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Identification of curaxin as a potential new therapeutic for JAK2 V617F mutant patients

by Stella Pearson, Rognvald Blance, Fei Yan, Ya-Ching Hsieh, Bethany Geary, Fabio M. R. Amaral, Tim C. P. Somervaille, Kristina Kirschner, Anthony D. Whetton, Andrew Pierce

Myelofibrosis is a myeloproliferative neoplasm (MPN) which typically results in reduced length and quality of life due to systemic symptoms and blood count changes arising from fibrotic changes in the bone marrow. While the JAK2 inhibitor ruxolitinib provides some clinical benefit, there remains a substantial unmet need for novel targeted therapies to better modify the disease process or eradicate the cells at the heart of myelofibrosis pathology. Repurposing drugs bypasses many of the hurdles present in drug development, such as toxicity and pharmacodynamic profiling. To this end we undertook a re-analysis of our pre-existing proteomic data sets to identify perturbed biochemical pathways and their associated drugs/inhibitors to potentially target the cells driving myelofibrosis. This approach identified CBL0137 as a candidate for targeting Jak2 mutation-driven malignancies. CBL0137 is a drug derived from curaxin targeting the Facilitates Chromatin Transcription (FACT) complex. It is reported to trap the FACT complex on chromatin thereby activating p53 and inhibiting NF-kB activity. We therefore assessed the activity of CBL0137 in primary patient samples and murine models of Jak2-mutated MPN and found it preferentially targets CD34+ stem and progenitor cells from myelofibrosis patients by comparison with healthy control cells. Further we investigate its mechanism of action in primary haemopoietic progenitor cells and demonstrate its ability to reduce splenomegaly and reticulocyte number in a transgenic murine model of myeloproliferative neoplasms.

Screening for psychosocial risk in caregivers of children with medical complexity during the COVID-19 pandemic: a cross-sectional study

Por: Pitch · N. · Verma · R. · Davidson · L. · Robertson · T. · Anagnostopoulos · G. · Sunkonkit · K. · Qazi · A. · Ambreen · M. · Mekhuri · S. · Miller · M. R. · Orkin · J. · Amin · R.
Objective

The primary objective was to quantify psychosocial risk in family caregivers (FCs) of children with medical complexity (CMC) during the COVID-19 pandemic using the Psychosocial Assessment Tool (PAT). The secondary objectives were to compare this finding with the average PAT score of this population before the COVID-19 pandemic and to examine potential clinical predictors of psychosocial risk in FCs of CMC.

Design

Cross-sectional study.

Participants

FCs of CMC were recruited from the Long-Term Ventilation Clinic at The Hospital for Sick Children, Toronto, Ontario, Canada. A total of 91 completed the demographic and PAT questionnaires online from 10 June 2021 through 13 December 2021.

Main outcome measures

Mean PAT scores in FCs were categorised as ‘Universal’ low risk, ‘Targeted’ intermediate risk or ‘Clinical’ high risk. The effect of sociodemographic and clinical variables on overall PAT scores was assessed using multiple linear regression analysis. Comparisons with a previous study were made using Mann-Whitney tests and 2 analysis.

Results

Mean (SD) PAT score was 1.34 (0.69). Thirty-one (34%) caregivers were classified as Universal, 43 (47%) as Targeted and 17 (19%) as Clinical. The mean PAT score (1.34) was significantly higher compared with the mean PAT score (1.17) found prior to the COVID-19 pandemic. Multiple linear regression analysis demonstrated an overall significant model, with the number of hospital admissions since the onset of COVID-19 being the only variable associated with the overall PAT score.

Conclusion

FCs of CMC are experiencing significant psychosocial stress during the COVID-19 pandemic. Timely and effective interventions are warranted to ensure these individuals receive the appropriate support.

Danish Pathology Life Course (PATHOLIFE) cohort: a register based cohort extending upon a national tissue biobank

Por: Nielsen · P. Y. · Bartholdy · A. · Gjerdrum · L. M. R. · Westendorp · R. G. J. · Mortensen · L. H. · Bhatt · S. · Jensen · M. K.
Purpose

The Danish Pathology Life Course (PATHOLIFE) cohort was established to facilitate epidemiological research relating histological and cytological features extracted from patient tissue specimens to the rich life course histories, including both prior and future register data, of the entire Danish population. Research results may increase quality of diagnosis, prognosis and stratification of patient subtypes, possibly identifying novel routes of treatment.

Participants

All Danish residents from 1 January 1986 to 31 December 2019, totalling 8 593 421 individuals.

