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Background: Alopecia areata (AA) is a chronic autoimmune disease that leads to a high psychiatric, economic and systemic disease burden. A comprehensive understanding of AA epidemiology is essential for evaluating healthcare source utilization; however, a systematic approach to summarizing epidemiological data on AA is lacking., Objectives: To investigate systematically the global, regional and national incidence and prevalence of AA., Methods: A structured search was conducted using the databases MEDLINE, Embase, Cochrane Library, Web of Science, SciELO and Korean Journal Database from their date of inception to 4 October 2023. Studies that reported the prevalence or incidence of AA were included. We used a Bayesian hierarchical linear mixed model to analyse prevalence estimates. The primary outcomes of our study were the global, regional and national prevalence of physician-diagnosed AA for the overall population, for adults and for children. The incidence data were summarized descriptively., Results: In total, 88 studies from 28 countries were included in the analysis. The reported incidence of AA tended to be higher in adults aged 19-50 years, and this trend was consistent with its estimated prevalence. The reported prevalence in overall populations tended to be higher in men vs. women. The estimated lifetime prevalence rate of AA was 0.10% [95% credible interval (CrI) 0.03-0.39] in the general population worldwide, 0.12% (95% CrI 0.02-0.52) in adults and 0.03% (95% CrI 0.01-0.12) in children. The estimated prevalence of AA was highest in the Asian region and lowest in the African region., Conclusions: In this study, 48% of the Global Burden of Disease regions had insufficient data on the prevalence or incidence of AA. Further studies are needed to provide epidemiological information on middle- and low-income countries. Our study may serve as a crucial reference in terms of healthcare policy decisions., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: To compare the predictive performance of CHA 2 DS 2 -VASc and HAS-BLED scores in atrial fibrillation (AF) patients with and without cancer., Methods and Results: Using data from the Clinical Practice Research Datalink in England, we performed a retrospective cohort study of patients with new diagnoses of AF from 2009 to 2019. Cancer was defined as history of breast, prostate, colorectal, lung, or haematological cancer. We calculated the CHA 2 DS 2 -VASc and HAS-BLED scores for the 1-year risk of stroke and major bleeding events. Scores performance was estimated by discrimination [area under the receiver operating characteristic curve (AUC)] and calibration plots. Of 141 796 patients with AF, 10.3% had cancer. The CHA 2 DS 2 -VASc score had good to modest discrimination in prostate cancer AUC = 0.74 (95% confidence interval: 0.71, 0.77), haematological cancer AUC = 0.71 (0.66, 0.76), colorectal cancer AUC = 0.70 (0.66, 0.75), breast cancer AUC = 0.70 (0.66, 0.74), and lung cancer AUC = 0.69 (0.60, 0.79), compared with no-cancer AUC = 0.73 (0.72, 0.74). HAS-BLED discrimination was poor in prostate cancer AUC = 0.58 (0.55, 0.61), haematological cancer AUC = 0.59 (0.55, 0.64), colorectal cancer AUC = 0.57 (0.53, 0.61), breast cancer AUC = 0.56 (0.52, 0.61), and lung cancer AUC = 0.59 (0.51, 0.67), compared with no-cancer AUC = 0.61 (0.60, 0.62). Both the CHA 2 DS 2 -VASc score and HAS-BLED score were well calibrated across all study cohorts., Conclusion: Amongst certain cancer cohorts in the AF population, CHA 2 DS 2 -VASc performs similarly in predicting stroke to AF patients without cancer. Our findings highlight the importance of cancer diagnosis during the development of risk scores and opportunities to optimize the HAS-BLED risk score to better serve cancer patients with AF., Competing Interests: Conflict of interest: I have read the journal’s policy and the authors of this manuscript have the following competing interests: D.M.A. received research grants from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, UCB, and the Leo Foundation. The remaining authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Vitiligo is a chronic autoimmune disease characterised by depigmented skin patches, which can pose substantial psychosocial challenges particularly in individuals with dark skin tones. Despite its impact on quality of life, there is an absence of standardised global epidemiological data. We sought to address this gap with the present study., Methods: In this study we did a systematic review and modelling analysis to estimate the global, regional, and national prevalence and incidence of vitiligo. We did a comprehensive search of nine digital libraries (PubMed, Embase, Web of Science, Scientific Electronic Library Online, KCI Korean Journal Database, Russian Science Citation Index, Western Pacific Region Index Medicus, Informit, and Health Research and Development Information Network) from inception up to May 25, 2023. We included cross-sectional or cohort studies reporting the incidence rate or prevalence of vitiligo, or data from which incidence rate or prevalence could be calculated, in the general population of a country or area of a country. Summary estimate data were extracted. A main outcome was to estimate the worldwide, regional, and country-specific lifetime prevalence of vitiligo diagnosed by physicians or dermatologists among the general population and in adults and children (as per age groups defined in included studies). We used a Bayesian hierarchical linear mixed model to estimate prevalence, and calculated number of affected individuals using the UN population structure in 2022. In estimating lifetime prevalence, studies reporting point or period prevalence were excluded. Our other main outcome was to estimate incidence rates of vitiligo, but due to a small number of studies, the data on incidence were presented in a descriptive summary. This study was registered on PROSPERO, CRD42023390433., Findings: Our search identified 22 192 records, of which 90 studies met our inclusion criteria. Of these studies, six focused on the incidence of vitiligo, 79 reported on the prevalence of vitiligo, and five provided data on both incidence and prevalence. 71 studies reported on lifetime prevalence. In the most recent years studied, incidence rates in the general population ranged from 24·7 cases (95% CI 24·3-25·2) per 100 000 person-years in South Korea in 2019, to 61·0 cases (60·6-61·4) in the USA in 2017. In individual studies, incidence rates showed an increasing trend over the periods studied. The global lifetime prevalence of vitiligo diagnosed by a physician or dermatologist was estimated at 0·36% (95% credible interval [CrI] 0·24-0·54) in the general population (28·5 million people [95% CrI 18·9-42·6]), 0·67% (0·43-1·07) in the adult population (37·1 million adults [23·9-58·9]), and 0·24% (0·16-0·37) in the child population (5·8 million children [3·8-8·9]). Vitiligo prevalence was higher in adults than in children across all regions. Central Europe and south Asia reported the highest prevalence (0·52% [0·28-1·07] and 0·52% [0·33-0·82], respectively, in the general population)., Interpretation: This study highlights the need for standardised epidemiological data collection globally to inform public health policies and improve vitiligo diagnosis and management. Emphasis on the impact on individuals with darker skin tones is crucial to reducing stigma and improving quality of life. Furthermore, our study highlights the need to conduct more research in regions and populations that have been historically under-represented, to effectively address the worldwide burden of vitiligo., Funding: None., Competing Interests: Declaration of interests IH reports being a consultant for AbbVie, Pfizer, Bayer, Incyte, UCB, Boeringher Ingelheim, Estee Lauder, Ferndale Laboratories, L’Oréal, Arcutis, Avita Novartis, Gladerma, Janssen, Clinuvel, and Almirall. KE reports being a consultant for AbbVie, Incyte, La Roche-Posay, Pfizer, Pierre Fabre, Sanofi, and MSD. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Anticoagulation of patients with atrial fibrillation (AF) and cancer is challenging because of their high risk for stroke and bleeding. Little is known of the variations of oral anticoagulant (OAC) prescribing in patients with AF with and without cancer., Methods: Patients with first-time AF during 2009-2019 from the Clinical Practice Research Datalink were included. Cancer diagnosis was defined as a history of breast, prostate, colorectal, lung, or hematological cancer. Competing-risk analysis was used to assess the risk of OAC prescribing in patients with AF and cancer adjusted for clinical and sociodemographic factors., Results: Of 177,065 patients with AF, 11.7% had cancer. Compared to patients without cancer, patients with cancer were less likely to receive OAC: prostate cancer (subhazard ratio [SHR], 0.95; 95% CI, 0.91-0.99), breast cancer (SHR, 0.93; 95% CI, 0.89-0.98), colorectal cancer (SHR, 0.93; 95% CI, 0.88-0.99), hematological cancer (SHR, 0.70; 95% CI, 0.65-0.75), and lung cancer (SHR, 0.44; 95% CI, 0.38-0.50). The cumulative incidence function (CIF) of OAC prescribing was lowest for patients with lung cancer and hematological cancer compared with patients without cancer. The difference between the CIF of OAC prescribing in patients with and without cancer becomes narrower in the most deprived areas. Elderly patients (aged ≥85 years) overall had the lowest CIF of OAC prescribing regardless of cancer status., Conclusions: In patients with AF, underprescribing of OAC is independently associated with certain cancer types. Patients with hematological and lung cancer are the least likely to receive anticoagulation therapy compared with patients without cancer. Underprescribing of OAC in cancer is linked to old age. Further studies of patients with AF and cancer are warranted to assess the net clinical benefit of anticoagulation in certain cancer types., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Patients with acute venous thromboembolism (VTE) need anticoagulation (AC) therapy for at least 3/6 months (primary treatment); after that period, they should receive a decision on the duration of therapy., Methods: This study examined the complications occurring during two years of follow-up (FU) in patients with a first VTE who were recruited in 20 clinical centers and had discontinued or prolonged AC. They were included in the START2-POST-VTE prospective observational study., Results: A total of 720 patients (53.5% males) who, after the completion of primary treatment, had received the decision to continue ( n = 281, 39%; 76.1% with a DOAC) or discontinue ( n = 439, 61%) AC were followed up for 2 years (total FU = 1318 years). The decision to prolong or suspend AC was made in similar proportions in patients with unprovoked or provoked index events. Courses of sulodexide treatment or Aspirin (100 mg daily) were prescribed to 20.3% and 4.5%, respectively, of the patients who discontinued AC. The bleeding rate was significantly higher in patients who extended AC (1.6% pt/y) than in those who stopped AC (0.1% pt/y; p = 0.001) and was higher in patients using standard-dose DOACs (3.1% pt/y) than in those using reduced-dose DOACs (0.4% pt/y). The recurrent VTE rates were similar between the two groups (2.2% pt/y during AC vs. 3% pt/y off AC)., Conclusion: Physicians' decisions about AC duration were independent of the unprovoked/provoked nature of the index event. The bleeding rate was higher in patients who continued AC using standard-dose DOACs. Surprisingly, the rate of thrombotic recurrence was not different between those who continued or discontinued AC. Randomized studies comparing different procedures to decide on the duration of AC after a first VTE are needed.

