Burdensome Disease Research Articles

The Relationship Between Indoxyl Sulfate Levels and Functional Ability of End-Stage Renal Disease Patients Undergoing Regular Haemodialysis Using the Karnofsky Scale Measuring Instrument at Haji Adam Malik Central General Hospital Medan

Background: ESRD is a burdensome disease with high prevalence, mortality, and treatment costs. Indoxyl sulfate is one of the most studied solutes accumulating in plasma when the kidneys fail. Clinical studies have shown that indoxyl sulfate can predict the prognosis of CKD and CVD in CKD patients. Serum levels of IS are associated with all-cause mortality and cardiovascular mortality in CKD patients. The general objective of this study was to determine the relationship between indoxyl sulfate levels and the functional ability of CKD patients undergoing regular hemodialysis using the Karnofsky scale measuring instrument at the Haji Adam Malik Central General Hospital Medan. Methods: This research is an observational analytic study with a cross-sectional design. Data collection involved recording indoxyl sulfate levels in kidney failure patients undergoing hemodialysis at Haji Adam Malik Hospital. Results: Of all 56 study samples, the mean age was 49.35 years, with a standard deviation of 12.3 years. Most patients were male, from the Batak ethnicity, with hypertension as the etiology. The mean indoxyl sulfate level was 47.32 µg/mL with a 29.19 µg/mL standard deviation. Most patients presented with functional ability calculated by Karnofsky score in category A. The analysis results with the Spearman test showed a moderate negative correlation between indoxyl sulfate levels and the functional ability of patients. Conclusion: Indoxyl sulfate levels can be an objective parameter to predict a patient's functional ability. Keywords: Indoxyl Sulfate, Haemodialysis, End Stage Renal Disease, Functional Ability

HEALTH COACHING IMPROVES EVERYDAY COGNITION AMONG INDIVIDUALS AT RISK FOR ALZHEIMER’S DISEASE

Abstract Alzheimer’s disease (AD) is the 7th leading cause of death and 6th most burdensome disease among US older adults. With pharmacological treatments for AD being predominantly ill-effective, alternative, non-pharmacological prevention and treatment strategies warrant exploration. Personal health coaching provides individualized strategies designed to improve physical, social, and emotional health leading to positive behavior changes that may improve cognitive ability. The purpose of the present investigation was to examine the effects of a Health Coaching (HC) intervention on cognitive outcomes. Adults (n=182) over 45 years of age were randomly assigned to HC or control arm of a 12-month intervention. Participants (age = 61.9 + 8.4 years) had their cognition (ECog-12) tested at baseline, 16, and 52 weeks. Participants assigned to the HC intervention met with a health coach once per month to establish healthful goals and implementation strategies improving the health and well-being of the participants. The control group received bi-weekly emails including similar information presented during the health coaching sessions. Results revealed a main effect for time for improved ECog-12 scores (p=.04) with a 3.2% improvement in ECog-12 after 52 weeks. Upon further analysis, HC had a significant improvement in cognitive performance after both 16 and 52 weeks, while the control group remained unchanged. Improvement in self-reported cognition was 4.0% (p=.03) and 5.5% (p=.01) in the HC group after 16 and 52 weeks, respectively. These results suggest HC is an effective non-pharmacological prevention strategy for cognitive decline among a group of adults at-risk for developing AD.

Cerebral perfusion simulation using realistically generated synthetic trees for healthy and stroke patients

Background and objectiveCerebral vascular diseases are among the most burdensome diseases faced by society. However, investigating the pathophysiology of diseases as well as developing future treatments still relies heavily on expensive in-vivo and in-vitro studies. The generation of realistic, patient-specific models of the cerebrovascular system capable of simulating hemodynamics and perfusion promises the ability to simulate diseased states, therefore accelerating development cycles using in silico studies and opening opportunities for the individual assessment of diseased states, treatment planning, and the prediction of outcomes. By providing a patient-specific, anatomically detailed and validated model of the human cerebral vascular system, we aim to provide the basis for future in silico investigations of the cerebral physiology and pathology. MethodsIn this retrospective study, a processing pipeline for patient-specific quantification of cerebral perfusion was developed and applied to healthy individuals and a stroke patient. Major arteries are segmented from 3T MR angiography data. A synthetic tree generation algorithm titled tissue-growth based optimization (GBO)1 is used to extend vascular trees beyond the imaging resolution. To investigate the anatomical accuracy of the generated trees, morphological parameters are compared against those of 7 T MRI, 9.4 T MRI, and dissection data. Using the generated vessel model, hemodynamics and perfusion are simulated by solving one-dimensional blood flow equations combined with Darcy flow equations. ResultsMorphological data of three healthy individuals (mean age 47 years ± 15.9 [SD], 2 female) was analyzed. Bifurcation and physiological characteristics of the synthetically generated vessels are comparable to those of dissection data. The inability of MRI based segmentation to resolve small branches and the small volume investigated cause a mismatch in the comparison to MRI data. Cerebral perfusion was estimated for healthy individuals and a stroke patient. The simulated perfusion is compared against Arterial-Spin-Labeling MRI perfusion data. Good qualitative agreement is found between simulated and measured cerebral blood flow (CBF)2. Ischemic regions are predicted well, however ischemia severity is overestimated. ConclusionsGBO successfully generates detailed cerebral vascular models with realistic morphological parameters. Simulations based on the resulting networks predict perfusion territories and ischemic regions successfully.

