Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.

BACKGROUND: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. METHODS AND FINDINGS: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. CONCLUSIONS: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01212328.

Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact.

The Global Diabetes Compact is a WHO-driven initiative uniting stakeholders around goals of reducing diabetes risk and ensuring that people with diabetes have equitable access to comprehensive, affordable care and prevention. In this report we describe the development and scientific basis for key health metrics, coverage, and treatment targets accompanying the Compact. We considered metrics across four domains: factors at a structural, system, or policy level; processes of care; behaviours and biomarkers such as glycated haemoglobin (HbA1c); and health events and outcomes; and three risk tiers (diagnosed diabetes, high risk, or whole population), and reviewed and prioritised them according to their health importance, modifiability, data availability, and global inequality. We reviewed the global distribution of each metric to set targets for future attainment. This process led to five core national metrics and target levels for UN member states: (1) of all people with diabetes, at least 80% have been clinically diagnosed; and, for people with diagnosed diabetes, (2) 80% have HbA1c concentrations below 8·0% (63·9 mmol/mol); (3) 80% have blood pressure lower than 140/90 mm Hg; (4) at least 60% of people 40 years or older are receiving therapy with statins; and (5) each person with type 1 diabetes has continuous access to insulin, blood glucose meters, and test strips. We also propose several complementary metrics that currently have limited global coverage, but warrant scale-up in population-based surveillance systems. These include estimation of cause-specific mortality, and incidence of end-stage kidney disease, lower-extremity amputations, and incidence of diabetes. Primary prevention of diabetes and integrated care to prevent long-term complications remain important areas for the development of new metrics and targets. These metrics and targets are intended to drive multisectoral action applied to individuals, health systems, policies, and national health-care access to achieve the goals of the Global Diabetes Compact. Although ambitious, their achievement can result in broad health benefits for people with diabetes.

Is Electronic Information Exchange Associated With Lower 30-Day Readmission Charges Among Medicare Beneficiaries?

OBJECTIVE: Fragmented readmissions, when admission and readmission occur at different hospitals, are associated with increased charges compared with nonfragmented readmissions. We assessed if hospital participation in health information exchange (HIE) was associated with differences in total charges in fragmented readmissions. DATA SOURCE: Medicare Fee-for-Service Data, 2018. STUDY DESIGN: We used generalized linear models with hospital referral region and readmission month fixed effects to assess relationships between information sharing (same HIE, different HIEs, and no HIE available) and total charges of 30-day readmissions among fragmented readmissions; analyses were adjusted for patient-level clinical/demographic characteristics and hospital-level characteristics. DATA EXTRACTION METHODS: We included beneficiaries with a hospitalization for acute myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease, syncope, urinary tract infection, dehydration, or behavioral issues with a 30-day readmission for any reason. PRINCIPAL FINDINGS: In all, 279,729 admission-readmission pairs were included, 27% of which were fragmented (n=75,438); average charges of fragmented readmissions were $64,897-$71,606. Compared with fragmented readmissions where no HIE was available, the average marginal effects of same-HIE and different-HIE admission-readmission pairs were -$2329.55 (95% CI: -7333.73, 2674.62) and -$3905.20 (95% CI: -7592.85, -307.54), respectively. While the average marginal effects of different-HIE pairs were lower than those for no-HIE fragmented readmissions, the average marginal effects of same-HIE and different-HIE pairs were not significantly different from each other. CONCLUSIONS: There were no statistical differences in charges between fragmented readmissions to hospitals that share an HIE or that do not share an HIE compared with hospitals with no HIE available.

Association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Egyptian children and adolescents.

BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.

5-Year simulation of diabetes-related complications in people treated with tirzepatide or semaglutide versus insulin glargine.

