Safety of Administering Live Vaccines During Pregnancy : A Systematic Review and Meta-Analysis of Pregnancy Outcomes

Live-attenuated vaccines (LAV) are currently contraindicated during pregnancy, given uncertain safety records for the mother-infant pair. LAV might, however, play an important role to protect them against serious emerging diseases, such as Ebola and Lassa fever. For this systematic review we searched relevant databases to identify studies published up to November 2019. Controlled observational studies reporting pregnancy outcomes after maternal immunization with LAV were included. The ROBINS-I tool was used to assess risk of bias. Pooled odds ratios (OR) were obtained under a random-effects model. Of 2831 studies identified, fifteen fulfilled inclusion criteria. Smallpox, rubella, poliovirus, yellow fever and dengue vaccines were assessed in these studies. No association was found between vaccination and miscarriage (OR 0.98, 95% CI 0.87-1.10), stillbirth (OR 1.04, 95% CI 0.74-1.48), malformations (OR 1.09, 95% CI 0.98-1.21), prematurity (OR 0.99, 95% CI 0.90-1.08) or neonatal death (OR 1.06, 95% CI 0.68-1.65) overall. However, increased odds of malformations (OR 1.24; 95% CI 1.03-1.49) and miscarriage after first trimester immunization (OR 4.82; 95% CI 2.38-9.77) was found for smallpox vaccine. Thus, we did not find evidence of harm related to LAV other than smallpox with regards to pregnancy outcomes, but quality of evidence was very low. Overall risks appear to be small and have to be balanced against potential benefits for the mother-infant pair

Suitability of three different tools for the assessment of methodological quality in ex post facto studies

There is no clear candidate tool for assessing the methodological quality of ex post facto studies in systematic reviews and meta-analyses yet. Our purpose is to thoroughly analyze the psychometric properties of the three most comprehensive assessment tools of this kind published up to 2010. We selected these tools from a previous systematic review, and we applied each one to assess the quality of 10 prospective studies, 10 retrospective studies with quasi-control group, and 10 cross-sectional studies. Inter-rater reliability for the first two aforementioned research designs is moderate only for one of the selected tools, and moderate to high for all of them for cross-sectional studies. Agreement between tools is low in general, although the inferred aspects show that the tools have a relative good conceptual overlapping in most of the domains. According to these results we recommend two tools for assessing cross-sectional studies, but we consider that the tools applicable to prospective studies or retrospective studies with quasi-control group require further testing. The 30 concrete aspects that we have inferred from the items of the three analyzed tools can be used as starting point to develop a new tool of this kin

Deploying Machine Learning Models Using Progressive Web Applications: Implementation Using a Neural Network Prediction Model for Pneumonia Related Child Mortality in The Gambia.

BACKGROUND: Translating research outputs into practical tools for medical practitioners is a neglected area and could have a substantial impact. One of the barriers to implementing artificial intelligence (AI) and machine learning (ML) applications is their practical deployment in the field. Traditional web-based (i.e., server sided) applications are dependent on reliable internet connections, which may not be readily available in rural areas. Native mobile apps require device specific programming skills as well as contemporary hardware and software, with often rapid and unpredictable platform specific changes. This is a major challenge for using AI/ML tools in resource-limited settings. METHODS: An emerging technology, progressive web applications (PWAs), first introduced by Google in 2015, offers an opportunity to overcome the challenges of deploying bespoke AI/ML systems. The same PWA code can be implemented across all desktop platforms, iOS and Android phones and tablets. In addition to platform independence, a PWA can be designed to be primarily offline. RESULTS: We demonstrate how a neural network-based pneumonia mortality prediction triage tool was migrated from a typical academic framework (paper and web-based prototype) to a tool that can be used offline on any mobile phone-the most convenient deployment vehicle. After an initial online connection to download the software, the application runs entirely offline, reading data from cached memory, and running code via JavaScript. On mobile devices the application is installed as a native app, without the inconvenience of platform specific code through manufacturer code stores. DISCUSSION: We show that an ML application can be deployed as a platform independent offline PWA using a pneumonia-related child mortality prediction tool as an example. The aim of this tool was to assist clinical staff in triaging children for hospital admission, by predicting their risk of death. PWAs function seamlessly when their host devices lose internet connectivity, making them ideal for e-health apps that can help improve health and save lives in resource-limited settings in line with the UN Sustainable Development Goal 3 (SDG3)

Q-Coh : a tool to screen the methodological quality of cohort studies in systematic reviews and meta-analyses