Dysuricemia.

Gout results from elevated serum urate (SU) levels, or hyperuricemia, and is a globally widespread and increasingly burdensome disease. Recent studies have illuminated the pathophysiology of gout/hyperuricemia and its epidemiology, diagnosis, treatment, and complications. The genetic involvement of urate transporters and enzymes is also proven. URAT1, a molecular therapeutic target for gout/hyperuricemia, was initially derived from research into hereditary renal hypouricemia (RHUC). RHUC is often accompanied by complications such as exercise-induced acute kidney injury, which indicates the key physiological role of uric acid. Several studies have also revealed its physiological role as both an anti-oxidant and a pro-oxidant, acting as both a scavenger and a generator of reactive oxygen species (ROSs). These discoveries have prompted research interest in SU and xanthine oxidoreductase (XOR), an enzyme that produces both urate and ROSs, as status or progression biomarkers of chronic kidney disease and cardiovascular disease. The notion of "the lower, the better" is therefore incorrect; a better understanding of uric acid handling and metabolism/transport comes from an awareness that excessively high and low levels both cause problems. We summarize here the current body of evidence, demonstrate that uric acid is much more than a metabolic waste product, and finally propose the novel disease concept of "dysuricemia" on the path toward "normouricemia", or optimal SU level, to take advantage of the dual roles of uric acid. Our proposal should help to interpret the spectrum from hypouricemia to hyperuricemia/gout as a single disease category.

Health-related Quality of Life During the First 4 Years After Non–Muscle-invasive Bladder Cancer Diagnosis: Results of a Large Multicentre Prospective Cohort

BackgroundThe health-related quality of life (HRQoL) of patients with non–muscle-invasive bladder cancer (NMIBC) may be impaired due to the chronic and burdensome disease course, but longitudinal data are limited. ObjectiveTo evaluate HRQoL outcomes during the first 4 yr after NMIBC diagnosis, and to compare HRQoL across patient characteristics and with a normative population. Design, setting, and participantsPatients with NMIBC (n = 1019) were included from the multicentre prospective cohort UroLife. Data were collected at 6 wk (baseline), and 3, 15, and 51 mo after diagnosis. Longitudinal reference data were obtained from an age- and sex-matched normative population (n = 490). Outcome measurements and statistical analysisCancer- and NMIBC-specific HRQoL outcomes (range 0–100) were evaluated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-NMIBC24 questionnaires, respectively. Linear mixed modelling was used to analyse within-group changes and between-group differences. Results and limitationsThe majority of HRQoL outcomes remained stable over time. Observed changes were only of small clinical relevance. Improvements were noted in insomnia, social functioning, and three NMIBC-specific symptoms, while minor deteriorations in appetite and diarrhoea lasted until 51 mo. HRQoL in some domains was worse for high-grade NMIBC, high European Association of Urology (EAU) risk group, initial Bacillus Calmette-Guérin (BCG) treatment, being female, and being younger (<65 yr); yet differences were few, small, and temporary. No differences were observed across recurrence status. Compared with a normative population, clinically relevant worse scores were observed for six of 15 outcomes, which mostly recovered at 51 mo, except for minor symptoms of appetite loss and diarrhoea. ConclusionsNo remarkable changes in HRQoL were observed during the first 4 yr after NMIBC diagnosis. Grade, EAU risk group, initial treatment, recurrence, sex, and age did not importantly affect HRQoL. HRQoL was largely comparable with that of the general population, especially after 4 yr. Patient summaryQuality of life is not largely affected during the first 4 yr after non–muscle-invasive bladder cancer diagnosis.