AIM: This study compared the 5-year incidence rate of macrovascular and microvascular complications for tirzepatide, semaglutide and insulin glargine in individuals with type 2 diabetes, using the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes simulation model. RESEARCH DESIGN AND METHODS: This study was a 5-year SURPASS-2 trial extrapolation, with an insulin glargine arm added as an additional comparator. The 1-year treatment effects of tirzepatide (5, 10 or 15 mg), semaglutide (1 mg) and insulin glargine on glycated haemoglobin, systolic blood pressure, low-density lipoprotein and body weights were obtained from the SUSTAIN-4 and SURPASS-2 trials. We used the BRAVO model to predict 5-year complications for each study arm under two scenarios: the 1-year treatment effects persisted (optimistic) or diminished to none in 5 years (conservative). RESULTS: When compared with insulin glargine, we projected a 5-year risk reduction in cardiovascular adverse events [rate ratio (RR) 0.64, 95% confidence interval (CI) 0.61-0.67] and microvascular composite (RR 0.67, 95% CI 0.64-0.70) with 15 mg tirzepatide, and 5-year risk reduction in cardiovascular adverse events (RR 0.75, 95% CI 0.72-0.79) and microvascular composite (RR 0.79, 95% CI 0.76-0.82) with semaglutide (1 mg) under an optimistic scenario. Lower doses of tirzepatide also had similar, albeit smaller benefits. Treatment effects for tirzepatide and semaglutide were smaller but still significantly higher than insulin glargine under a conservative scenario. The 5-year risk reduction in diabetes-related complication events and mortality for the 15 mg tirzepatide compared with insulin glargine ranged from 49% to 10% under an optimistic scenario, which was reduced by 17%-33% when a conservative scenario was assumed. CONCLUSION: With the use of the BRAVO diabetes model, tirzepatide and semaglutide exhibited potential to reduce the risk of macrovascular and microvascular complications among individuals with type 2 diabetes, compared with insulin glargine in a 5-year window. Based on the current modelling assumptions, tirzepatide (15 mg) may potentially outperform semaglutide (1 mg). While the BRAVO model offered insights, the long-term cardiovascular benefit of tirzepatide should be further validated in a prospective clinical trial.

Renal function as an effect modifier of intensive glucose control in delaying cognitive function decline among individuals with type 2 diabetes: A revisit to the ACCORD MIND trial.

AIM: Dysglycaemia accelerates cognitive decline. Intensive glucose control may help delay or prevent cognitive function decline (CFD). We aimed to determine how patient characteristics influence the effect of intensive glucose control [glycated haemoglobin (HbA1c) <6.0%] on delaying CFD in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this post-hoc analysis of 2977 type 2 diabetes participants from the ACCORD MIND trial, we applied the causal forest and causal tree algorithms to identify the effect modifier of intensive glucose control in delaying CFD from 68 variables (demographics, disease history, medications, vitals and baseline biomarkers). The exposure was intensive versus standard glucose control (HbA1c <6.0% vs. 7.0%-7.9%). The main outcome was cognitive function changes from baseline to the 40th month follow-up, which were evaluated using the digit symbol substitution test, Rey auditory verbal learning test, mini-mental state examination and Stroop test. We used Cohen's d, a measure of standardized difference, to quantify the effect size of intensive glucose control on delaying CFD. RESULTS: Among all the baseline characteristics, renal function was the most significant effect modifier. Participants with urinary albumin levels <0.4 mg/dl [absolute function change (AFC): 0.51 in mini-mental state examination, 95% confidence interval (CI): 0.04, 0.98, Cohen's d: 0.25] had slower CFD with intensive glucose control. Patients with preserved renal function (estimated glomerular filtration rate between 60 and 90 ml/min/1.73 m2) were associated with small benefits (AFC: 1.28 in Stroop, 95% CI: 0.28, 2.27, Cohen's d: 0.12) when undergoing intensive glucose control. Conversely, participants with an estimated glomerular filtration rate <60 ml/min/1.73 m2 (AFC: -0.57 in the Rey auditory verbal learning test, 95% CI: -1.09, -0.05, Cohen's d: -0.30) exhibited faster CFD when undergoing intensive glucose control. Participants who were <60 years old showed a significant benefit from intensive glucose control in delaying CFD (AFC: 1.08 in the digit symbol substitution test, 95% CI: 0.06, 2.10, Cohen's d: 0.13). All p < .05. CONCLUSIONS: Our findings linked renal function with the benefits of intensive glucose control in delaying CFD, informing personalized HbA1c goals for those with diabetes and at risk of CFD.

