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OSF (Oral submucous fibrosis) is a chronic disease characterized by inflammation and progressive fibrosis of the submucosal tissues with the potential to progress into OSCC (Oral squamous cell carcinoma). Matrix metalloproteinases (MMP) are endopeptidases that play a role in extracellular matrix remodeling and pathophysiology of various diseases. The study aims to evaluate the gene polymorphism and protein expression of MMP-8 and their association with the severity of OSF. The cross-sectional study design involves patients diagnosed with OSF. DNA was extracted from saliva samples by the CTAB method followed by PCR and Sanger sequencing. The sequences were examined for MMP-8 polymorphism on Mega X software. ELISA was performed to assess the MMP-8 protein expression. The results of genetic polymorphism showed the alleles AG (rs11225395), TT (rs1861602574), CC (rs562617158), TT (rs2133511737), AA (rs1307439859), and CC (rs2133511706) consistent with disease severity. MMP-8 protein levels decreased with disease progression. Meanwhile, the association between the two showed a noteworthy significance with the presence of specific genetic variants, namely rs1320632, rs2133511732, rs1307439859, and rs2133511737, rs1307439859, rs562617158, rs11225395 shows a robust association with changes in MMP-8 protein expression. This study suggests a strong association between genotype and the modification of MMP-8 protein expression. In conclusion, MMP-8 may serve as a diagnostic biomarker in OSF., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The study was reviewed and approved by the Ethical Review Committee (ERC) Ziauddin University (Ref: 5790722RQPAT). Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2025. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Despite therapy advancements, amyloidosis mortality rates for older adults (aged ≥ 65) are rising. This study analyzes trends in amyloidosis-related mortality among older adults in the U.S. We conducted a cross-sectional analysis of death certificates from the CDC WONDER database for amyloidosis-related deaths from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) were calculated by age, race/ethnicity, urban-rural classification, and region. From 1999 to 2020, AAMR for amyloidosis in older adults (aged ≥ 65) in the U.S. increased from 2.7 to 5.6. Men consistently had higher AAMRs than women (men: 3.7 vs. women: 2.2 in 1999; men: 8.5 vs. women: 3.5 in 2020). In 2020, Non-Hispanic Blacks had the highest AAMR at 11.8, with an APC of 19.8 (95% CI 10.5-25.5). Regional differences were notable, with AAMRs highest in the Northeast (6.9) and lowest in the South (4.2). Large metropolitan areas had a higher AAMR (6.3) than non-metropolitan areas (4.6). Cardiac amyloidosis accounted for 68.8% of deaths, with AAMR rising from 1.7 to 4.2. There has been a significant increase in AAMRs for amyloidosis in the U.S. from 1999 to 2020, particularly among males, Non-Hispanic Blacks, and those in large metropolitan and Northeast areas. These findings stress the need for enhanced prevention and treatment strategies for older adults., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article. Ethical approval: This study was exempt from local institutional review board approval because it used deidentified public data and adhered to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines., (© 2025. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Introduction: Inflammatory bowel disease (IBD) is a global health issue profoundly impacting quality of life. The United States accounts for nearly a quarter of the world's IBD patients, with the highest prevalence rates. This study aims to identify the demographic and regional trends of IBD-related mortality in the U.S. from 1999 to 2020., Methodology: Our study utilized the CDC Wonder database to gather mortality data for IBD (Crohn's disease and ulcerative colitis) from 1999 to 2020. Results were presented as age-adjusted mortality rates (AAMR) per 100,000 population, with Joinpoint regression used to analyze trend changes and calculate annual percentage change (APC)., Results: A total of 62,310 IBD-related deaths were recorded. From 1999 to 2020, AAMR for Crohn's disease increased from 0.79 to 0.97, declining from 1999 to 2018 (APC: - 0.22) but surging from 2018 onwards (APC: 11.26). Women had a higher AAMR (0.81) compared to men (0.77). The highest rates were among non-Hispanic whites (0.86), followed by non-Hispanic blacks (0.48) and Hispanics (0.21). AAMR varied by state, ranging from 0.29 in Hawaii to 1.42 in Vermont. For ulcerative colitis, AAMR rose from 0.56 in 1999 to 0.63 in 2020, following a similar trend: a decline from 1999 to 2018 (APC: - 0.37) followed by an increase (APC: 12.21). State-specific AAMR ranged from 0.14 in Hawaii to 0.67 in Oregon., Conclusion: This study highlights a decrease in AAMR for both diseases from 1999 to 2018, followed by significant increases from 2018 to 2020, indicating a need for targeted interventions., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical approval: This study was exempted from the institutional review board's approval because it uses publicly available data that is de-identified. Research involving human and animal participants: All authors have confirmed that this study did not involve animal subjects or tissue., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Implantable cardioverter defibrillators (ICD) are battery-operated devices used to manage irregular heart rhythms and deliver therapeutic shocks to the heart. This updated systematic review and meta-analysis compares the efficacy and extraction-related outcomes of single-coil versus dual-coil ICDs in view of conflicting data., Methods: Several databases, including PubMed, Cochrane Library, and Google Scholar, were comprehensively explored dating from inception to April 1, 2024. Data were compared using odds ratio (OR), hazard ratio (HR), and mean differences (MD). A value of p < 0.05 indicated statistical significance., Results: Ultimately, 28 studies were included in this quantitative synthesis. Defibrillation threshold (DFT) indicated statistical superiority in the dual-coil cohort (MD: 0.58; 95% confidence interval [CI]: 0.07-1.09; p = 0.03). In addition, all-cause mortality was significantly elevated in the dual-coil cohort (HR: 0.91; 95% CI: 0.87-0.97; p = 0.001). Furthermore, implant time was significantly lower in the single-coil group (MD: -7.44; 95% CI: -13.44 to -1.43; p = 0.02). Other outcomes, including first shock efficacy, cardiac mortality, post-extraction major complications, post-extraction procedural success, and post-extraction mortality, did not demonstrate any significant statistical differences., Conclusion: In conclusion, despite the desirable safety profile of single-coil ICDs, the use of dual-coil ICDs continues to hold merit due to their superior efficacy and advanced sensing capabilities, especially in complex cases. In addition, the perceived risk of a greater adverse profile in dual-coil lead extraction can be refuted by preliminary aggregate results generated within this meta-analysis. However, further robust studies are warranted before arriving at a valid conclusion., (© 2025 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has emerged as a novel therapeutic option for the management of patients with diabetes, chronic kidney disease, or heart failure. We seek to summarize the evidence on the drug's effectiveness regarding cardiovascular (CV) outcomes., Methods: We conducted a literature search of Pubmed, Cochrane CENTRAL, Embase, and ClinicalTrials.gov from inception to September 2024. Trials exploring the effects of finerenone on CV outcomes were extracted and analyzed. The results of pooled analyses were presented as risk ratios (RRs) with 95% confidence intervals (CIs)., Results: A total of eight trials, incorporating 21 200 patients, were included. The pooled analysis demonstrated a significant reduction in all-cause death (RR 0.92, 95% CI: 0.85-0.99), major adverse CV events (RR 0.85, 95% CI: 0.81-0.90), heart failure-related hospitalizations or unplanned hospital visits (RR 0.82, 95% CI: 0.76-0.87) with finerenone administration compared to control. Finerenone use was associated with a trend of reduced risk of CV death without reaching statistical significance (RR 0.90, 95% CI: 0.81-1.00). The risk of myocardial infarction (RR 0.91, 95% CI: 0.74-1.12), adverse events (RR 0.96, 95% CI: 0.89-1.03), adverse events leading to discontinuation (RR 1.06, 95% CI: 0.96-1.17) remained comparable across both groups. However, an increased risk of hyperkalemia (RR 2.07, 95% CI: 1.88-2.27) was observed with finerenone therapy compared to the control group., Conclusion: Finerenone administration was associated with improved CV outcomes in the CV-renmetabolic conditions compared to the control group., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background and Aims: Several randomized clinical trials have been conducted assessing the potential efficacy of Farnesoid X receptor (FXR) agonists in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive review and analysis were needed to evaluate the findings of these trials. Hence, this systematic review and meta-analysis aim to study the association between FXR agonists and hepatic outcomes in patients with MASLD., Methods: Systematic review and meta-analysis evaluating the efficacy of FXR agonists in 1,227 patients assigned to the FXR intervention group compared to 650 patients in the placebo group. Changes in liver enzymes and hepatic steatosis assessed by MRI-PDFF were evaluated., Results: FXR agonist use was associated with a significant reduction in levels of AST, (WMD= -4.51, 95% CI=[-8.39,-0.63], P=0.02); ALT (WMD= -13.02, 95% CI=[-17.85,-8.19], P<0.00001); GGT (WMD= -32.20, 95% CI=[-38.63,-25.98], P<0.00001); MRI-PDFF, (SMD= -1.14, 95% CI=[-1.92,-0.35], P=0.005). FXR agonists did not significantly affect ALP levels, (WMD= 25.04, 95% CI=[19.22,30.87], P<0.00001] CONCLUSION: Results show promising evidence supporting the efficacy of FXR agonists in reducing hepatic steatosis and biomarkers of hepatic injury such as ALT, AST, and GGT., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