Competing Interests: Conflicts of interest None.

The association between younger age and poorer mental health during the COVID-19 pandemic has been documented. Whether these changes were associated with a change in antidepressant (AD) use is not well understood. This study aimed to estimate the impact of the COVID-19 pandemic on AD use by young adults in the ASL TO4 Regione Piemonte (Italy). The impact of the pandemic on the weekly prevalence of AD users was assessed using interrupted time-series analysis with autoregressive integrated moving average models. A total of 1071 subjects (18-22 years with ≥1 AD dispensation) were included in the study. The observed prevalence was lower than the predicted value for several weeks after the introduction of the lockdown. However, it was consistently higher than the predicted values from week 134. The maximum difference between observed and predicted values (25 subjects per 10,000 young adults) was found at week 170. Changes in AD use were observed in both genders and were more pronounced for selective serotonin reuptake inhibitors. In conclusion, the impact of the COVID-19 pandemic on the mental health of young adults is likely to be significant in the coming years, which may place a future burden on pharmaceutical public health and community health.

Background: The association between cancer and stroke or bleeding outcomes in atrial fibrillation is unclear. We sought to examine how certain types of cancer influence the balance between stroke and bleeding risk in patients with nonvalvular atrial fibrillation (NVAF)., Methods and Results: We estimated stroke and bleeding risk among adult patients with NVAF and certain types of cancer (breast, prostate, colorectal, lung, and hematological cancer) from 2009 to 2019 based on data from the UK Clinical Practice Research Datalink GOLD and Aurum databases. The control group included patients with NVAF only. Of 177 065 patients with NVAF, 11379 (6.4%) had cancer (1691 breast, 3955 prostate, 1666 colorectal, 2491 hematological, and 1576 lung). Compared with patients without cancer, stroke risk was higher in patients with breast cancer (adjusted hazard ratio [aHR], 1.20 [95% CI, 1.07-1.35) and with prostate cancer (aHR, 1.11 [95% CI, 1.01-1.12) if diagnosed within 6 months before NVAF. The risk of bleeding was increased in subjects with hematological cancer (aHR, 1.55 [95% CI, 1.40-1.71]), lung cancer (aHR, 1.49 [95% CI, 1.25, 1.77]), prostate cancer (aHR, 1.38 [95% CI, 1.28-1.49]), and colorectal cancer (aHR, 1.36 [95% CI, 1.21-1.53]), but not for subjects with breast cancer. The more recent the cancer diagnosis before NVAF diagnosis (within 6 months), the higher the risk of bleeding., Conclusions: Breast and prostate cancer are associated with increased stroke risk, whereas in some cancer types, the risk of bleeding seemed to exceed stroke risk. In these patients, prescribing of oral anticoagulant should be carefully evaluated to balance bleeding and stroke risk.

Background: Dementia affects ability to remember, think, or make decisions that interfere with doing everyday activities. There is no cure, therefore any prevention or delay of the onset is of importance. This study aims to investigate the association between zoster and influenza vaccinations and the risk of developing dementia., Methods: We conducted a retrospective population-based cohort study using electronic health records from 1469 general practices contributing to the Clinical Practice Research Datalink (CPRD) Aurum database with linked hospital episode statistics (HES) and Office for National Statistics (ONS) mortality records. We built two 'matched cohorts': zoster vaccine (854,745 exposed individuals) matched with 8.8 million comparators without a history of zoster vaccination, and influenza vaccine (742,487 exposed individuals) matched with 7.12 million comparators without a history of vaccination as another comparator group. The cohorts were then followed to assess the association of exposure (vaccine) with outcome (dementia diagnosis)., Results: Zoster vaccination was associated with a lower risk of dementia diagnosis (adjusted hazard ratio (HR) 0.78 with 95% CI: 0.77-0.79), Alzheimer's diagnosis (adjusted HR 0.91 with 95% CI: 0.89-0.92 and other types of dementia (adjusted HR 0.71 with 95% CI: 0.69-0.72). Influenza vaccination also was associated with a slightly reduced hazard of dementia risk (adjusted HR 0.96 with 95% CI: 0.94-0.97)., Conclusion: Both zoster vaccine for prevention of shingles / herpes zoster and influenza vaccine to prevent influenza were associated with diminished risk of dementia, with the zoster association appearing more pronounced., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: English primary care faces significant challenges, including 'persistent high turnover' of general practitioners (GPs) in some partnerships. It is unknown whether there are specific predictors of persistent high turnover and whether it is associated with poorer population health outcomes., Design: A retrospective observational study., Methods: We linked workforce data on individual GPs to practice-level data from Hospital Episode Statistics and the GP Patient Survey (2007-2019). We classified practices as experiencing persistent high turnover if more than 10% of GPs changed in at least 3 consecutive years. We used multivariable logistic or linear regression models for panel data with random effects to identify practice characteristics that predicted persistent high turnover and associations of practice outcomes (higher emergency hospital use and patient experience of continuity of care, access to care and overall patient satisfaction) with persistent high turnover., Results: Each year, 6% of English practices experienced persistent high turnover, with a maximum of 9% (688/7619) in 2014. Larger practices, in more deprived areas and with a higher morbidity burden were more likely to experience persistent high turnover. Persistent high turnover was associated with 1.8 (95% CI 1.5 to 2.1) more emergency hospital attendances per 100 patients, 0.1 (95% CI 0.1 to 0.2) more admissions per 100 patients, 5.2% (95% CI -5.6% to -4.9%) fewer people seeing their preferred doctor, 10.6% (95% CI-11.4% to -9.8%) fewer people reporting obtaining an appointment on the same day and 1.3% (95% CI -1.6% to -1.1%) lower overall satisfaction with the practice., Conclusions: Persistent high turnover is independently linked to indicators of poorer service and health outcomes. Although causality needs to be further investigated, strategies and policies may be needed to both reduce high turnover and support practices facing challenges with high GP turnover when it occurs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Evidence regarding fertility trends and obstetric outcomes among patients with psoriasis is limited by studies of small sample sizes, noninclusion of comparators, and the lack of accurate pregnancy records., Objective: To investigate fertility rates and obstetric outcomes of pregnancies in female patients with psoriasis compared with age- and general practice-matched comparators without psoriasis., Design, Setting, and Participants: This population-based cohort study used data from 887 primary care practices that contributed to the UK Clinical Practice Research Datalink GOLD database between 1998 and 2019, linked to a pregnancy register and Hospital Episode Statistics. There were 6 223 298 patients of common childbearing ages (15-44 years), and 63 681 patients with psoriasis had at least 1 year of follow-up data prior to the diagnosis of psoriasis. For each patient with psoriasis, 5 patients were matched by age from the same general practice. The median follow-up duration was 4.1 years. Data analysis was performed in 2021., Exposures: Patients with psoriasis were identified using clinical diagnostic codes from consultations., Main Outcomes and Measures: Fertility rates were calculated as the number of pregnancies per 100 patient-years. The outcomes of each pregnancy recorded in the pregnancy register or Hospital Episode Statistics were screened to identify obstetric outcomes. A negative binomial model was used to examine the association between psoriasis and the fertility rate. Logistic regression was applied to compare the association between psoriasis and obstetric outcomes., Results: A total of 63 681 patients with psoriasis and 318 405 matched comparators were included in the analysis (median [IQR] age, 30 [22-37] years). Lower fertility rates (rate ratio, 0.75; 95% CI, 0.69-0.83) were found in patients with moderate to severe psoriasis. Compared with matched comparators without psoriasis, pregnancies in patients with psoriasis had a higher risk of loss (odds ratio, 1.06; 95% CI, 1.03-1.10); however, there was no increase in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes., Conclusion and Relevance: In this cohort study, patients with moderate to severe psoriasis had a lower fertility rate, and the risk of pregnancy loss was higher than in matched comparators without psoriasis. Future research should identify the mechanism of increased risk of pregnancy loss among patients with psoriasis.

