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Zahra Aghapour,1,2 Pourya Gholizadeh,3 Khudaverdi Ganbarov,4 Abed Zahedi Bialvaei,5 Suhad Saad Mahmood,6 Asghar Tanomand,7 Mehdi Yousefi,8 Mohammad Asgharzadeh,9 Bahman Yousefi,9 Hossein Samadi Kafil11Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 3Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 4Department of Microbiology, Baku State University, Baku, Azerbaijan; 5Department of Microbiology, Iran University of Medical Sciences, Tehran, Iran; 6Department of Biotechnology, College of Science, University of Baghdad, Baghdad, Iraq; 7Department of Microbiology, Maragheh University of Medical Sciences, Maragheh, Iran; 8Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 9Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, IranAbstract: Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance.Keywords: colistin, Enterobacteriaceae, two-component system, lipid A, mcr genes

Equity and gender, despite being universal concerns for all health programmes in Bangladesh, are often missing in many of the health agenda. The health programmes fail to address these important dimensions unless these are specifically included in the planning stage of a programme and are continually monitored for progress. This paper presents the situation of equity in health in Bangladesh, innovations in monitoring equity in the use of health services in general and by the poor in particular, and impact of targeted non-health interventions on health outcomes of the poor. It was argued that an equitable use of health services might also result in enhanced overall coverage of the services. The findings show that government services at the upazila level are used by the poor proportionately more than they are in the community, while at the private facilities, the situation is reverse. Commonly-used monitoring tools, at times, are not very useful for the programme managers to know how well they are doing in reaching the poor. Use of benefit-incidence ratio may provide a quick feedback to the health facility managers about their extent of serving the poor. Similarly, Lot Quality Assurance Sampling can be an easy-to-use tool for monitoring coverage at the community level requiring a very small sample size. Although health problems are biomedical phenomena, their solutions may include actions beyond the biomedical framework. Studies have shown that non-health interventions targeted towards the poor improve the use of health services and reduce mortality among children in poor households. The study on equity and health deals with various interlocking issues, and the examples and views presented in this paper intend to introduce their importance in designing and managing health and development programmes. [ABSTRACT FROM AUTHOR]

Background: Upazila Health Complexes (UzHC) serve as the backbone of primary healthcare (PHC) at the sub-district level in Bangladesh, delivering comprehensive healthcare services including both inpatient and outpatient services to the grassroots levels. However, not all the prescribed medicines and diagnostics services are always available at these facilities for outpatient care. This results in out-of-pocket expenditure (OOPE) to the patients for getting prescribed medicines and diagnostics services which has not been properly explored. Thus, we aimed to estimate the overall provider and user costs for outpatient care services at selected UzHCs in Bangladesh., Methods: An ingredient-based costing approach was applied to estimate the costs for the most commonly reported illnesses at outpatient of UzHCs from a societal perspective. We conducted a health facility survey at four purposively selected UzHCs to estimate provider costs and a patient exit survey among 452 patients of selected illnesses to estimate the user costs. Commonly reported illnesses were identified in consultation with healthcare providers of these facilities. The difference between costs of prescribed and provided medicines at UzHCs was estimated using the market prices. Data was collected between February to March 2021., Results: The societal costs of the common outpatient illness or symptoms varied significantly, ranging from BDT 642 to BDT 1,384 per episode. Antenatal care had the highest cost burden at BDT 1,384, followed by respiratory illness at BDT 783 and urinary tract infection at BDT 670. On average, the provider spent BDT 289 for treating an outpatient, while a patient incurred BDT 446 as OOPE. Further, a patient was expected to spend an average of BDT 341 for purchasing medicines not provided from UzHCs., Conclusion: Our study found significant gaps between prescribed and provided medicines at UzHCs, leading to higher OOPE for patients. The current healthcare resource allocation strategy does not consider the outpatient load and healthcare demand at PHC facilities, which further exacerbates this gap. Addressing this gap requires a fundamental shift towards a demand-driven resource allocation model within the healthcare financing strategy to improve healthcare access and achieve health for all., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Hasan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction Autism spectrum disorder (ASD) is a complicated disorder that affects communication, social interaction, and behavior. Several investigations have documented increased oxidative stress and damage in individuals with ASD compared with neurotypical controls. Saliva can be used as a non-invasive technique to assess oxidative stress biomarkers. This study aimed to explore the association between oxidative stress and oral health in a sample of high-functioning children with autism in Erbil City. Methods We conducted a case-control study with 96 participants aged 5-12 years, which included 48 children with ASD and 48 healthy controls. Stimulated saliva samples were collected and centrifuged. Oxidative stress biomarkers (malondialdehyde [MDA], glutathione [GSH], and uric acid) and gingival/plaque indices were also measured. Data were analyzed using SPSS, with significance set at p≤0.05. Results The data showed no significant differences between the ASD and control groups in the gingival index, salivary malondialdehyde, glutathione, or uric acid levels. However, the control group had a significantly higher mean plaque index than the ASD group (P = 0.003). Conclusion Sample size and confounding variables may influence the absence of significant differences in gingival index and salivary oxidative stress biomarkers between groups. The higher plaque index in controls aligns with plaque gingivitis. Age differences could impact oral health interpretations. Further research is needed to understand significant factors and the clinical significance of these findings in pediatric ASD populations. Most autistic children were from educated families and had good oral hygiene in addition to special care by the staff of the center., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics and Scientific Committee of Kurdistan Higher Council of Medical Specialties for Scientific issued approval 2275-08/12/ 2022. This study was submitted to the Ethics and Scientific Committee of the Kurdistan Higher Council of Medical Specialties for scientific and ethical approval, which was achieved (2275-08/12/2022). This study was explained to the parents, and written consent was obtained. Confidentiality and anonymity of data were ensured. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mahmood et al.)