Berberine protects mice against type 2 diabetes by promoting PPARγ-FGF21-GLUT2-regulated insulin sensitivity and glucose/lipid homeostasis

Type 2 diabetes (T2D) is a chronic, burdensome disease that is characterized by disordered insulin sensitivity and disturbed glucose/lipid homeostasis. Berberine (BBR) has multiple therapeutic actions on T2D, including regulation of glucose and lipid metabolism, improvement of insulin sensitivity and energy expenditure. Recently, the function of BBR on fibroblast growth factor 21 (FGF21) has been identified. However, if BBR ameliorates T2D through FGF21, the underlying mechanisms remain unknown. Herein, we used T2D wild type (WT) and FGF21 global knockout (FKO) mice [mouse T2D model: established by high-fat diet (HFD) feeding plus streptozotocin (STZ) injection], and hepatocyte-specific peroxisome proliferator activated receptor γ (PPARγ) deficient (PPARγHepKO) mice, and cultured human liver carcinoma cells line, HepG2 cells, to characterize the role of BBR in glucose/lipid metabolism and insulin sensitivity. We found that BBR activated FGF21 expression by up-regulating PPARγ expression at the cellular level. Meanwhile, BBR ameliorated glucosamine hydrochloride (Glcn)-induced insulin resistance and increased glucose transporter 2 (GLUT2) expression in a PPARγ/FGF21-dependent manner. In T2D mice, BBR up-regulated the expression of PPARγ, FGF21 and GLUT2 in the liver, and GLUT2 in the pancreas. BBR also reversed T2D-induced insulin resistance, liver lipid accumulation, and damage in liver and pancreas. However, FGF21 deficiency diminished these effects of BBR on diabetic mice. Altogether, our study demonstrates that the therapeutic effects of BBR on T2D were partly accomplished by activating PPARγ-FGF21-GLUT2 signaling pathway. The discovery of this new pathway provides a deeper understanding of the mechanism of BBR for T2D treatment.

AF in TAVR patients: double trouble means double care

Abstract Introduction Atrial fibrillation (AF) and aortic stenosis share multiple common risk factors and aortic valve stenosis itself is associated with higher rate of AF. Patients submitted to transcatheter aortic valve replacement (TAVR) are particularly frail and AF is associated with increased mortality, ischemic and hemorrhagic events. Thus, a thorough approach, especially in such frail population, is warranted to reduce morbi-mortality. Bearing this in mind, a risk assessment tool derived from ENVISAGE-AF trial was recently developed to stratify the mortality risk of AF patients after completion of successful TVR. Purpose To characterize a population of patients with AF who implanted TAVR and test a newly proposed mortality score to estimate prognosis in this population. Methods Single-center observational retrospective study including consecutive pts with AF who implanted TAVI from 2017 to 2021. Clinical data was collected at baseline and during follow-up. The AF mortality score groups pts in three crescent strata of severity (0-10; 11-16; &amp;gt;16) by summing seven variables: age, creatinine clearance, duration of AF, NYHA class, alcohol consumption, peripheral artery disease and prior major bleeding. Kaplan Meyer survival analysis was performed using SPSS statistics. Results For 5 years, 621 pts underwent TAVR, of which 189 (30,4%) had previously diagnosed AF. 102pts were female, mean age of 82,6± 6,1 years. More than half (53%) had permanent AF, 28% paroxysmal AF and 19% persistent AF. During a mean follow up of 953 days, 8 (4,2%) pts suffered a major hemorrhagic event, two pts had ischemic arterial events (peripheral and mesenteric) and no venous thrombotic events were observed. As anticipated, event rate was high: at 1 year follow-up, 27 were admitted for cardiovascular events (3 with acute myocardial infarction and 4 with stroke). 26 pts died after 1-year (13,7%) and 30 died during available FUP (15,8%). The aforementioned AF mortality score was applied to our pts at baseline, before TAVR: 63%, 17.5% and 8.5% of patients were categorized as low, moderate or high risk. Patients in the high risk group (score&amp;gt;16) had a significantly higher rate of events during follow-up – figure1. Lower and intermediate group failed to show a clear separation in terms of risk estimation between them, which may be attributed to the paucity of events in these two groups. Conclusion AF and aortic stenosis are both burdensome diseases and AF increases the risk of events in TAVR population. We showed that a newly proposed score that stemmed from ENVISGE-AF can effectively select pts at high risk of mortality, in whom close clinical surveillance should be particularly rigorous.

