Clinical Practice Guidelines for the Management of Type 2 Diabetes in South Asia: A Systematic Review.

BACKGROUND: Clinical practice guidelines (CPGs) are a helpful tool for the evidence-based management of Type 2 Diabetes Mellitus (T2D). The aim of this systematic review was to synthesize and appraise the scope and quality of South Asian T2D CPGs. METHODS: This PROPSERO registered (CRD42023425150) systematic review adhered to the 2020 PRISMA guidelines. We searched the PubMed, Embase, Cochrane, and Google Scholar databases for relevant guidelines. Data synthesis was performed using a qualitative approach and methodological quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: We identified eleven unique CPGs (three each from Pakistan and Sri Lanka, two from India, and one each from Bangladesh, Nepal, and Bhutan) which were published or updated between 2017 and 2023. The CPGs included recommendations regarding screening, diagnosis, prevention, and management of T2D and its acute and chronic complications, comorbidities, and fasting with T2D. The AGREE II mean domain scores ranged from 37 % to 80 %; three CPGs were 'recommended for clinical use,' seven were 'recommended for use with modifications' and one was deemed unfit for implementation. CONCLUSION: The present review summarized and appraised broadly CPGs from South Asia for T2D and can help direct improvements to future iterations.

Inhibition of EGFR/ErbB does not protect against C. difficile toxin B.

Clostridioides difficile is a common cause of diarrhea and mortality, especially in immunosuppressed and hospitalized patients. C. difficile is a toxin-mediated disease, but the host cell receptors for C. difficile toxin B (TcdB) have only recently been revealed. Emerging data suggest TcdB interacts with receptor tyrosine kinases during infection. In particular, TcdB can elicit Epidermal Growth Factor Receptor (EGFR) transactivation in human colonic epithelial cells. The mechanisms for this function are not well understood, and the involvement of other receptors in the EGFR family of Erythroblastic Leukemia Viral Oncogene Homolog (ErbB) receptors remains unclear. Furthermore, in an siRNA-knockdown screen for protective genes involved with TcdB toxin pathogenesis, we show ErbB2 and ErbB3 loss resulted in increased cell viability. We hypothesize TcdB induces the transactivation of EGFR and/or ErbB receptors as a component of its cell-killing mechanism. Here, we show in vivo intrarectal instillation of TcdB in mice leads to phosphorylation of ErbB2 and ErbB3. However, immunohistochemical staining for phosphorylated ErbB2 and ErbB3 indicated no discernible difference between control and TcdB-treated mice for epithelial phospho-ErbB2 and phospho-ErbB3. Human colon cancer cell lines (HT29, Caco-2) exposed to TcdB were not protected by pre-treatment with lapatinib, an EGFR/ErbB2 inhibitor. Similarly, lapatinib pre-treatment failed to protect normal human colonoids from TcdB-induced cell death. Neutralizing antibodies against mouse EGFR failed to protect mice from TcdB intrarectal instillation as measured by edema, inflammatory infiltration, and epithelial injury. Our findings suggest TcdB-induced colonocyte cell death does not require EGFR/ErbB receptor tyrosine kinase activation.

Cecum axis (CecAx) preservation reveals physiological and pathological gradients in mouse gastrointestinal epithelium.

The mouse cecum has emerged as a model system for studying microbe-host interactions, immunoregulatory functions of the microbiome, and metabolic contributions of gut bacteria. Too often, the cecum is falsely considered as a uniform organ with an evenly distributed epithelium. We developed the cecum axis (CecAx) preservation method to show gradients in epithelial tissue architecture and cell types along the cecal ampulla-apex and mesentery-antimesentery axes. We used imaging mass spectrometry of metabolites and lipids to suggest functional differences along these axes. Using a model of Clostridioides difficile infection, we show how edema and inflammation are unequally concentrated along the mesenteric border. Finally, we show the similarly increased edema at the mesenteric border in two models of Salmonella enterica serovar Typhimurium infection as well as enrichment of goblet cells along the antimesenteric border. Our approach facilitates mouse cecum modeling with detailed attention to inherent structural and functional differences within this dynamic organ.

Gaps in hygiene promotion at schools in Pakistan: qualitative descriptive research.

