Ophthalmologic profile of patients with systemic sclerosis.

PURPOSE: To study the ophthalmologic manifestations of systemic sclerosis (SSc) and its correlation with autoantibody profile. METHODS: A cross-sectional study on 200 eyes of 100 consecutive adult patients diagnosed with SSc was performed at a tertiary care center in Northern India. The examination of ocular adnexa, anterior segment, and posterior segment with slit-lamp biomicroscopy, tear film break-up time (TBUT), Schirmer's II test, and choroidal thickness measurement by swept-source ocular coherence tomography was done. Autoantibody profile was available for 85 patients, and its statistical association with the ocular examination findings was analyzed. RESULTS: In total, 100 patients (93 females and 7 males) were included. The mean age was 45.11 ± 11.68 years, and the mean disease duration was 6.93 ± 3.68 years. Meibomian gland disease was more commonly found in patients with the diffuse subtype of SSc (P = 0.037). Choroidal thickness was increased in 34% and decreased in 7% (reference range = 307 ± 79 mm) patients. Reduced TBUT, meibomian gland dysfunction, and eyelid stiffness had a statistically significant association with the presence of anti-Scl-70 antibody (P = 0.003, <0.0001, and 0.004, respectively). These patients had ocular fatigue, foreign body sensation, and burning sensation. No significant association was noted with the presence of SS-A/Ro and SS-B/La antibodies. CONCLUSION: This study highlights the need for an active comprehensive ophthalmic evaluation. Approximately 75% of the patients in our cohort had ocular involvement to varying extent. An isolated presence of anti-Scl70 antibody was also found to have a positive association with dry eye disease.

Impact of Hospital Affiliation With a Flagship Hospital System on Surgical Outcomes.

OBJECTIVE: To compare general surgery outcomes at flagship systems, flagship hospitals, and flagship hospital affiliates versus matched controls. SUMMARY BACKGROUND DATA: It is unknown whether flagship hospitals perform better than flagship hospital affiliates for surgical patients. METHODS: Using Medicare claims for 2018 to 2019, we matched patients undergoing inpatient general surgery in flagship system hospitals to controls who underwent the same procedure at hospitals outside the system but within the same region. We defined a "flagship hospital" within each region as the major teaching hospital with the highest patient volume that is also part of a hospital system; its system was labeled a "flagship system." We performed 4 main comparisons: patients treated at any flagship system hospital versus hospitals outside the flagship system; flagship hospitals versus hospitals outside the flagship system; flagship hospital affiliates versus hospitals outside the flagship system; and flagship hospitals versus affiliate hospitals. Our primary outcome was 30-day mortality. RESULTS: We formed 32,228 closely matched pairs across 35 regions. Patients at flagship system hospitals (32,228 pairs) had lower 30-day mortality than matched control patients [3.79% vs. 4.36%, difference=-0.57% (-0.86%, -0.28%), P<0.001]. Similarly, patients at flagship hospitals (15,571/32,228 pairs) had lower mortality than control patients. However, patients at flagship hospital affiliates (16,657/32,228 pairs) had similar mortality to matched controls. Flagship hospitals had lower mortality than affiliate hospitals [difference-in-differences=-1.05% (-1.62%, -0.47%), P<0.001]. CONCLUSIONS: Patients treated at flagship hospitals had significantly lower mortality rates than those treated at flagship hospital affiliates. Hence, flagship system affiliation does not alone imply better surgical outcomes.

Behavioural disorders after prenatal exposure to anaesthesia for maternal surgery.