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Due to its prevalence and socio-economic burden on health systems, diabetes mellitus (DM) is considered a major health emergency. This retrospective, observational study aimed to describe a population of DM-naïve patients of the Local Health Authority (LHA) ASL TO4 Regione Piemonte and the prescriptive behavior of LHA general practitioners. Drug dispensing data collected between January 2018 and December 2021 was analyzed. Adult patients were included if they received their first prescription for an antidiabetic drug (AD) in 2019 and had ≥2 prescriptions/year of ADs during the follow-up. Patients who started antidiabetic therapy with metformin were selected to investigate comorbidities, medication adherence, and first treatment intensification. Comorbidities were identified through a modified version of the Rx-Risk Index; adherence was measured as the continuous measure of medication availability (CMA). Among 1927 DM-naïve patients, 1361 started therapy with metformin. Most of them received drugs related to cardiovascular diseases, hypertension, and infectious diseases during the study period. Median CMA was 58.8%, with the majority of patients being partially adherent to ADs (40 ≤ CMA < 80). Initial antidiabetic therapy was mostly modified (switch, add-on) with SGLT-2 inhibitors and sulfonylureas. These findings help to identify areas of intervention to improve the use of ADs in the LHA.

Background: Pediatric central nervous system (CNS) tumors are the leading cause of pediatric cancer mortality. Research addressing genomic biomarkers and clinical outcomes is needed to inform therapeutic decision-making., Methods: We conducted a retrospective analysis of pediatric patients (age <21) diagnosed with a primary CNS tumor at four upstate New York hospitals from 2008 to 2021. Clinical and histopathologic data were identified from each patient, including genomic analysis of somatic mutations and tumor mutational burden (TMB) where available. These variables were each compared with overall survival using Cox regression analyses. Multivariable analysis was conducted to identify patient characteristics that may independently predict survival., Results: We identified 119 patients. Common tumor types included low-grade glioma (N = 51), high-grade glioma (N = 29), and medulloblastoma (N = 11). Common driver mutations included TP53 inactivation (N = 16), BRAF-KIAA1549 fusion (N = 16), FGFR1 amplification (N = 12), BRAF V600E mutation (N = 12), NF1 loss (N = 12), and H3F3A K28M mutation (N = 6). Median TMB was one mutation/megabase (mut/Mb, range = 0-132). Overall survival was 79.9%. Variables associated with poorer survival on univariable analysis were higher TMB (p = .002, HR 4.97), high-grade tumors (p = .009, HR 84.3), and high-grade glioma histology (p = .021, HR 3.14). Multivariable analyses further identified TMB (p = .011, HR 4.46) and high-grade histology (p = .015, HR 5.28) as independently predictive of worse survival. Tumor progression was more common in high-TMB (N = 15, 44%) than in low-TMB tumors (N = 19, 35%)., Conclusions: High TMB is correlated with higher rates of progression and death as compared to low-TMB tumors. These findings may help identify patients who may benefit from alternative treatments, such as immunotherapies., (© 2022 Wiley Periodicals LLC.)

The rapid evolution of anti-cancer therapy (including chemotherapy, targeted therapy, and immunotherapy) in recent years has led to a more favorable efficacy and safety profile for a growing cancer population, and the improvement of overall survival and reduction of morbidity for many cancers. Anti-cancer therapy improves outcomes for cancer patients; however, many classes of anti-cancer therapy have been implicated in the induction of bullous dermatologic adverse events (DAE), leading to reduced patient quality of life and in some cases discontinuation of life-prolonging or palliative therapy. Timely and effective management of adverse events is critical for reducing treatment interruptions and preserving an anti-tumor effect. Bullous DAE may be limited to the skin or have systemic involvement with greater risk of morbidity and mortality. We present the epidemiology, diagnosis, pathogenesis, and management of bullous DAE secondary to anti-cancer therapies to enable clinicians to optimize management for these patients.

Background: It is unclear howmetal augments,polyethylene (PE) liner thickness, and length of cemented stemcontribute to load transferwhen reconstructing uncontained tibial metaphyseal bone loss of Anderson Orthopedic Research Institute (AORI) Type II defects during revision total knee arthroplasty (rTKA).The aimof this study is to understand the impact of these three variableson load transfer through the tibial baseplate. For a fixed defect depth, we hypothesized that there is a particular combination of liner and augment thickness and stem length that minimizes bone stress, reducing the risk of aseptic loosening., Methods: We conducted a finite element analysis (FEA) to model stresses at the bone-cement interface with different iterations of metal augments, PE liner thicknesses andfully-cemented stems lengths., Results: For a 20 mm tibial defect, constructs with thicker metal augments and thinner polyethylene liners were superior. Constructswith a fully cemented stem further reduced bone stress on the tibial plateau. Bone stress was lowest when a 100 mm fully-cemented stem was used, while stems between 30 mm - 80 mm produced similar results., Conclusions: When addressing a tibial bone defect of AORI Type II in rTKA, our FEA model demonstrates that surgeons should opt to use the thickest metal augments in combination with afully-cemented stem with an added length of at least 30 mm, which allows for surgical flexibility together with the most stable construct.Our study is notably limited by lack of modeling of knee joint moments, which are important when considering micromotion, bone-implant interface and stem effectiveness., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yale Center for Clinical Investigation (YCCI) Provided the PI with internal funding, which has a CTSA Grant UL1 TR001863 from the National Center for Advancing Translational Science (NCATS)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Pharmacological treatment of benign prostatic hyperplasia (BPH)/benign prostatic obstruction (BPO)-associated lower urinary tract symptoms (LUTS) aims at improving patients' quality of life by managing urinary symptoms and preventing complications and disease progression. However, continuous use of drugs to treat BPH/BPO-associated LUTS decreases over time. The aim of this retrospective observational study was to describe use of α1-adrenoceptor antagonists (ABs) and steroid 5α-reductase inhibitors (5ARIs) by adult (age ≥ 40 years) men in the ASL TO4, a Local Health Authority in the northern area of the city of Turin (Italy)., Methods: Persistence measures were adopted as a robust, informative, and feasible way to understand medication-taking behavior and to assess patient compliance., Results: A total of 4309 men (median age 71 years) were enrolled. Monotherapy was the treatment option prescribed to the largest part of the study population. However, ≥two drugs were prescribed to a substantial proportion of men (23%). Men prescribed alfuzosin or dutasteride had significantly greater persistence, which decreased over time., Conclusions: Unmet needs and areas of intervention for healthcare systems aimed at improving the use of drugs for BHP/BPO-associated LUTS in the ASL TO4 Regione Piemonte were identified.