Findings to date

We provide an overview of the subpopulation of Danish residents who have had a tissue specimen investigated within the Danish healthcare system, including both the primary sector and hospitals. We demonstrate heterogeneity in sociodemographic and prognostic factors between the general Danish population and the above mentioned subpopulation, and also between the general Danish population and subpopulations of patients with tissue specimens from selected anatomical sites. Results demonstrate the potential of the PATHOLIFE cohort for integrating many different factors into identification and selection of the most valuable tissue blocks for studies of specific diseases and their progression. Broadly, we find that living with a partner, having higher education and income associates with having a biopsy overall. However, this association varies across different tissue and patient types, which also display differences in time-to-death and causes of death.

Future plans

The PATHOLIFE cohort may be used to study specified patient groups and link health related events from several national health registries, and to sample patient groups, for which stored tissue specimens are available for further research investigations. The PATHOLIFE cohort thereby provides a unique opportunity to prospectively follow people that were characterised and sampled in the past.

Behavioural factors associated with fear of litigation as a driver for the increased use of caesarean sections: a scoping review

Por: Elaraby · S. · Altieri · E. · Downe · S. · Erdman · J. · Mannava · S. · Moncrieff · G. · Shamanna · B. R. · Torloni · M. R. · Betran · A. P.
Objective

To explore the behavioural drivers of fear of litigation among healthcare providers influencing caesarean section (CS) rates.

Design

Scoping review.

Data sources

We searched MEDLINE, Scopus and WHO Global Index (1 January 2001 to 9 March 2022).

Data extraction and synthesis

Data were extracted using a form specifically designed for this review and we conducted content analysis using textual coding for relevant themes. We used the WHO principles for the adoption of a behavioural science perspective in public health developed by the WHO Technical Advisory Group for Behavioural Sciences and Insights to organise and analyse the findings. We used a narrative approach to summarise the findings.

Results

We screened 2968 citations and 56 were included. Reviewed articles did not use a standard measure of influence of fear of litigation on provider’s behaviour. None of the studies used a clear theoretical framework to discuss the behavioural drivers of fear of litigation. We identified 12 drivers under the three domains of the WHO principles: (1) cognitive drivers: availability bias, ambiguity aversion, relative risk bias, commission bias and loss aversion bias; (2) social and cultural drivers: patient pressure, social norms and blame culture and (3) environmental drivers: legal, insurance, medical and professional, and media. Cognitive biases were the most discussed drivers of fear of litigation, followed by legal environment and patient pressure.

Conclusions

Despite the lack of consensus on a definition or measurement, we found that fear of litigation as a driver for rising CS rates results from a complex interaction between cognitive, social and environmental drivers. Many of our findings were transferable across geographical and practice settings. Behavioural interventions that consider these drivers are crucial to address the fear of litigation as part of strategies to reduce CS.

Cohort profile of PLUTO: a perioperative biobank focusing on prediction and early diagnosis of postoperative complications

Por: de Mul · N. · Verlaan · D. · Ruurda · J. P. · van Grevenstein · W. M. U. · Hagendoorn · J. · de Borst · G.-J. · Vriens · M. R. · de Bree · R. · Zweemer · R. P. · Vogely · C. · Haitsma Mulier · J. L. G. · Vernooij · L. M. · Reitsma · J. B. · de Zoete · M. R. · Top · J. · Kluijtmans · J
Purpose

Although elective surgery is generally safe, some procedures remain associated with an increased risk of complications. Improved preoperative risk stratification and earlier recognition of these complications may ameliorate postoperative recovery and improve long-term outcomes. The perioperative longitudinal study of complications and long-term outcomes (PLUTO) cohort aims to establish a comprehensive biorepository that will facilitate research in this field. In this profile paper, we will discuss its design rationale and opportunities for future studies.

Participants

Patients undergoing elective intermediate to high-risk non-cardiac surgery are eligible for enrolment. For the first seven postoperative days, participants are subjected to daily bedside visits by dedicated observers, who adjudicate clinical events and perform non-invasive physiological measurements (including handheld spirometry and single-channel electroencephalography). Blood samples and microbiome specimens are collected at preselected time points. Primary study outcomes are the postoperative occurrence of nosocomial infections, major adverse cardiac events, pulmonary complications, acute kidney injury and delirium/acute encephalopathy. Secondary outcomes include mortality and quality of life, as well as the long-term occurrence of psychopathology, cognitive dysfunction and chronic pain.

Findings to date

Enrolment of the first participant occurred early 2020. During the inception phase of the project (first 2 years), 431 patients were eligible of whom 297 patients consented to participate (69%). Observed event rate was 42% overall, with the most frequent complication being infection.

Future plans

The main purpose of the PLUTO biorepository is to provide a framework for research in the field of perioperative medicine and anaesthesiology, by storing high-quality clinical data and biomaterials for future studies. In addition, PLUTO aims to establish a logistical platform for conducting embedded clinical trials.