BACKGROUND: The association between prenatal exposure to general anaesthesia for maternal surgery during pregnancy and subsequent risk of disruptive or internalising behavioural disorder diagnosis in the child has not been well-defined. METHODS: A nationwide sample of pregnant women linked to their liveborn infants was evaluated using the Medicaid Analytic eXtract (MAX, 1999-2013). Multivariate matching was used to match each child prenatally exposed to general anaesthesia owing to maternal appendectomy or cholecystectomy during pregnancy with five unexposed children. The primary outcome was diagnosis of a disruptive or internalising behavioural disorder in children. Secondary outcomes included diagnoses for a range of other neuropsychiatric disorders. RESULTS: We matched 34,271 prenatally exposed children with 171,355 unexposed children in the database. Prenatally exposed children were more likely than unexposed children to receive a diagnosis of a disruptive or internalising behavioural disorder (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.23-1.40). For secondary outcomes, increased hazards of disruptive (HR, 1.32; 95% CI, 1.24-1.41) and internalising (HR, 1.36; 95% CI, 1.20-1.53) behavioural disorders were identified, and also increased hazards of attention-deficit/hyperactivity disorder (HR, 1.32; 95% CI, 1.22-1.43), behavioural disorders (HR, 1.28; 95% CI, 1.14-1.42), developmental speech or language disorders (HR, 1.16; 95% CI, 1.05-1.28), and autism (HR, 1.31; 95% CI, 1.05-1.64). CONCLUSIONS: Prenatal exposure to general anaesthesia is associated with a 31% increased risk for a subsequent diagnosis of a disruptive or internalising behavioural disorder in children. Caution is advised when making any clinical decisions regarding care of pregnant women, as avoidance of necessary surgery during pregnancy can have detrimental effects on mothers and their children.

Rheumatoid arthritis synovial fluid shows enrichment of T-cells producing GMCSF which are polyfunctional for TNFα and IFNγ.

OBJECTIVES: GMCSF+T-cells may be involved in pathogenesis of rheumatoid arthritis (RA), and polyfunctionality may be a marker of pathogenicity. Although, higher frequencies of CD4+GMCSF+ T-cells have been reported, there are no data on CD8+GMCSF+ T-cells or polyfunctionality.Our objective was to enumerate frequencies of CD8+GMCSF+ T cells in RA blood and synovial fluid (SF), and assess their polyfunctionality, memory phenotype and cytotoxic ability. METHODS: This study included RA patients (blood samples,in some with paired synovial fluid (SF)), healthy controls (HC) (blood) and SpA patients (SF). In some RA patients' blood was sampled twice, before and 16-24 weeks after methotrexate (MTX) treatment. After mononuclear cell isolation from blood and SF, ex-vivo stimulation using PMA/Ionomycin was done, and cells were stained (surface and intracellular after permeabilisation/fixation). Subsequently, frequencies of GMCSF+CD8+ and CD4+ T-cells, polyfunctionality (TNFα, IFNγ, IL-17), phenotype (memory) and perforin/granzyme expression were assessed by flowcytometry. RESULTS: There was no significant difference in frequencies of GMCSF+CD8+ (3.7, 4.1%, p=0.540) or GMCSF+CD4+ T-cells (4.5, 5.2%, p=0.450) inblood of RA and HC. However, there was significant enrichment of both CD8+GMCSF+ (5.8, 3.9%, p=0.0045) and CD4+GMCSF+ (8.5, 4.5%, p=0.0008) T-cells inSF compared to blood in RA patients. Polyfunctional triple cytokine positive TNFα+IFNγ+GMCSF+CD8+T-cells (81, 36%, p=0.049) and CD4+T-cells (48, 32%, p=0.010) was also higher in SF compared to blood in RA. CD8+ T cells showed higher frequency of effector-memory phenotype and granzyme-B expression in RA-SF. On longitudinal follow-up, blood CD4+GMCSF+ T-cells significantly declined (4.6, 2.9%, p=0.0014) post-MTX. CONCLUSIONS: We report a novel finding of enrichment of CD8+GMCSF+ in addition to CD4+GMCSF+ T-cells in RA-SF. These cells showed higher polyfunctionality for TNFα and IFNγ, and effector memory phenotype suggesting their involvement in RA pathogenesis.

Assessing the Ambulatory Surgery Center Volume-Outcome Association.