Two novel inhibitors of isocitrate dehydrogenase (IDHi), ivosidenib and enasidenib, significantly improve survival for AML patients with an IDH1 or IDH2 mutation, respectively; however, rash has been reported as a toxicity of IDHi. The objective of our study is to determine the incidence, grade, clinical, and histopathologic features of dermatologic adverse events (DAEs) secondary to IDHi. This study is a retrospective analysis of 169 patients who were treated with either ivosidenib or enasidenib as single agent or in combination with induction chemotherapy at Memorial Sloan Kettering Cancer Center from January 1, 2013 to April 1, 2021. DAEs thought to be possibly, probably, or definitely related to IDHi occurred in 55 of 169 patients [0.32, 95 % CI: 0.25 - 0.40]. Of a total 81 DAEs observed, the most common DAE types were inflammatory dermatoses (27 %); cutaneous vascular manifestations (8%); cutaneous infections (7%); and pruritus (2%). Notably, 50% of infections and 15.5% of rashes were high grade. Knowledge of these findings is critical to optimize the treatment and quality of life of patients with AML on IDHi., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT)., Design: Randomised, double blind, placebo controlled clinical trial., Setting: 28 outpatient clinics specialising in venous thromboembolism., Participants: 402 adults (≥18 years) with symptomatic isolated distal DVT., Interventions: After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion., Main Outcomes Measures: The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes., Results: 200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred., Conclusions: Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage., Trial Registration: EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure for at www.icmje.org/disclosure-of-interest/ and declare: support from Bayer Italy. WA has received payment or honorariums for lectures from Aspen, Bayer, Bristol Myers Squibb, Leo Pharma, Norgine, Pfizer, Sanofi, and Werfen, and has participated on advisory boards for Bayer, Leo Pharma, Norgine, Sanofi, and Viatris; GP has received consulting fees from Alfa Sigma. All other authors have no financial relationships or other relationships or activities to disclose., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The diagnosis of psoriasis may be missed or delayed in primary care settings., Aim: To examine trends in healthcare events before a diagnosis of psoriasis., Design and Setting: Two matched case-control studies using electronic healthcare records delineated from the Clinical Practice Research Datalink (CPRD GOLD and Aurum) in the UK., Method: Individuals aged ≥18 years with an incident diagnosis of psoriasis (case group) between 1 January 2010 and 29 December 2017 were identified and matched by age, sex, and general practice with six individuals without psoriasis (control group). Healthcare activities were examined and annual incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for 10 years before the index date were compared between case and control groups., Results: There were 17 320 people with psoriasis and 99 320 controls included from CPRD GOLD, and 11 442 people with psoriasis and 65 840 controls extracted from CPRD Aurum. Data from CPRD GOLD showed that people with psoriasis were up to eight times more likely to be diagnosed with pityriasis rosea at 6 months (IRR 7.82, 95% CI = 4.09 to 14.95) before the index date than the control group. The case group were twice as likely to be diagnosed with eczema (IRR 1.90, 95% CI = 1.76 to 2.05) or tinea corporis (IRR 1.99, 95% CI = 1.74 to 2.27) 1 year before the index date. The case group were more likely to report dry skin, rash, skin texture changes, and itching than the control group up to 5 years before the index date. The most frequently reported clinical feature was rash with an IRR of 2.71 (95% CI = 2.53 to 2.92) at 1 year before the index date. The case group were prescribed topical corticosteroids (IRR 1.97, 95% CI = 1.88 to 2.07) or topical antifungals (IRR 1.92, 95% CI = 1.78 to 2.07) in the year before the index date twice as often as those in the control group., Conclusion: Findings suggest that the diagnosis of psoriasis may be missed or delayed in a UK primary care setting for up to 5 years for some individuals, hence leading to a potentially detrimental delay in establishing an appropriate treatment regimen., (© The Authors.)

Background: Patients with cancer are commonly characterized by abnormalities in laboratory coagulation tests, underlying a subclinical hypercoagulable condition. Due to the involvement of the hemostatic system in cancer patients, some of its biomarkers, such as fibrinogen, could be a useful tool in predicting cancer risk. We performed a case-cohort study to evaluate the relationship among fibrinogen levels and colorectal cancer (CRC)., Methods: In the framework of Moli-sani Study ( N = 24,325, enrolled 2005-2010) a subcohort of 1,290 individuals (55.0% women; mean age 55.0 ± 12.0 years) was selected and compared with 126 CRC cases identified during a follow-up of 4.3 years. Incident cases of colorectal cancer were ascertained by direct linkage with hospital discharge forms according to the International Classification of Disease (ICD-9-CM) codes: 153-154. Events were validated through medical records and confirmed by histological reports. Fibrinogen levels were measured in frozen citrated plasma samples. Hazard Ratio (HR) and 95% confidence interval (CI), adjusted by relevant covariates were estimated by a Cox regression model using Prentice method., Results: Individuals with levels of fibrinogen ≥400 mg/dL had a higher hazard to develop colorectal cancer when compared to those with lower levels after adjustment for sex and age (HR: 1.81; 95% CI 1.12-2.92). Additional adjustment for CRC family history, income, physical activity, diabetes medication and hypercholesterolemia did not modify the result (HR: 1.91; 95% CI 1.15-3.17). Analyses stratified by age and sex showed a most evident association in elderly (HR: 2.30; 95% CI: 1.10-4.81) and in women (HR: 2.28; 95% CI: 1.08-4.81). Sensitivity analyses confirmed the main findings, showing independence from a potential role of confounding by a large panel of biomarkers, including inflammation and hemostasis factors., Conclusion: Our results, based on a case-cohort study from a general adult population apparently free from any cancer during the recruitment, showed that fibrinogen levels ≥400 mg/dL were positively and independently associated with CRC, suggesting that this glycoprotein could be a potential biomarker for this type of cancer and supporting the "common soil hypothesis" in the pathophysiology of cardiovascular disease and tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Parisi, Panzera, Russo, Gamba, De Curtis, Di Castelnuovo, Marchetti, Cerletti, Falanga, de Gaetano, Donati, Iacoviello, Costanzo and the Moli-sani Study Investigators.)

Objective: To assess the diagnostic Read code usage for 18 conditions by examining their frequency and diversity in UK primary care between 2000 and 2013., Design: Population-based cohort study SETTING: 684 UK general practices contributing data to the Clinical Practice Research Datalink (CPRD) GOLD., Participants: Patients with clinical codes for at least one of asthma, chronic obstructive pulmonary disease, diabetes, hypertension (HT), coronary heart disease, atrial fibrillation (AF), heart failure, stroke, hypothyroidism, chronic kidney disease, learning disability (LD), depression, dementia, epilepsy, severe mental illness (SMI), osteoarthritis, osteoporosis and cancer., Primary and Secondary Outcome Measures: For the frequency ranking of clinical codes, canonical correlation analysis was applied to correlations of clinical code usage of 1, 3 and 5 years. Three measures of diversity (Shannon entropy index of diversity, richness and evenness) were used to quantify changes in incident and total clinical codes., Results: Overall, all examined conditions, except LD, showed positive monotonic correlation. HT, hypothyroidism, osteoarthritis and SMI codes' usage had high 5-year correlation. The codes' usage diversity remained stable overall throughout the study period. Cancer, diabetes and SMI had the highest richness (code lists need time to define) unlike AF, hypothyroidism and LD. SMI (high richness) and hypothyroidism (low richness) can last for 5 years, whereas cancer and diabetes (high richness) and LD (low richness) only last for 2 years., Conclusions: This is an under-reported research area and the findings suggest the codes' usage diversity for most conditions remained overall stable throughout the study period. Generated mental health code lists can last for a long time unlike cardiometabolic conditions and cancer. Adopting more consistent and less diverse coding would help improve data quality in primary care. Future research is needed following the transfer to the Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) coding., Competing Interests: Competing interests: DMA reports research grants from Abbvie, Almirall, Celgene, Eli Lilly, Novartis, UCB and the Leo Foundation., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Conflicts of interest None disclosed.