Health State Utility Values for Children and Adolescents with Type 1 Diabetes: A Systematic Review and Meta-analysis.

Type 1 diabetes mellitus (T1DM) is one of the most burdensome chronic diseases in the world. Health utility values are an important tool for quantifying this disease burden and conducting cost-utility analyses. This review aimed to derive a reference set of health utility values for children and adolescents with T1DM. We searched MEDLINE and Embase from inception to March 2023 for health utility values of T1DM children and adolescents (aged ≤18 years) measured using direct and indirect preference elicitation approaches. Utility estimates were pooled by meta-analyses with subgroup analyses to evaluate differences by populations and elicitation approaches. Six studies involving 1276 participants were included in this study. Meta-analysis showed the overall utility value of children and adolescents with T1DM was 0.91 (95% CI 0.89-0.93). The utility value of T1DM children and adolescents with complications was 0.90 (95% CI 0.88-0.92), which was lower than those without complications (0.96, 95% CI 0.95-0.97). The utility value of children (aged <13 years) was higher than adolescents (aged 13-18 years) (0.90 vs. 0.85). The utility value measured by the EQ-5D-3L (0.91) was higher than the HUI3 (0.89), the SF-6Dv1 (0.83), and the time trade-off (0.81). The parent proxy-reported was similar to the patient self-reported (0.91 vs. 0.91). This study developed a reference set of pooled utility estimates for children and adolescents with T1DM, which is helpful for understanding the overall health status of T1DM and conducting economic evaluations. Further studies are needed to explore the utilities of T1DM with different types of complications.

Abstract 12 — Prevalence and Risk Factors of Non-Alcoholic Fatty Liver Disease in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Study

Background Rheumatoid arthritis (RA) is a debilitating and financially burdensome disease because of frequent presence of comorbidities including metabolic and cardiovascular abnormalities. Growing evidence suggests a link between RA and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and explore the risk factors of developing NAFLD in RA population. Methods This population-based, cross-sectional study utilized data on US adults aged [Formula: see text]20 years old from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, a representative sample of the general US population. Diagnosis of RA was derived from questionnaire data. NAFLD was defined by controlled attenuation parameter (CAP) scores of [Formula: see text]278 dB/m using vibration controlled transient elastography (VCTE) in the absence of other liver disease. Weighted multiple regression analysis was further performed to assess the independent risk factors. Results Of 2,848 people included in this study, 224 of them had self-reported RA. The prevalence of NAFLD in the overall sample was 41%, with a numerically higher prevalence in RA patients than those without arthritis (47% vs. 40%, p=0.30). Compared to those without NAFLD, RA patients with concomitant NAFLD had more prevalent metabolic comorbidities including obese (75% vs. 32%, p=0.006), central obesity (100% vs. 71%, p=0.008), diabetes (39% vs. 14%, p=0.003) and hyperlipidemia (88% vs. 76%, p=0.042). Regarding laboratory findings, RA patients with NAFLD exhibited higher levels of triglyceride (188 mg/dL vs. 131 mg/dL, p=0.010), fasting plasma glucose (131 mg/dL vs. 109 mg/dL, p=0.010) and HbA1c (5.77% vs. 6.41%, p=0.002). Meanwhile, elevated levels of liver enzymes (ALT: 29 U/L vs. 19 U/L, p=0.015; AST: 25 U/L vs. 19 U/L, p=0.007) and inflammatory indicator CRP (5.1 mg/dL vs. 3.4 mg/dL, p&lt;0.001]) were more frequently reported in RA patients with NAFLD as compared with those without. Further, weighted multivariate logistic regression analysis showed that the presence of central obesity (adjusted OR=1.56 [95% CI 1.16-2.11], p=0.008) and diabetes (adjusted OR=1.28 [95% CI 1.07-1.54], p=0.014) were significantly associated with prevalent NAFLD in patients with RA. Conclusion In this population-based study, about one in two patients with RA had NAFLD, which is higher than its overall prevalence among general population. Central obesity and diabetes are predisposing factors for NAFLD in RA. Our results highlight the importance of active NAFLD screening in RA population, especially for high-risk subsets.

Treatment-Resistant Depression in America Latina study: one-year follow-up of treatment resistant depression patients under standard of care reveals insights on quality of life, disability, work impairment, and depressive symptoms.