Trial registration number

NCT05331118.

Clinical spectrum of COVID-19 complications in young adults: combined analysis of the American Heart Association COVID-19 Cardiovascular Disease Registry and the Outcomes Registry for Cardiac Conditions in Athletes

Por: Bavishi · A. · Kliethermes · S. A. · Petek · B. · Moulson · N. · Mellacheruvu · P. · Churchill · T. W. · Harmon · K. · Patel · M. R. · Baggish · A. L. · Drezner · J. A. · Mutharasan · R. K.
Background

While young adults 18–24 years old bear a significant proportion of COVID-19 diagnoses, the risk factors for hospitalisation and severe COVID-19 complications in this population are poorly understood.

Objective

The objective of this study was to identify risk factors for hospitalisation and other COVID-19 complications across the health spectrum of young adults diagnosed with COVID-19 infection.

Study design

Retrospective cohort study.

Participants

Young adults (aged 18–24) with confirmed COVID-19 infection from the American Heart Association (AHA) COVID-19 Cardiovascular Disease Registry of hospitalised patients and the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study of collegiate athletes. The AHA registry included 636 young adults from 152 hospitals. The ORCCA registry consisted of 3653 competitive college athletes from 42 colleges and universities.

Intervention

None (exposure to COVID-19).

Primary and secondary outcome measures

Main outcomes included hospitalisation, death, major adverse cardiovascular events (MACE) and other severe clinical events.

Results

In comparison to the ORCCA registry, patients in the AHA registry were more likely to be female (59% vs 33%); had higher average body mass index (BMI) (32.4 vs 25.6); and had increased prevalence of diabetes (10% vs 0.4%), hypertension (7% vs 0.6%), chronic kidney disease (2% vs 0%) and asthma (14% vs 8%), all with p

Conclusions

The risk of cardiac events in young adults aged 18–24 diagnosed with COVID-19 infection is low. Patients who were hospitalised (AHA registry) were more likely to have pre-existing medical comorbidities and higher BMI than healthy collegiate athletes (ORCCA registry). Once hospitalised, elevated BMI is associated with increased mortality although other drivers of MACE and other severe clinical events remain unclear.

Knowledge, attitudes and practices of COVID-19 in rural Bangladesh: a cross-sectional study

Por: Siddiquea · B. N. · Afroz · A. · Chowdhury · M. R. K. · Savira · F. · Alif · S. M. · Bhattacharya · O. · Hossain · M. N. · Ali · L. · Chowdhury · H. A. · Shetty · A. · Islam · M. S. · Billah · B.
Objectives

Understanding the knowledge, attitudes and practices (KAP) of COVID-19 within distinct populations may aid further public health messaging. This study’s aims were to explore KAP towards COVID-19 in rural Bangladesh and identify any potential links to sociodemographics, existing clinical conditions and sources of information.

Design

Cross-sectional community-based study.

Setting

Participants were recruited from 18 villages using multistage cluster random sampling.

Methods

Data were collected through face-to-face interviews, from June to November 2021, using a structured questionnaire. Data included sociodemographics, clinical conditions, sources of information and KAP of COVID-19 questions. X2 test, multiple logistic regression and correlation analyses were performed.

Results

A total of 1603 participants were included with mean ages of 42.3±14.2 years, ranging from 18 to 60 years. Of these, 51% were male, 42.2% had secondary education and 45% had comorbidities. Television was the main source of COVID-19 information (55.8%). The overall correct response rate of KAP questions was 90%, 78% and 59%, respectively. In stepwise multiple logistic regression, good knowledge was associated with higher education (adjusted OR (AOR): 4.61, 95% CI: 2.40 to 8.85, p

Conclusion

This study uncovered gaps in understanding and practices, and identified targeted intervention especially for young and less educated people using mass media to promote updated knowledge regarding COVID-19 and the efficacy of preventive practices.

Interventions to reintroduce or increase assisted vaginal births: a systematic review of the literature

Por: Torloni · M. R. · Opiyo · N. · Altieri · E. · Sobhy · S. · Thangaratinam · S. · Nolens · B. · Geelhoed · D. · Betran · A. P.
Objective

To synthesise the evidence from studies that implemented interventions to increase/reintroduce the use of assisted vaginal births (AVB).

Design

Systematic review.

Eligibility criteria

We included experimental, semi-experimental and observational studies that reported any intervention to reintroduce/increase AVB use.

Data sources

We searched PubMed, EMBASE, CINAHL, LILACS, Scopus, Cochrane, WHO Library, Web of Science, ClinicalTrials.gov and WHO.int/ictrp through September 2021.

Risk of bias

For trials, we used the Cochrane Effective Practice and Organisation of Care tool; for other designs we used Risk of Bias for Non-Randomised Studies of Interventions.