Background: Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, and AF incidence is expected to increase. Guidelines recommend using oral anticoagulants (OACs) to prevent the development of stroke. However, studies have reported the frequent underuse of OACs in AF patients. The objective of this study is to describe nonvalvular atrial fibrillation (NVAF) incidence in England and assess the clinical and socioeconomic factors associated with the underprescribing of OACs., Methods and Findings: We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) database to identify patients with NVAF aged ≥18 years and registered in English general practices between 2009 and 2019. Annual incidence rate of NVAF by age, deprivation quintile, and region was estimated. OAC prescribing status was explored for patients at risk for stroke and classified into the following: OAC, aspirin only, or no treatment. We used a multivariable multinomial logistic regression model to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) of the factors associated with OAC or aspirin-only prescribing compared to no treatment in patients with NVAF who are recommended to take OAC. The multivariable regression was adjusted for age, sex, comorbidities, socioeconomic status, baseline treatment, frailty, bleeding risk factors, and takes into account clustering by general practice. Between 2009 and 2019, 12,517,191 patients met the criteria for being at risk of developing NVAF. After a median follow-up of 4.6 years, 192,265 patients had an incident NVAF contributing a total of 647,876 person-years (PYR) of follow-up. The overall age-adjusted incidence of NVAF per 10,000 PYR increased from 20.8 (95% CI: 20.4; 21.1) in 2009 to 25.5 (25.1; 25.9) in 2019. Higher incidence rates were observed for older ages and males. Among NVAF patients eligible for anticoagulation, OAC prescribing rose from 59.8% (95% CI: 59.0; 60.6) in 2009 to 83.2% (95% CI: 83.0; 83.4) in 2019. Several conditions were associated with lower risk of OAC prescribing: dementia [RRR 0.52 (0.47; 0.59)], liver disease 0.58 (0.50; 0.67), malignancy 0.74 (0.72; 0.77), and history of falls 0.82 (0.78; 0.85). Compared to white ethnicity, patients from black and other ethnic minorities were less likely to receive OAC; 0.78 (0.65; 0.94) and 0.76 (0.64; 0.91), respectively. Patients living in the most deprived areas were less likely to receive OAC 0.85 (0.79; 0.91) than patients living in the least deprived areas. Practices located in the East of England were associated with higher risk of prescribing aspirin only over no treatment than practices in London (RRR 1.22; 95% CI 1.02 to 1.45). The main limitation of this study is that these findings depends on accurate recording of conditions by health professionals and the inevitable residual confounding due to lack of data on certain factors that could be associated with under-prescribing of OACs., Conclusions: The incidence of NVAF increased between 2009 and 2015, before plateauing. Underprescribing of OACs in NVAF is associated with a range of comorbidities, ethnicity, and socioeconomic factors, demonstrating the need for initiatives to reduce inequalities in the care for AF patients., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DA received research grants from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, UCB, and the Leo Foundation.

Background: In response to the global COVID-19 pandemic, many in vitro diagnostic (IVD) tests for SARS-CoV-2 have been developed. Given the urgent clinical demand, researchers must balance the desire for precise estimates of sensitivity and specificity against the need for rapid implementation. To complement estimates of precision used for sample size calculations, we aimed to estimate the probability that an IVD will fail to perform to expected standards after implementation, following clinical studies with varying sample sizes., Methods: We assumed that clinical validation study estimates met the 'desirable' performance (sensitivity 97%, specificity 99%) in the target product profile (TPP) published by the Medicines and Healthcare products Regulatory Agency (MHRA). To estimate the real-world impact of imprecision imposed by sample size we used Bayesian posterior calculations along with Monte Carlo simulations with 10,000 independent iterations of 5,000 participants. We varied the prevalence between 1 and 15% and the sample size between 30 and 2,000. For each sample size, we estimated the probability that diagnostic accuracy would fail to meet the TPP criteria after implementation., Results: For a validation study that demonstrates 'desirable' sensitivity within a sample of 30 participants who test positive for COVID-19 using the reference standard, the probability that real-world performance will fail to meet the 'desirable' criteria is 10.7-13.5%, depending on prevalence. Theoretically, demonstrating the 'desirable' performance in 90 positive participants would reduce that probability to below 5%. A marked reduction in the probability of failure to hit 'desirable' specificity occurred between samples of 100 (19.1-21.5%) and 160 (4.3-4.8%) negative participants. There was little further improvement above sample sizes of 160 negative participants., Conclusion: Based on imprecision alone, small evaluation studies can lead to the acceptance of diagnostic tests which are likely to fail to meet performance targets when deployed. There is diminished return on uncertainty surrounding an accuracy estimate above a total sample size of 250 (90 positive and 160 negative)., (© 2022. The Author(s).)

Background: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a low-grade tumor characterized by diffuse leptomeningeal infiltrates. Symptoms are usually secondary to hydrocephalus. Hemiplegic migraine (HM)-like episodes have never been associated with DLGNT, but they have been reported with different inflammatory and tumoral entities involving leptomeninges., Observations: We report the case of a 10-year-old boy with recurrent episodes of right hyposthenia, aphasia, and headache lasting hours to days with complete remission. The electroencephalogram during the attack showed diffuse slower activity on the left hemisphere, which improved together with the symptoms. DLGNT was discovered during a follow-up magnetic resonance imaging and confirmed by biopsy., Conclusions: This is the first report of HM-like attacks in DLGNT. We discuss the pathogenetic hypotheses of our case and previously reported cases of "symptomatic" HM with leptomeningeal involvement., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Nutrition is an important, modifiable, environmental factor affecting human health by modulating epigenetic processes, including DNA methylation (5mC). Numerous studies investigated the association of nutrition with global and gene-specific DNA methylation and evidences on animal models highlighted a role in DNA hydroxymethylation (5hmC) regulation. However, a more comprehensive analysis of different layers of nutrition in association with global levels of 5mC and 5hmC is lacking. We investigated the association between global levels of 5mC and 5hmC and human nutrition, through the stratification and analysis of dietary patterns into different nutritional layers: adherence to Mediterranean diet (MD), main food groups, macronutrients and micronutrients intake., Methods: ELISA technique was used to measure global 5mC and 5hmC levels in 1080 subjects from the Moli-sani cohort. Food intake during the 12 months before enrolment was assessed using the semi-quantitative EPIC food frequency questionnaire. Complementary approaches involving both classical statistics and supervised machine learning analyses were used to investigate the associations between global 5mC and 5hmC levels and adherence to Mediterranean diet, main food groups, macronutrients and micronutrients intake., Results: We found that global DNA methylation, but not hydroxymethylation, was associated with daily intake of zinc and vitamin B3. Random Forests algorithms predicting 5mC and 5hmC through intakes of food groups, macronutrients and micronutrients revealed a significant contribution of zinc, while vitamin B3 was reported among the most influential features., Conclusion: We found that nutrition may affect global DNA methylation, suggesting a contribution of micronutrients previously implicated as cofactors in methylation pathways., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Prior malignancy exclusion criteria (PMEC) are often utilized in cancer clinical trials; however, the incidence of PMEC and the association of PMEC with trial participant age disparities remain poorly understood. This study aimed to identify age disparities in oncologic randomized clinical trials as a result of PMEC. Using a comprehensive collection of modern phase III cancer clinical trials obtained via ClinicalTrials.gov, we assessed the incidence and covariates associated with trials excluding patients with prior cancers within 5+ years from registration (PMEC-5). Using the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, we further sought to determine the correlation between PMEC-5 and age disparities. PMEC-5 were used in 41% of all trials, with higher PMEC-5 utilization among industry-supported trials as well as trials evaluating a targeted therapy. Comparing trial patient median ages with population-matched median ages by disease site and time-period, we assessed the association between PMEC-5 and age disparities among trial participants. PMEC-5 were independently associated with heightened age disparities, which further worsened with longer exclusionary timeframes. Together, PMEC likely contribute to age disparities, suggesting that eligibility criteria modernization through narrower PMEC timeframes may work toward reducing such disparities in cancer clinical trial enrollment.

Background: Non-communicable diseases (NCDs) account for 71% of deaths worldwide and individual behaviours such as sedentariness play an important role on their development and management. However, the detrimental effect of daily sitting on multiple NCDs has rarely been studied. This study sought (i) to investigate the association between sitting time and main NCDs and multimorbidity in the population of Catalonia and (ii) to explore the effect of physical activity as a modifier of the associations between sitting time and health outcomes., Methods: Cross-sectional data from the 2016 National Health Survey of Catalonia were analyzed, and multivariable logistic regression, adjusting for socio-demographics and individual risk factors (tobacco and alcohol consumption, diet, hyperlipidaemia, hypertension, body mass index) was used to estimated odds ratios (ORs) and 95% confidence intervals (CIs) of the association between sitting time and NCDs., Results: A total of 3320 people ≥15 years old were included in the study. Sitting more than 5 h/day was associated with a higher risk of cardiovascular disease (OR 1.90, 95% CI: 1.21-2.97), respiratory disease (OR 1.61, 95% CI: 1.13-2.30) and multimorbidity (OR 2.80, 95% CI: 1.53-5.15). Sitting more than 3 h/day was also associated with a higher risk of multimorbidity (OR 2.26, 95% CI: 1.23-4.16). Physical activity did not modify the associations between sitting time and any of the outcomes., Conclusions: Daily sitting time might be an independent risk factor for some NCDs, such as cardiovascular disease, respiratory disease and multimorbidity, independently of the level risk of physical inactivity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association.)

