Effectiveness and cost-effectiveness of guided self-help for depression for autistic adults: the Autism Depression Trial (ADEPT-2) – protocol for a multicentre, randomised controlled trial of a remotely delivered low-intensity intervention

Introduction
Depression is three to four times more prevalent in autistic people and is related to reduced quality of life. There is a need for empirically supported psychological interventions for depression specifically adapted to meet the needs of autistic adults. ADEPT-2 aims to establish the clinical and cost-effectiveness of an adapted low-intensity psychological intervention (guided self-help) for depression in autistic adults.

Methods and analysis
A two parallel-group multicentre pragmatic randomised controlled trial investigating the effectiveness of GSH for depression in autistic adults. Participants (n=248) aged ≥18 years with a clinical diagnosis of autism currently experiencing depression will be randomised to GSH or treatment as usual (TAU). GSH is a low-intensity psychological intervention based on the principles of behavioural activation adapted for autism. GSH comprises informational materials for nine individual sessions facilitated online by a GSH coach who has received training and supervision in delivering the intervention. The primary outcome will be Beck Depression Inventory-II depression scores at 16 weeks post randomisation with follow-up measures at 32 and 52 weeks. Additional measures of anxiety, patient-rated global improvement, quality of life, work and social adjustment, positive and negative affect will be measured 16 and 52 weeks post randomisation. The primary health economic analysis will assess the cost-effectiveness of GSH compared with TAU over 52 weeks, from a societal perspective including the National Health Service, personal social services, personal expenses, voluntary services and productivity. An embedded qualitative study will explore the acceptability, experiences and adherence of participants and therapists to treatment principles.

Ethics and dissemination
This trial has been approved by the East of England – Essex Research Ethics Committee on 10 June 2022 (REC Reference number: 22/EE/0091). The findings of the research will be submitted for publication in peer-reviewed journals and disseminated in an appropriate format to trial participants and the wider public.

Trial registration number
ISRCTN17547011.

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Novembre 2024

Secondary causal mediation analysis of a pragmatic clinical trial to evaluate the effect of chiropractic care for US active-duty military on biopsychosocial outcomes occurring through effects on low back pain interference and intensity

Objective
We evaluate change in low back pain (LBP) intensity and interference as the mechanism by which chiropractic care affects other biopsychosocial factors in US active-duty military members.

Design
We conducted secondary, exploratory mediation analysis of pragmatic, multisite, clinical trial (NCT01692275) post results using natural effect modeling. Mediators were the 6-week values of Patient-Reported Outcomes Measurement Information System (PROMIS)-29 pain interference and intensity. Outcomes were 12-week values of other PROMIS-29 biopsychosocial subdomains. Models evaluated overall and individual factor contribution and were adjusted for baseline age, sex, LBP duration, LBP intensity and mediator and outcome values.

Setting
Three US military treatment facilities.

Participants
750 US active-duty military members with LBP.

Interventions
Trial participants received 6 weeks of treatment with chiropractic care plus usual medical care or usual medical care alone.

Results
In multiple mediator models, pain interference and pain intensity explained much of the effect of chiropractic care on physical function (proportion mediated=0.77, 95% CI 0.43 to 2.0), fatigue (0.62, 95% CI 0.30 to 1.0), sleep disturbance (0.49, 95% CI 0.31 to 1.5) and social roles (0.81, 95% CI 0.50 to 2.0). Mental health was not evaluable due to the low prevalence of symptoms reported. The combined models of pain interference and pain intensity did not have a higher proportion mediated than the individual pain intensity models except for fatigue outcome models.

Conclusion
Pain intensity appeared to be the mechanism by which much of the change in biopsychosocial factors occurred and should be considered a key clinical indicator for improvement in biopsychosocial health when chiropractic care is added to usual medical care for US active-duty military members.

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Novembre 2024

Effects of low-dose aspirin in bipolar disorder: study protocol for a randomised controlled trial (the A-Bipolar RCT)

Introduction
Accumulating data support the association between increased inflammation and bipolar disorder (BD), and preliminary data suggest that augmentation with low-dose aspirin (LDA) may protect against the onset and deterioration of BD via anti-inflammatory pathways. The A-bipolar randomised controlled trial (RCT) aims to investigate whether adding LDA to standard treatment improves day-to-day mood instability (MI) in BD.