This paper presents and elaborates on empirical methods and approaches used to identify Zero-Dose (ZD) and Under-immunized (UI) children as well as the communities that these children reside in within Bangladesh. This paper also describes demand- and supply side-barriers that lead to children being ZD and UI in the country. Time period for the study was December 2022-May 2023. The study methodology encompassed secondary data analysis using data from national surveys, primary data collection and analysis via a lot quality assurance sampling (LQAS) survey and also, qualitative data collection and analysis. Study population included caregivers of children aged 4.5 months (4 months 15 days) to 23 months for the LQAS survey. The qualitative component included policymakers, program managers and service providers working in immunization as well as mothers in the selected study areas who had a living child aged less than 2 years as the study population. Our data analysis confirms existence of ZD and UI children in areas which were categorized into haor (wetlands), hilly, char (sandy/silty land surrounded by water), coastal, plain land and urban slums. Determinant analysis showed that the mother's level of education, antenatal visits made, and access to media were significantly associated with children being ZD or UI. Reproductive autonomy emerged as a key factor that had prominent impact on a child being ZD. The qualitative analysis indicated the importance of population migration, health workforce shortages and lack of access to transportation as prominent barriers to immunization. Notably, the methods and approaches used in this study are both effective and easily replicable to identify ZD and UI children. The drivers of ZD and UI along with the barriers to immunization provide potential areas for intervention by policy-makers and can apprise about interventions to be tested in future implementation research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jannat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Bangladesh is rapidly urbanizing and approximately half of its urban population resides in deprived slums with limited access to basic needs. However, there is a dearth of information on vulnerability levels among slum dwellers. We aimed to assess the level of vulnerability within and between slums via various socioeconomic and health indicators., Methods: A cross-sectional survey of 810 randomly selected households was conducted in two purposively selected slums, Korail and Shyampur, in Dhaka from November to December 2021. Data was collected on various indicators, including demographics, education, employment, access to utility, and healthcare services. Principal component factor analysis was employed to identify the key indicators to construct the socioeconomic and health vulnerability index for the urban slums of Bangladesh (SEHVI-BD). Kaiser-Meyer-Olkin, Bartlett's test, and Cronbach's alpha coefficient test were used to assess indicators' suitability. The selected indicators were used to generate an index on a scale of 100, with a higher index value indicating a higher level of vulnerability. The estimated scores were used to categorize the vulnerability status into three levels: mild, moderate, and severe vulnerability. The Mann-Whitney-U test and Kruskal-Wallis test were applied between the generated index and other socioeconomic variables to validate the relationship., Results: A total of 27 socioeconomic and health indicators were identified that explained 60% of the variance. The indicators were then grouped into six domains on the basis of their relevance. The prevalence of severe vulnerability in the Korail slum was approximately 9% and moderate vulnerability was 30% whereas these values were approximately 58% and 37%, respectively, in the Shyampur slum. The difference in the vulnerability level between the two slums was also evident across the domains. Households in the poorest wealth quintile, with lower education levels of household heads, and having irregular income experienced higher levels of vulnerability., Conclusions: The SEHVI-BD offers a critical tool for policymakers to identify and address vulnerabilities, facilitating more targeted public health interventions in urban Bangladesh and similar low-income settings. This study further emphasizes the importance of integrating comprehensive vulnerability assessments into public health policies to reduce inequalities and improve well-being, especially for the urban marginalized slum population., (© 2024. The Author(s).)

Objective: The COVID-19 pandemic imposed unprecedented challenges to health systems globally. This study explored slum dwellers' experience of receiving essential health services during the pandemic and the challenges faced by healthcare providers in urban areas of Bangladesh., Design: The study followed a cross-sectional study design using qualitative methods., Setting: The study was conducted in Dhaka and Gazipur City Corporations during November 2020-February 2021., Participants: 17 key informant interviews were carried out with healthcare providers and policy-makers and 22 in-depth interviews were carried out with slum dwellers. Thematic analysis was performed., Results: The study identified challenges to the provision of essential healthcare in selected areas of Dhaka and Gazipur City Corporations during the COVID-19 pandemic. The lack of information on the availability of functional healthcare facilities, fear of contracting COVID-19 and restrictions on movement and transportation, resulted in delays in seeking essential healthcare during a pandemic. Access to healthcare facilities was further hindered by various hospitals' decision to refuse care to general patients without valid, negative COVID-19 test results. Healthcare providers identified patients' tendency to hide COVID-19 symptoms as a barrier to providing healthcare services to general patients. Conversely, patients concealed their symptoms to avoid COVID-19 tests and gain access to required treatment. In addition, the reallocation of human resources for COVID-19 treatment disrupted the delivery of essential health services., Conclusion: The pandemic affected the accessibility of the slum population to essential healthcare and disrupted health service delivery. The findings of the study have highlighted gaps in the health system during an emergency response period like COVID-19. The study will assist the government and other stakeholders in designing tailored interventions and allocating resources in a more efficient manner to ensure universal health coverage in the face of health emergencies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bangladesh has made substantial progress in maternal health. However, persistent inequities in service use undermine the achievements at the national level. In 2007, the government introduced a Maternal Health Voucher Scheme (MHVS) to reduce barriers to service utilization. The current study explores the impact of MHVS on reducing distance inequality in utilization across the maternal and newborn continuum of care (MNCoC)., Methods: A cross-sectional survey was conducted from October'2017 to April'2018 in four selected MHVS sub-districts of Chattogram and Sylhet Divisions of Bangladesh. 2,400 women with at-least one child aged below two years were randomly selected. Both bivariate and multivariate analyses were carried out to explore the absolute and relative influence of the voucher scheme and chi-square test was used for hypothesis testing., Results: Nineteen percent of the women were MHVS beneficiaries and 23% of them lived within 5 km of the health facility. Among the beneficiaries no significant differences were observed in the utilization of at-least 4 antenatal visits, skilled-assistance at delivery, postnatal care, and MNCoC between those living closer to the health facility and those living far away. However, a higher facility delivery rate was observed among beneficiary women living closer. By contrast, for non-beneficiaries, a significant difference was found in service use between women living closer to health facilities compared to those living further away., Conclusion: The study found the use of MNCoC to be similar for all MHVS beneficiaries irrespective of their distance to health facilities whereas non-beneficiary women living further away had lower utilization rates. MHVS could have potentially reduced distance-related inequality for its beneficiaries. However, despite the provision of transport incentives under MHVS the reduction in inequality in facility delivery was limited. We propose a revision of the transportation incentive adjusting for distance, geographical remoteness, road condition, and transport cost to enhance the impact of MHVS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chowdhury et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Our study explored the impact of the COVID-19 pandemic on the food environment from the perspective of the urban poor and food vendors., Design: This was a qualitative study conducted during September 2020 and February 2021., Setting: The study was carried out in two purposively selected informal settlements of Dhaka City, Bangladesh., Participants: We conducted 21 in-depth interviews with residents of informal settlements and 10 key informant interviews with food vendors and food aid workers., Result: The availability of staple foods was not disrupted during the pandemic but some perishables foods became more expensive due to supply chain disruptions and increased transportation costs. Limited market hours affected market access and mobility restrictions adversely affected local vendors. Cart vendors selling perishables incurred business losses they could ill afford. Demand for food reduced as employment disruption lead to reduced purchasing power and, therefore, reduction of quantity, quality and desirability of foods purchased. Respondents reported skipping meals and going hungry. The aid received was considered inadequate to meet needs., Conclusion: The food environment of the urban poor was disrupted from both supply and demand sides and the organisational response (both government and non-government) was severely inadequate. The social safety net needs to be extended and redesigned to ensure food security and health for the urban working poor in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiovascular events have been reported to occur in one in five patients receiving chimeric antigen receptor T-cell (CAR-T) therapy. Commonly reported effects including cardiomyopathy, heart failure, myocardial infarction (MI), and arrhythmia. Here, we present a novel case of a patient who developed acute ST segment elevations during CAR-T cell infusion., Case Summary: A 76-year-old man with diffuse large B cell lymphoma was admitted for an investigational CD-19 directed, autologous CAR-T cell therapy. Less than 5 min into the CAR-T cell infusion, he developed severe chest pain, dyspnea, flushing, hypotension, and tachycardia. Electrocardiogram (EKG) showed inferior ST elevations and reciprocal lateral ST depressions. Emergent coronary angiography revealed mild non-obstructive coronary disease. ST segment changes and patient symptoms resolved after catheterization., Discussion: Given the complete resolution of symptoms and EKG abnormalities in the context of non-obstructive coronary artery disease, this clinical presentation was thought to be most consistent with ST elevation MI due to coronary vasospasm. The mechanism of this vasospasm is as yet not understood and may be related to an anaphylactic reaction or a cardiotoxicity related to the cell therapy agent. As the use of CAR-T therapy continues to expand, there is a need to further characterize the full spectrum of its cardiotoxic effects., Competing Interests: Conflict of interest: S.S.M. has received advisory fees from Nektar Therapeutics, Health & Wellness Partners, Medicure. All other authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient's immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality., Methods and Results: From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104-647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan-Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6-4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4-8.8) after adjusting for cancer burden., Conclusion: Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin., Competing Interests: Conflict of interest S.S.M. has received consulting fees from Nektar Therapeutics, Health & Wellness Partners, Medicure. P.A.R. has received consulting fees from AbbVie, BMS, Janssen, Novartis, BeiGene, Kite/Gilead, Intellia Therapeutics, Sana Biotechnology, CVS Caremark, Genmab, Pharmacyclics, Takeda, Karyopharm, Nektar Therapeutics, Nurix Therapeutics, and ADC Therapeutics. M.A.P. reports consulting fees from Adicet, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma, is participating in DSMB of Cidara Therapeutics, Medigene, and Sellas Life Sciences, and is on the scientific advisory board of NexImmune and Omeros. M.B.G. has received institutional grant funding from Sanofi, Amgen, and Actinium and consulting fees from Sanofi, Novartis, and Allogene. M.L.P. has received royalties from Juno and Sers and consulting fees from Novartis, Cellectar, Synthekine, Kite, Seres, Magenta, WindMIL, Rheos, Nektar, Notch, Priothera, Ceramedix, Lygenesis, and Pluto. R.S. has received consulting fees from Mudexus and MyBiotics. G.S. has received research funding from Janssen, Amgen, Beyond Spring, and BMS and is on DSMB of ArcellX. E.H.Y. has received institutional grand funding from CSL Behring, Boehringer Ingelheim, BMS and Eli and Lilly and consulting fees from Pfizer. J.P.L. has received institutional grants from Genentech, Janssen, and Epizyme and consulting fees from Abbvie, Astellas, AstraZeneca, Bayer, Beigene, BMS, Calithera, Constellation, Caribou Biosciences, Eisai, Lilly, Epizyme, Genmab, Grail, Incyte, Jansssen, MEI Pharma, Merck, Mustang Bio, Novartis, Pfizer, Roche/Genentech, Seagen, Second Genome, Sutro, ADC Therapeutics, Miltenyi, and Karyopharm. T.G.N. has received consulting fees from BMS, Genentech, Abbvie, Roche, CRO Oncology, and Sanofi and participates in DSMB of Genentech and received research grant funding from AstraZeneca and BMS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Bangladesh National Tuberculosis (TB) Control Programme (NTP) has deployed improved diagnostic technologies which may drive up the programme costs. We aimed to estimate the supply-side costs associated with the delivery of the NTP and the funding gap between the cost of implementation and available funding for the Bangladesh NTP., Methods: An ingredient-based costing approach was applied using WHO's OneHealth Tool software. We considered 2016, as the base year and projected cost estimates up to 2022 using information on NTP planned activities. Data were collected through consultative meetings with experts and officials/managers, review of documents and databases, and visits to five purposively selected TB healthcare facilities. The estimated costs were compared with the funds allocated to the NTP between 2018 and 2022 to estimate the funding gap., Findings: The estimated total cost of NTP was US$ 49.22 million in 2016, which would increase to US$ 146.93 million in 2022. Human resources (41.1%) and medicines and investigations/ supplies (38.0%) were the major two cost components. Unit costs were highest for treating extensively drug-resistant TB at US$ 7,422.4 in 2016. Between 2018-2022, NTP would incur US$ 536.8 million, which is US$ 235.18 million higher than the current allocation for NTP., Conclusion: Our results indicated a funding gap associated with the NTP in each of the years between 2018-2022. Policy planners should advocate for additional funding to ensure smooth delivery of TB services in the upcoming years. The cost estimates of TB services can also be used for planning and budgeting for delivering TB services in similar country contexts., Competing Interests: All other authors declare no conflicts of interest., (Copyright: © 2023 Hasan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bangladesh initiated the Maternal Health Voucher Scheme (MHVS) in 2007 to improve maternal and child health practices and bring equity to the mainstream of health systems by reducing financial and institutional barriers. In this study, we investigated whether the MHVS has an association with immunization coverage in a rural area of Bangladesh. Between 30 October 2016 and 15 June 2017, we carried out a cross-sectional survey in two low performing areas in terms of immunization coverage- Chattogram (erstwhile Chittagong division) and Sylhet division of Bangladesh. We calculated the coverage of fully immunized children (FIC) for 1151 children aged 12-23 months of age. We compared the coverage of FIC between children whose mothers enrolled in MHVS and children whose mother did not. We analyzed immunization coverage using crude odds ratio (OR) and adjusted OR (aOR) from binary logistic regression models. The overall coverage of FIC was 86%. Ninety-three percent children whose mothers were MHVS members were fully immunized whereas the percentage was 84% for the children of mothers who were not enrolled in MHVS. Multivariate analysis also shows that FIC coverage was higher for children whose mothers enrolled in MHVS compared to those children whose mothers did not; the aOR was 2.03 (95% confidence interval 1.11-3.71). MHVS provides a window for non-targeted benefits of childhood vaccination. Providing health education to pregnant mothers during prenatal care may motivate them to immunize their children. Programmes targeted for mothers during pregnancy, childbirth and post-natal may further increase utilization of priority health services such as childhood immunization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sultana, Hossain, Das, Pallikadavath, Koeryaman, Rahman, Chowdhury, Bhuiya, Mahmood and Hanifi.)