Objective: To describe the distribution of consultations at the practice level and examine whether increases are uniform or driven by people who consult more frequently., Design: Retrospective cohort study., Setting: UK general practice data from the Clinical Practice Research Datalink (CPRD) GOLD database., Participants: 1 699 709 314 consultation events from 12 330 545 patients, in 845 general practices (1 April 2000 to 31 March 2019)., Methods: Consultation information was aggregated by financial year into: all consultations/all staff; all consultations/general practitioners (GPs); face-to-face consultations/all staff; face-to-face consultations/GPs. Patients with a number of consultations above the 90th centile, within each year, were classified as frequent attenders. Negative binomial regressions examined the association between available practice characteristics and consultation distribution., Results: Among frequent attenders, all consultations by GPs increased from a median (25th and 75th centile) of 13 (10 and 16) to 21 (18 and 25) and all consultations by all staff increased from 27 (23-30) to 60 (51-69) over the study period. Approximately four out of ten consultations of any type concerned frequent attenders and the proportion of consultations attributed to them increased over time, particularly for face-to-face consultations with GPs, from a median of 38.0% (35.9%-40.3%) in 2000-2001 to 43.0% (40.6%-46.4%) in 2018-2019. Regression analyses indicated decreasing trends over time for face-to-face consultations and increasing trends for all consultation types, for both GPs and all staff. Frequent attenders consulted approximately five times more than the rest of the practice population, on average, with adjusted incidence rate ratios ranging between 4.992 (95% CI 4.917 to 5.068) for face-to-face consultations with all staff and 5.603 (95% CI 5.560 to 5.647) for all consultations with GPs., Conclusions: Frequent attenders progressively contributed to increased workload in general practices across the UK from 2000 to 2019. Important knowledge gaps remain in terms of the demographic, social and health characteristics of frequent attenders and how UK general practices can be prepared to meet the needs of these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Neuromedin U (NMU) is a neuropeptide involved in gut-brain axis, energy balance and immune response. We aimed at analysing the association between NMU epigenetic variability and metabolic indices and the potential mediating role of low-grade inflammation in a general population of Italian adults. NMU Blood DNA methylation levels at two CpG islands ( NMU76 and NMU32 ) were analysed using pyrosequencing in a randomly selected sub-cohort of 1,160 subjects from the Moli-sani study (≥35years; 49.20% men). Multivariable regressions adjusted for age, sex, smoking, alcohol and vegetable consumption were performed to estimate the associations between methylation and metabolic phenotypes (BMI, waist-to-hip ratio, blood pressure, glucose, HOMA-IR, lipids, lipoprotein(a) and apolipoproteins). Mediation analysis was performed to identify the influence of low-grade inflammation in the association using a composite index based on C reactive protein, granulocyte-to-lymphocyte ratio (GLR), platelet and white blood cell counts (INFLA-score).Using principal component analysis four methylation factors were identified: NMU76-F1, NMU76-F2, NMU32-F1 and NMU32-F2 . NMU76-F1 was FDR significantly associated with total cholesterol (for 1 SD increase: β = 4.5 ± 1.4 mg/dL of, R 2 = 10.8%, p = 0.001), ApoB (0.03 ± 0.01 g/L, 12.2%, p = 0.0004), with INFLA-score (1.05 ± 0.22, p = 2.7E-6) and GLR (-0.27 ± 0.03, 30.4%, p = 1.3E-20). GLR and lymphocyte numbers mediate the association of NMU76-F1 with cholesterol (24.0% of total effect, Sobel p = 0.013) and ApoB (42.6%, p = 9E-7), respectively.These findings suggest that NMU promoter methylation patterns could mark a pathway linking lipids with haematopoiesis and systemic inflammation.

Objective: To quantify general practitioners' (GPs') turnover in England between 2007 and 2019, describe trends over time, regional differences and associations with social deprivation or other practice characteristics., Design: A retrospective study of annual cross-sectional data., Setting: All general practices in England (8085 in 2007, 6598 in 2019)., Methods: We calculated turnover rates, defined as the proportion of GPs leaving a practice. Rates and their median, 25th and 75th percentiles were calculated by year and region. The proportion of practices with persistent high turnover (>10%) over consecutive years were also calculated. A negative binomial regression model assessed the association between turnover and social deprivation or other practice characteristics., Results: Turnover rates increased over time. The 75th percentile in 2009 was 11%, but increased to 14% in 2019. The highest turnover rate was observed in 2013-2014, corresponding to the 75th percentile of 18.2%. Over time, regions experienced increases in turnover rates, although it varied across English regions. The proportion of practices with high (10% to 40%) turnover within a year almost doubled from 14% in 2009 to 27% in 2019. A rise in the number of practices with persistent high turnover (>10%) for at least three consecutive years was also observed, from 2.7% (2.3%-3.1%) in 2007 to 6.3% (5.7%-6.9%) in 2017. The statistical analyses revealed that practice-area deprivation was moderately associated with turnover rate, with practices in the most deprived area having higher turnover rates compared with practices in the least deprived areas (incidence rate ratios 1.09; 95% CI 1.06 to 1.13)., Conclusions: GP turnover has increased in the last decade nationally, with regional variability. Greater attention to GP turnover is needed, in the most deprived areas in particular, where GPs often need to deal with more complex health needs. There is a large cost associated with GP turnover and practices with very high persistent turnover need to be further researched, and the causes behind this identified, to allow support strategies and policies to be developed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality., Aim: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients., Methods: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores., Results: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation., Conclusion: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The association between psoriasis and the risk of cancer has been investigated in numerous studies utilising electronic health records (EHRs), with conflicting results in the extent of the association., Objectives: To assess concordance and timing of cancer recording between primary care, hospital and death registration data for people with and without psoriasis., Methods: Cohort studies delineated using primary care EHRs from the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases, with linkage to hospital episode statistics (HES), Office for National Statistics (ONS) mortality data and indices of multiple deprivation (IMD). People with psoriasis were matched to those without psoriasis by age, sex and general practice. Cancer recording between databases was investigated by proportion concordant, that being the presence of cancer record in both source and comparator datasets. Delay in recording cancer diagnoses between CPRD and HES records and predictors of discordance were also assessed., Results: 58,904 people with psoriasis and 350,592 comparison patients were included using CPRD GOLD; whereas 213,400 people with psoriasis and 1,268,998 comparison patients were included in CPRD Aurum. For all cancer records (excluding keratinocyte), concordance between CPRD and HES was greater than 80%. Concordance for same-site cancer records was markedly lower (<68% GOLD-linked data; <72% Aurum-linked data). Concordance of non-Hodgkin lymphoma and liver cancer recording between CPRD and HES was lower for people with psoriasis compared to those without., Conclusions: Concordance between CPRD and HES is poor when restricted to cancers of the same site, with greater discordance in people with psoriasis for some cancers of specific sites. The use of linked patient-level data is an important step in reducing misclassification of cancer outcomes in epidemiological studies using routinely collected electronic health records., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MKR reports receiving research funding from Novo Nordisk, consultancy fees from Novo Nordisk and Roche Diabetes Care, and modest owning of shares in GlaxoSmithKline. CEMG reports receiving honorariums or research grants from AbbVie, Almirall, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Sandoz, Sanofi, and UCB Pharma. DMA reports research grants from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, UCB, and the Leo Foundation. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Objective: Syndemic conditions have been linked to engagement in receptive condomless anal sex (CAS) and HIV seroconversion. However, little is known about the biological pathways whereby syndemics could amplify vulnerability to HIV and other sexually transmitted infections (STIs)., Design: HIV-negative sexual minority men (i.e. gay, bisexual and other MSM) were recruited from four STI clinics in South Florida for a cross-sectional study., Methods: Participants completed assessments for four syndemic conditions: depression, posttraumatic stress disorder, hazardous alcohol use and any stimulant use (i.e. any self-reported use or reactive urine toxicology results). Cytokine and chemokine levels were measured using LEGENDplex from the rectal swabs of 92 participants reporting receptive CAS and no antibiotic use in the past three months., Results: After controlling for age, race/ethnicity, preexposure prophylaxis (PrEP) use and number of receptive CAS partners, a greater number of syndemic conditions was associated with higher levels of rectal cytokines/chemokines relevant to immune activation, inflammation and the expansion and maintenance of T-helper 17 target cells, including rectal interferon-gamma (β = 0.22; P = 0.047), CXCL-8 (β = 0.24; P = 0.025) and interleukin-23 (β = 0.22; P = 0.049). Elevations in rectal cytokine or chemokine levels were most pronounced among participants experiencing two or more syndemic conditions compared with those experiencing no syndemic conditions. PrEP use was independently associated with elevations in multiple rectal cytokines/chemokines., Conclusion: Syndemic conditions could increase biological vulnerability to HIV and other STIs in sexual minority men by potentiating rectal immune dysregulation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We conducted a systematic review and a meta-analysis to assess the association of anticoagulants and their dosage with in-hospital all-cause mortality in COVID-19 patients. Articles were retrieved until January 8, 2021, by searching in seven electronic databases. The main outcome was all-cause mortality occurred during hospitalization. Data were combined using the general variance-based method on the effect estimate for each study. Separate meta-analyses according to type of COVID-19 patients (hospitalized or intensive care unit [ICU] patients), anticoagulants (mainly heparin), and regimens (therapeutic or prophylactic) were conducted. A total of 29 articles were selected, but 23 retrospective studies were eligible for quantitative meta-analyses. No clinical trial was retrieved. The majority of studies were of good quality; however, 34% did not distinguish heparin from other anticoagulants. Meta-analysis on 25,719 hospitalized COVID-19 patients showed that anticoagulant use was associated with 50% reduced in-hospital mortality risk (pooled risk ratio [RR]: 0.50, 95% confidence interval [CI]: 0.40-0.62; I 2 : 87%). Both anticoagulant regimens (therapeutic and prophylactic) reduced in-hospital all-cause mortality, compared with no anticoagulation. Particularly in ICU patients, the anticoagulant therapeutic regimen was associated with a reduced in-hospital mortality risk (RR: 0.30, 95% CI: 0.15-0.60; I 2 : 58%) compared with the prophylactic one. However, the former was also associated with a higher risk of bleeding (RR: 2.53, 95% CI: 1.60-4.00; I 2 : 65%). Anticoagulant use, mainly heparin, reduced all-cause mortality in COVID-19 patients during hospitalization. Due to the higher risk of bleeding at therapeutic doses, the use of prophylactic dosages of anticoagulant is probably to be preferred in noncritically ill COVID-19 patients., Competing Interests: The authors report no conflict of interest related to the current work. A.D.C. reports grants from ERAB (the European Foundation for Alcohol Research), outside the submitted work. Dr. Costanzo reports grants from ERAB (the European Foundation for Alcohol Research), personal fees from The Dutch Beer Institute foundation—The Brewers of Europe, outside the submitted work., (Thieme. All rights reserved.)