Importance: In surgical patients, it is well known that higher hospital procedure volume is associated with better outcomes. To our knowledge, this volume-outcome association has not been studied in ambulatory surgery centers (ASCs) in the US. Objective: To determine if low-volume ASCs have a higher rate of revisits after surgery, particularly among patients with multimorbidity. Design, Setting, and Participants: This matched case-control study used Medicare claims data and analyzed surgeries performed during 2018 and 2019 at ASCs. The study examined 2328 ASCs performing common ambulatory procedures and analyzed 4751 patients with a revisit within 7 days of surgery (defined to be either 1 of 4735 revisits or 1 of 16 deaths without a revisit). These cases were each closely matched to 5 control patients without revisits (23 755 controls). Data were analyzed from January 1, 2018, through December 31, 2019. Main Outcomes and Measures: Seven-day revisit in patients (cases) compared with the matched patients without the outcome (controls) in ASCs with low volume (less than 50 procedures over 2 years) vs higher volume (50 or more procedures). Results: Patients at a low-volume ASC had a higher odds of a 7-day revisit vs patients who had their surgery at a higher-volume ASC (odds ratio [OR], 1.21; 95% CI, 1.09-1.36; P = .001). The odds of revisit for patients with multimorbidity were higher at low-volume ASCs when compared with higher-volume ASCs (OR, 1.57; 95% CI, 1.27-1.94; P < .001). Among patients with multimorbidity in low-volume ASCs, for those who underwent orthopedic procedures, the odds of revisit were 84% higher (OR, 1.84; 95% CI, 1.36-2.50; P < .001) vs higher-volume centers, and for those who underwent general surgery or other procedures, the odds of revisit were 36% higher (OR, 1.36; 95% CI, 1.01-1.83; P = .05) vs a higher-volume center. The findings were not statistically significant for patients without multimorbidity. Conclusions and Relevance: In this observational study, the surgical volume of an ASC was an important indicator of patient outcomes. Older patients with multimorbidity should discuss with their surgeon the optimal location of their care.

Current veterinary regulations and way ahead.

This article aims to perform a comparative systematic review of regulations in veterinary medicine between the years 2016 to 2023. It explores the complex web of veterinary medicine regulations in various agencies and the nations, including USA (United States of America), EU (European Union), UK (United Kingdom), Japan, Australia, and India. Current article provides the comparative study on the veterinary regulations of different countries, including acts, directives, and drug approval processes. Such as, the specific legislation is needed to address zoonotic diseases. The strategic and regulated stockpiling of the veterinary drugs especially in chronic veterinary disease outbreak. It is essential to develop the dedicated Veterinary Pharmacopoeia for the regulated standardization of the raw materials as well as the formulations. Veterinary medical device is a field which is highly unregulated. There is a need to have regulations for the same. It is important to have dedicated veterinary pharmacovigilance centers which help in improving quality of medications to the livestock farms. After comparing the regulations of different countries. We observed that there is the absence of the zoonotic diseases and pharma stockpiling in every country. There is also an absence of the dedicated veterinary pharmacopoeia in every country. USA and Australia have the veterinary medical device regulation which is not there in other countries. Around the globe only Australia has the dedicated pharmacovigilance center. Including these recommendations into regulatory framework enhances the quality and safety of veterinary medicine. The current article adds a valuable resource for policymakers, veterinarians, and stakeholders in the field of animal health care.

Analyzing the performance of synthesized nano-catalysts for transesterification of waste cooking oil as environment friendly drilling fluid.

Ester-based drilling fluids (EBDF) are preferred over oil-based drilling fluids (OBDF) and water-based drilling fluids (WBDF) because of their great biodegradability, low toxicity, and improved performance. In this work, waste cooking oil methyl ester (WCOME) was used to prepare an environmentally friendly EBDF. Through a transesterification process utilizing a modified calcium oxide based heterogenous catalyst, the waste cooking oil is transformed into waste cooking oil methyl ester. Response surface approach was used to strengthen the transesterification. The optimize conditions for CaO/Al2O3 resulted in the highest yield of 96.56% at a molar ratio of 11.9:1, 3.19 wt % of CaO/Al2O3, 53.79 °C, and 76.86 min. In contrast, CaO/TiO2 yielded 98.15% at a molar ratio of 11.99:1, with a CaO/TiO2 of 2.53 wt % at 59.79 in 68.14 min. Additionally, two separate densities of 9 ppg and 12 ppg EBDF are formulated with two distinct oil-to-water ratios (70:30 and 80:20) using synthesized WCOME. To assess the effectiveness of formulated EBDF thorough rheological investigation is conducted at 150°. Additionally, the filtration loss at HPHT conditions, emulsion stability, and Barite sag analysis of the drilling fluid are all analyzed at before ageing and after dynamic ageing. With better rheological features, less fluid loss, good emulsion stability, and minimal barite sagging, the designed EBDF performs efficiently. The drilling fluid met the API requirement and demonstrated stability even after ageing at 250 °F for 72 h, suggesting that it may be used for extended periods of time in drilling.

