National Retrospective Cohort Study Research Articles

Trends in clinical characteristics and outcomes of all critically ill COVID-19 adult patients hospitalized in France between March 2020 and June 2021: a national database study

IntroductionStudies regarding coronavirus disease 2019 (COVID-19) were mainly performed in the initial wave, but some small-scale data points to prognostic differences for patients in successive waves. We therefore aimed to study the impact of time on prognosis of ICU-admitted COVID-19 patients.MethodWe performed a national retrospective cohort study, including all adult patients hospitalized in French ICUs from March 1, 2020 to June 30, 2021, and identified three surge periods. Primary and secondary outcomes were in-hospital mortality and need for invasive mechanical ventilation, respectively.Results105,979 critically ill ICU-admitted COVID-19 patients were allocated to the relevant three surge periods. In-hospital mortality for surges 1, 2, and 3 was, respectively, 24%, 27%, and 24%. Invasive mechanical ventilation was the highest level of respiratory support for 42%, 32%, and 31% (p < 0.001) over the whole period, with a decline in the use of vasopressors over time. Adjusted for age, sex, comorbidities, and modified Simplified Acute Physiology Score II at ICU admission, time period was associated with less invasive mechanical ventilation and a high risk of in-hospital death. Vaccination against COVID-19 was associated with a lower likelihood of invasive mechanical ventilation (adjusted sub-hazard ratio [aSHR] = 0.64 [0.53–0.76]) and intra-hospital death (aSHR = 0.80, [0.68–0.95]).ConclusionIn this large database of ICU patients admitted for COVID-19, we observed a decline in invasive mechanical ventilation, vasopressors, and RRT use over time but a high risk of in-hospital death. Vaccination was identified as protective against the risk of invasive mechanical ventilation and in-hospital death.

Risks of Leukemia in Various Industrial Groups in Korea: A Retrospective National Cohort Study

It is known that occupational exposure to specific agents is associated with leukemia. However, whether the occupational risks of leukemia differ among various industrial groups remains unclear. Therefore, the purpose of this study was to elucidate the occupational risks of leukemia among different worker groups by industry. Data for a total of 11,050,398 people from the National Health Insurance System's claim data from 2007 to 2015 were analyzed. By cohort inclusion of workers whose industry had not changed for three years and with total workers as a control group, the risk for a specific industry group was expressed as an age-standardized incidence ratio (SIR). Among groups by industry, 'Manufacture of motor vehicles and engines for motor vehicles', 'Sale of motor vehicle parts and accessories', and 'Personal care services' showed significantly higher SIRs. In division analysis, the 'Manufacture of other machinery and equipment' and 'Waste collection, treatment and disposal activities' divisions showed significantly higher SIRs than other divisions. We identified an increased risk of leukemia in workers of certain industries in Korea. Based on the results of this study, it is necessary to create a policy to protect workers at risk of leukemia. Various additional studies are needed to protect workers by revealing more precise relationships between individual hazardous substances, processes, and leukemia.

Reproductive outcomes after surgical sperm retrieval in couples with male factor subfertility: a 10-year retrospective national cohort

To determine any significant differences in the reproductive outcome from intracytoplasmic sperm injection (ICSI) with surgical sperm retrieval (SSR) between cycles using fresh and cryopreserved sperm and between cycles using epididymal and testicular sperm. A retrospective national cohort study using data from the UK Human Fertilisation and Embryology Authority, including all ICSI cycles performed in the United Kingdom over a 10-year period. Hospital. All nondonor ICSI cycles from 2008 to 2017 categorized by sperm source and cryopreservation status. Intracytoplasmic sperm injection with SSR using fresh or cryopreserved sperm and using ejaculated, testicular, and epididymal sperm. Live birth rate, pregnancy rate, and implantation rate. We analyzed data from 214,649 ICSI cycles, including 199,818 cycles of ejaculated sperm, 5,646 cycles of epididymal sperm, and 9,185 cycles of testicular sperm. Live births rates per ICSI cycle were 28.5%, 30.6%, and 28.7% for ejaculated, epididymal, and testicular sperm cycles, respectively. Epididymal sperm cycles had a higher live birth rate than that of testicular sperm cycles (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.014-1.123). This was despite a higher mean male age (42.5 vs. 40.6 years; 95% CI of difference, 1.81-1.85 years) and female age (34.3 vs. 34.0 years; 95% CI of difference, 0.32-0.34 years) in epididymal cycles than in testicular cycles. Implantation (61.2% vs. 58.0%; OR, 1.086; 95% CI, 1.041-1.133) and clinical pregnancy rates (34.3% vs. 31.3%; OR, 1.085; 95% CI, 1.039-1.132) were also higher in epididymal cycles than in testicular cycles. There were no statistically significant differences in outcomes between cycles using fresh sperm and those using cryopreserved sperm for SSR-ICSI. Our study indicates that reproductive outcomes of SSR-ICSI are at least comparable with those of ICSI using ejaculated sperm and does not support the preferential use of fresh sperm over cryopreserved sperm in SSR-ICSI. Births per SSR-ICSI cycle were higher for cycles using epididymal sperm than for cycles using testicular sperm; however, the differences were small, which may provide reassurance to patients undergoing these procedures. The results must be interpreted with caution because multivariable analysis was not possible because of aggregation of data.