In the current study, we presented the genome sequence and taxonomic classification of the new extensively drug-resistant (XDR) Salmonella enterica serovar Typhi strain JRCGR-ST-AK02. Its genome size was found to be 4,780,534 bp, containing 4864 genes. Taxonomic classification was performed based on the Average Nucleotide Identity (ANI), Genome-to-Genome Distance Calculator (GGDC) and Average Amino Acid Identity (AAI) analysis. Pan-genome analysis revealed 34,4915 core genes, which are predominantly involved in general functions and carbohydrate metabolism. We used a subtractive genomics approach and identified the PocR protein as a drug target. Its 3D structure was built using homology modeling, and an e-pharmacophore hypothesis was created using its binding site. The pharmacophore hypothesis was screened against FDA-approved ligands library and a total of 2018 out 9392 drugs were selected for molecular docking. Cangrelor and Pentagastrin presented docking scores of -9.503 and -9.081 kcal/mol, respectively. The binding dynamics of these promising FDA-approved drugs were further confirmed through 200 ns molecular dynamics simulation, highlighting their stable and strong interactions with the PocR protein. Our study highlights the potential of Cangrelor and Pentagastrin for repurposing against XDR Salmonella Typhi. By identifying these drugs as promising candidates, we pave the way for new treatments for XDR Salmonella Typhi infections., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may influence the work reported in this study., (Copyright © 2024. Published by Elsevier B.V.)

Background: HIV remains a leading cause of death in the U.S. Previous research has examined mortality patterns among older adults with HIV, revealing regional and demographic disparities. This study aims to assess demographic and regional trends in HIV-related mortality among young adults from 1999 to 2020., Methods: Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database was used to identify young adults aged 15-44 where HIV was mentioned as either underlying or contributory cause of mortality between 1999 and 2020, using the B20-B24 codes from the International Statistical Classification of Diseases and Related Health Problems-10th Revision (ICD-10). Age-adjusted mortality rates (AAMRs) per 100,000 population and annual percentage change (APC) were determined., Results: The AAMRs for HIV in young adults consistently declined from 1999 to 2018, followed by a period of stability from 2018 to 2020 (annual percentage change: 0.5%; 95% confidence interval [95% CI], -7.4 to 9.0), with 64% deaths occurred in medical facilities. Overall, males had a twice AAMR than females (female: 2.22, 95% CI 2.19-2.24; male: 5.19, 95% CI 5.15-5.23). Non-Hispanic (NH) Blacks had sevenfold higher mortality rates than Whites (AAMR 14.88 vs. 2.036). The Southern region experienced threefold higher mortality compared to the Midwest. Metropolitan adults had a twofold higher AAMR than nonmetropolitan adults. States in the top 90th percentile for HIV-related mortality, including Mississippi, Maryland, Florida, Louisiana, and the District of Columbia, exhibited six times higher mortality compared to states in the bottom 10th percentile, such as North Dakota, Idaho, Wyoming, Montana, and Utah., Conclusions: To address these disparities and ensure continued progress, urgent measures are required., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: High morbidity and mortality make pancreaticoduodenectomy (PD) one of the most complicated surgical procedures. This meta-analysis aimed to compare the outcomes of robotic pancreaticoduodenectomy (RPD) versus open pancreaticoduodenectomy (OPD)., Method: A comprehensive literature search of PubMed, Cochrane Central, and Google Scholar was conducted from inception to November 2024. Studies comparing RPD and OPD in adults aged ≥ 18 years were included. Data for the outcomes of interest were extracted., Results: Forty-one studies with a total of 54,287 patients were pooled. RPD is significantly superior to OPD in terms of overall postoperative complications (RR = 0.91, 95% CI: [0.86-0.97]; p = 0.001), wound infections (RR = 0.63, 95% CI: [0.49-0.81], p = 0.0004), estimated blood loss (WMD = -171.99 ml, 95% CI: [ -217.76 to -126.22], p < 0.01) and hospitalization duration (WMD = -1.33 days, 95% CI: [ -1.84 to -0.82], p < 0.01) with a longer operating time (WMD = 73.22 min, 95% CI: [56.20 to 90.23], p < 0.01)., Conclusion: In conclusion, RPD shows a lower risk of wound infections and overall postoperative morbidity compared to OPD. It has lower estimated blood loss, shorter hospitalization duration, and a longer operating time. The two approaches were comparable in terms of resection quality. More high-quality RCTs are required to draw definite conclusions., Competing Interests: Declarations. Ethical Approval: Not Applicable. Informed Consent: Not Applicable. Consent to Publish: Not Applicable. Competing Interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Smokeless tobacco (SLT) encompasses products that are not burnt but instead consumed orally or nasally. One-third of tobacco is consumed in the smokeless form in South Asia. Despite its widespread usage, there has been limited empirical research on the prevalence and factors influencing SLT consumption in Pakistan. This study aimed to provide an assessment of SLT knowledge, attitudes, and usage in Pakistan., Methods: Using an online questionnaire, a cross-sectional survey was conducted across Pakistan. Convenience sampling was used to disseminate, and expert approval was sought followed by a pilot study to validate the questionnaire. A comprehensive questionnaire was developed using elements from the Global Adult Tobacco Survey and other tools which had previously been utilized within Pakistan. Participants' responses were described using descriptive statistics, and SPSS version 26 was used to perform linear and logistic regression. A p-value of less than 0.05 was considered statistically significant., Results: Data was collected from 1,195 participants among which 85.86% of participants had heard of SLTs prior to the survey. Sex, province, household income and previous doctor visits were significant determinants to product knowledge through which 72.55% agreed that these products can lead to serious illnesses but 30% noted a lack of knowledge on legality. General attitudes agreed that it makes one feel unwell (44.1%), gives a sense of guilt (43.85%) and more research is needed on it (54.39%). Negative health effects were the biggest deterrent from pursuing these products for 60.33% of participants. Among significant factors influencing the use of SLTs, the greatest odds of use were found with use as an alternative to cigarettes (OR 4.45) and secondly, due to its availability in a liked flavor (OR 2.27). About 31% reported to have used the product once, with 69.82% of current users expressing a desire to quit., Conclusions: Although adequate knowledge and aligning attitudes exist for SLTs, light is shed in the face of a sustaining public health problem. We offer important insights that can guide the creation of focused interventions meant to lower SLT use, and the health hazards associated with it in the Pakistani community by highlighting important myths, incentives, and deterrents., Competing Interests: Declarations. Ethics approval and consent to participate: Our study obtained ethical clearance from the Ethical Review Committee (ERC) at the Aga Khan University (ID: 2023-8608-24823). The form initially obtained informed consent, detailing the scope of the study, the right of the participant to withdraw from the study at any time and the maintenance of confidentiality of the participants. If the participant agreed to take part in the study, they were able to fill the rest of the questionnaire. To maintain the privacy of the participants, identifiers such as name were not asked. In addition, to maintain anonymity, the questionnaire did not record respondents’ names. There were no risks, immediate benefits, or incentives for participation in the survey. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Giant intracranial aneurysms (GIAs) of the anterior communicating artery (AComm) are rare and challenging to treat due to their distinct angioarchitecture., Research Question: To review demographic, morphological, clinical, and prognostic factors in the treatment of giant AComm aneurysms to inform decision-making., Materials and Methods: Medline, Scopus, and Cochrane databases were searched for records examining cases diagnosed with giant AComm aneurysms. The study type, sample size, patient age, aneurysm site, aneurysm size, presenting complaints, and treatment modality were tabulated, and methodological quality was assessed. Additionally, two cases from our institution were included., Results: The data from 24 retrieved records, including 45 cases (60% treated with direct clipping/clip reconstruction, 20% with surgical bypass±trapping, and 16% with endovascular/combined methods) were obtained. The mean age was 52 years with an overall male preponderance (3:1). 73% presented with symptoms; mostly visual impairment/loss and subarachnoid hemorrhage. 82% had favorable outcomes (mRS 0-2). 56% had a mean maximum diameter between 25 and 30 mm. Cases treated by direct clipping/reconstruction were primarily ruptured, while cases treated by surgical bypass/trapping were unruptured or asymptomatic. Endovascular/combined methods were utilized for only few cases., Discussion and Conclusion: Immediate suspicion is warranted for visual impairment with headaches in adults or seizures in the elderly. Direct clipping is the first-line treatment for ruptured cases closely followed by surgical bypass and trapping for unruptured cases. There is limited data on endovascular/combined methods. Evidence from case reports/series should be interpreted with caution. Both inter-modality and intra-modality nuances exist., Competing Interests: 1.Roua Nasir: Declaration of Interest: None2.Midhat e Zahra Naqvi: Declaration of Interest: None3.Salaar Ahmed: Declaration of Interest: None4.Maarij ul Hassan: Declaration of Interest: None5.Rabeet Tariq: Declaration of Interest: None6.Saad Akhter Khan: Declaration of Interest: None7.Pia Koeskemeier: Declaration of Interest: None8.Rajiv K. Khajuria: Declaration of Interest: None9.Mohammad Hamza Bajwa: Declaration of Interest: None10.Sajjad Muhammad: Declaration of Interest: None, (© 2025 The Authors.)