Data extraction and synthesis

Due to heterogeneity in interventions, we did not conduct meta-analyses. We present data descriptively, grouping studies according to settings: high-income countries (HICs) or low/middle-income countries (LMICs). We classified direction of intervention effects as (a) statistically significant increase or decrease, (b) no statistically significant change or (c) statistical significance not reported in primary study. We provide qualitative syntheses of the main barriers and enablers for success of the intervention.

Results

We included 16 studies (10 from LMICs), mostly of low or moderate methodological quality, which described interventions with various components (eg, didactic sessions, simulation, hands-on training, guidelines, audit/feedback). All HICs studies described isolated initiatives to increase AVB use; 9/10 LMIC studies tested initiatives to increase AVB use as part of larger multicomponent interventions to improve maternal/perinatal healthcare. No study assessed women’s views or designed interventions using behavioural theories. Overall, interventions were less successful in LMICs than in HICs. Increase in AVB use was not associated with significant increase in adverse maternal or perinatal outcomes. The main barriers to the successful implementation of the initiatives were related to staff and hospital environment.

Conclusions

There is insufficient evidence to indicate which intervention, or combination of interventions, is more effective to safely increase AVB use. More research is needed, especially in LMICs, including studies that design interventions taking into account theories of behaviour change.

PROSPERO registration number

CRD42020215224.

Evaluation of COVID-19 vaccine acceptance and uptake in rural Bangladesh: a cross-sectional study

Por: Savira · F. · Alif · S. M. · Afroz · A. · Siddiquea · B. N. · Shetty · A. · Chowdhury · H. A. · Bhattacharya · O. · Chowdhury · M. R. K. · Islam · M. S. · Ali · L. · Billah · B.
Objective

The objective of this study was to evaluate the acceptance and uptake of COVID-19 vaccines in rural Bangladesh.

Design

This was a cross-sectional study conducted between June and November 2021.

Setting

This study was conducted in rural Bangladesh.

Participants

People older than 18 years of age, not pregnant and no history of surgery for the last 3 months were eligible to participate.

Primary and secondary outcomes

The primary outcomes were proportions of COVID-19 vaccine acceptance and roll-out participation among the rural population. The secondary outcome was identification of correlates which contributed to COVID-19 vaccine acceptance and roll-out participation. X2 tests and multivariable logistic regression analyses were performed to identify relevant correlates such as sociodemographic factors, clinical conditions and COVID-19-related factors.

Results

A total of 1603 participants were enrolled. The overall COVID-19 vaccine acceptance was very high (1521/1601, 95%), and half of the participants received at least one dose of the COVID-19 vaccine. Majority of participants wanted to keep others safe (89%) and agreed to the benefits of COVID-19 vaccines (88%). To fulfil the requirement of online registration for the vaccine at the time, 62% of participants had to visit an internet café and only 31% downloaded the app. Over half (54%) of participants were unaware of countries they knew and trust to produce the COVID-19 vaccine. Increased age, being housewives, underweight and undergraduate education level were associated with vaccine acceptance, while being female, increased age and being overweight/obese were associated with vaccine uptake. Trust in the health department and practical knowledge regarding COVID-19 vaccines were positively associated with both vaccine acceptance and uptake.

Conclusion

This study found a very high COVID-19 vaccine acceptance in rural Bangladesh. Policymakers should support interventions aimed at increasing vaccine and general health literacy and ensure ongoing vaccine supply and improvement of infrastructure in rural areas.

Impact of the COVID-19 pandemic on expectant and new parents experience of pregnancy, childbirth, breast feeding, parental responsiveness and sensitivity, and bonding and attunement in high-income countries: a systematic review of the evidence

Por: Adesanya · A. M. · Barrett · S. · Moffat · M. · Aquino · M. R. J. · Nicholson · W. · Turner · G. · Cook · E. · Tyndall · S. · Rankin · J.
Objectives

To review the evidence on how pregnancy, birth experience, breast feeding, parental responsiveness and sensitivity, and bonding and attunement were impacted by COVID-19.

Methods

We searched eight literature databases and websites of relevant UK-based organisations. The review focused on evidence during pregnancy and the early years (0–5 years). Studies of any study design published in English from 1 March 2020 to 15 March 2021 and conducted in high-income countries were included. Screening and data extraction were undertaken in duplicate. Evidence was synthesised using a narrative approach. Study quality of included studies was assessed using the Mixed Methods Appraisal Tool.