Methods and analysis
A two-arm, triple-blind, parallel-group, superiority RCT including 250 patients with newly diagnosed BD treated at the Copenhagen Affective Disorder Clinic, Denmark. Participants are randomised 1:1 to either 150 mg of acetylsalicylic acid daily (LDA) or a placebo for six months in addition to their regular treatment. Mood instability, calculated from daily smartphone-based mood evaluations, is the primary outcome measure due to its internal validity as a real-life measure for patients and external validity as it reflects patients’ illness severity and functioning. Analyses will be conducted as intention-to-treat analyses using a linear mixed model including time (categorical) and the time–treatment interaction as fixed effects and with an unstructured covariance pattern to account for repeated measurements on each study participant. The trial is Good Clinical Practice monitored.

Ethics and dissemination
The Danish Research Ethics Committee (H-21014515) and the data agency, Capital Region of Copenhagen (P-2021-576) approved the trial. Results will be published in peer-reviewed journals.

Trial registration number
NCT05035316.

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Novembre 2024

Inappropriate antibiotic prescription for acute tonsillitis in low- and middle-income countries (LMICs): a systematic review and meta-analysis protocol

Introduction
Tonsillitis is a self-limiting inflammatory process of the tonsils. In high-income countries, guidelines have been developed to decide if a patient needs an antibiotic or not. These guidelines help to reduce unnecessary antibiotic prescriptions and prevent the development of antimicrobial resistance (AMR). In low- and middle-income countries (LMICs), medical practitioners have the tendency to prescribe antibiotics in all cases of tonsillitis; there is an overprescription of antibiotics. These prescriptions are probably unjustified and seem to be responsible for the increased AMR seen in developing countries. The aim of this review will be to estimate the proportion of unjustified antibiotic prescriptions in LMICs.

Methods and analysis
We will conduct a systematic review of all observational studies on the diagnosis and treatment of tonsillitis in LMICs. The selected database will include PubMed, Web of Sciences Global Index Medicus and the Grey literature. The search will include studies published from January 2012 until December 2024. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and bias will be assessed by a Risk of Bias Assessment Tool for observational studies by Hoy et al. A meta-analysis will be conducted for homogeneous studies, eventually using the random effect model. Subgroup analysis will include a period of study, study quality, countries and/or subregions of LMICs involved, study setting, age of participants, tools and definition used.

Ethics and dissemination
Formal ethical approval is not required, as primary data will not be collected. The results will be disseminated through peer-reviewed publications and presented at scientific conferences.

PROSPERO registration number
CRD 42022384957

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Novembre 2024

Rivaroxaban for 18 Months Versus 6 Months in Patients With Cancer and Acute Low-Risk Pulmonary Embolism: An Open-Label, Multicenter, Randomized Clinical Trial (ONCO PE Trial)

Circulation, Ahead of Print. Background: The optimal duration of anticoagulation therapy for patients with cancer and acute low-risk pulmonary embolism (PE) is clinically relevant, but evidence is lacking. Prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding.Methods: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 32 institutions in Japan, we randomly assigned patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, in a 1:1 ratio, to receive either an 18-month or a 6-month rivaroxaban treatment. The primary end point was recurrent venous thromboembolism (VTE) at 18 months. The major secondary end point was major bleeding at 18 months according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that an 18-month treatment was superior to a 6-month treatment in terms of the primary end point.Results: From February 2021 to March 2023, 179 patients were randomized, and after the exclusion of one patient who withdrew consent, 178 were included in the intention-to-treat population: 89 patients in the 18-month rivaroxaban group and 89 in the 6-month rivaroxaban group. The mean age was 65.7 years; 47% of the patients were men, and 12% had symptoms of PE at baseline. The primary end point of recurrent VTE occurred in 5 of the 89 patients (5.6%) in the 18-month rivaroxaban group and in 17 of the 89 (19.1%) in the 6-month rivaroxaban group (odds ratio, 0.25 [95% CI, 0.09–0.72];P=0.01). Among 22 recurrent VTE, 5 patients presented with a symptomatic recurrent VTE; recurrent PE occurred in 11 patients, including 2 with main and 4 with lobar PEs; and recurrent deep vein thrombosis was seen in 11 patients, including 3 with proximal deep vein thromboses. The major secondary end point of major bleeding occurred in 7 of the 89 patients (7.8 %) in the 18-month rivaroxaban group and in 5 of the 89 patients (5.6%) in the 6-month rivaroxaban group (odds ratio, 1.43 [95% CI, 0.44–4.70];P=0.55).Conclusions: In patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, the 18-month rivaroxaban treatment was superior to the 6-month rivaroxaban treatment with respect to recurrent VTE events.