Contribution of Estimates of Glomerular Filtration to the Extensive Disparities in Preemptive Listing for Kidney Transplant

The use of race coefficients in equations for estimated glomerular filtration rate (eGFR) may have contributed to racial disparities in access to preemptive (without dialysis exposure) kidney transplantation (Ktx). In this retrospective national cohort study of incident kidney transplant candidates in the United States from 2001 to 2019, we describe temporal trends and racial disparities in preemptive listing and the distribution of eGFR at listing, using eGFR as reported and after removing the race coefficient for Black candidates. Among 511,686 candidates, preemptive listing increased over time, from 18% in 2001 to 33% in 2019. Non-Black candidates were listed preemptively nearly twice as frequently as Black candidates in 2019 (38% vs. 21% preemptive) and at higher eGFR values (median 15.6 vs. 15.0 ml/min per 1.73 m2). After adjusting for candidate characteristics, including listing eGFR without the race coefficient, preemptive Black candidates still had significantly lower odds of preemptive deceased donor (DD) kidney transplantation compared to non-Black candidates (odds ratio 0.87, 95% confidence interval: 0.78-0.98). Over the last 2 decades, Black patients were consistently less likely to be listed preemptively and were listed at lower eGFR values. Adjusting for listing eGFR with the race coefficient computationally removed did not eliminate the racial disparity, suggesting that additional efforts are needed to achieve equity in preemptive transplantation beyond adopting race-free eGFR equations.

Hospitalization, death, and probable reinfection in Peruvian healthcare workers infected with SARS-CoV-2: a national retrospective cohort study

BackgroundPeru has some of the worst outcomes worldwide as a result of the SARS-CoV-2 pandemic; it is presumed that this has also affected healthcare workers. This study aimed to establish whether occupation and other non-occupational variables were risk factors for possible reinfection, hospitalization, and mortality from COVID-19 in cohorts of Peruvian healthcare workers infected with SARS-CoV-2.MethodsRetrospective cohort study. Healthcare workers who presented SARS-CoV-2 infection between March 1, 2020, and August 6, 2021, were included. Occupational cohorts were reconstructed from the following sources of information: National Epidemiological Surveillance System, molecular tests (NETLAB), results of serology and antigen tests (SICOVID-19), National Registry of Health Personnel (INFORHUS), and National Information System of Deaths (SINADEF). The incidence of probable reinfection, hospitalization, and death from COVID-19 was obtained in the cohorts of technicians and health assistants, nursing staff, midwives, dentists, doctors, and other healthcare workers. We evaluated whether the occupation and other non-occupational variables were risk factors for probable reinfection, hospitalization, and death from COVID-19 using log-binomial and probit binomial models, obtaining the adjusted relative risk (RRAJ).Results90,398 healthcare workers were included in the study. Most cases were seen in technicians and health assistants (38.6%), and nursing staff (25.6%). 8.1% required hospitalization, 1.7% died from COVID-19, and 1.8% had probable reinfection. A similar incidence of probable reinfection was found in the six cohorts (1.7–1.9%). Doctors had a higher incidence of hospitalization (13.2%) and death (2.6%); however, they were also those who presented greater susceptibility linked to non-occupational variables (age and comorbidities). The multivariate analysis found that doctors (RRAJ = 1.720; CI 95: 1.569–1.886) had a higher risk of hospitalization and that the occupation of technician and health assistant was the only one that constituted a risk factor for mortality from COVID-19 (RRAJ = 1.256; 95% CI: 1.043–1.512).ConclusionsPeruvian technicians and health assistants would have a higher risk of death from COVID-19 than other healthcare workers, while doctors have a higher incidence of death probably linked to the high frequency of non-occupational risk factors. Doctors present a higher risk of hospitalization independent of comorbidities and age; likewise, all occupations show a similar risk of probable reinfection.