This research paper examines the financial and energy-related factors influencing the exchange rate in Pakistan, focusing on currency depreciation or appreciation between July 2006 and June 2021. The Autoregressive Distributed Lag (ARDL) Bounds Test is employed to analyze both short- and long-run dynamics. The findings reveal that foreign direct investment (FDI) supports strengthening the exchange rate, addressing concerns about short- and long-term profitability. Energy factors, such as fuel prices, positively impact the exchange rate in both the short and long term. Conversely, stock market declines and rising inflation are associated with significant changes in the exchange rate, including currency depreciation. Interestingly, remittances exhibit a complex relationship with the exchange rate, potentially resulting in adverse effects if not managed effectively. The study provides balanced policy implications for sustainable financial and energy development in emerging economies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors of this manuscript, Saif Ullah and Haitham Nobanee, currently serve as Associate Editors for Heliyon. The authors declare no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Introduction: Incentive-linked prescribing, which is when healthcare providers accept incentives from pharmaceutical companies for prescribing promoted medicines, is a form of bribery that harms patients and health systems globally. We developed a novel method using data collectors posing as pharmaceutical company sales representatives to evaluate private doctors' engagement in incentive-linked prescribing and the impact of a multifaceted educational intervention on reducing this practice in Karachi, Pakistan., Methods: We made a sampling frame of all doctors running for-profit, primary-care clinics and randomly allocated participants to control and intervention groups (1:1). The intervention group received a multifaceted seminar on ethical prescribing and reinforcement messages over 6 weeks. The control group attended a seminar without mention of ethical prescribing. The primary outcome was the proportion of participants agreeing to accept incentives in exchange for prescribing promoted medicines from data collectors posing as pharmaceutical company representatives, 3 months after the seminars., Results: We enrolled 419 of 440 eligible participants. Of 210 participants randomly allocated to the intervention group, 135 (64%) attended the intervention seminar and of 209 participants allocated to the control group, 132 (63%) attended the placebo seminar. The primary outcome was assessed in 130 (96%) and 124 (94%) of intervention and control participants, respectively. No participants detected the covert data collectors. 52 control group doctors (41.9%) agreed to accept incentives as compared with 42 intervention group doctors (32.3%). After adjusting for doctors' age, sex and clinic district, there was no evidence of the intervention's impact on the primary outcome (OR 0.70 [95% CI 0.40 to 1.20], p=0.192)., Conclusions: This first study to covertly assess deal-making between doctors and pharmaceutical company representatives demonstrated that the practice is strikingly widespread in the study setting and suggested that substantial reductions are unlikely to be achieved by educational interventions alone. Our novel method provides an opportunity to generate evidence on deal-making between doctors and pharmaceutical companies elsewhere., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The growing incidence of obesity has led to a proportionate rise in type 2 diabetes mellitus (T2DM) and its associated complications. We aimed to compare the long-term outcomes of Roux-en-y Gastric Bypass surgery (RYGB) and conventional medical management in T2DM obese patients., Methods: PubMed, Google Scholar, and Clinicaltrial.gov were searched from inception to September 2023. Randomized Controlled Trials (RCTs) and cohort studies were included in this meta-analysis. The primary outcomes were the T2DM remission at 1, 2, 3, and 5 years and the accomplishment of the ADA composite triple treatment goal. The revised Cochrane risk of bias tool 2.0 and New-Castle Ottawa scale were used to assess the quality of the studies. This meta-analysis was registered prospectively on PROSPERO CRD42023466324., Results: Of the 3,323 studies yielded from our initial search, 22 were included in this evidence analysis, with 5,176 total patients (1,984 and 3,192 patients in RYGB and conventional medical management groups). A significant increase in the accomplishment in the ADA's composite triple treatment goal was observed in RYGB group as compared to the conventional medical management group (RR 2.41, 95% CI 1.39-4.15, p-value 0.002, I 2 35%). Diabetes remission was a clinically successful outcome after 1, 2, 3, and 5 years of the RYGB surgery in the patients (1 year; RR 4.74, 95%CI 2.46-9.12, p-value < 0.00001, I 2 0%, 2 years; RR 8.95, 95% CI 1.71-46.71, p-value 0.009, I 2 92%3 years; RR 18.18 95%CI 7.57-43.62, p-value < 0.00001, I 2 0%, 5 years; RR 0.22, 95% CI 2.31-16.75, p-value 0.0003, I 2  = 71%)., Conclusion: The pooled analysis of the given data concluded that the RYGB surgery was more effective in treating T2DM in patients than conventional medical management., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01526-z., Competing Interests: Conflict of interestThe authors declared that they have no conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Importance: Male postpartum depression is prevalent across populations; however, there is limited evidence on strategies to address it, particularly in low-income settings., Objective: To evaluate the effectiveness of Learning Through Play Plus Dads (LTP + Dads), a nonspecialist-delivered psychosocial intervention, in improving symptoms of male postpartum depression compared to treatment as usual., Design, Setting, and Participants: This cluster randomized clinical trial was conducted in Karachi, Pakistan, between June 2018 and November 2019. Assessors were blind to treatment allocation. Participants were recruited from 2 large towns in the city of Karachi via basic health units. Fathers aged 18 years and older with a DSM-5 diagnosis of major depressive episode and a child younger than 30 months were recruited. Of 1582 fathers approached, 1527 were screened and 357 were randomized in a 1:1 ratio to either the intervention or treatment as usual; 328 were included in the final analysis. Data were analyzed from April to June 2022., Interventions: LTP + Dads is a manualized intervention combining parenting skills training, play therapy, and cognitive behavior therapy. The intervention was delivered by community health workers via 12 group sessions over 4 months., Main Outcomes and Measures: The primary outcome was change in 17-item Hamilton Depression Rating Scale score at 4 months. Secondary outcomes included anxiety symptoms; parenting stress; intimate partner violence; functioning; quality of life; and child social, emotional, and physical health outcomes. Assessments were completed at baseline and 4 and 6 months postrandomization., Results: Of the 357 fathers included (mean [SD] age, 31.44 [7.24] years), 171 were randomized to the intervention and 186 to treatment as usual. Participants randomized to the intervention demonstrated significantly greater improvements in depression (group difference ratio [GDR], 0.66; 95% CI, 0.47 to 0.91; P < .001), anxiety (GDR, 0.62; 95% CI, 0.48 to 0.81; P < .001), parenting stress (GDR, -12.5; 95% CI, -19.1 to -6.0; P < .001), intimate partner violence (GDR, 0.89; 95% CI, 0.80 to 1.00; P = .05), disability (GDR, 0.77; 95% CI, 0.61 to 0.97; P = .03), and health-related quality of life (GDR, 12.7; 95% CI, 0.17 to 0.34; P < .001) at 4 months. The difference in depression and parenting stress was sustained at 6 months. Children of fathers randomized to the parenting intervention had significantly greater improvements in social-emotional development scores (mean difference, -20.8; 95% CI, -28.8 to -12.9; P < .001) at 6 months., Conclusions and Relevance: The psychosocial parenting intervention in this study has the potential to improve paternal mental health and child development in Pakistan. Further studies in other populations and with longer follow-up are warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT03564847.

