Explore the vast range of titles available.

Background: Drug-induced colitis is a known complication of therapies that alter the immune balance, damage the intestinal barrier or disturb intestinal microbiota. Immune checkpoint inhibitors (ICI) directed against cancer cells may result in activated T lymphocyte-induced immune-related adverse events (AEs), including immune-related colitis and hepatitis. The aim of this review article is to summarize the incidence of gastrointestinal (GI) and hepatic AEs related to ICI therapy. We have also looked at the pathogenesis of immune-mediated AEs and propose management strategies based on current available evidence. Methods: A literature search using PubMed and Medline databases was undertaken using relevant search terms pertaining to names of individual drugs, mechanism of action, related AEs and their management. Results: ICI-related GI AEs are common, and colitis appears to be the most common side effect, with some studies reporting incidence as high as 30%. The incidence of both all-grade colitis and hepatitis were highest with combination therapy with anti-CTLA-4/PD-1; severity of colitis was dose-dependent (anti-CTLA-4). Early intervention is associated with better outcomes. Conclusion: ICI-related GI and hepatic AEs are common and clinicians need to be aware. Patients with GI AEs benefit from early diagnosis using endoscopy and computed tomography. Early intervention with oral steroids is effective in the majority of patients, and in steroid-refractory colitis infliximab and vedolizumab have been reported to be useful; mycophenolate has been used for steroid-refractory hepatitis.

In the context of the global increase in the rate of cesarean deliveries, with an associated higher morbidity and mortality, this study aimed to investigate the role of maternal age and parity in the cesarean section rate among women in the Hail Region of Saudi Arabia. This retrospective cohort study used data collected from the labor ward of the Maternity and Child Health Hospital, Hail, over a period of 8 months, forming a cohort of 500 women. Women were categorized into four different parity classes. The results revealed that there was no significant relationship between cesarean deliveries and maternal age (p-value, 0.07). There was no significant difference in the mode of delivery between the study’s parity cohort group. A significant increase in cesarean deliveries was noticed among obese women with a BMI between 35–39.9 (52.14%). This increase was even greater among those with a BMI above 40 (63.83%). Fetal distress, malpresentation and abruptio placenta were the most significant indications for CS among all age groups (p-value 0.000, 0.021, and 0.048, respectively). Conclusions: The number of cesarean deliveries has no association with parity or age. However, there was a statistically significant association with BMI, a perineal tear after previous vaginal delivery, and a history of diabetes mellitus and gestational diabetes. The most reported reasons for CS were fetal distress, malpresentation, and abruptio placenta among all age groups.

Medical emergencies in dental settings can arise unexpectedly and demand prompt, skilled management. Dentists are often the first responders; therefore, competence in Basic Life Support (BLS) and cardiopulmonary resuscitation (CPR) is essential. This study aims to evaluate the knowledge, attitudes, and perceived structural clinical readiness regarding BLS and CPR among dentists practicing in Saudi Arabia and predictors of good knowledge and confidence in performing CPR. A cross-sectional study was conducted among 400 licensed dentists from public and private sectors in Saudi Arabia. Data were collected through a validated, self-administered online questionnaire comprising four sections: sociodemographic characteristics, knowledge, attitudes, and clinical readiness. Binary logistic regression analyses identified predictors of good knowledge and confidence in performing CPR, adjusting for age, gender, designation, experience, workshop attendance, and previous emergency encounters. Overall, 26.0% of participants demonstrated good knowledge of BLS/CPR, 41.0% had moderate knowledge, and 33.0% had low knowledge 26.0% demonstrated good knowledge. Attendance at a BLS/CPR workshop within the last five years (OR = 4.91; 95% CI [2.60-9.24];  < 0.001) and prior emergency encounters (OR = 12.97; 95% CI [6.99-24.06];  < 0.001) were strong predictors of good knowledge. Confidence in performing CPR was associated with recent workshop attendance (OR = 6.93; 95% CI [4.19-11.46];  < 0.001), while male gender showed lower confidence (OR = 0.59; 95% CI [0.37-0.93];  = 0.023). Only 44.5% reported clinic-level emergency protocols, and 7.5% had an automated external defibrillator. Dentists in Saudi Arabia exhibit positive attitudes but insufficient knowledge and confidence regarding BLS/CPR. Regular refresher training, simulation-based education, and enforcement of clinic-level emergency preparedness are essential to enhance patient safety and professional competence.