This study aimed to compare the zinc (Zn) nanoparticles obtained from plant extracts with different zinc sources and to reveal the effects of different Zn sources on growth performance, egg quality traits and blood serum parameters of laying quail. Treatment groups as follows: control and 3 and 6 mg/kg inorganic, organic, and plant extract-derived nano-Zn particles to quail diet supplementation. Animals were fed on experimental diets for 6 weeks. Different Zn sources supplemented into quail diets did not significantly affect live weights (P > 0.05). On the other hand, different Zn sources increased egg yields (P < 0.05). Plant extract-derived nano-Zn supplementations into quail diets increased feed consumption, feed conversion ratio, and egg weights (P < 0.05). However, 6 mg/kg plant extract-derived nano-Zn supplementations reduced egg weights. Different Zn sources did not have any significant effects on egg yolk weight (g) and egg yolk color L*b* values (P > 0.05). For blood serum parameters, 6 mg/kg plant extract-derived nano-Zn supplementations increased blood serum AST, ALT, and Zn values (P < 0.05). No adverse effect was observed on the measured values in laying Japanese quails. The findings suggest that plant extract-derived nano-Zn particles could reliably be used in quail feeding., (© 2023 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)

Background: Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS., Objectives: This study aimed to detail the role of GCS and GRS in ICI myocarditis., Methods: In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death., Results: Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002)., Conclusions: GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health (P30CA008748 to DG and CLC; R01HL137562, R01HL130539; and T32HL007208-39 to DAZ). Dr Mahmood has received consultancy fees from Health and Wellness Partners, OMR Globus, Alpha Detail, and Opinion Research Team. Dr Zhang is consultant for MERCK. Dr Sullivan has served as a consultant for Merck and Novartis. Dr Heinzerling has received consultancy, advisory board, and speaker fees from Merck Sharp & Dohme, BMS, Roche, Novartis, Amgen, Sun Pharma, Pierre Fabre, and CureVac. Dr Gavira has received research support from Amgen. Dr Zubiri has served as a consultant to Merck and is supported by a SEOM (Sociedad Española de Oncología Médica) grant. Dr Yang has received research funding from CSL Behring. Dr Nohria has received research support from Amgen and has been a consultant for Takeda Oncology, Boehringer Ingelheim, and AstraZeneca; and he has received support from the Catherine Geoff Fitch fund and Gelb Master Clinician Fund. Dr Fradley has received consulting fees from AstraZeneca and Abbott and has received a research grant from Medtronic. Dr Neilan is supported by a gift from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, and a Hassenfeld Scholar Award; has received advisory fees from AbbVie, Amgen, C4 Therapeutics, H3-Biomedicine, Genentech, Roche, BMS, and Intrinsic Imaging; has received grant funding from AstraZeneca; and he is also supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL130539, R01HL137562, K24HL150238). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. All rights reserved.)