1088. Evaluating the Effect of Donepezil on Mortality Among Alzheimer’s Disease Patients With and Without COVID-19 Infection

Abstract Background Dementia has been identified as an independent risk factor for increased severity of COVID-19 infection. Donepezil, a cholinesterase inhibitor approved for Alzheimer’s disease (AD), has anti-inflammatory properties. Previous studies have found that donepezil reduced all-cause mortality for people living with AD. The anti-inflammatory effects of donepezil have not been studied in patients with COVID-19 and AD. Here, we compare mortality rates of patients with AD to assess the impact of donepezil on the severity of COVID-19 infections. Survival following SARS-CoV2-2 test, stratified by result and Donepezil Kaplan-Meier curves of all-cause mortality for Veterans with Alzheimer’s Disease taking donepezil (black) compared to those who were not taking donepezil (grey), further stratified by those with a positive SARS-CoV-2 PCR test (solid lines) or no evidence of a COVID-19 infection during the study period (dashed lines). While donepezil has a positive effect on survival, the adjusted survival odds ratio is not greater among those with vs. without a COVID-19 infection. Methods Using administrative data from the Veterans Healthcare Administration (VHA), we conducted a national retrospective cohort study of Veterans with AD who were tested for SARS-CoV-2 between March 1, 2020 and December 31, 2021 in the VHA. Among these patients, we assessed all-cause 30-day mortality stratified by COVID-19 infection and donepezil use and considered the interaction of these two factors. For Veterans with a positive test, the date of first positive test was used to assess mortality; for Veterans without a COVID-19 diagnosis or positive test, date of first negative test was used. Results During the study period, 582 Veterans with Alzheimer’s disease were positive for COVID-19 and 14430 had no test or diagnosis indicating COVID-19 infection. Among people with AD and COVID-19, all-cause 30-day mortality was 29% (47/163) for people taking donepezil compared to 38% (159/419) for those who were not. Among people with AD without COVID-19, all-cause 30-day mortality was 5% (189/4189) for people taking donepezil compared to 7% (712/10241) for those who were not. In a multivariable logistic regression, the decrease in mortality associated with donepezil did not differ between people with and without COVID-19 (OR (95% CI) = 0.71 (0.47, 1.07) vs. OR (95% CI) = 0.68 (0.57, 0.80), interaction P = 0.818). Conclusion While all-cause mortality was lower for patients taking donepezil compared to those not taking donepezil, the protective effect of donepezil was not increased in AD patients with COVID-19 over those without COVID-19. The population differences and inflammatory biomarkers of AD patients treated with and without donepezil merit further study. Disclosures Robin L. Jump, MD, PhD, Merck: Grant/Research Support|Pfizer: Advisor/Consultant.

651. Ceftazidime/avibactam utilization in the national Veterans Affairs (VA) Healthcare System

Abstract Background Multidrug-resistant infections are challenging to treat, due to underlying patient conditions, pathogen characteristics, and high resistance rates to antibiotic treatments. Ceftazidime/avibactam (CAZ-AVI, approved in 2015) is approved to treat complicated intra-abdominal infections, complicated urinary tract infections, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia. As newer antibiotic therapies come to market, limited data exist about their use in real-world practice. Therefore, we sought to describe the utilization of CAZ-AVI in clinical practice. Methods This national retrospective cohort study included hospitalized VA patients receiving CAZ-AVI from 2015 through 2021. Cultures, infection diagnoses, demographics, comorbidities, treatments, and clinical outcomes were assessed in this cohort. Results During the study period, 1,048 unique patients received CAZ-AVI, with a mean age of 71.5 (±11.9) years. The study cohort was predominantly male (98.3%) and White (66.2%, Black 27.7%). The most common organism-culture site combinations were Klebsiella-urine (19.6%), Pseudomonas aeruginosa-respiratory (14.0%), Pseudomonas aeruginosa-urine (10.1%), Escherichia coli-urine (6.9%) and Klebsiella-blood (6.9%). The median time to CAZ-AVI initiation from admission was 6 days, with a subsequent median 14-day hospital stay. Median length of CAZ-AVI therapy was 8 days. Most patients changed antibiotic therapy 3 times before starting CAZ-AVI. Treatment heterogeneity was high both prior to CAZ-AVI initiation (89.6%) and during CAZ-AVI treatment (85.6%). The most common concomitant antibiotic therapies during CAZ-AVI treatment were vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). Inpatient mortality in this cohort was 23.6%, and about one-third of patients had a subsequent hospitalization with CAZ-AVI treatment (35.1% in 2021). Conclusion Utilization of CAZ-AVI increased from 2015 to 2018 and has since stabilized in the national VA Healthcare System. CAZ-AVI has been utilized in complex, difficult-to-treat patients with substantial treatment heterogeneity and variation in causative organism-culture site. Disclosures Aisling R. Caffrey, PhD, M.S., AbbVie Inc.: Grant/Research Support|Gilead Sciences Inc.: Grant/Research Support|Merck &amp; Co., Inc: Advisor/Consultant|Merck &amp; Co., Inc: Grant/Research Support|Shionogi Inc.: Grant/Research Support Haley J. Appaneal, PharmD, Ph.D., Shionogi Inc: Grant/Research Support Kerry L. LaPlante, Pharm.D., FCCP, FIDSA, FIDP, AbbVie Inc.: Grant/Research Support|Gilead Sciences, Inc.: Grant/Research Support|Melinta Therapeutics, Inc.,: Grant/Research Support|Merck &amp; Co., Inc.: Advisor/Consultant|Merck &amp; Co., Inc.: Grant/Research Support|Nabriva Therapeutics US, Inc.,: Grant/Research Support|Ocean Spray Cranberries, Inc.: Grant/Research Support|Pfizer Pharmaceuticals: Grant/Research Support|Shionogi, Inc.: Grant/Research Support|Tetraphase Pharmaceuticals.: Grant/Research Support.