Mortality Among Older Medical Patients at Flagship Hospitals and Their Affiliates.

BACKGROUND: We define a "flagship hospital" as the largest academic hospital within a hospital referral region and a "flagship system" as a system that contains a flagship hospital and its affiliates. It is not known if patients admitted to an affiliate hospital, and not to its main flagship hospital, have better outcomes than those admitted to a hospital outside the flagship system but within the same hospital referral region. OBJECTIVE: To compare mortality at flagship hospitals and their affiliates to matched control patients not in the flagship system but within the same hospital referral region. DESIGN: A matched cohort study PARTICIPANTS: The study used hospitalizations for common medical conditions between 2018-2019 among older patients age ≥ 66 years. We analyzed 118,321 matched pairs of Medicare patients admitted with pneumonia (N=57,775), heart failure (N=42,531), or acute myocardial infarction (N=18,015) in 35 flagship hospitals, 124 affiliates, and 793 control hospitals. MAIN MEASURES: 30-day (primary) and 90-day (secondary) all-cause mortality. KEY RESULTS: 30-day mortality was lower among patients in flagship systems versus control hospitals that are not part of the flagship system but within the same hospital referral region (difference= -0.62%, 95% CI [-0.88%, -0.37%], P<0.001). This difference was smaller in affiliates versus controls (-0.43%, [-0.75%, -0.11%], P=0.008) than in flagship hospitals versus controls (-1.02%, [-1.46%, -0.58%], P<0.001; difference-in-difference -0.59%, [-1.13%, -0.05%], P=0.033). Similar results were found for 90-day mortality. LIMITATIONS: The study used claims-based data. CONCLUSIONS: In aggregate, within a hospital referral region, patients treated at the flagship hospital, at affiliates of the flagship hospital, and in the flagship system as a whole, all had lower mortality rates than matched controls outside the flagship system. However, the mortality advantage was larger for flagship hospitals than for their affiliates.

Disseminated Nasal subtype Extranodal NK/T-cell lymphoma and its diagnostic difficulties in antemortem biopsies.

Extranodal NK/T- cell lymphoma (ENKTCL) is an aggressive lymphoma driven by Epstein-Barr virus (EBV) infection in genetically susceptible individuals. It was historically called a lethal midline granuloma. Due to the angio-destructive nature of ENKTCL, lymphoma cells are often accompanied and masked by necrosis and dense inflammation in the biopsy. Further, the biopsy may show vasculitis, which can mimic granulomatosis with polyangiitis. Due to these masquerades, ENKTCL is often misdiagnosed in the biopsy. Several biopsies may be required to establish the diagnosis. We describe the clinical course and autopsy findings of a young female who presented with a hard-palate ulcer. Antemortem biopsies failed to establish the diagnosis. The autopsy revealed an advanced nasal subtype of Extranodal NK/T-cell lymphoma with dissemination to the kidneys, adrenals, liver, spleen, and small intestine.

Large-Scale Purification and Characterization of Recombinant Receptor-Binding Domain (RBD) of SARS-CoV-2 Spike Protein Expressed in Yeast.

SARS-CoV-2 spike protein is an essential component of numerous protein-based vaccines for COVID-19. The receptor-binding domain of this spike protein is a promising antigen with ease of expression in microbial hosts and scalability at comparatively low production costs. This study describes the production, purification, and characterization of RBD of SARS-CoV-2 protein, which is currently in clinical trials, from a commercialization perspective. The protein was expressed in Pichia pastoris in a large-scale bioreactor of 1200 L capacity. Protein capture and purification are conducted through mixed-mode chromatography followed by hydrophobic interaction chromatography. This two-step purification process produced RBD with an overall productivity of ~21 mg/L at >99% purity. The protein's primary, secondary, and tertiary structures were also verified using LCMS-based peptide mapping, circular dichroism, and fluorescence spectroscopy, respectively. The glycoprotein was further characterized for quality attributes such as glycosylation, molecular weight, purity, di-sulfide bonding, etc. Through structural analysis, it was confirmed that the product maintained a consistent quality across different batches during the large-scale production process. The binding capacity of RBD of spike protein was also assessed using human angiotensin-converting enzyme 2 receptor. A low binding constant range of KD values, ranging between 3.63 × 10-8 to 6.67 × 10-8, demonstrated a high affinity for the ACE2 receptor, revealing this protein as a promising candidate to prevent the entry of COVID-19 virus.