The first COVID-19 case in Bangladesh was detected on March 8, 2020. Since then, efforts are being made across the country to raise awareness among the population for preventing the spread of this virus. We aimed to examine the urban slum dwellers' knowledge, attitude, and practice (KAP) towards COVID-19 transmission-prevention. A phone-based cross-sectional survey was conducted in five slums of Dhaka City. Total 476 adult slum dwellers were interviewed between October 31 to December 1, 2020 using a pre-tested questionnaire. During an interview, information was collected on participants' demographic characteristics and KAP items towards COVID-19. We used quartiles for categorization of knowledge and practice score where the first quartile represents poor, the second and third quartiles represent average while the fourth quartile represents good. Attitude score was standardized using z-score and identified as positive and negative attitude. Multiple linear regression models were used separately to identify the socioeconomic predictors of the KAP scores. The results showed that 25% of the respondents had good knowledge and 25% had poor knowledge, 48% had a positive attitude and 52% had a negative attitude, and 21% maintained good practice and 33% maintained poor practice towards COVID-19 transmission-prevention. About 75% respondents relied on television for COVID-19 related information. Regression results showed that knowledge and attitude scores were significantly higher if respondents had primary or secondary and above level of education compared to the uneducated group. Female respondents maintained significantly good practice compared to their male counterparts (β = 6.841; p<0.01). This study has found that one third of the studied slum dwellers maintained poor practice and one fourth had poor knowledge towards COVID-19 transmission-prevention. As KAP domains are significantly correlated, efforts are needed to raise awareness of COVID-19 particularly targeting individuals with average and lower knowledge to improve attitude and practice for the prevention of COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Hasan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: We aimed to rapidly assess the health system impact of COVID-19 in the urban slums of Bangladesh., Design: Setting and participants A cross-sectional survey among 476 households was conducted during October-December 2020 in five selected urban slums of Dhaka North, Dhaka South and Gazipur City Corporation. In-depth interviews with purposively selected 22 slum dwellers and key informant interviews with 16 local healthcare providers and four policymakers and technical experts were also conducted., Outcome Measures: Percentage of people suffering from general illness, percentage of people suffering from chronic illness, percentage of people seeking healthcare, percentage of people seeking maternal care, health system challenges resulting from COVID-19., Results: About 12% of members suffered from general illness and 25% reported chronic illness. Over 80% sought healthcare and the majority sought care from informal healthcare providers. 39% of the recently delivered women sought healthcare in 3 months preceding the survey. An overall reduction in healthcare use was reported during the lockdown period compared with prepandemic time. Mismanagement and inefficient use of resources were reported as challenges of health financing during the pandemic. Health information sharing was inadequate at the urban slums, resulting from the lack of community and stakeholder engagement (51% received COVID-19-related information, 49% of respondents knew about the national hotline number for COVID-19 treatment). Shortage of human resources for health was reported to be acute during the pandemic, resulting from the shortage of specialist doctors and uneven distribution of health workforce. COVID-19 test was inadequate due to the lack of adequate test facilities and stigma associated with COVID-19. Lack of strong leadership and stakeholder engagement was seen as the barriers to effective pandemic management., Conclusion: The findings of the current study are expected to support the government in tailoring interventions and allocating resources more efficiently and timely during a pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: Squamous cell carcinoma (SCC) is the most common form of carcinoma in cattle. Histopathological grading systems have been utilized over several decades for estimating the malignancy of cattle SCCs. This study aimed to detect p53 and Mdm2 expression in different SCC cases in cattle and correlate their expression with the SCC histopathological grading., Materials and Methods: Cattle SCC cases were collected at the Veterinary Teaching Hospital in Nineveh. The SCC grading system categorized the cases histologically based on their differentiation grade into three groups: Well, moderately, and poorly differentiated. The SCC cases were subsequently verified for p53 and Mdm2 immunoexpression., Results: Fourteen of 16 examined cattle SCC samples tested positive for p53 expression. Moreover, 15 out of the 16 SCC samples tested positive for Mdm2 expression. The increased immunoreactivity of both p53 and Mdm2 was associated with a poor histological grading of the cattle SCC. There is a positive correlation between the nuclear expression of p53 and Mdm2, and the degree of differentiation and the number of mitotic figures in the examined cattle SCC samples., Conclusion: Our results demonstrate an increased p53 and Mdm2 expression in cattle SCC cases characterized by poor histopathological grading, thus suggesting an essential role of these molecules in the development of moderately and poorly differentiated SCC in cattle., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Al-Jameel, et al.)

Background: Although mental health is an important part of health and wellbeing, very little is known about the impact of the COVID-19 pandemic on the mental health of marginalized communities like urban slum dwellers. Our study estimated the prevalence of generalized anxiety disorder and insomnia among the residents of the informal settlements of Dhaka, Bangladesh, during the COVID-19 pandemic. Methods: A cross-sectional phone-based survey was conducted from October to November 2020 among adult residents of five informal settlements of Dhaka city randomly chosen from an existing Urban Health and Demographic Surveillance Systems (UHDSS) run by icddr,b. Data on Generalized Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI) were collected. A multinomial logistic regression was performed to assess the associated factors of anxiety and insomnia. Results: Of the total 586 participants, the prevalence of mild to severe anxiety and insomnia were 53% and 43%, respectively. As per the multinomial regression analysis, participants with mild anxiety were significantly more likely to be older (>50 years) and afraid of COVID-19 infection. Likewise, participants with moderate/severe anxiety were significantly more likely to share less household facilities (e.g., toilet, kitchen, water) (OR: 2.23; 95% CI: 1.31-3.79), to have difficulties in food availability (OR: 2.76; 95% CI: 1.10-6.93), to be afraid of self (OR: 5.27; 95% CI: 2.82-9.88), and to worry about the family members (OR: 2.26; 95% CI: 1.23-4.17) getting infected. Participants with mild insomnia were significantly more likely to share fewer household facilities and be afraid of being infected with COVID-19 infection. Moreover, participants with moderate/severe insomnia were significantly more likely to be female (OR: 1.90; 95% CI: 1.02-3.56), to receive food aid (OR: 0.50; 95% CI: 0.29-0.88), to be afraid of self (OR: 3.85; 95% CI: 1.81-8.19), and to worry about someone like friends or neighbors (OR: 2.45; 95% CI: 1.07-5.58) getting infected with COVID-19. Conclusions: We found elevated prevalence of both anxiety and insomnia among the urban poor of Bangladesh in the context of COVID-19. This indicates the importance of integrating mental health in the mitigation and recovery efforts related to similar crises for the urban poor in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Koly, Khanam, Islam, Mahmood, Hanifi, Reidpath, Khatun and Rasheed.)