Comparative safety of sulfonylureas among U.S. nursing home residents.

The comparative safety of sulfonylureas (SUs) in nursing home (NH) residents remains understudied despite widespread use. We compared the effects of three SU medications and initial SU doses on adverse glycemic and cardiovascular events among NH residents. This national retrospective cohort study linked Medicare claims with Minimum Data Set 2.0 assessments for long-stay NH residents aged ≥65 years between January 2008 and September 2010. Exposures were the SU medication initiated (glimepiride, glipizide, or glyburide) and doses (standard or reduced). One-year outcomes were hospitalizations or emergency department visits for severe hypoglycemia, heart failure (HF), stroke, and acute myocardial infarction (AMI). After the inverse probability of treatment and inverse probability of censoring by death weighting, we estimated hazard ratios (HR) using Cox regression models with robust 95% confidence intervals (CI). The cohort (N=6821) included 3698 new glipizide, 1754 glimepiride, and 1369 glyburide users. Overall, the mean (standard deviation) age was 81.4 (8.2) years, 4816 (70.6%) were female, and 5164 (75.7%) were White non-Hispanic residents. The rates of severe hypoglycemia were 30.3 (95% CI 22.3-40.1), 49.0 (95% CI 34.5-67.5), and 35.9 (95% CI 22.2-54.9) events per 1000 person-years among new glipizide, glimepiride, and glyburide users, respectively (glimepiride versus glipizide HR 1.6, 95% CI 1.0-2.4, p=0.04; glyburide versus glipizide HR 1.2, 95% CI 0.7-1.9, p=0.59). The rates of severe hypoglycemia were 27.1 (95% CI 18.6-38.0) and 42.8 (95% CI 33.6-53.8) events per 1000 person-years among new users of reduced and standard SU doses, respectively (HR 2.2, 95% CI 1.4-3.5, p < 0.01). Rates of HF, stroke, and AMI were similar between medications and doses. Among long-stay NH residents, new use of glimepiride and standard SU doses resulted in higher rates of severe hypoglycemic events. Cardiovascular outcomes may not be affected by the choice of SU medication or dose.

Utility of Spine Surgery Fellowship Training for Orthopaedic Surgeons in the United States.

Orthopaedic spine surgeons gain surgical experience through cases conducted during residency and fellowship training. This study elucidates the incremental benefit in spine surgery volume from orthopaedic spine surgery fellowship training. This was a retrospective national cohort study of orthopaedic surgery residents and orthopaedic spine surgery fellows graduating from US Accreditation Council for Graduate Medical Education-accredited training programs during the 2017 to 2020 academic years. Comparisons in spine surgery case volume were made with parametric tests. One hundred fourteen spine surgery fellows and 3,000 orthopaedic surgery residents were included. There was a 3.5-fold increase in total spine surgery cases conducted during fellowship versus residency (314 ± 129 vs. 89 ± 61, P < 0.001). Spine surgery fellows one standard deviation more than the mean reported 443 total spine cases. The largest differences between fellows and residents were Decompression (104 ± 48 vs. 28 ± 23, P < 0.001), Posterior Arthrodesis (94 ± 46 vs. 21 ± 18, P < 0.001), Anterior Arthrodesis (64 ± 31 vs. 13 ± 13, P < 0.001), and Instrumentation (43 ± 25 vs. 22 ± 12, P < 0.001). Spine surgery fellowship training affords orthopaedic surgeons the opportunity to increase spine surgery case volume by over threefold. The greatest increases in case volume were reported for Decompression, Posterior Arthrodesis, Anterior Arthrodesis, and Instrumentation.