The evaluation of the methodological quality of primary studies in a systematic review is a key process to enhance the likelihood of achieving valid results. When considering non-randomized designs as cohort studies, this process becomes even more critical, since these designs are more susceptible to bias than randomized controlled trials are. Taking this into account, a tool, named Q-Coh, was designed with the aim to screen the methodological quality of the primary studies with a cohort design priming specificity over sensitivity in a reasonable application time. After applying it to 21 prospective cohort studies by three raters, all domains had a moderate to good agreement, with all except one of them having statistically significant kappa values. Despite there is no gold standard for the methodological quality, arguments supporting its validity are given. Future research should assess the psychometric properties of Q-Coh in the context of real meta-analyses, evaluate the influence of the raters' substantive and methodological expertise on these properties, and explore different ways of including the domains-based ratings of the quality provided by Q-Coh into meta-analysesLa valoración de la calidad metodológica de estudios primarios en una revisión sistemática es un proceso clave para mejorar la validez de los resultados. Al considerar diseños no aleatorizados como los estudios de cohortes, este proceso se vuelve aún más crítico, ya que estos diseños son más susceptibles a sesgos que los estudios controlados mediante aleatorización. Teniendo esto en cuenta se diseñó Q-Coh, una herramienta cuyo objetivo es valorar la calidad metodológica de estudios primarios con un diseño de cohortes, primando la especificidad sobre la sensibilidad y con un tiempo de aplicación razonable. Después de ser aplicada a 21 estudios de cohortes por tres evaluadores, todas las dimensiones obtuvieron un acuerdo entre moderado y bueno, teniendo todas excepto una de ellas valores de kappa estadísticamente significativos. A pesar de no existir ningún criterio de referencia estándar para valorar la calidad metodológica, se dan argumentos que respaldan la validez de Q-Coh. Investigaciones futuras deberán estudiar las propiedades psicométricas de la herramienta en el contexto de meta-análisis reales, evaluar la influencia de los conocimientos sustantivos y metodológicos de los evaluadores sobre dichas propiedades, y explorar diferentes vías para incluir en los meta-análisis las puntuaciones de calidad de las dimensiones proporcionados por Q-Coh

Risk factors of infant mortality in rural The Gambia: a retrospective cohort study

Objective: The main objective was to assess the risk factors for infant mortality among children living in the Health and Demographic Surveillance System (HDSS) in Farafenni, The Gambia. Our secondary objective was to assess these risks separately in the neonatal and postneonatal (>28 days) period. Design: Retrospective cohort study. Setting: HDSS in an urban centre and surrounding area in The Gambia. Patients: 7365 infants (47% female) born between 2014 and 2018, of which 126 (1.71%) died in the first year. Main outcome measures: Infant mortality. Results: Risk factors for mortality were death of any sibling (HR 2.78, 95% CI 1.54 to 5.00), having a twin (HR 1.96, 95% CI 1.01 to 3.80), being born in the harvest season (HR 1.55, 95% CI 1.07 to 2.24), living in a rural village (HR 4.34, 95% CI 2.03 to 9.29) and longer distance to the nearest village with a public health centre (HR 1.33, 95% CI 1.11 to 1.59). In addition, no breast feeding (HR 10.73, 95% CI 6.83 to 16.86) and no BCG vaccination in the first week of life (HR 3.47, 95% CI 1.07 to 11.24) were associated with infant mortality. Similar risk factors were found in the neonatal and postneonatal periods. Conclusion: Most risk factors associated with infant mortality (neonatal and postneonatal) are not easily modifiable at the individual level and would require programmatic approaches to target vulnerable infants and facilitate access to health services