Analysing driving factors of India's transportation sector CO2 emissions: Based on LMDI decomposition method.

India is the world's third-largest carbon dioxide (CO2) emitter, with the transportation sector accounting for most of this emission. Using the logarithmic-mean Divisia index (LMDI) decomposition method and Tapio decoupling, this study examines the driving factors and their relationship with economic growth for the Indian transportation sector. Transportation-related energy consumption is decomposed into six factors. From 2001 to 2020, CO2 emissions from the Indian transportation sector increased from 155.9 Mt to 368.2 Mt. Roadways produce 88% of all CO2 emissions. Energy systems, economic advancement, and population scale increase CO2 emissions, whereas energy performance and transportation form decrease. Transport advancement demonstrates both tendencies intermittently. CO2 emissions from Indian transportation exhibit a weak decoupling. The increasing demand for vehicles, reliance on conventional fuel, and increase in energy consumption indicate a positive correlation with the increase in the nation's CO2 emissions, while the transition from coal to electric locomotives and the increased use of electric vehicles offset the increase in emissions. In short, the government should update strategic sustainable transport policy measures and emphasize renewable energy. This study will assist policymakers in formulating robust sustainable transportation policies.

Analgesic Effects of Magnesium Sulphate as an Adjuvant to Fentanyl for Monitored Anaesthesia Care During Hysteroscopy.

BACKGROUND: Magnesium sulphate (MgSO4) is conventionally used in the treatment of eclampsia, refractive arrhythmias, asthma, etc. In our study, we aimed to study the analgesic effects of MgSO4 as an adjuvant to fentanyl and reduce the intraoperative opioid requirement to decrease their adverse effects. METHODS: A total of 122 patients scheduled for hysteroscopy were randomly divided into two groups. Patients in the magnesium group (group A) received intravenous MgSO4 50 mg/kg in 100 ml of isotonic saline over 15 minutes before anaesthesia induction and then 15 mg/kg per hour by continuous intravenous infusion. Patients in the control group (group B) received an equal volume of isotonic saline as a placebo. All the patients were induced with fentanyl and propofol. Perioperative haemodynamic monitoring and postoperative assessment of pain were done. RESULTS: Only 18% of the patients in group A required rescue analgesics as compared to 39.3% of patients in group B. The patients receiving MgSO4 displayed lower verbal numeric rating scale scores in the postoperative period. In addition, the intraoperative requirement of fentanyl (101 (21.33) vs. 144 (28.4) µg, mean (SD)) and propofol (121 (13.3) vs. 140 (16.5) mg, mean (SD)) was significantly lower in group A as compared to that in group B. CONCLUSION: MgSO4, when administered as an adjuvant to opioids, provided effective postoperative analgesia thereby reducing the need for rescue analgesics. It also decreases intraoperative fentanyl consumption and its dose-related side effects.

Three-Year Experience and Outcomes of Near-Early Internal Fixation for Femoral Neck Fractures in Pediatric Trauma Patients: A Retrospective Study.

Background The fractured neck of the femur in children is commonly caused by high-energy trauma, and despite its low incidence, complications are more frequent. Delayed presentation is not unusual in developing countries. The interval between injury and surgery is thought to be a critical factor in determining outcomes. This study aims to evaluate the effectiveness of "near early" internal fixation (24-72 hours) for fractured neck of the femur in children. Methods This is a retrospective observational study that analyzed complete case records from a period of seven years. Cases were classified according to the Delbet classification and outcomes were assessed using the Ratliff criteria with a minimum follow-up of three years. Results The study included 24 male and 11 female patients, with an average age of 11.28 years. The most common cause of injury was road traffic accidents. The fracture distribution in the study population was as follows: Delbet type II in 18 patients, Delbet type III in 10 patients, and Delbet type IV in seven patients. In our study, all patients underwent near-early fixation, meaning their fractures were fixed within 24-72 hours of injury. The average time for the clinical-radiological union was 8 weeks, and the most common complication was premature physeal fusion, followed by osteonecrosis. Conclusion In developing countries, where patients often experience delayed referrals and lack of awareness, near-early fixation (24-72 hours) of a fractured neck of the femur in children is a crucial option that holds significant value.