Depressive Disorders are on the rise worldwide. This is also the case in Latin America (LatAm). Treatment-Resistant Depressive Disorder (TRD) poses additional burden to patients with depression. Impacts quality of life (QoL) and other dimensions, and standard of care (SOC) is insufficient to achieve the desired clinical outcomes. Evidence from LatAm is, however, lacking. The present study was devised as a 1-year follow-up of the SOC in TRD patients in LatAm to explore the burden of TRD. This was an observational, multinational, longitudinal study. Patients with clinical diagnosis of TRD in LatAm were included in a 1-year follow-up with SOC. Beyond the Sociodemographic characterization, outcome measures were QoL (EQ-5D-5L), disability (Sheehan Disability Scale - SDS), work productivity (Work Productivity and Activity Incapacity Questionnaire: depression - WPAI:D) and depression severity (Patient Health Questionnaire-PHQ9). Patients were assessed every 3-months and comparison was performed based on change from baseline to each visit and end of study (EOS - 12 months). Patients averaged 48 (± 13.12) years, mostly female (80.9%) and married/consensual union (42.5%) or single patients (34.4%). Despite the SOC treatment, three-quarters of the patients remained symptomatic at EOS, regardless of the significant longitudinal decrease (p ≤ 0.001). Similar trends were found for disability (p ≤ 0.001) -82.2% of the patients reporting work/school disruption at EOS-, percentage of work (34%) and activity impairment (40%) at EOS (p ≤ 0.001) and only 29.2% of patients with depressive severity "none" at EOS (p ≤ 0.001). The results portray the need to improve clinical outcomes in this complex and burdensome disease in LatAm. Here we show that the burden of TRD remains significant in essential dimensions of everyday life at EOS underlining the need for better therapeutic solutions. The improvements in most patients do not provide the desired outcome of return to the state before the condition. Further research should focus on identifying which treatments provide better outcomes in a real-world context.

Qualitative assessment of the patient experience of primary hyperoxaluria type 1: an observational study

BackgroundWithout effective intervention, primary hyperoxaluria type 1 (PH1) causes oxalate-induced kidney damage, leading to end-stage kidney disease and serious complications throughout the body. Although PH1 carries a heavy burden that impacts quality of life, literature on the experiences of those living with PH1 and caring for patients with PH1 is limited. This study aimed to describe the diagnostic journey in PH1 and characterize patients’ and caregivers’ self-reported experiences throughout the disease course.MethodsThis was an observational study involving in-depth, semi-structured telephone interviews. Dominant trends were assessed using constant comparative analysis to identify themes in interviewees’ descriptions of their experiences. Individuals aged ≥ 12 years and caregivers of children aged 6–17 years with genetically confirmed PH1 were eligible. Informed consent/assent and ability to read and speak English were required.ResultsInterviewees (16 patients, 12 caregivers) reported a prolonged diagnostic journey due to low disease awareness, among other factors. Upon diagnosis, PH1 was frequently symptomatic, typically involving kidney stone-related symptoms but also potentially symptoms arising beyond the kidneys. PH1 most commonly led to worry and social impairment in adolescents, impaired physical function in adults, and a range of impacts on caregivers. In late-stage disease, dialysis was the most burdensome aspect of living with PH1 (due to time requirements, limitations from living with a catheter, etc.), and this burden was exacerbated by the COVID-19 pandemic. Benefits desired from PH1 management included reductions in laboratory measures of oxalate burden, kidney stone and urination frequency, and oxalate-related skin ulcers.ConclusionsPH1 greatly impacts patients’ and caregivers’ lives, primarily due to burdensome disease manifestations and associated emotional, physical, and practical impacts, as well as disease management challenges – particularly those related to dialysis in late-stage disease.

Spanish consensus on the management of chronic rhinosinusitis with nasal polyps (POLIposis NAsal / POLINA 2.0).

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a high prevalent and burdensome disease for individuals and health systems which management involves many specialties: otorhinolaryngology, allergology, pulmonology, primary care, pharmacy, and paediatrics. A multidisciplinary approach and the participation of the patient in decision making are essential, both for the diagnosis and for the therapeutic strategy. The authors of the consensus aim to translate the current knowledge into an easy-to-read practical guide and emphasize those aspects in which there is still discussion or unmet needs due to the lack of proper scientific evidence. An iterative approach for the development of an evidence-based systematic review with recommendations was used, using a standard quality assessment scheme (Scottish Intercollegiate Guidelines Network -SIGN- and National Institute for Health and Care Excellence -NICE-), and a critical evaluation of the guideline has been carried out through the instrument Appraisal of Guidelines for Research and Evaluation (AGREE II) and Recommendation Excellence (AGREE REX). Based on the foregoing, the POLINA has been considered a guideline of good quality by an independent agency. The POLINA consensus contributes with new schemes for the definition of control, therapeutic management including severity evaluation and surgery, and indications for biologic use and response. Finally, this guideline focuses on the research unmet needs in CRSwNP.