Results

The search yielded 9776 publications, of which 26 met our inclusion criteria. Significant knowledge gaps on how COVID-19 affected pregnancy and breast feeding limited healthcare providers’ ability to provide consistent evidence-based information and care at the start of the pandemic. There was an enduring sense of loss about loved ones being restricted from taking part in key moments. Parents were concerned about the limitations of virtual healthcare provision. Some parents reported more opportunities for responsive breast feeding and improved parent–infant bonding due to reduced social and work pressures. Women from minoritised ethnic groups were less likely to continue breast feeding and attributed this to a lack of face-to-face support.

Conclusions

The evidence suggests that new and expectant families have been both negatively and positively impacted by the COVID-19 pandemic and the resulting restrictions. The impacts on parents’ opportunities to bond with their young children and to be attuned to their needs were felt unequally. It is important that emergency response policies consider the mother and the partner as a family unit when making changes to the delivery of maternal and child health and care services, so as to mitigate the impact on the family and existing health inequalities.

PROSPERO registration number

CRD42021236769.

Cohort profile: Health trajectories of Immigrant Children (CRIAS)-a prospective cohort study in the metropolitan area of Lisbon, Portugal

Por: Muggli · Z. · Mertens · T. · Amado · R. · Teixeira · A. L. · Vaz · D. · Pires · M. · Loureiro · H. · Fronteira · I. · Abecassis · A. · Silva · A. C. · Martins · M. R. O.
Purpose

The CRIAS (Health trajectories of Immigrant Children in Amadora) cohort study was created to explore whether children exposed to a migratory process experience different health risks over time, including physical health, cognitive, socioemotional and behavioural challenges and different healthcare utilisation patterns.

Participants

The original CRIAS was set up to include 604 children born in 2015, of whom 50% were immigrants, and their parents. Recruitment of 420 children took place between June 2019 and March 2020 at age 4/5 years, with follow-up carried out at age 5/6 years, at age 6/7 years currently under way.

Findings to date

Baseline data at age 4/5 years (2019–2020) suggested immigrant children to be more likely to belong to families with less income, compared with non-immigrant children. Being a first-generation immigrant child increased the odds of emotional and behavioural difficulties (adjusted OR 2.2; 95% CI: 1.06 to 4.76); more immigrant children required monitoring of items in the psychomotor development test (38.5% vs 28.3%). The prevalence of primary care utilisation was slightly higher among immigrant children (78.0% vs 73.8%), yet they received less health monitoring assessments for age 4 years. Utilisation of the hospital emergency department was higher among immigrants (53.2% vs 40.6%). Age 5 years follow-up (2020–2021) confirmed more immigrant children requiring monitoring of psychomotor development, compared with non-immigrant children (33.9% vs 21.6%). Economic inequalities exacerbated by post-COVID-19 pandemic confinement with parents of immigrant children 3.2 times more likely to have their household income decreased.

Future plans

Further follow-up will take place at 8, 10, 12/13 and 15 years of age. Funds awarded by the National Science Foundation will allow 900 more children from four other Lisbon area municipalities to be included in the cohort (cohort-sequential design).

Sexual harassment before and during the COVID-19 pandemic among adolescent girls and young women (AGYW) in Nairobi, Kenya: a cross-sectional study

Por: Bevilacqua · K. G. · Williams · A. · Wood · S. N. · Wamue-Ngare · G. · Thiongo · M. · Gichangi · P. · Decker · M. R.
Objectives

Sexual harassment among adolescent girls and young women (AGYW) is a prevalent and understudied form of gender-based violence (GBV) with negative impacts on health and well-being. The COVID-19 pandemic raised global concern about GBV within homes; less is known about how it affected GBV in public spaces.

Methods

Present analyses use cross-sectional data from a cohort of adolescents and young adults residing in Nairobi, Kenya, restricted to female participants. Data were collected August–October 2020 via phone after implementation of COVID-19 restrictions. Prevalence of past-year sexual harassment and harassment relative to COVID-19 restrictions were calculated for overall sample, and by individual, household, and pandemic-related factors. Multivariate negative binomial regression models examine correlates of (1) past-year sexual harassment and (2) increases in sexual harassment relative to COVID-19 restrictions.

Results

Overall, 18.1% of AGYW experienced past-year sexual harassment at the 2020 survey. Among this group, 14.6% experienced sexual harassment pre-COVID-19 only, 18.8% after only and 66.6% at both time points. Among the latter group, 34.9% reported more occurrences following COVID-19 restrictions, 20.5% reported less occurrences and 44.7% reported no change in occurrence. Overall, 42.0% of AGYW experienced an increase in sexual harassment while 58.0% experienced no increase since COVID-19. In adjusted models, past-year sexual harassment was associated with higher educational attainment (adjusted risk ratio, aRR 2.11; 95% CI 1.27 to 3.52) and inability to meet basic financial needs (aRR 1.67; 95% CI 1.05 to 2.66). Increased sexual harassment since COVID-19 was associated with having full control to leave the home (aRR 1.69; 95% CI 1.00 to 2.90).