Gastric cancer is described as a malignancy occurring in the region between the gastroesophageal junction and the pylorus. According to the histology, majority of gastric cancers are classified as adenocarcinomas. The prevalence of bone metastasis in the general population is 2-3%. Here, an unusual case of a 73-year-old male is discussed who presented on September 10, 2023, with symptoms of lower back pain and bowel and urinary incontinence. His MRI results showed mild indentation along with nerve impingement and hypertrophied ligamentum flavum at the level of L5/S1. Within D11 and D12 vertebral bodies, diffuse abnormal signals were appreciated predominantly along posterior corners. CT scan of the abdomen showed sessile hypodense area along the mucosa of the posterior wall of the gastric antrum. Histopathology further confirmed the diagnosis with the appearance of signet ring cells. He was managed with supportive care and palliative radiotherapy. The patient expired on the 28th day of being discharged.

Introduction: Gliomas are the most common primary malignant intraparenchymal brain tumors with a dismal prognosis. With growing advances in artificial intelligence, machine learning and deep learning models are being utilized for preoperative, intraoperative and postoperative neurological decision-making. We aimed to compile published literature in one format and evaluate the quality of level 1a evidence currently available., Methodology: Using PRISMA guidelines, a comprehensive literature search was conducted within databases including Medline, Scopus, and Cochrane Library, and records with the application of artificial intelligence in glioma management were included. The AMSTAR 2 tool was used to assess the quality of systematic reviews and meta-analyses by two independent researchers., Results: From 812 studies, 23 studies were included. AMSTAR II appraised most reviews as either low or critically low in quality. Most reviews failed to deliver in critical domains related to the exclusion of studies, appropriateness of meta-analytical methods, and assessment of publication bias. Similarly, compliance was lowest in non-critical areas related to study design selection and the disclosure of funding sources in individual records. Evidence is moderate to low in quality in reviews on multiple neuro-oncological applications, low quality in glioma diagnosis and individual molecular markers like MGMT promoter methylation status, IDH, and 1p19q identification, and critically low in tumor segmentation, glioma grading, and multiple molecular markers identification., Conclusion: AMSTAR 2 is a robust tool to identify high-quality systematic reviews. There is a paucity of high-quality systematic reviews on the utility of artificial intelligence in glioma management, with some demonstrating critically low quality. Therefore, caution must be exercised when drawing inferences from these results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To generate consensus and provide expert clinical practice statements for the management of adult sepsis in resource-limited settings., Methods: An international multidisciplinary Steering Committee with expertise in sepsis management and including a Delphi methodologist was convened by the Asia Pacific Sepsis Alliance (APSA). The committee selected an international panel of clinicians and researchers with expertise in sepsis management. A Delphi process based on an iterative approach was used to obtain the final consensus statements., Results: A stable consensus was achieved for 30 (94%) of the statements by 41 experts after four survey rounds. These include consensus on managing patients with sepsis outside a designated critical care area, triggers for escalating clinical management and criteria for safe transfer to another facility. The experts agreed on the following: in the absence of serum lactate, clinical parameters such as altered mental status, capillary refill time and urine output may be used to guide resuscitation; special considerations regarding the volume of fluid used for resuscitation, especially in tropical infections, including the use of simple tests to assess fluid responsiveness when facilities for advanced hemodynamic monitoring are limited; use of Ringer's lactate or Hartmann's solution as balanced salt solutions; epinephrine when norepinephrine or vasopressin are unavailable; and the administration of vasopressors via a peripheral vein if central venous access is unavailable or not feasible. Similarly, where facilities for investigation are unavailable, there was consensus for empirical antimicrobial administration without delay when sepsis was strongly suspected, as was the empirical use of antiparasitic agents in patients with suspicion of parasitic infections., Conclusion: Using a Delphi method, international experts reached consensus to generate expert clinical practice statements providing guidance to clinicians worldwide on the management of sepsis in resource-limited settings. These statements complement existing guidelines where evidence is lacking and add relevant aspects of sepsis management that are not addressed by current international guidelines. Future studies are needed to assess the effects of these practice statements and address remaining uncertainties., Competing Interests: Declarations. Conflicts of interest: Massimo Antonelli: Grants from GE and Fisher & Paykel; Lecture fees from Menarini, Shionogi, Fisher & Paykel, Dimar. Jan De Waele: Consulted for Biomerieux, Menarini, MSD, Pfizer, Roche Diagnostics, ThermoFisher and Viatris (fees and honoraria paid to institution). Supported by a Sr Clinical Research Grant from the Research Foundation Flanders (FWO, Ref.1881020N). Jigeeshu Divatia: Lecture fees from Edwards India paid to my institution. Simon Finfer: Supported by an NHMRC Investigator Fellowship (Leadership Level 3 App 2017580), has received consulting fees paid to his employer from RevImmune Inc. and owns options in Sepsis Scout. Naomi E Hammond: Supported by an NHMRC Investigator Fellowship (Emerging Leader Level 1 App 1196320), has received consulting fees paid to her employer from RevImmune Inc. Arthur Kwizera: Grants from the Wellcome Trust; NIHR; Fisher & Paykel Ltd; Gradian Health Systems; Vygon Ltd; Speaker support from the ESICM; Makerere University Research and Innovation Fund. Marlies Ostermann: Institution received research funding from Baxter and Biomerieux. Ethical approval and consent: The study protocol was registered on clinicaltrials.gov [NCT05909384]. Oxford Tropical Research Ethics Committee (OxTREC) confirmed that the study was exempt from ethics review in March 2023. Consent to participate and publish: All authors and collaborators consented to participate in and publish this study., (© 2024. The Author(s).)