Background: The world has been grappling with the COVID-19 pandemic, a dire public health crisis, since December 2019. Preventive and control measures have been adopted to reduce the spread of COVID-19. To date, the public's knowledge, attitudes, and practices regarding COVID-19 across Bangladesh have been poorly understood. Therefore, it is important to assess people's knowledge, attitudes, and practices (KAP) toward the disease and suggest appropriate strategies to combat COVID-19 effectively., Objective: This study aimed to assess the KAP of Bangladeshi people toward COVID-19 and to identify their determinants., Methods: We conducted a country-wide cross-sectional telephonic survey from May 7 to 29, 2020. A purposive sampling method was applied, and adult Bangladeshi citizens who have mobile phones were approached to participate in the survey. Interviews were conducted based on verbal consent. Multiple logistic regression analyses and several tests were performed to identify the factors associated with KAP related to COVID-19., Results: A total of 492 of 576 Bangladeshi adults aged 18 years and above completed the interview, with a response rate of 85.4% (492/576). Of the 492 participants, 321 (65.2%) were male, and 304 (61.8%) lived in a rural area. Mean scores for knowledge, attitudes, and practices were 10.56 (SD 2.86), 1.24 (SD 0.83), and 3.17 (SD 1.5), respectively. Among the 492 respondents, 273 (55.5%) had poor knowledge, and 251 (49%) expressed a negative attitude; 192 out of 359 respondents (53.5%) had poor practices toward COVID-19. Mean scores of knowledge, attitudes, and practices differed significantly across various demographic and socioeconomic groups. Rural residents had lower mean scores of knowledge (mean 9.8, SD 3.1, P<.001) and adherence to appropriate practice measures (mean 4, SD 1.4, P<.001) compared to their urban counterparts. Positive and statistically strong correlations between knowledge and attitudes (r=0.21, P<.001), knowledge and practices (r=0.45, P<.001), and attitudes and practices (r=0.27, P<.001) were observed. Television (53.7%) was identified as the major source of knowledge regarding COVID-19. Almost three-quarters of the respondents (359/492, 73%) went outside the home during the lockdown period. Furthermore, the study found that good knowledge (odds ratio [OR] 3.13, 95% CI 2.03-4.83, and adjusted OR 2.33, 95% CI 1.16-4.68) and a positive attitude (OR 2.43, 95% CI 1.59-3.72, and adjusted OR 3.87, 95% CI 1.95-7.68) are significantly associated with better practice of COVID-19 health measures., Conclusions: Evidence-informed and context-specific risk communication and community engagement, and a social and behavior change communication strategy against COVID-19 should be developed in Bangladesh based on the findings of this study, targeting different socioeconomic groups., (©Md Golam Rabbani, Orin Akter, Md Zahid Hasan, Nandeeta Samad, Shehrin Shaila Mahmood, Taufique Joarder. Originally published in JMIR Formative Research (https://formative.jmir.org), 05.11.2021.)

Background: Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs)., Objectives: This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy., Methods: In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC 025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR)., Results: The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC 025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC 025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%., Conclusions: In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients., Competing Interests: Funding Support and Author Disclosures This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. This study was supported in part by NIH/NCI grant RO1-CA 233610 (Dr Herrmann). Dr Perales has received personal fees from Abbvie, Bellicum, Bristol Myers Squibb, Celgene, Cidara Theraputics, Incyte, Kite/Gilead, Medigene, Miltenyi, MolMed, Nektar Therapeutics, NexImmune, Novartis, Omeros, Merck, Servier, and Tekeda; has served on data safety and monitoring boards for Cidara Therapeutics, Medigene, and Servier; and has received clinical trial support from Incyte, Kite/Gilead, and Miltenyi. Data presented in this study do not represent the opinion of the United States Food and Drug Administration (FDA). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited., Objectives: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis., Methods: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block., Results: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE., Conclusions: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis., Competing Interests: Funding Support and Author Disclosures Dr. Thavendiranathan was supported, in part, through the Canadian Institutes of Health Research New Investigator Award (FRN 147814) and a Canada Research Chair in Cardio-Oncology. This work is supported by the New York Academy of Medicine's Glorney-Raisbeck Award to Dr. Mahmood. Dr. Sullivan was supported, in part, through the National Institutes of Health (NIH)/National Cancer Institute (RO1CA229851, UH2CA207355, RO1CA193970). Dr. C.L. Chen, and Dr. D. Gupta were supported, in part, through the NIH/National Cancer Institute P30CA008748. Dr. Neilan was supported, in part, through the Kohlberg Foundation, the NIH/National Heart, Lung, and Blood Institute (RO1HL130539, RO1HL137562, and K24HL150238), and the NIH/Harvard Center for AIDS Research (P30 AI060354). Dr. Thavendiranathan has received Speakers Bureau fees from Amgen, Takeda, and BI. Dr. Mahmood has received consulting fees from OMR Globus, Alpha Detail, and Opinion Research Team. Dr. Nohria has received research grant support from Amgen; and has served a consultant for Takeda Oncology. Dr. Heinzerling has received consulting, advisory board, and speaker fees from MSD, BMS, Roche, Novartis, Amgen, and Curevac. Dr. Sullivan has served as a consultant for Merck and Novartis. Dr. Groarke has received research support from Amgen. Dr. Neilan has received advisory fees from Parexel, BMS, H3 Biomedicine, AbbVie, and Intrinsic Imaging. Dr. Neilan has received grant support from AstraZeneca. Dr. Wintersperger has received research support and speaker honoraria from Siemens Healthineers (the University Health Network has a master research agreement with Siemens Healthineers); and is an inventor of the IG fitting method owned by the University Health Network (US10314548B2). Dr. Yang has received research funding from CSL Behring. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis., Methods: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested., Results: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39)., Conclusions: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification., Competing Interests: Competing interests: SSM has received consultancy fees from OMR Globus, Alpha Detail, and Opinion Research Team. RS has been a consultant to Merck and Novartis. LH has received consultancy, advisory board, and speaker fees from MSD, BMS, Roche, Novartis, Amgen, and Curevac. LZu has been a consultant to Merck. JG has received research support from Amgen. AN has received research support from Amgen and has been a consultant for Takeda Oncology and AstraZeneca. TGN has received advisory fees from Parexel, AbbVie, H3-Biomedicine, Aprea Therapeutics, BMS, and Intrinsic Imaging. TGN has received grant funding from AstraZeneca., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Coronavirus disease 2019 (COVID-19) affects vulnerable populations (VP) adversely., Purpose: To evaluate overall imaging utilization in vulnerable subgroups (elderly, racial/ethnic minorities, socioeconomic status [SES] disadvantage) and determine if a particular subgroup has worse outcomes from COVID-19., Materials/methods: Of 4110 patients who underwent COVID-19 testing from March 3-April 4, 2020 at NewYork-Presbyterian Hospital (NYP) health system, we included 1121 COVID-19 positive adults (mean age 59±18 years, 59% male) from two academic hospitals and evaluated imaging utilization rates and outcomes, including mortality., Results: Of 897 (80%) VP, there were 465 (41%) elderly, 380 (34%) racial/ethnic minorities, and 479 (43%) SES disadvantage patients. Imaging was performed in 88% of patients and mostly portable/bedside studies, with 87% of patients receiving chest radiographs. There were 83% hospital admissions, 25% ICU admissions, 23% intubations, and 13% deaths. Elderly patients had greater imaging utilization, hospitalizations, ICU/intubation requirement, longer hospital stays, and >4-fold increase in mortality compared to non-elderlies (adjusted hazard ratio[aHR] 4.79, p<0.001). Self-reported minorities had fewer ICU admissions (p=0.03) and reduced hazard for mortality (aHR 0.53, p=0.004; complete case analysis: aHR 0.39, p<0.001 excluding "not reported"; sensitivity analysis: aHR 0.61, p=0.005 "not reported" classified as minorities) with similar imaging utilization, compared to non-minorities. SES disadvantage patients had similar imaging utilization and outcomes as compared to their counterparts., Conclusions: In a predominantly hospitalized New York City cohort, elderly patients are at highest mortality risk. Racial/ethnic minorities and SES disadvantage patients fare better or similarly to their counterparts, highlighting the critical role of access to inpatient medical care during the COVID-19 pandemic., Competing Interests: Disclosures: All authors have no disclosures., (2020 by the Radiological Society of North America, Inc.)