Conclusions

Sexual harassment among AGYW in Nairobi, Kenya was prevalent before and during COVID-19 restrictions. Safety in public spaces remains a highly gendered issue that impacts women’s safety and ability to participate in public life. Prevention and support services to address sexual harassment remain an important element in ensuring safe, sustainable public spaces.

Preterm delivery and its associated factors among mothers in Bangladesh: survey in Rajshahi district

Por: Hossain · M. A. · Al Mamun · A. S. M. · Aik · S. · Karim · M. R. · Zeshan · M. H. L. · Sabiruzzaman · M. · Islam · M. S. · Ahmed · S. · Hossain · M. G.
Objectives

Preterm delivery (PD) is a worldwide health burden particularly in low-income and middle-income countries such as Bangladesh. It is a key indicator of neonatal mortality and a risk of morbidity in later life. This study aimed to determine the prevalence of PD and its associated factors among mothers in Northern region of Bangladesh.

Setting and participants

Multistage sampling technique was used to select samples covering all the population from 9 Upazilas in Rajshahi district with 233 community clinics. A total of 540 mothers and their under-5 children were enrolled for the study. Descriptive statistics, 2 test and logistic regression model were used to analyse the data.

Results

Among all live births, the prevalence of PD was found to be 14.6%. Multiple binary logistic regression model suggested five factors of PD: (1) mothers who used contraceptive pill had lower chance of PD (p

Conclusion

Approximately one in seven infants was born preterm in our study area. Family planning method, number of antenatal care visit, mothers’ age at marriage and high fever during pregnancy were the most important predictors of PD, these factors could be considered to reduce PD among Bangladeshi mothers. PD risk could be reduced by counselling and encouraging women to take antenatal care facilities from trained health providers.

Key learnings from an outcome and embedded process evaluation of a direct to beneficiary mobile health intervention among marginalised women in rural Bihar, India

Por: Irani · L. · Verma · S. · Mathur · R. · Verma · R. K. · Mohan · D. · Dhar · D. · Seth · A. · Chaudhuri · I. · Chaudhury · M. R. · Purthy · A. · Nanda · A. · Singh · S. · Gupta · A. · LeFevre · A. E.
Introduction

Mobile Vaani was implemented as a pilot programme across six blocks of Nalanda district in Bihar state, India to increase knowledge of rural women who were members of self-help groups on proper nutrition for pregnant or lactating mothers and infants, family planning and diarrhoea management. Conveners of self-help group meetings, community mobilisers, introduced women to the intervention by giving them access to interactive voice response informational and motivational content. A mixed methods outcome and embedded process evaluation was commissioned to assess the reach and impact of Mobile Vaani.

Methods

The outcome evaluation, conducted from January 2017 to November 2018, used a quasi-experimental pre–post design with a sample of 4800 married women aged 15–49 from self-help group households, who had a live birth in the past 24 months. Surveys with community mobilisers followed by meeting observations (n=116), in-depth interviews (n=180) with self-help group members and secondary analyses of system generated data were conducted to assess exposure and perceptions of the intervention.

Results

From the outcome evaluation, 23% of women interviewed had heard about Mobile Vaani. Women in the intervention arm had significantly higher knowledge than women in the comparison arm for two of seven focus outcomes: knowledge of how to make child’s food nutrient and energy dense (treatment-on-treated: 18.8% (95% CI 0.4% to 37.2%, p

Conclusion

Low population awareness and programme exposure are underpinned by broader population level barriers to mobile phone access and use among women and missed opportunities by the programme to improve targeting and programme promotion. Further research is needed to assess programmatic linkages with changes in health practices.

18F-FDG-PET hypometabolism as a predictor of favourable outcome in epilepsy surgery: protocol for a systematic review and meta-analysis

Por: Courtney · M. R. · Antonic-Baker · A. · Sinclair · B. · Nicolo · J.-P. · Neal · A. · Law · M. · Kwan · P. · O'Brien · T. J. · Vivash · L.
Introduction

A substantial proportion of patients who undergo surgery for drug resistant focal epilepsy do not become seizure free. While some factors, such as the detection of hippocampal sclerosis or a resectable lesion on MRI and electroencephalogram-MRI concordance, can predict favourable outcomes in epilepsy surgery, the prognostic value of the detection of focal hypometabolism with 18F-fluorodeoxyglucose positive emission tomography (18F-FDG-PET) hypometabolism is uncertain. We propose a protocol for a systematic review and meta-analysis to examine whether localisation with 18F-FDG-PET hypometabolism predicts favourable outcomes in epilepsy surgery.