The sibling effect on neurodevelopment of preschoolers under China's newly relaxed child policy: A national retrospective cohort study.

The change in Chinese fertility policy brings new challenges and considerations for children's health outcomes; however, very little is known about the interaction between siblings, family socioeconomic status (SES), and neurodevelopment in the Chinese preschool-age population. Therefore, this study aimed to develop a new explanatory pathway from sibling effect to early childhood development and explored the mediation effect of family SES in the pathway. From April 2018 to December 2019, we conducted a national retrospective cohort study in 551 cities in China, and a total of 115,915 preschool-aged children were selected for the final analysis. Children's neurodevelopment, including Communication, Gross motor, Fine motor, Problem-solving, and Personal-social, was assessed with the Ages & Stages Questionnaires, Third Edition (ASQ-3). Hypothesis tests and multilevel regression models were used to assess the associations and their strength between sibling effect and neurodevelopmental delay. Pathway analysis was used to verify the mediation effect of SES. The results showed that there were significant risk effects of a sibling on preschoolers' overall neurodevelopment including communication, gross motor, fine motor, and problem-solving delay. The adjustment of family SES, however, brought a reversal of this association. The results of the mediation model illustrated a direct, protective effect of one-sibling status (βASQ-delay = -0.09; βASQ-scores = 0.07; p < 0.001), and an indirect, risk effect from one-sibling status through family SES to neurodevelopment outcomes (βASQ-delay =0.12; βASQ-scores = -0.12; p < 0.001). The total sibling effect was weakened but remained negative (βASQ-delay =0.03; βASQ-scores = -0.05; p < 0.001). This study concluded that family SES mediated the negative effects of one sibling on early child development. To enhance the positive influence of sibling addition, we suggested providing more resources and instructions to the families with less educated and poorer employed parents under the coming multi-child era.

Associations of preterm and early-term birth with suspected developmental coordination disorder: a national retrospective cohort study in children aged 3–10 years

BackgroundThis study analyzed the motor development and suspected developmental coordination disorder of very and moderately preterm (< 34+0 gestational age), late preterm (34+0–36+6 gestational week), and early-term (37+0–38+6 gestational week) children compared to their full-term peers with a national population-based sample in China.MethodsA total of 1673 children (799 girls, 874 boys) aged 3–10 years old were individually assessed with the Movement Assessment Battery for Children-second edition (MABC-2). The association between gestational age and motor performance of children was analyzed using a multilevel regression model.ResultsThe global motor performance [β = – 5.111, 95% confidence interval (CI) = – 9.200 to – 1.022; P = 0.015] and balance (β = – 5.182, 95% CI = – 5.055 to – 1.158; P = 0.003) for very and moderately preterm children aged 3–6 years old were significantly lower than their full-term peers when adjusting for confounders. Late preterm and early-term children showed no difference. Moreover, very and moderately preterm children aged 3–6 years had a higher risk of suspected developmental coordination disorder (DCD) (≤ 5 percentile of MABC-2 score) when adjusting for potential confounders [odds ratio (OR) = 2.931, 95% CI = 1.067–8.054; P = 0.038]. Late preterm and early-term children showed no difference in motor performance from their full-term peers (each P > 0.05).ConclusionsOur findings have important implications for understanding motor impairment in children born at different gestational ages. Very and moderately preterm preschoolers have an increased risk of DCD, and long-term follow-up should be provided for early detection and intervention.

Sex differences in the impact of diabetes mellitus on tuberculosis recurrence: a retrospective national cohort study

ObjectivesWhether diabetes mellitus (DM) increases tuberculosis (TB) recurrence risk is debatable. We determined the effect of DM on TB recurrence. MethodsThis retrospective nationwide cohort study included patients with TB who successfully completed TB treatment during 2011-2017 and were followed up for TB recurrence until August 2020. We performed subdistribution hazard model analyses stratified by sex to assess DM risk related to TB recurrence after successful treatment. ResultsOf 199,571 participants who had received successful TB treatment, 47,952 (24%) had DM. There were more men (64.4%), positive acid-fast bacilli smears (35.9%), and positive cultures (49.5%) in the DM group. There were 6208 (3.1%) TB recurrences during 5.1 years of follow-up: 38.9% and 26.6% occurred 1 and 1-2 years after treatment completion, respectively. The recurrence rate was higher in the DM group (3.8%) than in the non-DM group (2.9%, P <0.0001). DM was associated with a higher TB recurrence risk, especially in men (adjusted hazard ratio 1.23, 95% confidence interval 1.15-1.32) but not in women (adjusted hazard ratio 0.96, 95% confidence interval 0.85-1.09). ConclusionThe TB recurrence rate after successful treatment was higher in patients with DM than in patients without DM. DM is associated with TB recurrence in men.