Q-Coh : A tool to assess the methodological quality of cohort studies

Durante décadas ha habido una necesidad de revisiones de la literatura que resuma el conocimiento que produce la comunidad científica. Inicialmente, expertos en las correspondientes áreas de conocimiento recopilaban y resumían los estudios publicados sobre ciertos temas siguiendo métodos más bien subjetivos y opacos. Eran las llamadas revisiones narrativas. Sin embargo, la necesidad de una metodología más objetiva y transparente dio lugar a revisiones sistemáticas y meta-análisis, que pusieron al alcance de clínicos, investigadores, políticos y pacientes estudios que sintetizan un número de manuscritos inmanejable y exponencialmente creciente, relacionando enormes cantidades de información con la identificación de intervenciones beneficiosas y dañinas. Sin embargo, estas metodologías aún tienen algunas limitaciones, como es el caso de la calidad de los estudios primarios que son revisados. Pese a que la inclusión de ensayos clínicos aleatorizados en revisiones sistemáticas está ampliamente aceptada, la inclusión de estudios observacionales (en los que el investigador no interviene en la asignación del valor de la variable de exposición) aún es objeto de debate. Sin embargo, gran parte del conocimiento clínico y de salud se obtiene a partir de estudios observacionales. Un motivo dado habitualmente es que los estudios observacionales, en gran medida debido a la ausencia de un procedimiento de asignación aleatoria, son más susceptibles de estar sesgados. Es cierto que los ensayos clínicos aleatorizados son menos susceptibles al sesgo, pero es difícil justificar que la evidencia aportada por estudios observacionales de alta calidad es menos válida que la 'evidencia' aportada por ensayos clínicos aleatorizados de baja calidad únicamente en base a la etiqueta de su diseño. Por lo tanto, es de gran importancia ser capaces de valorar la calidad de estudios observacionales de manera válida y fiable. Tal y como se muestra en esta tesis doctoral, a día de hoy se han publicado docenas de herramientas de evaluación de calidad para estudios observacionales, pero muy pocas cumplen los criterios que se esperarían de un instrumento de medida, especialmente cuando se trata de estudios de cohortes. Una vez confirmado este vacío se desarrolló una nueva herramienta de evaluación de calidad para estudios de cohortes siguiendo los criterios de desarrollo establecidos por la American Psychological Association, el National Council on Measurement in Education y la American Educational Research Association: se definieron claramente el propósito del test y el constructo a medir, se describieron las especificaciones del test, se desarrollaron, probaron y evaluaron los ítems, y finalmente se integró todo en una hoja de cálculo interactiva. Para medir las propiedades psicométricas de esta nueva herramienta de evaluación de la calidad, que se denominó 'Q-Coh', fue aplicada por tres evaluadores a 21 estudios de cohortes de diversas temáticas y diversos niveles de calidad. Además, pese a que no hay ningún gold standard para la calidad metodológica, se analizó la validez de la herramienta Q-Coh usando diferentes estrategias. Los resultados muestran que la proporción de acuerdo entre pares de evaluadores fue superior al 80% en todos los casos, con valores de kappa no sólo buenas a muy buenas, sino también estadísticamente significativas en la mayoría de las inferencias. Esto es muy positivo, especialmente considerando las dificultades existentes en el desarrollo de una herramienta de evaluación de la calidad con índices de fiabilidad aceptables. También los resultados referidos a la validez de Q-Coh apuntan en la buena dirección. Las revisiones de la literatura llevan décadas evolucionando y, a medida que su relevancia aumentaba, también lo hizo la necesidad de procedimientos más objetivos, precisos y fiables. En este contexto de constante mejora, Q-Coh trata de ayudar a llenar un importante vacío aportando su granito de arena.For decades there has been a need for reviews of the literature to summarize the knowledge that the scientific community produces. Initially, experts in the correspondent areas collected and summarized the published studies on certain topics following rather subjective and opaque methods. These were the so-called narrative reviews. However, the need for a more objective and transparent methodology gave rise to systematic reviews and meta-analysis, which provided clinicians, researchers, policy-makers, and patients with a synthesis of an unmanageable and exponentially increasing number of manuscripts by linking and correlating huge amounts of information with identification of beneficial or harmful interventions. However, these methodologies still have some limitations to overcome, as is the case of the quality of the primary studies that are reviewed. Although the inclusion of experiments in systematic reviews is well established, the inclusion of observational studies is still under debate. However, much of clinical and public health knowledge is provided by observational studies, and the area of psychology is not an exception. A usual reason given for this is that observational studies, mainly because of their lack of randomized allocation procedure, are more susceptible to bias. It is true that randomized controlled studies are less prone to bias, but it is difficult to justify that evidence given by high quality observational studies is more valid than 'evidence' given by low quality randomized controlled trials only because of their design label. Therefore, it is of high importance to be able to validly and reliably assess the quality of observational studies. As shown in this doctoral thesis, dozens of quality assessment tools for observational studies have been developed so far, but very few meet the criteria that should be expected from an assessment instrument, especially when cohort studies are on focus. Once this gap was confirmed, a new quality assessment tool for cohort studies was developed following the standardized development criteria established by the American Psychological Association, the National Council on Measurement in Education, and the American Educational Research Association: the purpose of the test and construct to be measured were clearly defined, the test specifications were delineated, items were developed, tested and evaluated, and finally the test was assembled into an interactive spreadsheet. In order to assess the psychometric properties of this new quality assessment tool, which was named 'Q-Coh', it was applied by three different raters to 21 cohort studies of diverse topics with a wide range of quality levels. Additionally, despite there is no gold standard for the methodological quality, the validity of the Q-Coh was also studied using different approaches. The results showed that the proportion of agreement between pairs of raters was over 80% in all cases, with not only good to very good kappa values, but also being statistically significant in most inferences. This is very positive, especially considering the existing difficulties in developing a quality assessment tool with acceptable reliability scores. Also regarding the QCoh's validity the results point to the good direction. Literature reviews have been evolving for decades, and as their relevance grew, so did the demands for more objective, precise, and reliable procedures. In this context of constant refinement, the Q-Coh tries to help filling an important gap contributing in its small way