In a Drug Prescription Network (DPN), each drug is represented as a node and two drugs co-prescribed to the same patient are represented as an edge linking the nodes. The use of DPNs is a novel approach that has been proposed as a means to study the complexity of drug prescription. The aim of this study is to demonstrate the analytical power of the DPN-based approach when it is applied to the analysis of administrative data. Drug prescription data that were collected at a local health unit (ASL TO4, Regione Piemonte, Italy), over a 12-month period (July 2018-June 2019), were used to create several DPNs that correspond to the five levels of the Anatomical Therapeutic Chemical classification system. A total of 5,431,335 drugs prescribed to 361,574 patients (age 0-100 years; 54.7% females) were analysed. As indicated by our results, the DPNs were dense networks, with giant components that contain all nodes. The disassortative mixing of node degrees was observed, which implies that non-random connectivity exists in the networks. Network-based methods have proven to be a flexible and efficient approach to the analysis of administrative data on drug prescription.

Background:  Elevated levels of key enzymes of the fibrinolytic system, such as tissue plasminogen activator (tPA), are reported as predictors of poor outcome in cancer patients. Limited information is available about their potential predictive value for breast cancer (BC) risk in the general population., Aim:  We examined the association of tPA levels with BC risk in a case-cohort study including women from the prospective Moli-sani cohort., Methods:  A sample of 710 women (mean age: 54.6 ± 12.1 years) was selected as a subcohort and compared with 84 BC cases, in a median follow-up of 4.2 years. Incident cases of BC were validated through medical records. tPA plasma levels were measured using an enzyme-linked immunosorbent assay kit. Hazard ratio (HR) and 95% confidence interval (CI), adjusted for relevant covariates, were estimated by a Cox regression model using the Prentice method., Results:  Compared with the lowest quartile (<4.9 ng/mL), women in the highest quartile of tPA (>11.2 ng/mL) had increased risk of BC (HR IVvsI : 2.20, 95% CI: 1.13-4.28) after adjusted for age, smoking, education, menopause, and residence. Further adjustment for biochemical markers did not modify this association. The risk of BC increased by 34% for each increase in 1 standard deviation of log-transformed tPA levels ( p  = 0.046). Elevated levels of tPA were associated mainly with estrogen-receptor-positive BC (2.08, 95% CI: 1.18-3.66)., Conclusion:  Higher levels of tPA, reported to predict cardiovascular risk, are a potential biomarker for BC risk, supporting the hypothesis of a "common soil" linking the pathogenic mechanisms of hormone-dependent tumors and cardiovascular disease., Competing Interests: None declared., (Thieme. All rights reserved.)

During the COVID-19 pandemic in Italy, people and families experienced a new and sudden situation that forced them to stay in their homes for a long period (February 25- May 26). In this context, many people found themselves in great difficulty, not only because of the fear of contagion or the economic problems deriving from the closure of production activities but also because the virus profoundly changed the way of life in society. The "Social distancing" concept became central in all personal relationships, including close family relationships. In this situation, our paper seeks to understand the role of spirituality and religiosity in reacting to this difficult situation and in particular on the physical and psychological health of the people involved. The data we present here are part of a multidisciplinary research with a quantitative theoretical framework. As the data was collected during the first Italian lockdown, a total of 1,250 adults from all over Italy participated in the on-line questionnaire. Among the main results it emerged that the participants perceived lower levels of spiritual well-being and mental health than the pre-pandemic situation with a significant gender difference; in fact, women perceived lower mental health than men. At the same time, it is evident that spirituality and religious practices are a protective factor connected not only with psychological and mental but also physical health. Finally, it appears evident that the family is a protective factor with respect to mental health, even in a period so full of stress factors, those who did not live alone and especially those who had to take care of small children reported higher perceived mental health and a greater ability to activate coping resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Coppola, Rania, Parisi and Lagomarsino.)

The COVID-19 pandemic of 2020 in Italy had its first epidemic manifestations on January 31, 2020. The socio-sanitary rules imposed by the government concerned the social distance and management of intimate relationships, the sense of individual responsibility toward public health. Physical distancing and housing isolation have produced new representations of intrafamily, generational, neighborhood, community responsibility, bringing out a new "medicalized dimension" of society. In light of this contextual framework, the research aims are to analyze how: the perception of individual responsibility for public and familial health and physical distancing has redrawn the relation between subjects-family-community; the State's technical-health intervention has reformulated the idea of social closeness, but also how the pandemic fear and social confinement has re-evaluated a desire for community, neighborhood, proximity; during the lockdown families, friends, neighbors have reconstructed feelings of closeness and forms of belonging. The methodology used is quanti-qualitative and involved 300 women through an online questionnaire. The data collected highlight how the house during the lockdown is perceived as a safe place and how women implement both the recommendations and the behaviors aimed at preventing contagion, but also ways that allow coping with the situation from a perspective of well-being. Furthermore, the data show how the dimension of distancing has loosened the relational dimension outside the family unit, with a greater distancing compared to pre-pandemic data. However, the majority of women report that they have joined solidarity initiatives, demonstrating that they want to maintain ties and participate actively in community life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Parisi, Lagomarsino, Rania and Coppola.)