Postoperative morbidity and mortality after adenoidectomy: A national population-based study of 51 746 surgeries.

To investigate postoperative morbidity and mortality after paediatric adenoidectomy. This was a retrospective national population-based cohort study of data from the Swedish National Patient Register (NPR) and The Swedish Cause of Death Register (CDR). All patients aged 0-18 years who underwent adenoidectomy from 2007 to 2017 (without concomitant tonsil surgery) were included in this study. To evaluate postoperative morbidity and mortality, all diagnostic and surgical codes registered in the NPR for health care contacts within 30 days of surgery were analysed. The patients retrieved from the NPR were matched with the CDR to identify any deaths occurring within 30 days of the surgery. A total of 51746 adenoidectomies were included in this study. No deaths related to adenoidectomy were identified. All types of haemorrhagic complications were rare. Only 0.1% of the surgeries resulted in an outpatient contact due to postoperative haemorrhage and only 0.1% of the adenoidectomies resulted in a readmission due to haemorrhage. The rarest haemorrhagic complication was RTT (return to theatre), with only 4 events (0.01%). Postoperative haemorrhage was most frequent on the first day after surgery. Other complications were rare as well, requiring a total of 922 (2.6%) outpatient visits and 75 (0.2%) readmissions in the adenoidectomy group, with postoperative infection being the most commonly reported. Overall, adenoidectomy should be considered a safe surgical procedure associated with few postoperative complications. No deaths related to adenoidectomy were found. Severe complications, such as late postoperative haemorrhage after adenoidectomy, were rare, and haemorrhage resulting in RTT was even rarer. The highest rate of postoperative haemorrhage was observed the first day after surgery, and most haemorrhagic complications occurred within a week. Comparisons with studies on tonsil surgery show that adenoidectomy is associated with substantially lower postoperative morbidity.

Trends in incidence, treatment and survival of Merkel cell carcinoma in England 2004-2018: a cohort study.

Merkel cell carcinoma (MCC) is a rare tumour with neuroendocrine differentiation and high associated mortality. Studies that describe the epidemiology of MCC are often limited by small sample size, short duration of follow-up, absence of nationwide data and paucity of data on different risk factors. To determine the incidence, demographics and survival for MCC in England between 2004 and 2018. This national retrospective cohort study identified all cases of MCC in England from 2004 to 2018 using national population-based data from the National Disease Registration Service. Crude counts, European age-standardized incidence rates (EASRs) and joinpoint analysis were conducted. Patient demographics and treatments received were described. Multivariable Cox regression analysis was used to study risk factors for MCC-specific mortality, by including a priori defined demographic factors, tumour characteristics and immunosuppression. Treatment data were not included in the Cox regression analysis. A total of 3775 MCC tumours were registered. The median age at diagnosis was 81 years (interquartile range 74-87). Overall, 96·6% of patients identified as White ethnicity, and 8·3% of patients were immunosuppressed. The most common site was the face (27·4%). Patients most often presented with stage one disease (22·8%); however, stage was unknown in 31·0%. In total, 80·7% of patients underwent surgical excision, 43·5% radiotherapy and 9·2% systemic therapy. The EASR increased from 0·43 per 100 000 person-years (PYs) to 0·65 per 100 000 person-years between 2004 and 2018, representing a significant annual percentage change of 3·9%. The EASR was greater in men than in women for all years, with an overall male-to-female ratio of 1·41 : 1. The highest EASR was in South West England. Five-year disease-specific survival was 65·6% [95% confidence interval (CI) 63·8-67·4], with a median follow-up of 767 days. MCC-specific mortality increased with age [hazard ratio (HR) 1·02, 95% CI 1·02-1·03], deprivation (HR 1·43, 95% CI 1·16-1·76), immunosuppression (HR 2·80, 95% CI 2·34-3·34) and stage at diagnosis (HR 8·24, 95% CI 5·84-11·6). This study presents the largest national MCC dataset in Europe, and the most complete reporting of MCC incidence and survival ever published. With the EASR of MCC increasing and high associated mortality, this study encourages further research into the pathology, diagnosis and therapeutic options for MCC to support management guidelines.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING)

BackgroundStudies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. MethodsA national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. Findings4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53–65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5–0.8) and 0.7 (0.6–0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2–2.0) and 1.4 (1.2–1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1–2), 1.2 (1.1–1.4) and 1.5 (1.2–1.8) for prednisolone ≤7.5 mg respectively]. InterpretationThere was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study.