This editorial provides an introduction to the special issue on "Lessons about intervening in accountability ecosystems: implementation of community scorecards in Bangladesh and Uganda". We start by describing the rationale for this work in the two study countries. While our project, the Future Health Systems (FHS) project, had been working over the course of more than a decade to strengthen health services, particularly for low income households in rural areas, our teams increasingly recognized how difficult it would be to sustain service improvements without fundamental changes to local accountabilities. Accordingly, in the final phase of the project 2016-2018, we designed, implemented and assessed community scorecard initiatives, in both Bangladesh and Uganda, with the aim of informing the design of a scalable social accountability initiative that could fundamentally shift the dynamics of health system accountability in favor of the poor and marginalized.We describe the particular characteristics of our approach to this task. Specifically we (i) conducted a mapping of accountabilities in each of the contexts so as to understand how our actions may interact with existing accountability mechanisms (ii) developed detailed theories of change that unpacked the mechanisms through which we anticipated the community scorecards would have effect, as well as how they would be institutionalized; and (iii) monitored closely the extent of inclusion and the equity effects of the scorecards. In summarizing this approach, we articulate the contributions made by different papers in this volume.

Background: The government of Bangladesh initiated community clinics (CC) to extend the reach of public health services and these facilities were planned to be run through community participation. However, utilisation of CC services is still very low. Evidence indicates community score card is an effective tool to increase utilisation of services from health facility through regular interface meeting between service providers and beneficiary. We investigated whether community scorecards (CSC) improve utilisation of health services provided by CCs in rural area of Bangladesh., Methods: This study was conducted from December 2017 to November 2018. Three intervention and three control CCs were selected from Chakaria, a rural sub-district of Bangladesh. CSC was introduced with the Community Groups and Community Support Groups in intervention CCs between January to October 2018. Data were collected through observation of CCs during operational hours, key informant interviews, focus group discussions, and from DHIS2. Utilisation of CC services was compared between intervention and control areas, pre and post CSC intervention., Results: Post CSC intervention, community awareness about CC services, utilisation of clinic operational hours, and accountability of healthcare providers have increased in the intervention CCs. Utilisation of primary healthcare services including family planning services, antenatal care, postnatal care and basic health services have significantly improved in intervention CCs., Conclusion: CSC is an effective tool to increase the service utilization provided by CCs by ensuring community awareness and participation, and service providers' accountability. Policy makers and concerned authorities may take necessary steps to integrate community scorecard in the health system by incorporating it in CCs.

Background: Engaging communities in health facility management and monitoring is an effective strategy to increase health system responsiveness. Many developing countries have used community scorecard (CSC) to encourage community participation in health. However, the use of CSC in health in Bangladesh has been limited. In 2017, icddr,b initiated a CSC process to improve health service delivery at the community clinics (CC) providing primary healthcare in rural Bangladesh. The current study presents learnings around feasibility, acceptability, initial outcome and challenges of implementing CSC at community clinics., Methods: A pilot study conducted between January'2018-December'2018 explored feasibility and acceptability of CSC using a thematic framework. The tool was implemented in purposively selected three CCs in Chakaria and one CC in Teknaf sub-district of Bangladesh. Qualitative data from 20 Key-Informant Interviews and four Focus Group Discussions with service users, healthcare providers, and government personnel, document reviews and meeting observations were used in analysis., Results: The study showed that participants were enthusiastic and willing to take part in the CSC intervention. They perceived CSC to be useful in raising awareness about health in the community and facilitating structured monitoring of CC services. The process facilitated building stronger community ownership, enhancing accountability and stakeholder engagement. The participants identified issues around service provision, set SMART (specific, measurable, attainable, relevant and time-bound) targets and indicators on supplies, operations, logistics, environment, and patient satisfaction through CSC. However, some systematic and operational challenges of implementation were identified including time and resource constraint, understanding and facilitation of CSC, provider-user conflict, political influence, and lack of central level monitoring., Conclusion: The findings suggest that CSC is a feasible and acceptable tool to engage community and healthcare providers in monitoring and managing health facilities. For countries with health systems faced with challenges around accountability, quality and coverage, CSC has the potential to improve community level health-service delivery. The findings are intended to inform program implementers, donors and other stakeholders about context, mechanisms, outcomes and challenges of CSC implementation in Bangladesh and other developing countries. However, proper contextualization, institutional capacity building and policy integration will be critical in establishing effectiveness of CSC at scale.

Context.—: Cardiac complications of immune checkpoint inhibitor therapy are rare, but reports of myocarditis are increasing. The findings have been described in case reports as lymphocytic myocarditis, but its histopathology is underreported., Objective.—: To review the histology of myocardial biopsy-proven cases of immune checkpoint-associated myocarditis and provide immunohistochemical characterization of the inflammatory infiltrate., Design.—: We have encountered 6 patients with biopsy-proven myocarditis in conjunction with therapy using anti-programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) agents with and without cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors and characterized the histopathology and immune cell profile., Results.—: The myocarditis was multifocal/diffuse and characterized by a predominant CD163-positive histiocytic infiltrate, with an associated CD8+ and PD-1+ T-lymphocytic infiltrate, some of which were granzyme B positive. Cardiac myocytes showed immunoreactivity for PD-L1 in areas of injury, confirmed using 2 different anti-PD-L1 clones. Four of 6 patients recovered from their cardiac injury. One patient had residual tachycardia-bradycardia syndrome and 1 patient expired., Conclusions.—: The diffuse lymphohistiocytic myocarditis associated with this therapy is relatively distinctive, and this diagnosis is strongly suggested based on the histopathologic findings in the correct clinical setting., (© 2020 College of American Pathologists.)