Severity and determinants of psychosocial comorbidities in granulomatosis with polyangiitis and their impact on quality of life.

Depression, anxiety, sleep disturbances, and fatigue are inadequately addressed comorbidities in granulomatosis with polyangiitis (GPA). We determined the prevalence, severity, determinants, and the impact of these comorbidities on quality-of-life (QoL) in GPA. This observational study included adult GPA patients; patients with RA and lupus were included as comparators. Patient Health Questionnaire-9 for depression, Generalized Anxiety Disorder 7-item scale for anxiety, Epworth Sleepiness Scale for sleep disturbances, and Fatigue Severity Scale for fatigue were administered prospectively to estimate prevalence and severity. QoL and disability were estimated using PROMIS-HAQ, HAQ-health and HAQ-pain. Correlations among these parameters were assessed. Stepwise regression analyses were performed to identify determinants of depression, anxiety, excessive sleepiness, and fatigue. One hundred eighty-one patients-62 GPA [mean age 43 (13) years], 57 RA and 62 SLE- were included. The prevalence of depression (47%), excessive sleepiness (21%), and fatigue (39%) in GPA were comparable to RA and lupus; anxiety was less prevalent (29% versus 46% and 53%, p = 0.02). Severity was mostly mild-moderate. Younger age [OR = 0.93 (0.89-0.98)], higher BMI [OR = 1.2 (1.0-1.4)], and greater disease damage [OR = 2.0 (1.3-3.3)] independently predicted presence of depression. Higher BMI [OR = 1.3 (1.1-1.5)] and concomitant FMS [OR = 80.9 (5.1-1289.2)] were independently associated with excessive sleepiness. No association with disease activity, duration, or gender was seen. GPA patients with depression, anxiety, excessive sleepiness, and fatigue had worse PROMIS-HAQ, HAQ-pain, and HAQ-health. In conclusion, depression, anxiety, sleep disturbances, and fatigue are common in GPA. Although their severity is mostly mild-moderate, they impair QoL significantly. Potentially modifiable determinants that can form targets for future interventions have been identified.

Sudden Sensorineural Hearing Loss Associated with Oral Consumption of Hand Sanitizer: A Case Report.

Introduction: Pediatric sudden sensorineural hearing loss (SSNHL) is a rare otological emergency. With the emergence of the Coronavirus 19 pandemic, alcohol-based hand sanitizers are among the essential household items. Many hand sanitizers are frequently coupled with scents that young children may find pleasant. Case Report: A 5-year-old girl presented to our clinic with hearing loss after the consumption of alcohol-based hand sanitizer. A pure tone audiogram showed bilateral SSNHL. The child was prescribed systemic corticosteroids resulted in a slight improvement in hearing thresholds. The child was followed up at 6 and 18 months showing no further improvement in hearing thresholds. Conclusion: Although various infective, vascular, and immune responses have been proposed, alcohol-based hand sanitizer consumption has not been reported to present with SSNHL to the best of our knowledge. In the current scenario of the Coronavirus pandemic, otorhinolaryngologists must keep in mind that SSNHL may occur as a result of hazardous alcohol-based hand disinfectant consumption.

Comparison of two doses of leucovorin in severe low-dose methotrexate toxicity - a randomized controlled trial.

BACKGROUND: Leucovorin (folinic acid) is a commonly used antidote for severe toxicity with low-dose methotrexate, but its optimum dose is unclear, varying from 15 to 25 mg every 6-h. METHODS: Open-label RCT included patients with severe low-dose (≤ 50 mg/week) methotrexate toxicity defined as WBC ≤ 2 × 10^9/L or platelet ≤ 50 × 10^9/L and randomized them to receive either usual (15 mg) or high-dose (25 mg) intravenous leucovorin given every 6-h. Primary outcome was mortality at 30-days and secondary outcomes were hematological recovery and mucositis recovery. TRIAL REGISTRATION NUMBER: CTRI/2019/09/021152. RESULTS: Thirty-eight patients were included, most with underlying RA who had inadvertently overdosed MTX (taken daily instead of weekly). At randomization, the median white blood and platelet count were 0.8 × 10^9/L and 23.5 × 10^9/L. 19 patients each were randomized to receive either usual or high-dose leucovorin. Number (%) of deaths over 30-days was 8 (42) and 9 (47) in usual and high-dose leucovorin groups (Odds ratio 1.2, 95% CI 0.3 to 4.5, p = 0.74). On Kaplan-Meier, there was no significant difference in survival between the groups (hazard ratio 1.1, 95% CI 0.4 to 2.9, p = 0.84). On multivariable cox-regression, serum albumin was the only predictor of survival (hazard ratio 0.3, 95% CI 0.1 to 0.9, p = 0.02). There was no significant difference in hematological or mucositis recovery between the two groups. CONCLUSION: There was no significant difference in survival or time-to hematological recovery between the two doses of leucovorin. Severe low-dose methotrexate toxicity carried a significant mortality.