While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size. Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome. 6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32-1.44), and mortality (RR 0.82, 0.41-1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28-0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33-0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control. There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.

Longitudinal association between triglyceride glucose index and depression progression in middle-aged and elder adults: A national retrospective cohort study

Background and aimsPsychological symptoms are prevalent among individuals with non-communicable diseases, while the longitudinal association between triglyceride glucose (TyG) index, an indicator of metabolic health, and depression progression remains unclear yet. This study aims to investigate the association of baseline TyG index and depression progression in middle-aged and elder adults. Methods and resultsThis retrospective cohort study enrolled 8287 participants aged 45 years or above from national China Health and Retirement Longitudinal Study in visit 1 (2011–2012), which were biennially followed for depression score until visit 4 (2017–2018). Multivariate-adjusted regression models were used to evaluate the association of baseline TyG index with the individual level change rate and slope of depression score. The mean age (±SD) of participants was 58.25 ± 9.10 years, and 3806 (45.9%) were men. There was no significant difference of depression score at baseline across TyG quartile groups (P = 0.228). Participants in the highest quartile of TyG index had a 0.124 (95% CI: 0.018–0.230) higher change rate of depression score, and a 0.127 (95% CI: 0.019–0.235) higher change slope, compared to those in the lowest. The observed associations were consistent in multiple sensitivity analyses, and stable in men, the elder, and overweight people. ConclusionTyG index is positively associated with depression progression especially in men, the elder and overweight people, which provides new insights for the primary prevention of depression disorder.

Mortality and life-years lost following subsequent physical comorbidity in people with pre-existing substance use disorders: a national registry-based retrospective cohort study of hospitalised individuals in Czechia

Substance use disorders constitute a major global public health problem, attributable largely to their subsequent comorbidity with other health conditions. This study aimed to investigate the risk of all-cause death and life-years lost following hospitalisation for 28 subsequent physical comorbid conditions in people with a previous hospitalisation for substance use disorder, compared with matched counterparts without substance use disorder. We did a retrospective cohort study on data from Czech nationwide registers of all-cause hospitalisations and deaths during the period from Jan 1, 1994, to Dec 31, 2017. The cohorts consisted of individuals who had initially been hospitalised between 15 and 70 years of age (index hospitalisation) and who were subsequently hospitalised with one or more of 28 comorbid physical health conditions. We included individuals with an index hospitalisation for substance use disorders and up to three counterparts without substance use disorders with a subsequent hospitalisation for the same physical health condition, with matching on sex, age (±3 years), work status, and discharge year at first hospitalisation for the subsequent condition. Data on ethnicity were not available. Risk of death due to any cause following the first hospitalisation for each physical health condition until Dec 31, 2017, and life-years lost after disease onset at ages 30, 45, and 60 years, and before 81 years of age, were examined. From a total 56 229 563 records of hospitalisations identified, we included 121 153 people with hospitalisation for substance use disorders and 6 742 134 people without hospitalisation for substance use disorders in the study. The 28 condition-specific cohorts comprised a median of 6444 individuals (IQR 2033-12 358), ranging from 444 for multiple sclerosis to 36 356 for diseases of the circulatory system. Across the cohorts, the proportion of males ranged from 31·4% for thyroid disorder to 100·0% for prostate disorders. The mean baseline age ranged from 30·0 years (SD 9·1) for chronic viral hepatitis in people with pre-existing substance use disorders to 62·2 years (9·7) for Parkinson's disease in people without pre-existing substance use disorders. After adjusting for potential confounders using stratified Cox proportional hazards models, individuals with a pre-existing substance use disorder had an increased risk of death due to any cause after the onset of 26 out of 28 physical health conditions, relative to their counterparts without substance use disorders, with adjusted hazard ratios ranging from 1·15 (1·09-1·21) for chronic liver disease to 3·86 (2·62-5·67) for thyroid disorder. For seven subsequent health conditions, the risk of death was more than doubled in the group with pre-existing substance use disorders. When compared with the general population via mortality tables, people with pre-existing substance use disorders had substantial losses in life-years after the onset of most of the subsequent physical health conditions regardless of age of onset, and, for the majority of comorbidities, lost considerably more life-years than their counterparts without substance use disorders. A history of hospitalisation for substance use disorders appears to have a significant negative effect on prognosis following the development of various subsequent physical health conditions. These findings strongly suggest that clinical vigilance and high-quality integrated treatment for people with substance use disorders could be life-saving and should be given higher priority on the public health agenda. National Institute for Health and Care Research Applied Research Collaboration East of England at Cambridge and Peterborough National Health Service Foundation Trust.