For routine measurement of Voriconazole (VZ) in a pure and gel formulation, a quick and accurate RP-HPLC technique with UV detection (254 nm) was developed. With a flow rate of 1.0 ml/min using a mobile phase that contained acetonitrile and water mixed 50:50, v/v. Internal standard approach was used for quantification. The method shows good linearity (correlation coefficient = 0.9999) with acceptable accuracy, precision and robustness. Three elements were taken into account to measure robustness. Flow rate, mobile phase composition, and pH all have an impact on the response, but only the flow rate which causes a reduction in the concentration of the drug-has a significant impact on the response. Analyst, equipment, and days were taken into consideration for a precision measurement. The analytical procedure had good precision, as seen by the %RSD which is found to be less than 2.0. The proposed method was straightforward, extremely sensitive, exact, and accurate, and it had a retention time of less than 4 minutes, indicating that it is appropriate for daily quality control., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sheikh 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: This review aims to analyze sex-related differences in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS)., Methods: 10 studies were retrieved from PubMed and Embase comparing outcomes between men and women admitted with AMI complicated by CS. Pooled log odds ratios (OR) were calculated for binary outcomes using the Mantel-Haenszel method, and Hedges' g with the inverse-variance method was used for continuous outcomes., Results: The primary endpoints were in-hospital mortality and 30-day mortality. The secondary endpoints were reinfarction rate, length of hospital stay (LOS), requirement of renal replacement therapy (RRT), and stroke (ischemic and hemorrhagic). Males exhibited a lower risk of in-hospital mortality (OR 0.77, 95 % CI 0.69-0.85, I 2 = 97 %, p < 0.0001), 30-day mortality (OR 0.69, 95 % CI: 0.61-0.78, I² = 0 %, p < 0.0001) and stroke (OR 0.91, 95 % CI 0.87-0.95, I 2 = 36 %, p < 0.0001) compared to females. In contrast, males were more likely to require renal replacement therapy (RRT) (OR 1.27, 95 % CI 1.09-1.48, I 2 = 69 % p = 0.0017). However, there were no statistically significant differences between females and males in terms of reinfarction rate (OR 0.88, 95 % CI 0.66-1.18, I 2 = 56 %, p = 0.3936) or length of hospital stay during hospitalization (Hedges's g 0.35 days, 95 % CI -0.38-1.07, I 2 = 100 %, p = 0.34)., Conclusion: Females with AMI and CS have higher in-hospital mortality, 30-day mortality, and stroke risk than men. Men are more likely to require RRT. Further research is needed to understand underlying mechanisms and improve outcomes for both genders., Competing Interests: Declaration of competing interest All authors declare any conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The main objective was to assess the therapeutic efficacy of selenium alone versus a combination of myo-inositol and selenium (MI + Se) in treating patients with autoimmune thyroiditis (AIT). The study aims to determine which treatment option is more effective in restoring euthyroid state, as indicated by changes in thyroid-stimulating hormone (TSH), T3, T4, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb)., Methods: Google Scholar and PubMed databases were searched for randomized controlled trials (RCTs) and observational studies that reported outcomes of combined treatment (MI + Se) in restoring a euthyroid state, specifically comparing it with selenium-only (Se-only) treatment. Changes in TSH, T3, T4, TPOAb, and TgAb levels from baseline were defined as indicators to compare the effect of combined versus selenium-only treatment in restoring euthyroid levels. The Cochrane risk of bias tool and Newcastle Ottawa Scale were used to assess the quality of the randomized control trials included in the study. Review Manager (version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark) was used for statistical analysis., Result: We pooled three studies, enrolling 151 participants in the MI + Se group and 137 participants in the Se group. Supplementation of Se with MI demonstrated a significant reduction in TSH levels compared to Se alone (SMD = -1.15, 95% CI: -1.60 to -0.69, P  < .00001). MI + Se treatment also significantly reduced TgAb levels compared to Se (SMD = -0.51, 95% CI: -0.78 to -0.24, P  = .0002). In contrast, TPOAB, T3 and T4 levels were non-significantly reduced from baseline in patients treated with MI + Se when compared to Se alone (SMD = -0.81, 95% CI: -0.44 to 0.09, P  = .20), (SMD = 0.16, 95% CI: -0.09 to 0.42, P  = .22), and (SMD = 0.30, 95% CI: -0.23 to 0.83, P  = .26) respectively., Conclusion: Supplementation of Se with MI showed a significant reduction in TSH and TgAb levels compared to selenium-only treatment, with a non-significant reduction in TPOAB, T3, and T4 levels. This entails the need for powered clinical trials and observational studies with longer follow-ups to critically assess the role of combined therapy in restoring euthyroid state in patients with AIT., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Recent research indicates that intravenous ferric carboxymaltose (IV FCM) presents a promising solution for Restless Legs Syndrome (RLS), distinguishing itself from other iron sources with minimal to no adverse effects. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety profile of administering IV FCM in patients with RLS, assuming that RLS and Iron deficiency anemia (IDA) are correlated., Methodology: This study was conducted according to the PRISMA guideline, with search conducted on PubMed, Google Scholar, and the Medline library. Data was extracted from each study regarding RLS and the effect of IV FCM on it, while analysis was conducted on Review Manager Software., Results: This meta-analysis comprises of 7 randomized controlled trials (RCTs). All 7 studies reported international RLS severity scale (IRLS) and the pooled analysis revealed a significant reduction in IRLS score favoring IV FCM [WMD: -6.03, 95 % CI (-10.11, -1.96), p = 0.004]. 3 out of 7 studies reported short form-36 health survey (SF-36) and the pooled analysis revealed that the total score of SF-36 significantly favors the group taking IV FCM [WMD: 7.44, 95%CI (1.67, 13.20) p = 0.01]. 4 out of 7 studies reported visual analogue scale (VAS) for RLS severity and pooled analysis revealed that IV FCM significantly decreased VAS) of RLS severity score as compared to the control [MD -19.21, 95%CI (-31.90, -6.52) p0.003]., Conclusion: The study findings support the efficacy of IVFCM in reducing the severity of RLS symptoms. Significant improvements in the IRLS scores were observed, alongside enhancements in overall quality of life measured by SF-36 scores., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To assess the awareness among patients of prospective orthodontics about post-orthodontic retention., Methods: The cross-sectional study was conducted from May 2022 to May 2023 at the Department of Orthodontics, Ziauddin University, Karachi, and comprised patients of either gender enrolled for their first appointment at the outpatient clinic. Each patient received a validated questionnaire which explored their understanding, attitudes and expectations regarding the importance of retention after orthodontic treatment. Data was analysed using SPSS 25., Results: Of the 206 questionnaires distributed, 203(98.5%) were returned duly filled. The overall mean age of the sample was 20.25±5.24 years (range: 8-48 years). There were 131(64.5%) females with mean age 12±3.2 years, and 72(35.5%) males with mean age 16±2.1 years. Majority of the participants 133(64.9%) believed that movement of teeth cannot occur without orthodontic appliances, 115(56.1%) believed that parents and guardians were responsible for the stability of the treatment results, while 88(42.9%) believed that dentists/orthodontists were responsible for the stability of the treatment outcomes. There were 132(64.4%) subjects who found removable retainer as a favourable retention device, while 71(34.6%) favoured fixed retainers., Conclusions: There was a notable gap in patients' understanding of the retention phase, its importance and treatment durability expectations.