Methods and analysis

A systematic literature search of Medline, Embase and Web of Science will be undertaken. Publications which include evaluation with 18F-FDG-PET prior to surgery for drug resistant focal epilepsy, and which report ≥12 months of postoperative surgical outcome data will be included. Non-human, non-English language publications, publications with fewer than 10 participants and unpublished data will be excluded. Screening and full-text review of publications for inclusion will be undertaken by two independent investigators, with discrepancies resolved by consensus or a third investigator. Data will be extracted and pooled using random effects meta-analysis, with heterogeneity quantified using the I2 analysis.

Ethics and dissemination

Ethics approval is not required. Once complete, the systematic review will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42022324823.

Adolescents hospitalised for suicidality: biomarkers, social and affective predictors: a cohort study

Por: Nugent · N. R. · Armey · M. · Boker · S. · Brick · L. · Knopik · V. · McGeary · J. E. · Spirito · A. · Mehl · M. R.
Objectives

The present research examines genomics and in vivo dynamics of family context and experienced affect following discharge from psychiatric hospitalisation for suicidal thoughts and behaviours (STBs). The purpose of this paper is to provide an overview of a new model, description of model-guided integration of multiple methods, documentation of feasibility of recruitment and retention and a description of baseline sample characteristics.

Design

The research involved a longitudinal, multimethod observational investigation.

Setting

Participants were recruited from an inpatient child and adolescent psychiatric hospital. 194 participants ages 13–18 were recruited following hospitalisation for STB.

Primary and secondary outcome measures

Participants underwent a battery of clinical interviews, self-report assessments and venipuncture. On discharge, participants were provided with a phone with (1) the electronically activated recorder (EAR), permitting acoustic capture later coded for social context, and (2) ecological momentary assessment, permitting assessment of in vivo experienced affect and STB. Participants agreed to follow-ups at 3 weeks and 6 months.

Results

A total of 71.1% of approached patients consented to participation. Participants reported diversity in gender identity (11.6% reported transgender or other gender identity) and sexual orientation (47.6% reported heterosexual or straight sexual orientation). Clinical interviews supported a range of diagnoses with the largest proportion of participants meeting criteria for major depressive disorder (76.9%). History of trauma/maltreatment was prevalent. Enrolment rates and participant characteristics were similar to other observational studies.

Conclusions

The research protocol characterises in vivo, real-world experienced affect and observed family context as associated with STB in adolescents during the high-risk weeks post discharge, merging multiple fields of study.

Factors affecting vaccination demand in Indonesia: a secondary analysis and multimethods national assessment

Por: Jusril · H. · Rachmi · C. N. · Amin · M. R. · Dynes · M. · Sitohang · V. · Untung · A. S. B. · Damayanti · R. · Ariawan · I. · Pronyk · P. M.
Objectives

Vaccine hesitancy remains a major barrier to immunisation coverage worldwide. We explored influence of hesitancy on coverage and factors contributing to vaccine uptake during a national measles–rubella (MR) campaign in Indonesia.

Design

Secondary analyses of qualitative and quantitative data sets from existing cross-sectional studies conducted during and around the campaign.

Methods

Quantitative data used in this assessment included daily coverage reports generated by health workers, district risk profiles that indicate precampaign immunisation programme performance, and reports of campaign cessation due to vaccine hesitancy. We used t-test and 2 tests for associations. The qualitative assessment employed three parallel national and regional studies. Deductive thematic analysis examined factors for acceptance among caregivers, health providers and programme managers.

Results

Coverage data were reported from 6462 health facilities across 395 districts from 1 August to 31 December 2018. The average district coverage was 73%, with wide variation between districts (2%–100%). One-third of districts fell below 70% coverage thresholds. Sixty-two of 395 (16%) districts paused the campaign due to hesitancy. Coverage among districts that never paused campaign activities due to hesitancy was significantly higher than rates for districts ever-pausing the campaign (81% vs 42%; p

Conclusion

Barriers to vaccine uptake contributed to coverage gaps during national MR campaign in Indonesia. A range of supply-related and demand-related strategies were identified to address hesitancy contributors. Advancing a portfolio of tailored multilevel interventions will be critical to enhance vaccine acceptance.

Educational inequalities in adult mortality: a systematic review and meta-analysis of the Asia Pacific region

Por: Beck · K. C. · Balaj · M. · Donadello · L. · Mohammad · T. · Vonen · H. D. · Degail · C. · Eikemo · K. · Giouleka · A. · Gradeci · I. · Westby · C. · Sripada · K. · Jensen · M. R. · Solhaug · S. · Gakidou · E. · Eikemo · T. A.
Objectives

In this study, we aim to analyse the relationship between educational attainment and all-cause mortality of adults in the high-income Asia Pacific region.