BACTERIAL PROFILE AND ANTIBIOTIC SUSCEPTIBILITY PATTERN OF UROPATHOGENS CAUSING URINARY TRACT INFECTIONS: OBSERVATIONSINA NEW TERTIARY CARE INSTITUTE OF A RURAL AREA OF NORTHERN INDIA

Introduction: Urinary tract infections (UTIs) are among the most common and burdensome diseases affecting outpatients and hospitalized patients, Escherichia coli being the most commonly implicated bacterium. UTIs have been treated empirically in locations where microbiological facilities are either non-existent or too expensive. This study was conducted to fill in our lack of knowledge regarding the bacterial composition and antimicrobial susceptibility patterns of uropathogens in Raebareli (Uttar Pradesh), India, and to help formulate an antibiotic policy. Materials and Methods: This retrospective study was conducted at a 600-bed tertiary care hospital in rural India, from 11th August 2021 to 10th July 2022. The study excluded patients who were on antibiotic therapy and had been hospitalized a week before their OPD visit. Midstream urine samples collected aseptically were cultured semi-quantitatively. Organisms with significant colony counts were identified using routine biochemical techniques and antimicrobial susceptibility was tested against various antibiotics as per CLSI guidelines. The data was condensed and analyzed using SPSS version 23 softwares descriptive statistics feature. Results: A total of 5,982 urine samples were considered eligible during the study period. Most of the patients were 19-39 years old (40.67%), and the majority were females (55.25%). Most of the samples were received from General Medicine (32.77%). 056 (17.65%) samples showed significant bacterial growth. 258 (4.31%) samples were not considered for further analysis due to contamination during collection. E. coli was the most common organism isolated (53.5%), followed by Enterococcus faecalis (21.4%). E. coli isolates exhibited good sensitivity to Fosfomycin (90.97%), Gentamicin (80.71%), and Imipenem (80%). Vancomycin and Linezolid showed &gt;90% susceptibility to all the gram-positive isolates. 71.79% of the Staphylococcal isolates were MRSA. Discussion: This study marks the primary investigation into the susceptibility patterns displayed by bacterial strains causing urinary tract infections in Raebareli, Uttar Pradesh (UP) and enables a comparison with other areas of the nation. Age, sex and pyuria were all crucial factors in the incidence of UTI, and must be considered when assessing and managing UTI patients. There was no significant difference in the prevalence of UTI among various departments. E. coli is the leading cause of UTI worldwide, as in our study. The bacterial isolates exhibited noteworthy resistance to the first-line therapeutic agents which are commonly employed for treating UTIs. Our results indicate that fosfomycin, gentamicin, and nitrofurantoin are viable options for treating E. coli infections, while carbapenems and piperacillin-tazobactam can potentially manage other Gram-negatives. Vancomycin, linezolid and nitrofurantoin were the available options for Gram-positive isolates, Conclusion: Our study has revealed a significant number of Gram-negative bacterial isolates, with Escherichia coli being the main cause of UTIs. We have also conducted a comprehensive analysis of antibiogram data. Based on our findings, Nitrofurantoin and Fosfomycin are recommended to initially treat UTIs in our region. These results will apply to our inpatient and outpatient facilities and other departments within our organization.

Assessment and Management of Sleep Disturbances in Atopic Dermatitis: A Review.

Atopic dermatitis (AD) is a chronic burdensome inflammatory skin disease with well-established cutaneous and systemic comorbidities and disease burden. AD particularly has profound impacts on sleep in individuals of all ages. Sleep disturbances (SDs) affect 6.2% of school-age children and 33-87.1% of adults with AD. This narrative review addresses the burden of SD in AD patients, as well as biological mechanisms of SD in AD, including biological clocks influencing sleep, inflammation, and behavior. Approaches for early detection, diagnosis, objective quantification, patient education, and management are reviewed. It is imperative to break the itch-scratch cycle to reduce SDs and improve quality of life in individuals with AD.