Effectiveness of interventions to address obesity and health risk behaviours among people with severe mental illness in low- and middle-income countries (LMICs): a systematic review and meta analysis

Abstract Introduction People with severe mental illness (SMI) are more likely to have obesity and engage in health risk behaviours than the general population. The aims of this study are (1) evaluate the effectiveness of interventions that focus on body weight, smoking cessation, improving sleeping patterns, and alcohol and illicit substance abuse; (2) Compare the number of interventions addressing body weight and health risk behaviours in low- and middle-income countries (LMICs) v. those reported in published systematic reviews focusing on high-income countries (HICs). Methods Intervention studies published up to December 2020 were identified through a structured search in the following database; OVID MEDLINE (1946–December 2020), EMBASE (1974–December 2020), CINAHL (1975–2020), APA PsychoINFO (1806–2020). Two authors independently selected studies, extracted study characteristics and data and assessed the risk of bias. and risk of bias was assessed using the Cochrane risk of bias tool V2. We conducted a narrative synthesis and, in the studies evaluating the effectiveness of interventions to address body weight, we conducted random-effects meta-analysis of mean differences in weight gain. We did a systematic search of systematic reviews looking at cardiometabolic and health risk behaviours in people with SMI. We compared the number of available studies of LMICs with those of HICs. Results We assessed 15 657 records, of which 9 met the study inclusion criteria. Six focused on healthy weight management, one on sleeping patterns and two tested a physical activity intervention to improve quality of life. Interventions to reduce weight in people with SMI are effective, with a pooled mean difference of −4.2 kg (95% CI −6.25 to −2.18, 9 studies, 459 participants, I2 = 37.8%). The quality and sample size of the studies was not optimal, most were small studies, with inadequate power to evaluate the primary outcome. Only two were assessed as high quality (i.e. scored ‘low’ in the overall risk of bias assessment). We found 5 reviews assessing the effectiveness of interventions to reduce weight, perform physical activity and address smoking in people with SMI. From the five systematic reviews, we identified 84 unique studies, of which only 6 were performed in LMICs. Conclusion Pharmacological and activity-based interventions are effective to maintain and reduce body weight in people with SMI. There was a very limited number of interventions addressing sleep and physical activity and no interventions addressing smoking, alcohol or harmful drug use. There is a need to test the feasibility and cost-effectiveness of context-appropriate interventions to address health risk behaviours that might help reduce the mortality gap in people with SMI in LMICs

Pregnancy-related interventions in mothers at risk for gestational diabetes in Asian India and low and middle-income countries (PRIMORDIAL study): protocol for a randomised controlled trial.

INTRODUCTION: Lifestyle modification is the mainstay of gestational diabetes mellitus (GDM) prevention. However, clinical trials evaluating the safety and efficacy of diet or physical activity (PA) in low-income and middle-income settings such as Africa and India are lacking. This trial aims to evaluate the efficacy of yoghurt consumption and increased PA (daily walking) in reducing GDM incidence in high-risk pregnant women. METHODS AND ANALYSIS: The study is a 2×2 factorial, open-labelled, multicentre randomised controlled trial to be conducted in Vellore, South India and The Gambia, West Africa. 'High-risk' pregnant women (n=1856) aged ≥18 years and ≤16 weeks of gestational age, with at least one risk factor for developing GDM, will be randomised to either (1) yoghurt (2) PA (3) yoghurt +PA or (4) standard antenatal care. Participants will be followed until 32 weeks of gestation with total active intervention lasting for a minimum of 16 weeks. The primary endpoint is GDM incidence at 26-28 weeks diagnosed using International Association of the Diabetes and Pregnancy Study Groups criteria or elevated fasting glucose (≥5.1 mmol/L) at 32 weeks. Secondary endpoints include absolute values of fasting plasma glucose concentration at 32 weeks gestation, maternal blood pressure, gestational weight gain, intrapartum and neonatal outcomes. Analysis will be both by intention to treat and per-protocol. Continuous outcome measurements will be analysed using multiple linear regression and binary variables by logistic regression. ETHICS AND DISSEMINATION: The study is approved by Oxford Tropical Research Ethics Committee (44-18), ethics committees of the Christian Medical College, Vellore (IRB 11367) and MRCG Scientific Coordinating Committee (SCC 1645) and The Gambia Government/MRCG joint ethics committee (L2020.E15). Findings of the study will be published in peer-reviewed scientific journals and presented in conferences. TRIAL REGISTRATION NUMBER: ISRCTN18467720