Design

This study is a comprehensive systematic review and meta-analysis with no language restrictions on searches. Included articles were assessed for study quality and risk of bias using the Joanna Briggs Institute critical appraisal checklists. A random-effects meta-analysis was conducted to evaluate the overall effect of individual level educational attainment on all-cause mortality.

Setting

The high-income Asia Pacific Region consisting of Japan, South Korea, Singapore and Brunei Darussalam.

Participants

Articles reporting adult all-cause mortality by individual-level education were obtained through searches conducted from 25 November 2019 to 6 December 2019 of the following databases: PubMed, Web of Science, Scopus, EMBASE, Global Health (CAB), EconLit and Sociology Source Ultimate.

Primary and secondary outcome measures

Adult all-cause mortality was the primary outcome of interest.

Results

Literature searches resulted in 15 345 sources screened for inclusion. A total of 30 articles meeting inclusion criteria with data from the region were included for this review. Individual-level data from 7 studies covering 222 241 individuals were included in the meta-analyses. Results from the meta-analyses showed an overall risk ratio of 2.40 (95% CI 1.74 to 3.31) for primary education and an estimate of 1.29 (95% CI 1.08 to 1.54) for secondary education compared with tertiary education.

Conclusion

The results indicate that lower educational attainment is associated with an increase in the risk of all-cause mortality for adults in the high-income Asia Pacific region. This study offers empirical support for the development of policies to reduce health disparities across the educational gradient and universal access to all levels of education.

PROSPERO registration number

CRD42020183923.

Diabetes among adults in Bangladesh: changes in prevalence and risk factors between two cross-sectional surveys

Por: Chowdhury · M. A. B. · Islam · M. · Rahman · J. · Uddin · M. J. · Haque · M. R.
Objective/research question

To investigate the change in the prevalence and risk factors of diabetes among adults in Bangladesh between 2011 and 2018.

Design

The study used two waves of nationally representative cross-sectional data extracted from the Bangladesh Demographic and Health Surveys in 2011 and 2017–2018.

Setting

Bangladesh.

Participants

14 376 adults aged ≥35 years.

Primary outcome

Diabetes mellitus (type 2 diabetes).

Results

From 2011 to 2018, the diabetes prevalence among adults aged ≥35 years increased from 10.95% (880) to 13.75% (922) (p

Conclusion

A high prevalence of diabetes was observed and it has been steadily increasing over time. To enhance diabetes detection and prevention among adults in Bangladesh, population-level interventions focusing on health education, including a healthy diet and lifestyle, are required.

Comparative-effectiveness research of COVID-19 treatment: a rapid scoping review

Por: Pham · B. · Rios · P. · Radhakrishnan · A. · Darvesh · N. · Antony · J. · Williams · C. · Ramkissoon · N. · Cormack · G. V. · Grossman · M. R. · Kampman · M. · Patel · M. · Yazdi · F. · Robson · R. · Ghassemi · M. · Macdonald · E. · Warren · R. · Muller · M. P. · Straus · S. E. · Tricco · A
Objectives

The COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment.

Design

Rapid scoping review

Data sources

Medline, Embase and biorxiv/medrxiv from inception to 15 May 2021.

Setting

Hospital and community care.

Participants

COVID-19 patients of all ages.

Interventions

COVID-19 treatment.

Results

The literature search identified 616 relevant primary studies of which 188 were randomised controlled trials and 299 relevant evidence syntheses. The studies and evidence syntheses were conducted in 51 and 39 countries, respectively.

Most studies enrolled patients admitted to acute care hospitals (84%), included on average 169 participants, with an average age of 60 years, study duration of 28 days, number of effect outcomes of four and number of harm outcomes of one. The most common primary outcome was death (32%).

The included studies evaluated 214 treatment options. The most common treatments were tocilizumab (11%), hydroxychloroquine (9%) and convalescent plasma (7%). The most common therapeutic categories were non-steroidal immunosuppressants (18%), steroids (15%) and antivirals (14%). The most common therapeutic categories involving multiple drugs were antimalarials/antibiotics (16%), steroids/non-steroidal immunosuppressants (9%) and antimalarials/antivirals/antivirals (7%). The most common treatments evaluated in systematic reviews were hydroxychloroquine (11%), remdesivir (8%), tocilizumab (7%) and steroids (7%).

The evaluated treatment was in favour 50% and 36% of the evaluations, according to the conclusion of the authors of primary studies and evidence syntheses, respectively.

Conclusions

This rapid scoping review characterised a growing body of comparative-effectiveness primary studies and evidence syntheses. The results suggest future studies should focus on children, elderly ≥65 years of age, patients with mild symptoms, outpatient treatment, multimechanism therapies, harms and active comparators. The results also suggest that future living evidence synthesis and network meta-analysis would provide additional information for decision-makers on managing COVID-19.

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