Women going through menopause frequently experience vasomotor symptoms such as hot flashes, night sweats, and sleep disturbances, significantly influencing their quality of life. Hormonal therapy has been demonstrated to be beneficial in treating VMS. However, due to specific restrictions, it is not recommended for every woman. Fezolinetant, a neurokinin 3 antagonist and non-hormonal treatment for severe to moderate VMS, functions by inhibiting neuronal impulses originating from the hypothalamic thermoregulatory center. Current Skylight 2 and 4 trials statistically demonstrate the safety and acceptability of fezolinetant, with relatively few adverse effects reported. Fezolinetant has been shown great potential for treating menopausal-related VMS, supporting its further advancement. However, further investigation is required to thoroughly evaluate its safety, effectiveness, and its impact on sleep patterns., Competing Interests: Declarations. Ethical approval: Ethical approval is not required or applicable for this manuscript type as no human participants or animals were involved. Consent statement: The study was not done on patients or volunteers, therefore no written consent was required. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Over the past few years, the technology powering mobile devices such as smartphones has made significant progress. Furthermore, the healthcare industry is always progressing and actively embracing the latest technological advancements to achieve the highest level of efficiency. With the rising prevalence of smartphones and internet connection, customers are benefiting from reduced prices, convenient home delivery, and effortless accessibility through online pharmacies. Internet-based pharmacies facilitate the internet-based transaction of health-related products, such as drugs, dietary supplements, and various other wellbeing products., Objective of Study: The study assessed digital pharmacy applications in India using the Mobile App Rating Scale (MARS) on Android and iOS devices, aiming to evaluate their quality., Methods: An investigation examined the digital pharmacy applications in India that were accessible via the Android Market and App Store. The applications were assessed by two researchers using the MARS questionnaire, a tool that evaluates 23 variables categorized into five domains: Engagement, Functionality, Aesthetics, Information, and Subjective Quality. The grading system spanned from one to five for every category., Results: A Google Play Store and App Store investigation revealed 40 online pharmacy apps in India, with 13 rejected. Seven were non-English language-related apps and seven were not downloaded. Thirteen were chosen and evaluated using the MARS Scale. The MARS demonstrated significant positive associations across its components, namely Engagement, Functionality, Aesthetics, and Information. Specifically, greater levels of user functionality were shown to be indicative of superior app aesthetics and engagement. The mean rating of the 13 apps fell between the range of 3.11 to 4.32 on a 5-point scale., Conclusion: This is the first study to utilize the MARS scale to assess the efficacy of online pharmacy applications in India. This research enhanced the functionality and quality of various online pharmacy applications utilized in India., 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 © 2024 Sattar, Naveed, Rehman, Usman and Jamshed.)

Background: Globally, a rising trend has been observed in the prevalence of thyroid disorders, with many demographic and geographic factors influencing its epidemiology. Nonetheless, some cases often go undetected due to the inconsistent and non-specific nature of the clinical symptoms. Therefore, we aimed to determine the trend and relationship between various pathological findings in thyroid disease patients and their demographic factors to aid clinicians in making a prompt diagnosis and treatment plan., Methods: A descriptive correlational study was conducted from January 2020 to May 2022 at Jinnah Postgraduate Medical Center, Karachi. We collected data via random sampling from 258 patients suffering from thyroid disorders. We evaluated baseline patient characteristics, along with, thyroid scan and fine needle aspiration cytology (FNAC) reports, and local thyroid gland examination findings., Results: Out of 258 participants, 192 (74.4%) were females, whereas 66 (25.6%) were males, giving a female: male ratio of 2.9: 1. On local examination, 167 (64.7%) were found to have a solitary nodule, 79 (30.6%) had multinodular goiter. Findings revealed that benign follicular lesions had the highest prevalence (35.3%). Moreover, among the cancerous growth, papillary carcinoma presented the highest cases (12.4%). Of 258 cases, 24 patients had non-surgical interventions, while most (234) had surgical interventions. Total thyroidectomy was the most common procedure opted for by 45.3% (n = 117) of the participants, followed by lobectomy 70 (27.1%), near total thyroidectomy 43 (13.2%), modified radical neck dissection 5 (1.9%)., Conclusion: Our study showed that nearly all thyroid-related pathologies were more prevalent amongst females than males, with the majority having an acute to sub-acute clinical presentation. Multinodular goiter was a prominent finding indicating a greater need for screening tools and access to healthcare facilities, especially in rural areas, to allow future studies to compare provinces accurately., (© The Author(s) 2024.)

Cow milk protein allergy (CMPA) is one of the most common childhood allergies that manifests with a range of digestive symptoms and skin reactions, which usually resolve with age. In this report, we present the case of a one-month-old male who presented with a rare and severe manifestation of neonatal CMPA. The neonate underwent numerous hospital admissions due to a presentation that closely mimicked symptoms of a metabolic disorder and sepsis. Our primary objective is to highlight the significance of systematically considering or excluding a CMPA diagnosis, irrespective of the severity of presentation. This proactive approach may potentially reduce future complications among the affected paediatric population, thereby preventing prolonged hospitalisation and the associated disease burden, as seen in this case.

The effectiveness of concurrent exercise (CE) as an emerging approach for type-II diabetes mellitus (T2DM) patients was evaluated through a comprehensive search on Google Scholar, PubMed, Pedro, CINAHL, and Medline from 2015 to March 2023. Sixteen RCTs were selected which evaluated CE (aerobic + resistance in the same session) effects on a minimum of three days/week among T2DM patients, and the control group received usual care or no exercise. Studies that evaluated at least one glycaemic variable, i.e. HbA1C, fasting blood glucose level (FBGL), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), were eligible. Intervention with a follow-up period of ≥8 weeks, patients of any age and gender, and literature in the English language were included. A rigorous review was performed using the Cochrane Collaboration risk of bias tool (RoB 2) to minimise biases, which include the randomisation process, deviation from intended intervention, missing outcome data, outcome measurement, and selection bias. CE significantly improved HbA1C (95% CI of -0.654 to 0.363, I2 = 84.92% moderate heterogeneity), FBGL (95% CI of -0.239 to 1.145, I2 = 93.74% - high level of heterogeneity), and insulin resistance (HOMA-IR) (95% CI of -0.593 to 0.544, I2 = 92.85% - high level of heterogeneity). Collectively, findings indicate the potential of CE as an intervention to impact glycaemic control in T2DM patients positively. However, the relatively high I² values suggest notable variability among studies, and further research to explore the factors contributing to this heterogeneity, exercise protocol along with progression, and duration of diabetes are needed, which is more challenging to determine a precise dose-response relationship. Therefore, more studies are required to provide thorough insights into these components for T2DM management. Key Words: Glycated haemoglobin, Glycaemic control, Insulin resistance, Physical exercise, Type-II diabetes mellitus.

