratio 1.16, 95% confidence interval 1.03-1.30). However, on multivariate analysis, heart disease predicted poorer survival (adjusted odds ratio 0.76, 95% confidence interval 0.58-1.00). Other factors influencing survival corresponded with previous reports. CONCLUSIONS: Known heart disease independently predicted poorer post-OHCA survival. This study may provide information to guide future prospective studies specifically looking at family education for patients with heart disease and the effect on OHCA outcomes.

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.

BACKGROUND: A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. RESULTS: In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06-2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251-2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603-4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063-1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. MATERIALS AND METHODS: 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. CONCLUSIONS: In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.

Consecutive outbreaks of Vibrio cholerae O139 and V. cholerae O1 cholera in a fishing village near Karachi, Pakistan.

In July 2002 and June 2003, cholera outbreaks were detected by a diarrhoea surveillance system in a village outside Karachi, Pakistan. Specimens were culture confirmed. The first outbreak was caused by Vibrio cholerae O139 (n = 30) and the second outbreak by V. cholerae O1 (n = 39). Demographic and clinical features of patients were recorded and case-control studies were conducted following each outbreak. Clinical information was obtained for 29 of the 30 patients in the first outbreak, and 2 of the patients in the second outbreak were either out of the area or lost to follow-up, leaving 29 and 37 cases in the analysis for the first and second outbreak, respectively. Eighteen (49%) of the 37 V. cholerae O1 patients were under 2 years of age compared with 6 (21%) of the 29 V. cholerae O139 patients (P = 0.02). Vibrio cholerae O139-infected patients were more likely to be febrile (16/29) than those infected with V. cholerae O1 (2/37; P<0.001). A household contact with cholera was a risk factor in both outbreaks; water source was a risk factor in the first outbreak only. Geographically, cases were clustered during the first outbreak but not during the second. Person-to-person contact and water reservoirs appear to be the main transmission routes for cholera in this setting.

Thyroid Autoimmune Antibodies and Major Depressive Disorder in Women.

INTRODUCTION: Anti-thyroid antibodies are associated with extra-thyroid diseases such as Graves' ophthalmopathy and Hashimoto's encephalopathy. Some evidence suggests that anti-thyroid antibodies are also associated with depression. Interleukin (IL)-17 appears to play an important role in autoimmune thyroid disease. This study investigated whether specific thyroid autoantibodies and IL-17 distinguished persons with depression from non-depressed controls. MATERIALS AND METHODS: Forty-seven adult females with non-psychotic, current major depressive disorder and 80 healthy female controls participated in this study. Thyroid peroxidase antibodies, thyroglobulin antibodies, thyroid-stimulating hormone (TSH) receptor antibodies, free T3 and T4, TSH and IL-17 were measured from the serum. Measurements were repeated to assess test-retest reliability. Receiver operating characteristic (ROC) curves were used to estimate discriminatory values of the measurements. Differences between groups and associations between the clinical and biochemical assessments were analysed. RESULTS: Median TSH receptor antibody concentration was significantly higher in the depressed than control group (P <0.001). Area under the ROC curve was 0.80 (95% CI, 0.73 to 0.88). Higher TSH receptor antibody titres were associated with greater depression severity scores (r = 0.33, P <0.05). IL-17 levels were not associated with TSH receptor antibody levels or depression severity scores. Thyroid function and other thyroid autoantibodies were not associated with depression severity. CONCLUSION: TSH receptor antibodies might be a biomarker of immune dysfunction in depression.

Intravenous immune globulin for severe acute myocarditis in children.

We evaluated high-dose (2g/kg) intravenous immunoglobulin (IVIG) for severe acute myocarditis in 13 children and compared them for survival with 12 children with myocarditis treated with only conventional therapy. Baseline characteristics were similar between the two groups. Both groups had poor left ventricular ejection fraction (LVEF) on admission. The mortality rate was 8% in the IVIG treated children as compared to 46% in controls (P=0.04). Our study supports the use of IVIG in severe acute myocarditis in children.