Association between low cognitive performance and diabetes-related health indicators across racial and ethnic groups in adults with diabetes.

AIM: To examine the associations between low cognitive performance (LCP) and diabetes-related health indicators (including body mass index [BMI], HbA1c, systolic blood pressure [SBP], low-density lipoprotein [LDL] and self-reported poor physical health) and whether these associations vary across racial/ethnic subgroups. METHODS: We identified adults aged 60 years or older with self-reported diabetes from the 2011-2014 National Health and Nutrition Examination Survey. Individuals with cognitive test scores in the lowest quartile were defined as having LCP. We used regression models to measure the associations of LCP with diabetes-related biometrics (BMI, HbA1c, SBP and LDL); and self-reported poor physical health. Moreover, we explored potential variations in these associations across racial/ethnic subgroups. RESULTS: Of 873 (261 with LCP) adults with diabetes, LCP was associated with higher HbA1c, SBP and LDL (adjusted difference: 0.41%, 5.01 mmHg and 5.08 mg/dL, respectively; P < .05), and greater odds of reporting poor physical health (adjusted odds ratio: 1.59, P < .05). The association between LCP and HbA1c was consistent across racial/ethnic groups, and notably pronounced in Hispanic and Other. BMI worsened with LCP, except for non-Hispanic Black. Excluding the Other group, elevated SBP was observed in people with LCP, with Hispanic showing the most significant association. LDL levels were elevated with LCP for Hispanic and Other. Physical health worsened with LCP for both non-Hispanic Black and Hispanic. CONCLUSIONS: We quantified the association between LCP and diabetes-related health indicators. These associations were more pronounced in Hispanic and Other racial/ethnic groups.

Differences in PPD- and mitogen-induced T-cell activation marker expression characterize immunopathology in acute tuberculosis patients.

Impaired T-cell responses to mitogens and high T-cell activation marker (TAM) expression on Mycobacterium tuberculosis-specific T-cells characterize immunopathology in patients with tuberculosis (TB). In a study of patients with TB (n = 60) and asymptomatic contacts (controls, n = 37), we found that TB patients had higher CD38+ T-cell proportions specific for M. tuberculosis protein (PPDMtb), yet total proportions of PPDMtb-specific T-cells were comparable. Notably, both activated (CD38+) and total IFN-γ+ T-cells from TB patients had lower mitogen (phytohemagglutinin, PHA)-induced responses. This impaired mitogen response improved the classification efficacy of the TAM-TB assay, especially employing the PPD/PHA-induced T-cell ratio.

Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study.

SUMMARY: Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

Recent Progress in Folic Acid Detection Based on Fluorescent Carbon Dots as Sensors: A Review.

Folic acid (FA) is a water-soluble vitamin found in diverse natural sources and is crucial for preserving human health. The risk of health issues due to FA deficiency underscores the need for a straightforward and sensitive FA detection methodology. Carbon dots (CDs) have gained significant attention owing to their exceptional fluorescence performance, biocompatibility, and easy accessibility. Consequently, numerous research studies have concentrated on developing advanced CD fluorescent probes to enable swift and precise FA detection. Despite these efforts, there is still a requirement for a thorough overview of the efficient synthesis of CDs and their practical applications in FA detection to further promote the widespread use of CDs. This review paper focuses on the practical applications of CD sensors for FA detection. It begins with an in-depth introduction to FA and CDs. Following that, based on various synthetic approaches, the prepared CDs are classified into diverse detection methods, such as single sensing, visual detection, and electrochemical methods. Furthermore, persistent challenges and potential avenues are highlighted for future research to provide valuable insights into crafting effective CDs and detecting FA.

Tight-binding model predicts exciton energetics and structure for photovoltaic molecules.