Epilepsy among the older population of sub-Saharan Africa: Analysis of the global burden of disease database

IntroductionEpilepsy is considered one of the most burdensome neurologic diseases by the World Health Organization due to the high risk of morbidity and mortality. Few studies have investigated the epidemiology of idiopathic epilepsy in Sub-Saharan Africa (SSA). This study aims to characterize the disease burden of epilepsy among the older population in SSA via a large international database. MethodsDescriptive epidemiological data from the Global Burden of Disease (GBD) database was collected for idiopathic epilepsy in all regions of SSA. The “older” population was defined as 55 years of age and above. The variables of interest included mortality, incidence, prevalence, and disability-adjusted life years (DALYs) rates per one hundred thousand populations. ResultsThe average mortality rate was highest in Western SSA (6.34 per 100,000), and all regions were significantly higher than the global average (p < 0.001). DALYs and incidence rates of idiopathic epilepsy in all regions of SSA were significantly higher than the global averages (p < 0.01). Globally, the older population had a significantly higher mortality rate than the younger population (2.78 vs 1.62, respectively; p < 0.01). The older population had a higher mortality rate than the younger population in each region of SSA (p < 0.01). Conversely, for DALYs, the younger population had a higher disease burden than the older population globally and in each region of SSA (p < 0.01). ConclusionThis study is the first to examine the epidemiologic profile of idiopathic epilepsy in the older population in SSA. Our results indicate that, when compared with the global population, older adults in SSA suffer a greater disease burden and mortality. This study reports the immense need for increased resources and awareness regarding epilepsy in the elderly population of Africa.

Rutaecarpine Ameliorates Murine N-Methyl-N'-Nitro-N-Nitrosoguanidine-Induced Chronic Atrophic Gastritis by Sonic Hedgehog Pathway.

CAG is a burdensome and progressive disease. Numerous studies have shown the effectiveness of RUT in digestive system diseases. The therapeutic effects of RUT on MNNG-induced CAG and the potential mechanisms were probed. MNNG administration was employed to establish a CAG model. The HE and ELISA methods were applied to detect the treatment effects. WB, qRT-PCR, immunohistochemistry, TUNEL, and GES-1 cell flow cytometry approaches were employed to probe the mechanisms. The CAG model was successfully established. The ELISA and HE staining data showed that the RUT treatment effects on CAG rats were reflected by the amelioration of histological damage. The qRT-PCR and WB analyses indicated that the protective effect of RUT is related to the upregulation of the SHH pathway and downregulation of the downstream of apoptosis to improve gastric cellular survival. Our data suggest that RUT induces a gastroprotective effect by upregulating the SHH signaling pathway and stimulating anti-apoptosis downstream.

Management of pruritus in the elderly

Chronic pruritus (CP), afrequent (20.3%) symptom in the elderly, increases with age. It has asignificant impact on the quality of life, ranking among the 50most burdensome diseases worldwide (Global Burden of Disease Study). The aim is to provide an overview of the symptom CP in the elderly and to improve differentiation of underlying conditions and management of this entity. Aliterature search in PubMed was performed, using the terms 'pruritus', 'elderly' and 'gerontodermatology'. The main causes of CP in the elderly are the physiologic aging process (xerosis cutis, immunosenescence, neuropathy), the increase in potentially pruritic diseases with increasing age (diabetes mellitus, chronic renal failure), and polypharmacy. Therapeutic options relate to causes, severity of pruritus, and individual patient factors (multimorbidity, impaired organ function). The recently updated S2kguideline 'Diagnosis and therapy of chronic pruritus' ishelpful. CP in the elderly is challenging for both patients and physicians. Not only the difficulty of identifying the underlying cause, but the complexity of treatment and its tolerability and practicability determines these patients' further burden.