Background Malaria is a life-threatening, multisystem disease caused by the plasmodial parasite with a global incidence of approximately 229 million annually. The parasites are known to have unique and crucial interactions with various body tissues during its life cycle, notably the liver, spleen, and recent work has shown the bone marrow to be a reservoir of infection. Methods This study is a case series of patients in whom examination of bone marrow revealed malarial parasites. A retrospective record review of 35 parasite-positive bone marrow specimens examined at Aga Khan University Hospital (AKUH), Karachi, Pakistan, over the years 2007 to 2015 was conducted. Bone marrow aspirates were collected as per International Council for Standardization in Haematology (ICSH) guidelines. Results The median age of patients was 22 years (range 1–75), and 60 % (n = 21) were male. 22 patients had evidence of Plasmodium falciparum , 12 had evidence of Plasmodium vivax and 1 patient had a mixed infection. Gametocytes and trophozoites were the most common stages identified on both peripheral blood and bone marrow examinations. Indications for bone marrow examination included fever of unknown origin and the workup of cytopenias and malignancies. Conclusions The incidental finding of Plasmodium in samples of bone marrow suggests the reticuloendothelial system may be regularly harbour these parasites, be the infection acute or chronic in character.

Glucagon like-peptide 1 receptor (GLP-1R) agonists diminish appetite and may contribute to the weight loss in inflammatory bowel disease (IBD). The aim of this study was to determine, for the first time, the expression of GLP-1R by colon nerve fibres in patients with IBD, and functional effects of its agonists in cultured rat and human sensory neurons. GLP-1R and other nerve markers were studied by immunohistochemistry in colon biopsies from patients with IBD (n = 16) and controls (n = 8), human dorsal root ganglia (DRG) tissue, and in GLP-1R transfected HEK293 cells. The morphological effects of incretin hormones oxyntomodulin, exendin-4 and glucagon were studied on neurite extension in cultured DRG neurons, and their functional effects on capsaicin and ATP signalling, using calcium imaging. Significantly increased numbers of colonic mucosal nerve fibres were observed in IBD biopsies expressing GLP-1R (p = 0.0013), the pan-neuronal marker PGP9.5 (p = 0.0008), and sensory neuropeptide CGRP (p = 0.0014). An increase of GLP-1R positive nerve fibres in IBD colon was confirmed with a different antibody to GLP-1R (p = 0.016). GLP-1R immunostaining was intensely positive in small and medium-sized neurons in human DRG, and in human and rat DRG cultured neurons. Co-localization of GLP-1R expression with neuronal markers in colon and DRG confirmed the neural expression of GLP-1R, and antibody specificity was confirmed in HEK293 cells transfected with the GLP-1R. Treatment with oxyntomodulin, exendin-4 and GLP-1 increased neurite length in cultured neurons compared with controls, but did not stimulate calcium influx directly, or affect capsaicin responses. However, exendin-4 significantly enhanced ATP responses in human DRG neurons. Our results show that increased GLP-1R innervation in IBD bowel could mediate enhanced visceral afferent signalling, and provide a peripheral target for therapeutic intervention. The differential effect of GLP-1R agonists on capsaicin and ATP responses in neurons suggest they may not affect pain mechanisms mediated by the capsaicin receptor TRPV1, but may enhance the effects of purinergic agonists.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility. Availability of some hormones like free testosterone (fT), dehydroepiandrosterone sulfate (DHEAS), anti-Müllerian hormone (AMH), and androstenedione (A4) assay on a user-friendly immunoassay system will be a milestone in the diagnosis of PCOS. Aim of the study was to establish reference values of fT, total testosterone (TT), luteinizing hormones (LH), follicle stimulating hormones (FSH), prolactin (Prl), estradiol (E2), DHEAS, AMH, and A4. Serum specimens of 135 disease-free adult females were collected from Mohi Uddin Teaching Hospital, Mirpur, AJ&K, Pakistan (MOTH) which is the affiliated hospital of Mohi Uddin Islamic Medical College, Mirpur, AJK, Pakistan (MIMC) and after obtaining written informed consent. Blood specimens were analyzed in the Pathology Laboratory of MOTH using state-of-the-art fully automatic chemiluminescence analyzer Maglumi X8 (Snibe, China) for all nine parameters. Reference values of fertility hormones were AMH: 0.84-10.2 ng/mL (14.3-49.0 pmol/L); A4: 10.5-50.9 ng/dL (3.7-17.8 mmol/L); DHEAS: 81-426 µg/dL (0.8-10.2 µmol/L); E2: 18.9-147 pg/mL (70-542 pmol/L); fT: 0.5-2.57 pg/mL (1.7-8.9 pmol/L); FSH (follicular phase): 2.36-13.1 mIU/mL; LH (follicular phase): 0.66-14.7 mIU/mL; Prl: 3.85-30 ng/mL (81-623 mIU/L); and TT: 0.98-8.2 ng/dL (0.03-0.28 nmol/L). We have established reference values of nine hormones used for the diagnosis and monitoring of PCOS in Pakistani and other populations of sub-continent.