Conjugated molecules and polymers are being designed as acceptor and donor materials for organic photovoltaic (OPV) cells. OPV performance depends on generation of free charge carriers through dissociation of excitons, which are electron-hole pairs created when a photon is absorbed. Here, we develop a tight-binding model to describe excitons on homo-oligomers, alternating co-oligomers, and a non-fullerene acceptor - IDTBR. We parameterize our model using density functional theory (DFT) energies of neutral, anion, cation, and excited states of constituent moieties. A symmetric molecule like IDTBR has two ends where an exciton can sit; but the product wavefunction approximation for the exciton breaks symmetry. So, we introduce a tight-binding model with full correlation between electron and hole, which allows the exciton to coherently explore both ends of the molecule. Our approach predicts optical singlet excitation energies for oligomers of varying length as well as IDTBR in good agreement with time-dependent DFT and spectroscopic results.

Discovery of novel octahydroquinazoline scaffolds endowed with dual inhibition of tubulin polymerization/Eg5 against HCC: Apoptotic and radio-chemotherapeutic studies.

Mitotic kinesin Eg5 isozyme as a motor protein plays a critical role in cell division of tumor cells. Kinesin Eg5 selective inhibitors and Colchicine binding site suppressors are essential targets for many anticancer drugs and radio chemotherapies. On this work, a new series of octahydroquinazoline as anti-mitotic candidates 2-13 has been synthesized with dual inhibition of tubulin polymerization/Eg5 against HCC cell line. All octahydroquinazolines have been in vitro assayed against HepG-2 cytotoxicity, Eg5 inhibitory and anti-tubulin polymerization activities. The most active analogues 7, 8, 9, 10, and 12 against HepG-2 were further subjected to in vitro cytotoxic assay against HCT-116 and MCF-7 cell lines. Chalcones 9, 10, and 12 displayed the most cytotoxic potency and anti-tubulin aggregation in comparable with reference standard colchicine and potential anti-mitotic Eg5 inhibitory activity in comparison with Monastrol as well. Besides, they exhibited cell cycle arrest at the G2/M phase. Moreover, good convinced apoptotic activities have been concluded as overexpression of caspase-3 levels and tumor suppressive gene p53 in parallel with higher induction of Bax and inhibition of Bcl-2 biomarkers. Octahydroquinazoline 10 displayed an increase in caspase-3 by 1.12 folds compared to standard colchicine and induce apoptosis and demonstrated cell cycle arrest in G2/M phase arrest by targeting p53 pathway. Analogue 10 has considerably promoted cytotoxic radiation activity and boosted apoptotic induction in HepG-2 cells by 1.5 fold higher than standard colchicine.

Alterations in trace elements and cation profiles in transfusion-dependent thalassemia patients.

BACKGROUND: Transfusion-dependent thalassemia (TDT) is a severe form of beta-thalassemia, characterized by defective-globin production, resulting in a buildup of unpaired alpha globin chains. Patients with TDT can only survive if they receive safe blood transfusions regularly, which causes iron overload in their blood, which causes a variety of disorders. Cations and trace elements in TDT patients as a drug target deserve more studies. OBJECTIVES: In the present study, the cations and some trace elements were studied in TDT patients as a tool to adjust their level in the case of any disturbances. METHODS: Serum calcium, magnesium, zinc, copper, and iron were measured spectrophotometrically while manganese and cobalt were measured by flameless atomic absorption spectroscopy in 100 TDT patients and compared with 35 healthy control children. RESULTS: Patients with TDT exhibit a notable elevation in blood levels of iron, copper, copper/zinc ratio, and manganese, with a substantial reduction in serum levels of zinc, magnesium, calcium, and cobalt, as compared to the control group. These minerals have diverse associations with clinical data and transfusion frequencies. The receiver operating characteristic (ROC) analysis revealed that the elevated levels of iron, manganese, and calcium exhibit the greatest diagnostic capability, with a sensitivity and specificity of over 80 %, and a Youdin's J value of more than 0.6. CONCLUSION: The levels of cations and trace elements are disturbed in TDT patients. Hence, the monitoring and adjustment of the level of these minerals are important to prevent further consequences.

Conclusion of diagnostic odysseys due to inversions disrupting GLI3 and FBN1.