See-saws: the delicate balance of burden of treatment in chronic heart failure

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This work was supported as a part of a fully funded Clinical Academic Doctoral Fellowship at the University of Southampton, Portsmouth Hospitals University NHS Trust, and the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) Wessex. This article is independent research supported in part by the NIHR ARC Wessex. Carl May’s contribution was supported by NIHR ARC North Thames and Alison Richardson’s by NIHR ARC Wessex. Rosalynn Austin is funded by an NIHR ARC Wessex Internship. Background Burden of Treatment (BoT) is often described as a delicate balance between a patient’s capacity (capabilities and resources) to do the work of illness management and the workload (self-care, treatment and illness burden). Chronic heart failure (CHF) is regarded as a burdensome disease for both patients and healthcare services with the burden expected to rise. While research in BoT in CHF is increasing, the factors influencing the balance between capacity and workload has yet to be fully elucidated. Purpose To identify factors which may influence BoT in CHF. Methods Secondary analysis of 32 semi-structured interviews of participants with CHF who participated in the SYMPACT trial. All participants were asked to describe the balance between capabilities and workload of manging CHF using the metaphor of a see-saw. Responses to that question were examined for factors patients reported as altering the balance between capacity and workload. Results Most participants (n=31) described the seesaw as dynamic, where capacity and workload were balanced or unbalanced. If capacity &amp;gt; workload this was viewed as positive, "I would stay down because the things that you mentioned are very easy" (T137). When instead the balance reversed and capacity &amp;lt; workload it was viewed as negative, "The heavier you know with the work and the abilities less, you kind of think […] I’m good for nothing" (B001). Factors reported by patients, to alter their capacity included: ability to self-care, support from social networks, symptoms, illness identity, and quality of life. Workload was reported to be altered by nature of healthcare interactions, effectiveness of treatments, comorbidities and the feeling of overwhelming treatment burden (Figure 1). One participant described overwhelming burden with a different metaphor: "A huge weight around my neck. Pulling me down into a pit of despair" (S110), was reported as more accurate than a seesaw when thinking about treatment burden. Conclusions BoT is an important factor to consider in the clinical management of CHF. Modifiable factors such as symptoms, quality of life, and the nature of healthcare interactions are reported as altering the balance between a patient’s capacity and the workload associated with self-care.Factors balancing burden of treatment

Assessing the Link between Diabetic Metabolic Dysregulation and Breast Cancer Progression.

Diabetes mellitus is a burdensome disease that affects various cellular functions through altered glucose metabolism. Several reports have linked diabetes to cancer development; however, the exact molecular mechanism of how diabetes-related traits contribute to cancer progression is not fully understood. The current study aimed to explore the molecular mechanism underlying the potential effect of hyperglycemia combined with hyperinsulinemia on the progression of breast cancer cells. To this end, gene dysregulation induced by the exposure of MCF7 breast cancer cells to hyperglycemia (HG), or a combination of hyperglycemia and hyperinsulinemia (HGI), was analyzed using a microarray gene expression assay. Hyperglycemia combined with hyperinsulinemia induced differential expression of 45 genes (greater than or equal to two-fold), which were not shared by other treatments. On the other hand, in silico analysis performed using a publicly available dataset (GEO: GSE150586) revealed differential upregulation of 15 genes in the breast tumor tissues of diabetic patients with breast cancer when compared with breast cancer patients with no diabetes. SLC26A11, ALDH1A3, MED20, PABPC4 and SCP2 were among the top upregulated genes in both microarray data and the in silico analysis. In conclusion, hyperglycemia combined with hyperinsulinemia caused a likely unique signature that contributes to acquiring more carcinogenic traits. Indeed, these findings might potentially add emphasis on how monitoring diabetes-related metabolic alteration as an adjunct to diabetes therapy is important in improving breast cancer outcomes. However, further detailed studies are required to decipher the role of the highlighted genes, in this study, in the pathogenesis of breast cancer in patients with a different glycemic index.

Clinical Audit Report on Mental Health Screening by nurses at a Primary Health Care Centre

Mental health awareness is a vital part of a comprehensive National Mental Health and Wellbeing Strategy for the entire population [1]. The Ministry of Public Health (MOPH) in Qatar along with various stakeholders including PHCC are tasked with promoting and improving the delivery of Mental health services across the country as per Public Health Strategy 2017-2022 and the National Health Strategy 2018-2022 [2, 3]. The Qatar Global Burden of Disease 2010 reveals that major depressive disorder is the most burdensome disease in Qatar as per DALYs [4]. The WHO estimates about 30-50% patients attending primary care with depressive disorder are not detected and nearly two-thirds of people with a known mental disorder never seek help from a health professional due to stigma, discrimination, and negative stereotype [5]. Other reasons include limited time, access, affordability and lack of education and training. It was reported that an average delay between first symptoms presentation and intervention is approximately 11 years, which makes screening important as it allows for early identification and intervention. Recently MOPH launched Ma'ak Educational Program to enhance mental health and wellbeing in Qatar [6]. This can help bridge the gap and lead to better outcomes. Evidence suggests early treatment may also lessen long-term disability and suffering [7]. This Audit is done to review the adherence to mental health screening by nurses at our primary health care center (HC) and suggest measures to improve quality of patient care and health outcomes at PHCC if audit finds any gap in practice. A baseline audit sample of 354 health records was selected from the total volume of patients (18years and above) who were seen at nurses' station at our HC between 11th to 20th January 2023 and reviewed retrospectively against audit specific criterion. This data was then analysed to see how many of them had mental health screening performed using PHQ2 and GAD2 questionnaires. ..