The Safety of Performing Surgery at Ambulatory Surgery Centers Versus Hospital Outpatient Departments in Older Patients With or Without Multimorbidity.

BACKGROUND: Surgery for older Americans is increasingly being performed at ambulatory surgery centers (ASCs) rather than hospital outpatient departments (HOPDs), while rates of multimorbidity have increased. OBJECTIVE: To determine whether there are differential outcomes in older patients undergoing surgical procedures at ASCs versus HOPDs. RESEARCH DESIGN: Matched cohort study. SUBJECTS: Of Medicare patients, 30,958 were treated in 2018 and 2019 at an ASC undergoing herniorrhaphy, cholecystectomy, or open breast procedures, matched to similar HOPD patients, and another 32,702 matched pairs undergoing higher-risk procedures. MEASURES: Seven and 30-day revisit and complication rates. RESULTS: For the same procedures, HOPD patients displayed a higher baseline predicted risk of 30-day revisits than ASC patients (13.09% vs 8.47%, P < 0.0001), suggesting the presence of considerable selection on the part of surgeons. In matched Medicare patients with or without multimorbidity, we observed worse outcomes in HOPD patients: 30-day revisit rates were 8.1% in HOPD patients versus 6.2% in ASC patients ( P < 0.0001), and complication rates were 41.3% versus 28.8%, P < 0.0001. Similar patterns were also found for 7-day outcomes and in higher-risk procedures examined in a secondary analysis. Similar patterns were also observed when analyzing patients with and without multimorbidity separately. CONCLUSIONS: The rates of revisits and complications for ASC patients were far lower than for closely matched HOPD patients. The observed initial baseline risk in HOPD patients was much higher than the baseline risk for the same procedures performed at the ASC, suggesting that surgeons are appropriately selecting their riskier patients to be treated at the HOPD rather than the ASC.

Redefining Multimorbidity in Older Surgical Patients.

BACKGROUND: Multimorbidity in surgery is common and associated with worse postoperative outcomes. However, conventional multimorbidity definitions (≥2 comorbidities) label the vast majority of older patients as multimorbid, limiting clinical usefulness. We sought to develop and validate better surgical specialty-specific multimorbidity definitions based on distinct comorbidity combinations. STUDY DESIGN: We used Medicare claims for patients aged 66 to 90 years undergoing inpatient general, orthopaedic, or vascular surgery. Using 2016 to 2017 data, we identified all comorbidity combinations associated with at least 2-fold (general/orthopaedic) or 1.5-fold (vascular) greater risk of 30-day mortality compared with the overall population undergoing the same procedure; we called these combinations qualifying comorbidity sets. We applied them to 2018 to 2019 data (general = 230,410 patients, orthopaedic = 778,131 patients, vascular = 146,570 patients) to obtain 30-day mortality estimates. For further validation, we tested whether multimorbidity status was associated with differential outcomes for patients at better-resourced (based on nursing skill-mix, surgical volume, teaching status) hospitals vs all other hospitals using multivariate matching. RESULTS: Compared with conventional multimorbidity definitions, the new definitions labeled far fewer patients as multimorbid: general = 85.0% (conventional) vs 55.9% (new) (p < 0.0001); orthopaedic = 66.6% vs 40.2% (p < 0.0001); and vascular = 96.2% vs 52.7% (p < 0.0001). Thirty-day mortality was higher by the new definitions: general = 3.96% (conventional) vs 5.64% (new) (p < 0.0001); orthopaedic = 0.13% vs 1.68% (p < 0.0001); and vascular = 4.43% vs 7.00% (p < 0.0001). Better-resourced hospitals offered significantly larger mortality benefits than all other hospitals for multimorbid vs nonmultimorbid general and orthopaedic, but not vascular, patients (general surgery difference-in-difference = -0.94% [-1.36%, -0.52%], p < 0.0001; orthopaedic = -0.20% [-0.34%, -0.05%], p = 0.0087; and vascular = -0.12% [-0.69%, 0.45%], p = 0.6795). CONCLUSIONS: Our new multimorbidity definitions identified far more specific, higher-risk pools of patients than conventional definitions, potentially aiding clinical decision-making.