Recent infectious disease outbreaks, including the ongoing global COVID-19 pandemic and Ebola in the Democratic Republic of the Congo, have demonstrated the critical importance of resilient health systems in safeguarding global health security. Importantly, the human, economic and political tolls of these crises are being amplified by health systems' inabilities to respond quickly and effectively. Improving resilience within health systems can build on pre-existing strengths to enhance the readiness of health system actors to respond to crises, while also maintaining core functions. Using data gathered from a scoping literature review, interviews with key informants and from stakeholders who attended a workshop held in Dhaka, Bangladesh, we developed a Health System Resilience Checklist ('the checklist'). The aim of the checklist is to measure the specific capacities, capabilities and processes that health systems need in order to ensure resilience in the face of both infectious disease outbreaks and natural hazards. The checklist is intended to be adapted and used in a broad set of countries as a component of ongoing processes to ensure that health actors, institutions and populations can mount an effective response to infectious disease outbreaks and natural hazards while also maintaining core healthcare services. The checklist is an important first step in improving health system resilience to these threats, but additional research and resources will be necessary to further refine and prioritise the checklist items and to pilot the checklist with the frontline health facilities that would be using it. This will help ensure its feasibility and durability for the long-term within the health systems strengthening and health security fields., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented., Methods and Results: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE., Conclusion: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis., Objectives: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis., Methods: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death., Results: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8)., Conclusions: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: Chimeric antigen receptors redirect T cells (CAR-T) to target cancer cells. There are limited data characterizing cardiac toxicity and cardiovascular (CV) events among adults treated with CAR-T., Objectives: The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T., Methods: The registry included 137 patients who received CAR-T. Covariates included the occurrence and grade of cytokine release syndrome (CRS) and the administration of tocilizumab for CRS. Cardiac toxicity was defined as a decrease in the left ventricular ejection fraction or an increase in serum troponin. Cardiovascular events were a composite of arrhythmias, decompensated heart failure, and CV death., Results: The median age was 62 years (interquartile range [IQR]: 54 to 70 years), 67% were male, 88% had lymphoma, and 8% had myeloma. Approximately 50% were treated with commercial CAR-T (Yescarta or Kymriah), and the remainder received noncommercial products. CRS, occurring a median of 5 days (IQR: 2 to 7 days) after CAR-T, occurred in 59%, and 39% were grade ≥2. Tocilizumab was administered to 56 patients (41%) with CRS, at a median of 27 h (IQR: 16 to 48 h) after onset. An elevated troponin occurred in 29 of 53 tested patients (54%), and a decreased left ventricular ejection fraction in 8 of 29 (28%); each occurred only in patients with grade ≥2 CRS. There were 17 CV events (12%, 6 CV deaths, 6 decompensated heart failure, and 5 arrhythmias; median time to event of 21 days), all occurred with grade ≥2 CRS (31% patients with grade ≥2 CRS), and 95% of events occurred after an elevated troponin. The duration between CRS onset and tocilizumab administration was associated with CV events, where the risk increased 1.7-fold with each 12-h delay to tocilizumab., Conclusions: Among adults, cardiac injury and CV events are common post-CAR-T. There was a graded relationship among CRS, elevated troponin, and CV events, and a shorter time from CRS onset to tocilizumab was associated with a lower rate of CV events., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Biofilm formation and resistance to last-line antibiotics have restricted chemotherapy options toward infection eradication., Methodology: Fifty K. oxytoca isolates were collected from patients with antibiotic-associated haemorrhagic colitis (AAHC). Antibiotic susceptibility tests were conducted and phenotypic biofilm formation was assessed using microtitre tissue plate (MTP) assay. PCR was employed to amplify the adhesins, extended-spectrum β-lactamases (ESBLs), carbapenemase and colistin resistance genes. The expression of adhesin genes was evaluated using quantitative real-time PCR (RT-qPCR).Results/Key findings. The previous antibiotic consumption and hospitalization (P<0.05) and older ages (P=0.0033) were significantly associated with AAHC. None of the isolates produced biofilm strongly, but 70% of them produced moderate-level biofilm. The blaCTX-M (12/14), the blaIMP (8/14 MICIMI =4 µg ml -1 ) and blaOXA-48-like (5/14) and mcr-1 (4/14) genes were predominant, three of which harbouring all the genes. The expression of matB (0.023) and mrkA (0.011) was significantly different between multidrug-resistant and susceptible isolates. Furthermore, moderately biofilm producer isolates significantly exhibited higher expression of fimA (P=.0117), pilQ (P=0.002) and mrkA (P=0.020) genes compared to biofilm non-producers. No significant difference regarding gene expression was observed among ESBL alleles., Conclusion: Bacterial attachment by adhesins and biofilm formation among extensive drug-resistant K. oxytoca isolates hinder the efficient infection eradication. Hence, control and surveillance studies should be performed and other therapeutic auspicious approaches must be taken into account against AAHC, biofilm formation and drug resistance spread. Furthermore, previous antibiotic consumption and long-term hospitalization should be controlled.

Background: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs., Methods: Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death., Results: The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002)., Conclusion: The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.

Background: Cardiotoxicity associated with anthracycline-based chemotherapies has limited their use in patients with preexisting cardiomyopathy or heart failure. Dexrazoxane protects against the cardiotoxic effects of anthracyclines, but in the USA and some European countries, its use had been restricted to adults with advanced breast cancer receiving a cumulative doxorubicin (an anthracycline) dose > 300 mg/m 2 . We evaluated the off-label use of dexrazoxane as a cardioprotectant in adult patients with preexisting cardiomyopathy, undergoing anthracycline chemotherapy., Methods: Between July 2015 and June 2017, five consecutive patients, with preexisting, asymptomatic, systolic left ventricular (LV) dysfunction who required anthracycline-based chemotherapy, were concomitantly treated with off-label dexrazoxane, administered 30 min before each anthracycline dose, regardless of cancer type or stage. Demographic, cardiovascular, and cancer-related outcomes were compared to those of three consecutive patients with asymptomatic cardiomyopathy treated earlier at the same hospital without dexrazoxane., Results: Mean age of the five dexrazoxane-treated patients and three patients treated without dexrazoxane was 70.6 and 72.6 years, respectively. All five dexrazoxane-treated patients successfully completed their planned chemotherapy (doxorubicin, 280 to 300 mg/m 2 ). With dexrazoxane therapy, changes in LV systolic function were minimal with mean left ventricular ejection fraction (LVEF) decreasing from 39% at baseline to 34% after chemotherapy. None of the dexrazoxane-treated patients experienced symptomatic heart failure or elevated biomarkers (cardiac troponin I or brain natriuretic peptide). Of the three patients treated without dexrazoxane, two received doxorubicin (mean dose, 210 mg/m 2 ), and one received daunorubicin (540 mg/m 2 ). Anthracycline therapy resulted in a marked reduction in LVEF from 42.5% at baseline to 18%. All three developed symptomatic heart failure requiring hospitalization and intravenous diuretic therapy. Two of them died from cardiogenic shock and multi-organ failure., Conclusion: The concomitant administration of dexrazoxane in patients with preexisting cardiomyopathy permitted successful delivery of anthracycline-based chemotherapy without cardiac decompensation. Larger prospective trials are warranted to examine the use of dexrazoxane as a cardioprotectant in patients with preexisting cardiomyopathy who require anthracyclines., Competing Interests: Competing interestsDr. Lipshultz is a consultant for Clinigen Group plc, which manufactures dexrazoxane. Dr. Lipshultz has received investigator-initiated research grants from Pharmacia and Upjohn, Chiron Corporation, and Pfizer to study dexrazoxane., (© The Author(s). 2019.)