Many genetic testing methodologies are biased towards picking up structural variants (SVs) that alter copy number. Copy-neutral rearrangements such as inversions are therefore likely to suffer from underascertainment. In this study, manual review prompted by a virtual multidisciplinary team meeting and subsequent bioinformatic prioritisation of data from the 100K Genomes Project was performed across 43 genes linked to well-characterised skeletal disorders. Ten individuals from three independent families were found to harbour diagnostic inversions. In two families, inverted segments of 1.2/14.8 Mb unequivocally disrupted GLI3 and segregated with skeletal features consistent with Greig cephalopolysyndactyly syndrome. For one family, phenotypic blending was due to the opposing breakpoint lying ~45 kb from HOXA13 In the third family, long suspected to have Marfan syndrome, a 2.0 Mb inversion disrupting FBN1 was identified. These findings resolved lengthy diagnostic odysseys of 9-20 years and highlight the importance of direct interaction between clinicians and data-analysts. These exemplars of a rare mutational class inform future SV prioritisation strategies within the NHS Genomic Medicine Service and similar genome sequencing initiatives. In over 30 years since these two disease-gene associations were identified, large inversions have yet to be described and so our results extend the mutational spectra linked to these conditions.

Care fragmentation and readmission mortality and length of stay before and during the COVID-19 pandemic: data from the National Readmissions Database, 2018-2020.

IMPORTANCE: A quarter of all 30-day readmissions involve fragmented care, where patients return to a different hospital than their original admission; these readmissions are associated with increased in-hospital mortality and longer lengths-of-stay (LOS). The stress on healthcare systems at the beginning of the COVID-19 pandemic could worsen care fragmentation and related outcomes. OBJECTIVE: To compare fragmented readmissions in 2020 versus 2018-2019 and assess whether mortality and LOS in fragmented readmissions differed in the two time periods. DESIGN: Observational study SETTING: National Readmissions Database (NRD), 2018-2020 PARTICIPANTS: All adults (> 18 y/o) with 30-day readmissions MAIN OUTCOMES AND MEASURES: We examined the percentage of fragmented readmissions over 2018-2020. Using unadjusted and adjusted logistic and linear regressions, we estimated the associations between fragmented readmissions and in-hospital mortality and LOS. RESULTS: 24.0-25.7% of readmissions in 2018-2020 and 27.3%-31.0% of readmissions for COVID-19 were fragmented. 2018-2019 fragmented readmissions were associated with 18-20% higher odds of in-hospital mortality compared to nonfragmented readmissions. Fragmented readmissions for COVID-19 were associated with an 18% increase in in-hospital mortality (AOR 1.18, 95% CI 1.12, 1.24). The LOS of fragmented readmissions in March-November 2018-2019 were on average 0.81 days longer, while fragmented readmissions between March-November of 2020 were associated with a 0.88-1.03 day longer LOS. CONCLUSIONS AND RELEVANCE: A key limitation is that the NRD does not contain information on several patient/hospital-level factors that may be associated with the outcomes of interest. We observed increased fragmentation during COVID-19, but its impact on in-hospital mortality and LOS remained consistent with previous years.

Gender differences in learning and study strategies impact medical students' preclinical and USMLE step 1 examination performance.

BACKGROUND: Evaluation of students' learning strategies can enhance academic support. Few studies have investigated differences in learning strategies between male and female students as well as their impact on United States Medical Licensing Examination® (USMLE) Step 1 and preclinical performance. METHODS: The Learning and Study Strategies Inventory (LASSI) was administered to the classes of 2019-2024 (female (n = 350) and male (n = 262)). Students' performance on preclinical first-year (M1) courses, preclinical second-year (M2) courses, and USMLE Step 1 was recorded. An independent t-test evaluated differences between females and males on each LASSI scale. A Pearson product moment correlation determined which LASSI scales correlated with preclinical performance and USMLE Step 1 examinations. RESULTS: Of the 10 LASSI scales, Anxiety, Attention, Information Processing, Selecting Main Idea, Test Strategies and Using Academic Resources showed significant differences between genders. Females reported higher levels of Anxiety (p < 0.001), which significantly influenced their performance. While males and females scored similarly in Concentration, Motivation, and Time Management, these scales were significant predictors of performance variation in females. Test Strategies was the largest contributor to performance variation for all students, regardless of gender. CONCLUSION: Gender differences in learning influence performance on STEP1. Consideration of this study's results will allow for targeted interventions for academic success.