School health remains an ignored domain in Pakistan. This article presents gaps in understanding hygiene promotion efforts in school settings in urban squatter settlements by exploring perspectives of the key stakeholders and undertaking a review of the education curriculum. Using qualitative methodology, 13 in-depth interviews were held with the key informants (teachers, health and education officers) and three focus group discussions were conducted with 36 mothers. The study setting includes three schools located in a semi-urban area in the province of Sindh, Pakistan. The semi-structured guide was utilized to obtain perspectives of key stakeholders on factors constraining hygiene promotion efforts in school settings. The primary education curriculum was reviewed using the content analysis approach to assess the integration of hygiene concepts into the curriculum. Analysis of qualitative interviews and curriculum review resulted in five categories under a theme that addressed multiple factors constraining hygiene promotion in the school settings. These include (i) Gaps in the school curriculum, (ii) Poor accountability of the local administration in the upkeep of schools, (iii) Parent's negligence toward children's hygiene, (iv) Inadequate training of school teachers on hygiene concepts, and (v) Lack of interdepartmental coordination between health and education sectors. Hygiene promotion at schools has been deterred by multiple factors at the selected primary schools in Pakistan. Recommended actions include integration of health and hygiene concepts into the education curriculum, capacity building of teachers, reviving water, sanitation and hygiene infrastructure, coordination among Education and Health Departments and ownership among the local government to ensure cleanliness at schools.

Schools are not only expected to provide education to children, their mandate also includes health and hygiene promotion. Keeping in view the dearth of evidence in understanding the role of schools in hygiene promotion in the local context, this research was conducted in three semi-urban school settings in Sindh province, Pakistan. We aimed to identify factors that constrain hygiene promotion efforts at the school level. As part of this research, we interviewed multiple stakeholders. This includes (teachers, mothers, education and health officers) at the primary school level. Our findings revealed serious gaps in hygiene promotion at schools. This includes inadequate attention to hygiene concepts in the curriculum books, inconducive school environment, teachers' and parents' negligence toward children's hygiene and communication gap among them, and absence of coordination between health and education sectors. To conclude, multiple actions are needed to emphasize hygiene promotion at the school level. This ranged from revision in the education curriculum and training of teachers in hygiene promotion to instituting accountability mechanisms at the local Education Department and building strong coordination between Education and Health departments.

Perceptions and Understanding of Diabetes Mellitus Technology in Adults with Type 1 or Type 2 DM: A Pilot Survey from Pakistan.

INTRODUCTION: Diabetes mellitus technology (DMT) is increasingly used for routine management in developed countries, yet its uptake in developing countries is not as consistent. Multiple factors may influence this, including country specific patient perception regarding DMT. We conducted a pilot study in Pakistan to understand this important question which has not been studied yet. METHODS: A cross-sectional pilot study was conducted in Pakistan. An anonymous survey exploring perceptions of diabetes technology was circulated on social media platforms, collecting responses over 2 weeks. Target population included adults (≥18 years) living in Pakistan, with DM1 or 2. RESULTS: A total of 40 responses were received. The majority (36/40) reported using conventional glucometers. Nine used continuous glucose monitoring (CGM). Thirty-two of 40 patients believed DMT improved diabetes care, 22 felt it helped decreased risk of Diabetes-related complications. 15/40 stated that DMT results in increased cost of care. Sixteen reported their diabetes care teams had never discussed wearable DMT options whereas 11 disliked them because they did not want a device on their self. CONCLUSION: In our pilot study we have identified broad themes of opportunity and challenges to DMT use in Pakistan. Patients' perceptions regarding DMT were generally positive but significant barriers to its acceptance included high cost, lack of discussion between doctor and patient about available technology and personal hesitation. Limitations of our study include sampling bias (online survey) and small sample size, but this data can help inform larger studies, to look at this important topic in greater detail.

Predictors of Mortality in Patients Undergoing Mitral Valve Replacement.

OBJECTIVE: Although mitral valve replacement is frequently performed in patients of all age groups, there are few studies available which determine the causes of operative mortality in mitral valve replacement especially in our region. Therefore, the objective of this study was to identify factors that are significantly associated with operative mortality in mitral valve replacement. METHODS: From August 2012 to March 2013, 80 consecutive patients undergoing mitral valve replacement in a single tertiary hospital were included. Patients with a history of previous coronary artery bypass graft surgery or congenital heart problems were excluded from the sample. The included patients were observed for a period of 30 days. Pre and post-operative variables were used to identify significant predictors of mortality. RESULTS: The overall hospital mortality (30 days) was 15%. High post-perative creatinine (P =0.05), high ASO titre (P=0.03), young age (P=0.011), low cardiac output (P=0.0001), small mitral valve size (P=0.002) and new onset of atrial fibrillation (P=0.007) were the significant independent predictors of operative morality. CONCLUSION: Mitral valve replacement can be performed in third world countries with limited resources with low mortality. However, optimal selection of mitral valve size can help to improve operative mortality.