Objective: To report our initial experience of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/acute coronary syndrome (ACS) patients undergoing standard of care invasive management., Background: The rapid diffusion of the SARS-CoV-2 together with the need for isolation for infected patients might be responsible for a suboptimal treatment for SARS-CoV-2 ACS patients. Recently, the group of Sichuan published a protocol for COVID/ACS infected patients that see the thrombolysis as the gold standard of care., Methods: We enrolled 31 consecutive patients affected by SARS-COV-2 admitted to our emergencies room for suspected ACS., Results: All patients underwent urgent coronary angiography and percutaneous coronary intervention (PCI) when required except two patients with severe hypoxemia and unstable hemodynamic condition that were conservatively treated. Twenty-one cases presented diffuse ST-segment depression while in the remaining cases anterior and inferior ST-elevation was present in four and six cases, respectively. PCI was performed in all cases expect two that were diagnosed as suspected myocarditis because of the absence of severe coronary disease and three with apical ballooning at ventriculography diagnostic for Tako-Tsubo syndromes. Two patients conservatively treated died. The remaining patients undergoing PCI survived except one that required endotracheal intubation (ETI) and died at Day 6. ETI was required in five more patients while in the remaining cases CPAP was used for respiratory support., Conclusions: Urgent PCI for ACS is often required in SARS-CoV-2 patients improving the prognosis in all but the most advanced patients. Complete patient history and examination, routine ECG monitoring, echocardiography, and careful evaluation of changes in cardiac enzymes should be part of the regular assessment procedures also in dedicated COVID positive units., (© 2020 Wiley Periodicals, Inc.)

Objectives: The risk of dying by alcohol-specific causes in people with epilepsy has seldom been reported from population-based studies. We aimed to estimate the relative risk of alcohol-specific mortality in people with epilepsy, and the extent to which problematic alcohol use was previously identified in the patients' medical records. Method: We delineated cohort studies in two population-based datasets, the Clinical Practice Research Datalink (CPRD GOLD) in England (January 01, 2001-December 31, 2014) and the Secure Anonymised Information Linkage (SAIL) Databank in Wales (January 01, 2001-December 31, 2014), linked to hospitalization and mortality records. People with epilepsy were matched to up to 20 persons without epilepsy on gender, age (±2 years) and registered general practice. We identified alcohol-specific death from Office for National Statistics (ONS) records using specified ICD-10 codes. We further identified prescriptions, interventions and hospitalisations related to alcohol use. Results: In the CPRD GOLD, we identified 9,871 individuals in the incident epilepsy cohort and 185,800 in the comparison cohort and, in the SAIL Databank, these numbers were 5,569 and 110,021, respectively. We identified a five-fold increased risk of alcohol-specific mortality in people with epilepsy vs. those without the condition in our pooled estimate across the two datasets (deprivation-adjusted HR 4.85, 95%CI 3.46-6.79). Conclusions: People with epilepsy are at increased risk of dying by an alcohol-specific cause than those without the disorder. It is plausible that serious alcohol misuse could either contribute to the development of epilepsy or it could commence subsequent to epilepsy being diagnosed. Regardless of the direction of the association, it is important that the risk of dying as a consequence of alcohol misuse is accurately quantified in people affected by epilepsy. Systematically-applied, sensitive assessment of alcohol consumption by healthcare professionals, at opportunistic, clinical contacts, with rapid access to quality treatment services, should be mandatory and play a key role in reduction of health harms and mortality., Competing Interests: HCG is a member of Epilepsy Action Health & Clinical Advisory Panel. This is a voluntary position. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gorton, Webb, Parisi, Carr, DelPozo-Banos, Moriarty, Pickrell, John and Ashcroft.)

Background: Primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) can be challenging for high thrombus burden and catecholamine-induced vasoconstriction. The Xposition-S stent was designed to prevent stent undersizing and minimize strut malapposition. We evaluated 1-year clinical outcomes of a nitinol, self-apposing®, sirolimus-eluting stent, pre-mounted on a novel balloon delivery system, in de novo lesions of patients presenting with STEMI undergoing pPCI., Methods: The iPOSITION is a prospective, multicenter, post-market, observational study. The primary endpoint, target lesion failure (TLF), was defined as the composite of cardiac death, recurrent target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR)., Results: The study enrolled 247 STEMI patients from 7 Italian centers. Both device and procedural success occurred in 99.2% of patients, without any death, TV-MI, TLR, or stent thrombosis during the hospital stay and at 30-day follow-up. At 1 year, TLF occurred in 2.6%, cardiac death occurred in 1.7%, TV-MI occurred in 0.4%, and TLR in 0.4% of patients. The 1-year stent thrombosis rate was 0.4%., Conclusions: The use of an X-position S self-apposing® stent is feasible in STEMI pPCI, with excellent post-procedural results and 1-year outcomes.

Objectives: To evaluate the safety and efficacy of the Orsiro sirolimus-eluting stent (Biotronik) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Specific drug-eluting stent (DES) platforms might influence pPCI success rate in the mid-to-long term. Orsiro, a hybrid sirolimus DES with thin struts and a biodegradable polymer, may potentially cause less stent malapposition, stent-induced inflammation, and mechanical damage, improving clinical outcomes., Methods: We retrospectively enrolled all patients who received 1 or more Orsiro DES in the target vessel of pPCI at 9 Italian centers from January 2012 to March 2016. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, any myocardial infarction clearly attributable to the intervention culprit vessel (TVMI), and ischemic-driven target-lesion revascularization (ID-TLR) at 1-year follow-up. Secondary endpoints were: (1) DOCE at 6-month and 3-year follow-up; (2) any definite/probable stent thrombosis; and (3) any major bleeding., Results: The study cohort comprised 353 patients. At 1-year follow-up, we observed a 3.7% cumulative incidence of DOCE, consisting of 11 cardiac deaths (3.1%), 2 TVMIs (0.6%), and 2 ID-TLRs (0.6%). There was only 1 definite stent thrombosis (0.3%) and 8 bleedings (2.4%). Kaplan-Meier analysis showed DOCE-free survival rates of 96.6% at 6 months, 96.3% at 1 year, and 93.8% at 3 years., Conclusions: Our findings support the real-world safety and efficacy of the Orsiro stent for pPCI.

Background: The ULISSE registry evaluated the real-world performance of the Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) in a multicenter-independent cohort of patients undergoing percutaneous coronary intervention, including a large proportion of diabetes mellitus (DM) patients., Methods: In this subgroup analysis, 1,660 consecutive patients, 2,422 lesions, treated with BP-SES enrolled in the ULISSE registry were divided in two groups: DM (485 patients, 728 lesions) and non-DM (1,175 patients, 1,694 lesions). Primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac-death, target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR) at 1-year. Secondary endpoint was TLR at 1-year., Results: At 1-year follow-up TLF occurred in 5% overall patients and was significantly higher in DM patients (8 vs. 3.7%; p = .001), due to more cardiac deaths (3.4 vs. 1.1%; p = .002). TLR occurred in 3.2% overall patients, and it was not significantly higher in DM compared to non-DM patients (4.4 vs. 2.8%; p = .114). The incidence of stent thrombosis was low and similar between groups (0.4 vs. 0.9%; p = .526). Insulin-treated DM (ITDM) patients showed higher rate of TLF as compared to non-ITDM patients (13 vs. 6.5%; p = .041), but similar rate of TLR (6 vs. 4%; p = .405). After adjustment for relevant comorbidities, DM was not significantly associated with TLF or cardiac death in patients undergoing BP-SES implantation., Conclusions: This study is the first all-comers evaluation of BP-SES in DM patients. Our findings show that DM patients, mostly those with ITDM, still represent a vulnerable population and experience significantly higher rate of TLF. Overall BP-SES efficacy is considerable, although not statistically significant higher rate of TLR is still present in DM compared to non-DM patients., (© 2019 Wiley Periodicals, Inc.)

The diffusion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) forced the Italian population to restrictive measures that modified patients' responses to non-SARS-CoV-2 medical conditions. We evaluated all patients with acute coronary syndromes admitted in 3 high-volume hospitals during the first month of SARS-CoV-2 Italian-outbreak and compared them with patients with ACS admitted during the same period 1 year before. Hospitalization for ACS decreased from 162 patients in 2019 to 84 patients in 2020. In 2020, both door-to-balloon and symptoms-to-percutaneous coronary intervention were longer, and admission levels of high-sensitive cardiac troponin I were higher. They had a lower discharged residual left-ventricular function and an increased predicted late cardiovascular mortality based on their Global Registry of Acute Coronary Events (GRACE) scores., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)