Background Vedolizumab is a gut-selective, anti–lymphocyte trafficking biologic therapy for inflammatory bowel disease (IBD). Clinical trials have demonstrated the positive impact of vedolizumab on patient quality of life (QoL); however, real-world evidence of its impact is limited. We evaluated vedolizumab impact on QoL of patients with IBD during the first 52 weeks of treatment in real-world practice in the United Kingdom and Ireland. Methods In this prospective observational study, patients with IBD initiated on vedolizumab completed 4 validated IBD-specific QoL questionnaires at baseline and weeks 14, 26, and 52. The primary endpoint was change in mean Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score. Secondary endpoints included changes in mean scores and sub-scores for other QoL questionnaires. Results Overall, 61 patients were enrolled, including 22 with Crohn’s disease (CD) and 39 with ulcerative colitis (UC). At week 52, the mean change in SIBDQ scores from baseline was statistically significant (+ 12.3 [ p  = 0.0123] for CD and + 10.8 [ p  = 0.0037] for UC) and clinically meaningful (considered as a ≥ 10-point change). A significant improvement in mean SIBDQ scores was seen as early as week 14 for both CD and UC cohorts ( p  = 0.0256 and p  = 0.0348, respectively). Conclusions These real-world findings, using multiple validated tools, demonstrate that vedolizumab treatment for IBD is associated with measurable improvements in QoL from baseline.

High parity is associated with the risk of fetomaternal complications such as gestational diabetes mellitus, hypertensive disorders, maternal anemia, preterm labor, miscarriage, postpartum hemorrhage, and perinatal and preterm mortality. The objective of the study was to compare fetomaternal complications in women of high parity with women of low parity. This involved a cohort study on a sample size of 500 women who had singleton births. Data were collected from the Maternity and Child Hospital, Ha’il, Kingdom of Saudi Arabia. Participants were classified into two groups according to parity, i.e., women of low parity and women of high parity. Socio-demographic data and pregnancy complications, such as gestational diabetes, hypertension, preeclampsia, intrauterine growth restriction, etc., were retrieved from participants’ files. Participants were followed in the postnatal ward until their discharge. The results revealed that women of high parity mostly (49%) were married before 20 years of age, less educated, obese, and were of un-booked cases. Premature babies and fetal mortality are significantly high (0.000) in this group. There is a significant difference between the two groups with respect to maternal anemia, gestational diabetes mellitus, joint pain, perineal tear, miscarriage, postpartum hemorrhage, preeclampsia, vaginal tear, and cesarean section. Determinants responsible for high parity should be identified via evidence-based medicine. Public health education programs targeting couples, weight control, nutrition, and contraception would be a cost-effective strategy for reducing the risk of possible fetomaternal complications.

ObjectiveThe aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London.DesignObservational cohort study.SettingLondon North West Healthcare NHS Trust (LNWH).ParticipantsPatients tested and/or admitted for COVID-19 at LNWH during March and April 2020Main outcome measuresDescriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19.ResultsThe outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients.ConclusionThe findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

Background Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT 3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants ( n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity ( n  = 80) using the barostat, and/or high-resolution colonic manometry ( n  = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond. Trial registration ISRCTN, ISRCTN17508514 , Registered on 2 October 2017.