Ecological sustainability has become a top priority for worldwide policymakers due to severe consequences. Innovative approaches, like climate finance and financial technology (FinTech), are crucial in combating climate change and its environmental hazards. This study aims to investigate the role of climate finance on ecological sustainability with FinTech and institutional quality as moderators from 2010 to 2022 in 58 advanced countries. Besides that, the COVID-19 spillover shock effect (pre-post), socio-economic conditions, and trade openness are also considered as other variables in this study. The study employed the two-step Sys GMM approach, and the robustness was checked by the D-K regression and bootstrap panel quantile regression for empirical analysis. The results reveal that climate finance improves the trajectory of long-term ecological sustainability by significantly lowering the ecological footprint (EF). FinTech has a strong positive effect on ecological performance by decreasing the EF. Furthermore, the combined influence of CF∗FinTech has significantly boosted ecological sustainability by diminishing the EF. Institutional quality substantially enhances ecological sustainability by reducing the EF. Similarly, the interaction term CF∗IQ improves ecological performance by lowering the EF. The outcomes have significant implications for sustainable development policy, influencing the transition to low-carbon economies and meeting net-zero emissions within this decade, contributing to improved ecological sustainability., Competing Interests: Declaration of competing interest There is no conflict of interest between the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Despite advancements in coronary artery disease (CAD) management, major adverse cardiovascular events persist. Vitamin K antagonists and direct oral anticoagulants present bleeding risks. Low-dose rivaroxaban (2.5 mg) is approved by the European Society of Cardiology and the US Food and Drug Administration for CAD. The survival advantage and risk-benefit profile of combining low-dose rivaroxaban with aspirin for CAD patients remain uncertain. This meta-analysis aims to compare the efficacy of low-dose rivaroxaban plus aspirin versus aspirin monotherapy in CAD patients., Methods: We systematically searched databases for randomized controlled trials exploring low-dose rivaroxaban with aspirin in CAD patients. Of the 6220 studies screened, five met the inclusion criteria. Primary outcomes included myocardial infarction, stroke, major bleeding events, and all-cause mortality. The analysis employed a fixed-effects model, calculating hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Five randomized controlled trials involving 41,351 participants were included. Rivaroxaban (2.5 mg) significantly reduced all-cause mortality (HR, 0.88; 95% CI, 0.81-0.95; P = 0.002), myocardial infarction (HR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and stroke (HR, 0.61; 95% CI, 0.49-0.76; P < 0.00001) compared to aspirin alone. However, it increased major bleeding risk (HR, 1.66; 95% CI, 1.40-1.97; P < 0.01). Meta-regression revealed no dose-dependent impact on all-cause mortality., Conclusion: Low-dose rivaroxaban demonstrates survival benefits and reduces myocardial infarction and stroke risks in CAD patients, albeit with an increased risk of major bleeding. Consideration of patient bleeding risk is crucial when adding rivaroxaban to antiplatelet therapy. Further research is warranted to compare its effectiveness and safety with dual antiplatelet therapy or P2Y12 inhibitors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To find radiographic association of the root pulp visibility and periodontal ligament visibility stages of lower second molar teeth with chronological age., Methods: The prospective, analytical, cross-sectional study was conducted after approval from the ethics review committee of Ziauddin University, Karachi, and comprised digital orthopantomograms from 2020 to 2022. The orthopantomograms related to lower second molar teeth from the left side of the mandible of individuals of either gender aged 18-40 years. The orthopantomograms were subjected to stage classification to assess the radiographic root pulp visibility and periodontal ligament visibility of the lower second molar teeth. Data was analysed using SPSS 25., Results: Of the 260 orthopantomograms, 140(53.8%) belonged to female subjects and 120(46.2%) to male. The overall median age of the subjects was 24 years (interquartile range: 7 years). There were 164(63.1%) subjects aged 18-25 years, 70(26.9%) aged 26-33 years, and 26(10%) aged 34-40 years. A positive correlation was noted between age and stages of radiographic root pulp visibility and periodontal ligament visibility (p<0.05). The individuals found at stages 0 and 1 for root pulp visibility were aged at least 18 years, and for stage 2, the corresponding value was 21 years. For periodontal ligament visibility, the minimum age for stage 0 was 18 years, while for stages 1 and 2, the corresponding values were 21 and 25 years., Conclusions: Lower age was found to be associated more with stage 0 of root pulp visibility and periodontal ligament visibility.

In this study, SeDeM-ODT parametric tests were performed to determine the use of ludipress as a directly compressible tableting excipient for the development of a flurbiprofen orally disintegrating tablet. The preformulation features of different formulations (F1 -F9) were analyzed by the SeDeM-ODT tool which showed that all the powder blends were appropriate for direct compression since all the blends had index of good compressibility and bucodispersibility (IGCB) values above 5, signifying direct compression is the most appropriate method. The powder blend of the optimized formulation was assessed by the DSC-TGA technique. The optimization of nine different formulations blends of orally disintegrating tablets (ODTs) was prepared in various ratios by the implementation of design of experiments (DoE), using the central composite design by selecting ludipress (X1) (49-55%) and croscarmellose sodium (X2) (1-5%) while hardness, friability, and disintegration tests were selected as responses. The optimized formulations were evaluated by various tests and the results indicated that all the formulations were found to be in adequate range. Formulations were subjected to stability studies at accelerated states following ICH guidelines. Shelf life was found to be 51.144-56.186 months. Results of multiple-point dissolution studies revealed that formulations followed the Higuchi kinetic model. This study revealed that the SeDeM-ODT tool has been successfully used to determine the compression behavior of active compounds and their powder blends for the direct compression (DC) method in formulating flurbiprofen-ODT tablets., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fatima 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.)

Objectives. Antimicrobial resistance (AMR) poses a significant threat to global public health, with substantial mortality rates attributed to AMR-related infections. Pediatric populations face heightened vulnerability due to prevalent antimicrobial misuse. This study aimed at addressing the significant threat of antimicrobial resistance (AMR) and its associated mortality rates. Methods . This retrospective cross-sectional multicentric study investigated antibiotic prescribing patterns in pediatric wards of 4 secondary care hospitals affiliated with Aga Khan University Hospital. The study utilized the WHO Access, Watch, and Reserve (AWaRe) classification framework. Data from 6934 encounters were analyzed. Results . Antibiotics were prescribed in 78.1% of encounters, with intravenous administration being predominant (98.6%). Ceftriaxone was the most prescribed antibiotic agent (45.8%), and third-generation cephalosporins constituted the most prevalent antibiotic class (54.4%). Pneumonia exhibited the highest prescription rate (99.9%), with Watch group antibiotics being predominantly prescribed (>80%) across hospitals. Conclusion . These findings underscore the urgency for targeted interventions to optimize prescribing practices and mitigate resistance., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: This study aimed to investigate medical students' perceptions of telehealth in Pakistan and assess the relationship between students' proficiency in computers and technology, gender, and age., Methods: A cross-sectional study was conducted on 330 medical students from various universities in Karachi, Pakistan. Data on demographic characteristics, computer proficiency, and perceptions of telehealth were collected using a self-administered questionnaire. Descriptive statistics, chi-square tests, and Spearman's rank correlation coefficient were utilized for data analysis., Results: The study included 330 participants, predominantly from public universities (83.3%), with a mean age of 21.40 ± 4.24 years. Most participants were pursuing MBBS (67%). In terms of computer proficiency, 41.8% fell into the middle category. Gender correlated significantly with proficiency (p < 0.05), with females more often in the middle category and males in the not-that-amateur category. Age demonstrated a small positive correlation with proficiency (p < 0.05). A majority (77.6%) expressed a general interest in technology. Regarding healthcare apps, 51.8% had 1-3 apps, and 33.6% had none. Most participants believed telehealth would enhance healthcare (72.1%) and make it cheaper (63.3%). Additionally, 56.7% agreed that Pakistan should invest in telehealth, while only 2.7% disagreed., Conclusion: The study revealed that medical students in Pakistan exhibit an interest in technology and perceive telehealth as beneficial. These findings suggest that telehealth holds the potential to enhance healthcare opportunities in Pakistan. Therefore, investing in and expanding telehealth services may represent a viable solution for improving access to healthcare in the country., (© 2024. The Author(s).)