Risks and pregnancy outcome after fetal reduction in dichorionic twin pregnancies: a Danish national retrospective cohort study

Twin pregnancies carry a higher risk of congenital and structural malformations, and pregnancy complications including miscarriage, stillbirth, and intrauterine fetal death, compared with singleton pregnancies. Carrying a fetus with severe malformations or abnormal karyotype places the remaining healthy fetus at an even higher risk of adverse outcome and pregnancy complications. Maternal medical conditions or complicated obstetrical history could, in combination with twin pregnancy, cause increased risks for both the woman and the fetuses. To our knowledge, no previous studies have evaluated and compared the outcomes of all dichorionic twin pregnancies and compared the results of reduced twins with those of nonreduced and primary singletons in a national cohort. These data are important for clinicians when counseling couples about fetal reduction and its implications. This study aimed to describe and compare the risks of adverse pregnancy outcomes, including the risk of pregnancy loss, in a national cohort of all dichorionic twins-reduced, nonreduced, and primary singletons. In addition, we examined the implications of gestational age at fetal reduction on gestational age at delivery. This was a retrospective cohort study of all Danish dichorionic twin pregnancies, including pregnancies undergoing fetal reduction and a large proportion of randomly selected primary singleton pregnancies with due dates between January 2008 and December 2018. The primary outcome measures were adverse pregnancy outcomes (defined as miscarriage before 24 weeks, stillbirth from 24 weeks, or single intrauterine fetal death in nonreduced twin pregnancies), preterm delivery, and obstetrical pregnancy complications. Outcomes after fetal reduction were compared with those of nonreduced dichorionic twins and primary singletons. In total, 9735 dichorionic twin pregnancies were included, of which 172 (1.8%) were reduced. In addition, 16,465 primary singletons were included. Fetal reductions were performed between 11 and 23 weeks by transabdominal needle-guided injection of potassium chloride, and outcome data were complete for all cases. Adverse pregnancy outcome was observed in 4.1% (95% confidence interval, 1.7%-8.2%) ofreduced twin pregnancies, and 2.4% (95% confidence interval, 0.7%-6.1%) were delivered before 28 weeks, and 4.2% (95% confidence interval, 1.7%-8.5%) before 32 weeks. However, when fetal reduction was performed before 14 weeks, adverse pregnancy outcomes occurred in only 1.4% (95% confidence interval, 0.0%-7.4%), and delivery before 28 and 32 weeks diminished to 0% (95% confidence interval, 0.0%-5.0%) and 2.8% (95% confidence interval, 0.3%-9.7%), respectively. In contrast, 3.0% (95% confidence interval, 2.7%-3.4%) of nonreduced dichorionic twins had an adverse pregnancy outcome, and 1.9% (95% confidence interval, 1.7%-2.1%) were delivered before 28 weeks, and 7.3% (95% confidence interval, 6.9%-7.7%) before 32 weeks. Adverse pregnancy outcomes occurred in 0.9% (95% confidence interval, 0.7%-1.0%) of primary singletons, and 0.2% (95% confidence interval, 0.1%-0.3%) were delivered before 28 weeks, and 0.7% (95% confidence interval, 0.6%-0.9%) before 32 weeks. For reduced twins, after taking account of maternal factors and medical history, it was demonstrated that the later the fetal reduction was performed, the earlier the delivery occurred (P<.01). The overall risk of pregnancy complications was significantly lower among reduced twin pregnancies than among nonreduced dichorionic twin pregnancies (P=.02). In a national 11-year cohort including all dichorionic twin pregnancies, transabdominal fetal reduction by needle guide for fetal or maternal indication was shown to be safe, with good outcomes for the remaining co-twin. Results were best when the procedure was performed before 14 weeks.

S1427 Is Non-Alcoholic Fatty Liver Disease a Risk Factor for Ascending Cholangitis? A National Retrospective Cohort Study

S1427 Is Non-Alcoholic Fatty Liver Disease a Risk Factor for Ascending Cholangitis? A National Retrospective Cohort Study