Predictors of COVID-19 severity and outcomes in Indian patients with rheumatic diseases: a prospective cohort study.

Objective: There is dearth of data regarding the outcomes of coronavirus disease 2019 (COVID-19) among rheumatic and musculoskeletal disease (RMD) patients from Southeast Asia. We report the clinicodemographic profile and identify predictors of COVID-19 outcomes in a large cohort of Indian RMD patients. Methods: This prospective cohort study, carried out at the Postgraduate Institute of Medical Education and Research, Chandigarh (a tertiary care centre in India), included RMD patients affected with COVID-19 between April 2020 and October 2021. Demographic and clinical and laboratory details of COVID-19 and underlying RMD were noted. Predictors of mortality, hospitalization and severe COVID-19 were identified using stepwise multivariable logistic regression. Results: A total of 64 severe acute respiratory syndrome coronavirus-2-infected RMD patients [age 41.5 (19-85) years; 46 (72%) females] were included. Eighteen (28%) patients had severe COVID-19. Twenty-three (36%) required respiratory support [11 (17%) required mechanical ventilation]. Thirty-six (56%) patients required hospitalization [median duration of stay 10 (1-42) days]; 17 (27%) required intensive care unit admission. Presence of co-morbidities [odds ratio (OR) = 4.5 (95% CI: 1.4, 14.7)] was found to be an independent predictor of COVID-19 severity. Co-morbidities [OR = 10.7 (95% CI: 2.5, 45.4)] and underlying lupus [OR = 7.0 (95% CI: 1.2, 40.8)] were independently associated with COVID-19 hospitalization. Ongoing rheumatic disease activity [OR = 6.8 (95% CI: 1.3, 35.4)] and underlying diagnosis of lupus [OR = 7.1 (95% CI: 1.2, 42.4)] and SSc [OR = 9.5 (95% CI: 1.5, 61.8)] were found to be strong independent predictors of mortality. Age, sex, underlying RMD-associated interstitial lung disease and choice of immunosuppressive therapy were not associated with COVID-19 severity or adverse outcomes. Conclusion: The presence of co-morbidities was independently associated with COVID-19 severity and hospitalization. Ongoing rheumatic disease activity and the presence of lupus or SSc independently predicted mortality. Age, sex, type of immunosuppressive therapy and presence of RMD-associated interstitial lung disease did not affect COVID-19 severity or outcomes in Indian RMD patients.

Fick-Jacobs description and first passage dynamics for diffusion in a channel under stochastic resetting.

The transport of particles through channels is of paramount importance in physics, chemistry, and surface science due to its broad real world applications. Much insight can be gained by observing the transition paths of a particle through a channel and collecting statistics on the lifetimes in the channel or the escape probabilities from the channel. In this paper, we consider the diffusive transport through a narrow conical channel of a Brownian particle subject to intermittent dynamics, namely, stochastic resetting. As such, resetting brings the particle back to a desired location from where it resumes its diffusive phase. To this end, we extend the Fick-Jacobs theory of channel-facilitated diffusive transport to resetting-induced transport. Exact expressions for the conditional mean first passage times, escape probabilities, and the total average lifetime in the channel are obtained, and their behavior as a function of the resetting rate is highlighted. It is shown that resetting can expedite the transport through the channel-rigorous constraints for such conditions are then illustrated. Furthermore, we observe that a carefully chosen resetting rate can render the average lifetime of the particle inside the channel minimal. Interestingly, the optimal rate undergoes continuous and discontinuous transitions as some relevant system parameters are varied. The validity of our one-dimensional analysis and the corresponding theoretical predictions is supported by three-dimensional Brownian dynamics simulations. We thus believe that resetting can be useful to facilitate particle transport across biological membranes-a phenomenon that can spearhead further theoretical and experimental studies.