Noncompliance of pediatric cancer patients with chemotherapy: A single-center experience in a lower-middle income country.

Noncompliance with therapy is a big obstacle to successful therapy. We aimed to evaluate the prevalence and risk factors affecting the compliance of pediatric cancer patients with therapy in a tertiary care center far away from the capital in a lower-middle income country (LMIC). A retrospective cohort study of reports of all pediatric cancer patients who were diagnosed and started treatment between 2006 and 2010 at South Egypt Cancer Institute (SECI) was done. The following data were collected: Age, sex, diagnosis, compliance with therapy, and data on potential risk factors that might affect compliance, including time duration of travel from the patient's home to SECI, time lag between the first symptom until the first visit to SECI and until the start of treatment, results of reevaluation after the initial course of therapy, and therapy-related severe adverse events. Noncompliance with therapy was defined as when patients missed their determined therapy appointment for one week or more or abandoned therapy. This study included 510 patients. Eighty-three (16.3%) were non-compliant, as forty patients missed their therapy appointment (7.8%), and 43 abandoned further therapy (8.4%). Noncompliance was found to be more prevalent among patients with solid tumors. Non-compliant patients suffered a significantly higher relapse rate (47.7% vs. 11.2% in compliant patients, p < .001). Unfortunately, 75% of the abandoned patients who returned for further therapy suffered a relapse. Noncompliance with treatment is still a big problem facing cancer management in LMICs.

A histology guide for performing human cadaveric studies: SQIP 2024 what to look for with light microscopy.

Histological observation under light microscopy has long been used in human cadaveric studies. However, it can distort the interpretations of findings if not used appropriately; there is no guide for its proper use. The aim of this article is to revisit and discuss the correct use of histology in human cadaveric studies, following discussions with experts in multiple fields of medicine, and to create the first guide for such usage. We reached a consensus with the experts, agreeing that when this principle (structure, quantification, interaction, position: SQIP) is applied to histological observations, the findings will be interpreted correctly. Appropriate use of this recommendation can make human cadaveric studies more accurate and informative. This is the first histology guide for human cadaveric studies.

Ratios of Neutrophils and Platelets to Lymphocytes as Predictors of Postoperative Intensive Care Unit Admission and Length of Stay in Bariatric Surgery Patients: A Retrospective Study.

Background and Objectives: This study aimed to investigate the role of the pre- and postoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting intensive care unit (ICU) admission and postoperative length of stay (LOS) in bariatric surgery. Materials and Methods: We retrospectively analysed 96 patients who underwent bariatric surgery at our institution. The NLR and PLR were calculated in the pre- and postoperative stages. Changes in pre- and postoperative hematological ratios were compared using the Wilcoxon signed-rank test. The optimal cutoff values and area under the curve (AUC) for each ratio were calculated using receiver operating characteristic (ROC) analysis. Multivariate linear regression analysis was used to assess the relationship between each ratio and the postoperative LOS after adjusting for age, sex, and American Society of Anesthesiologists (ASA) score. Results: The median age of our patients was 35.50 years, and 54.2% were male. The preoperative NLR showed a significant increase from 1.44 to 6.38 postoperatively (p < 0.001). The PLR increased from 107.08 preoperatively to 183.58 postoperatively, p < 0.001). ROC analysis showed that the postoperative NLR was a moderate to high predictor of ICU admission (AUC = 0.700, optimal cutoff point = 5.987). The postoperative PLR had less predictive power for ICU admission (AUC = 0.641, optimal cutoff point = 170.950). Ratios that had a statistically significant relationship with the postoperative LOS were the preoperative NLR (standardized ß [95% CI]: 0.296 [0.115-0.598]), postoperative NLR (0.311 [0.034-0.161]), and postoperative PLR (0.236 [0.000-0.005]). Conclusions: The NLR and PLR demonstrated an independent relationship with the postoperative LOS after bariatric surgery and the predictive ability of ICU admission. Both ratios might be useful as simple markers to predict patient outcome after surgery.

A comprehensive review of discovery and development of drugs discovered from 2020-2022.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.