The novel coronavirus SARS-CoV-2 pandemic began in Wuhan (China) in December 2019. Due to the severity of the illness, extent and speed of its spread, vaccines were developed rapidly, and concerns have remained about their safety profile. Although the vaccines have proven to be safe and effective in most cases, as the number of people getting vaccinated for SARS-COV-2 increased, several adverse reactions following the administration of vaccine were reported, one of them being Multisystem Inflammatory Syndrome secondary to vaccination (MISV). Here, we report the case of a patient with MIS-V as well as a summary of all other published cases of this syndrome to-date.

Background & Objective: Acute appendicitis is one of the commonest causes of acute abdominal pain presenting to emergency department (ED) and Computerized Tomography scan (CT) is considered gold standard for its diagnosis. Internationally Low Dose Computerized Tomography scan (LDCT) in emergency department is recommended as a beneficial tool to diagnose acute appendicitis with less exposure to radiation and reduction in the rate of negative laparotomy. Local trials are needed to determine the diagnostic accuracy of LDCT as the first line imaging test for acute appendicitis. Our objective was to determine the diagnostic accuracy of LDCT as the first line imaging test for acute appendicitis., Methods: An observational study was conducted over a sample of 147 patients presented with suspected acute appendicitis to the emergency department of Ziauddin University Hospital, Karachi from November 2018 till May 2019. Non-probability consecutive technique used. Aged ≥ 16 years presented in emergency department with the history (symptoms) and physical examination (Signs) suspecting acute appendicitis were included. Patients with contraindications to CT scan e.g. pregnant women. Patients with signs of Acute Peritonitis requiring immediate surgery. CT scan refused by the patient or patient's attendant were excluded. Histopathology was the gold standard in diagnosing acute appendicitis. The data was analyzed using open epi sample size calculator., Results: One hundred forty six patients had positive findings on LDCT for acute appendicitis (99.3%) whereas only one patient had negative findings (0.7%). The sensitivity and specificity of LDCT for the detection of acute appendicitis were estimated as 96.45% and 16.67% by taking histopathology as gold standard. Negative predictive value (NPV) and positive predictive value (PPV) were estimated as 16.67% and 96.45% respectively. The overall accuracy of LDCT was 93.88%., Conclusion: Our study showed that for diagnosing acute appendicitis, LDCT is harmless, fast and economical imaging modality and has diagnostic accuracy with decrease in radiation dose., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: This study aimed to develop a stable and scalable enteric film-coated tablet for the gastric irritant dexibuprofen., Methods: Utilizing direct compression with super-disintegration (crospovidone), the optimal core batches were coated with Opadry white seal coat and enterically coated with Eudragit ® L100 with pigment (Talc), demonstrating a 12% weight increase; release and integrity were assessed using specific pH buffers and SEM, with stability testing confirming a six-month shelf life at 40 °C and 75% RH., Results: The optimized formulation achieved 99.87% release in phosphate buffer within 60 min, maintained integrity for 120 min in acidic conditions, and exhibited superior bioavailability compared to Innovifen with relative bioavailability ≈of 121% and elevated C max (18.35 µg/ml compared to 11.1 µg/ml)., Conclusion: These results highlight the potential of this formulation to enhance patient safety and efficacy through delayed enteric technology and fast intestinal release.

Tyrosine kinase inhibitors (TKIs) have changed the prognosis of Philadelphia-positive B-cell acute lymphoblastic leukemia (ALL); however, relapsed and refractory disease after multiple TKIs continues to be a clinical challenge. Brexucabtagene autoleucel (brexu-cel) is a novel FDA-approved therapy for relapsed and refractory ALL. Given the lengthy manufacturing time, bridging therapy is commonly employed prior to brexu-cel. Here we describe a case of a 75-year-old Hispanic male patient with relapsed/refractory Philadelphia-positive B-cell ALL with extramedullary disease involving abdominal lymph nodes and skin. He was initially treated with chemotherapy in combination with imatinib, and later received dasatinib and subsequently blinatumomab and nilotinib. As the patient progressed, he received ponatinib with low-dose salvage chemotherapy and did not show kinase domain mutation. In a final effort, a novel combination of ponatinib with asciminib was used as a bridge therapy before brexu-cel and later as maintenance therapy after brexu-cel. This novel combination was able to control disease prior to brexu-cel for 2 months and maintained remission for at least 10 months. This report shows that the novel combination of ponatinib and asciminib is tolerable and effective as a bridge and maintenance therapy after brexu-cel., Competing Interests: Authors do not have any competing interest pertaining to this submission., (Copyright 2024, Amin Muhammad et al.)

The purpose of the present study to prepare hydroxypropyl derivatives (HP) instant (partially cold-water swell-able) starches via extrusion technique (Ex) from sorghum and corn. The native and hydroxypropylated (at propylene level 5 % and 12 %) starch extrudates were evaluated for functional, structural, thermal and rheological properties. The development of extrudates provides ease to industries as they are easily soluble in aqueous mediums and does not require any prior heating. The degree of substitution (DS) for all extrudates varied between 0.0083 and 0.1530 which is under limit and save to consume. The X-ray diffraction (XRD) analysis revealed that all extrudates exhibited V-type pattern while the intensity of peaks increased due to hydroxypropylation. The starch extrudates showed gel-like behavior since storage modulus (G') was greater than loss modulus (G″). Non-Newtonian shear thinning behavior was observed for all extrudates. At lower temperature, HP-Ex at higher substitution level (12 %) demonstrated higher complex viscosity than native and low-substituted extrudates. Creep recovery of HP-Ex dispersion was more pronounced than native extrudates suggesting elastic nature of sorghum and corn starch extrudates. The differential scanning calorimetry (DSC) results revealed that HP-Ex were observed to gelatinize at lower temperatures and needed lower enthalpy of gelatinization (ΔH gel ) because of their weakened structure after modification., Competing Interests: Declaration of competing interest There is no conflict of interest to declare for this article and the manuscript is approved by all the authors for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Exercise instigates adaptations in structural as well as functional organisation of the body at tissue and organ levels. However, the effect of exercise on vascular wall morphology is still under investigation. The objective of the review is to provide a meta-analysis of data from the previously published research to provide compiled analysis to determine the effect of exercise on the thickness of large-sized vessel walls. This meta-analysis was executed at the Ziauddin College of Rehabilitation Sciences with an extensive literature search using databases and search engines such as Pubmed, CINAHL, Web of Science, Scopus, and Google Scholar between September 2022 and January 2023. Studies were appraised according to an estimate of mean difference and pooled effect size was calculated using a random effect model. The risk of bias was also calculated using SYRCLE's risk of bias tool and CAMARADES. Overall, five eligible pre-clinical trials using rat models with pertinent data to determine the effect of exercise on vessel wall thickness were included in the meta-analysis. The results showed that aerobic exercise significantly reduced the vessel wall thickness (SMD -0.854 5%; CI: -1.365 to -0.344; p <0.001). Moreover, no significant publication bias was found through funnel plot and statistical test (Egger's p = 0.276; Begg's p = 0.624). However, an extensive review of the literature currently available on the topic has shown mixed findings that are consistent with the study and vice versa. Therefore, it indicated the need for sub-group analysis with different types of exercises for more peculiar clinical approaches. Key Words: Morphometry, Animal studies meta-analysis, Media thickness, Physical activity, Vascular morphology.