Background: Mechanisms underlying impaired exercise capacity and increased cardiovascular mortality observed in breast cancer (BC) patients remain unclear. The prevalence, functional, and prognostic significance of elevated resting heart rate (HR) and abnormal heart rate recovery (HRR) in breast cancer (BC) requires evaluation., Methods: In a single-center, retrospective, case-control study of women referred for exercise treadmill testing (ETT), 448 BC patients (62.6 ± 10.0 years) were compared to 448 cancer-free, age-matched controls. Elevated resting HR was defined as HR ≥80 bpm at rest. Abnormal HRR at 1-minute following exercise was defined as ≤12 bpm if active recovery or ≤18 bpm if passive recovery. Association of these parameters with exercise capacity and all-cause mortality was evaluated., Results: Elevated resting HR (23.7% vs 17.0%, P = 0.013) and abnormal HRR (25.9% vs 20.3%, P = 0.048) were more prevalent in BC cohort than controls. In adjusted analyses, BC patients with elevated resting HR (-0.9 METs (SE 0.3); P = 0.0003) or abnormal HRR (-1.3 METs (SE 0.3); P < 0.0001) had significant reductions in metabolic equivalents (METs) achieved during exercise. Elevated resting HR was not associated with mortality. There was a trend toward increased mortality in BC cohort with abnormal HRR (adjusted hazard ratio 2.06 (95% CI 0.95-4.44, P = 0.07))., Conclusions: Women across the BC survivorship continuum, referred for ETT, have an increased prevalence of elevated resting HR and abnormal HRR relative to cancer-free, age-matched female controls. These parameters were associated with decreased exercise capacity. Strategies to modulate these abnormalities may help improve functional capacity in this cohort., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background : Improving maternal health is a major development goal, with ambitious targets set for high-mortality countries like Bangladesh. Following a steep decline in the maternal mortality ratio over the past decade in Bangladesh, progress has plateaued at 196/100,000 live births. A voucher scheme was initiated in 2007 to reduce financial, geographical and institutional barriers to access for the poorest. Objective : The current paper reports the effect of vouchers on the use of continuum of maternal care. Methods : Cross-sectional surveys were carried out in the Chattogram and Sylhet divisions of Bangladesh in 2017 among 2400 women with children aged 0-23 months. Using Cluster analysis utilisation groups for antenatal care, facility delivery and postnatal care were formed. Clusters were regressed on voucher receipt to identify the underlying relationship between voucher receipt and utilisation of care while controlling for possible confounders. Results : Four clusters with varying levels of utilisation were identified. A significantly higher proportion of voucher-recipients belonged to the high-utilisation cluster compared to non-voucher recipients (43.5% vs. 15.4%). For the poor voucher recipients, the probability of belonging to the high-utilisation cluster was higher compared to poor non-voucher recipients (33.3% vs. 6.8%) and the probability of being in the low-utilisation cluster was lower than poor non-voucher recipients (13.3% vs. 55.4%). Conclusion : The voucher programme enhanced uptake of the complete continuum of maternal care and the benefits extended to the most vulnerable women. However, a lack of continued transition through the continuum of maternal care was identified. This insight can assist in designing effective interventions to prevent intermittent or interrupted care-seeking. Programmes that improve access to quality healthcare in pregnancy, childbirth and the postnatal period can have wide-ranging benefits. A coherent continuum-based approach to understanding maternal care-seeking behaviour is thus expected to have a greater impact on maternal, newborn and child health outcomes.

Ibrutinib, a novel and potent Bruton tyrosine kinase inhibitor, is an effective and well-tolerated treatment for a variety of B-cell lymphomas. However, its use is associated with an increased incidence of atrial fibrillation (AF), ranging from 4% to 16%. We reviewed the original clinical trials that led to the approval of ibrutinib, as well as several other prospective and retrospective studies, to better appreciate the incidence of ibrutinib-associated AF. Based on 16 studies included in our analysis, the incidence of ibrutinib-associated AF was 5.77 per 100 person-years, which is much higher than rates previously reported with ibrutinib and compared with the general adult population. New onset AF in cancer patients is associated with a significantly higher risk of heart failure and thromboembolism, even after adjusting for known risk factors. In addition, ibrutinib poses unique challenges due to its interactions with many medications that are commonly used to manage AF. Ibrutinib also inhibits platelet activation and decisions regarding anticoagulation have to be carefully weighed against this increased risk of bleeding. Ibrutinib's interaction with calcium channel blockers, digoxin, amiodarone, and direct oral anticoagulants can result in either ibrutinib or other drug-related toxicity and careful selection and dose adjustment may be needed. Ibrutinib-associated AF can be a therapy-limiting side effect and physicians should be familiar with the special management considerations imposed by this agent. We review the potential mechanisms and incidence of ibrutinib-associated AF and propose an algorithm for its management., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The hemodynamic effects of mechanical ventilation can be grouped into three clinically relevant concepts. First, since spontaneous ventilation is exercise. In patients increased work of breathing, initiation of mechanical ventilatory support may improve O 2 delivery because the work of breathing is reduced. Second, changes in lung volume alter autonomic tone, pulmonary vascular resistance, and at high lung volumes compress the heart in the cardiac fossa similarly to cardiac tamponade. As lung volume increases so does the pressure difference between airway and pleural pressure. When this pressure difference exceeds pulmonary artery pressure, pulmonary vessels collapse as they pass form the pulmonary arteries into the alveolar space increasing pulmonary vascular resistance. Hyperinflation increases pulmonary vascular resistance impeding right ventricular ejection. Anything that over distends lung units will increase their vascular resistance, and if occurring globally throughout the lung, increase pulmonary vascular resistance. Decreases in end-expiratory lung volume cause alveolar collapse increases pulmonary vasomotor tone by the process of hypoxic pulmonary vasoconstriction. Recruitment maneuvers that restore alveolar oxygenation without over distention will reduce pulmonary artery pressure. Third, positive-pressure ventilation increases intrathoracic pressure. Since diaphragmatic descent increases intra-abdominal pressure, the decrease in the pressure gradient for venous return is less than would otherwise occur if the only change were an increase in right atrial pressure. However, in hypovolemic states, it can induce profound decreases in venous return. Increases in intrathoracic pressure decreases left ventricular afterload and will augment left ventricular ejection. In patients with hypervolemic heart failure, this afterload reducing effect can result in improved left ventricular ejection, increased cardiac output and reduced myocardial O 2 demand. This brief review will focus primarily on mechanical ventilation and intrathoracic pressure as they affect right and left ventricular function and cardiac output., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Fulminant myocarditis has been reported in patients treated with immune checkpoint inhibitors. We present the first described case of acute immune-mediated myocarditis and myositis associated with durvalumab plus tremelimumab combination therapy. The patient was undergoing treatment for advanced endometrial cancer., Case Presentation: A 75-year-old Caucasian female presented with difficulty ambulating due to neck protraction, imbalance, and increased shortness of breath with exertion 3 weeks after her first durvalumab and tremelimumab administration for advanced endometrial cancer. While the patient's initial laboratory data showed an acute transaminitis and elevated creatine phosphokinase (CPK), consistent with myositis, she developed complete heart block and ventricular dysfunction, with elevated troponins. Endomyocardial biopsy confirmed a diagnosis of immune-mediated myocarditis. She was treated with high-dose steroids and mycophenolate mofetil, which led to eventual native conduction and left ventricular ejection fraction recovery. Upon discharge, she was titrated off of steroids over 8 weeks and her mycophenolate was subsequently stopped. A follow-up computed tomography scan revealed progression of metastatic disease. The patient remains alive using supplemental oxygen 3 months after admission., Conclusions: Durvalumab plus tremelimumab combination therapy can lead to fulminant immune-mediated myocarditis. This patient's myocarditis was amenable to treatment with high-dose intravenous steroids and mycophenolate.

Background: Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized., Objectives: The authors sought to understand the presentation and clinical course of ICI-associated myocarditis., Methods: After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block., Results: The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates., Conclusions: Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)