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Novembre 2024

Pain during prolonged sitting in subjects with patellofemoral pain in Dutch physical therapy clinics: an online questionnaire-based analysis

Objectives
This study aimed to describe (1) differences between subjects with patellofemoral pain (PFP) with and without pain during prolonged sitting (PDPS), (2) minimum knee flexion angle and time to onset/disappearance of PDPS and (3) differences between those with PDPS at smaller/greater flexion angles and with fast/slow onset and disappearance of PDPS.

Design
Patient-reported online questionnaire.

Setting
Private physical therapy clinics in the Netherlands between May 2021 and March 2023.

Participants
87 participants (61 (70%) females, mean age 22.0 years (IQR 4.0), body mass index 23.1 (4.7)).

Outcome measures
Visual Analogue Scale for worst pain (VAS-W) and sitting pain (VAS-W sitting), the Anterior Knee Pain Scale (AKPS), knee flexion angle to provoke PDPS and time to onset/disappearance of PDPS.

Results
63 of 87 (72%) participants reported PDPS. Participants with PDPS experienced bilateral symptoms of PFP more frequently (71% vs 46%, p=0.44) and scored 12 points lower on the AKPS (p

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Novembre 2024

Uses of private health provider data for governance in low-income and middle-income countries: results from a scoping review

This work grew from an interest in understanding how private data are used for health system governance in low-income and middle-income countries (LMICs).
Objective
We conducted a scoping review to understand how the public sector collects routine data from the private health sector and uses it for governance purposes. The private health sector was defined to include both formal and informal, for-profit or non-profit, actors delivering healthcare services.

Findings
We identified 4014 individual English language studies published between 2010 and 2021. We reviewed titles and abstracts of all, with 50% reviewed by two authors to ensure a common application of inclusion criteria. 89 studies were selected for review in full; following this, 26 articles were included in the final selection as they directly report on the use of routine private sector data for governance in LMICs. Only English language studies were included, limiting the scope of possible conclusions.

Results
Data were most commonly collected by the Ministry of Health or a subministerial office, with extraction from District Health Information System 2 specifically cited for three studies. 16 studies collected data on infrastructure and distribution, 15 on service delivery, 12 on health financing, 7 on pharmaceuticals and other consumables, 4 on health workforce, 4 on quality of care and 4 on epidemic surveillance.

Conclusion
The studies identified provide examples of the public sector’s capacity to collect and use data routinely collected from the private sector to perform essential governance functions. The paucity of studies identified is an indication that more attention is needed to ensure that this key area of health system governance is undertaken and that lessons learnt are shared. This review provides insights to understanding private sector health data collection and use for governance in LMICs, and for guiding activities to assess and improve this according to country context and capacity.

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Novembre 2024

Intracytoplasmic sperm injection compared with in vitro fertilisation in patients with non-male factor infertility with low oocyte retrieval: a single-centre, retrospective cohort study

Objective
To investigate the effects of in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) on the clinical outcomes of non-male factor patients aged >35 with three or fewer oocytes retrieved.

Design
Retrospective cohort study.

Setting
Reproductive centre of a university-affiliated hospital in China.

Participants
547 women with non-male factor infertility who underwent assisted reproductive technology (ART) treatment with three or fewer oocytes retrieved were identified from June 2019 to May 2022. Of these 547 patients, 334 were treated with IVF and 213 with ICSI.

Outcome measures
The primary outcomes were normal fertilisation rate, live birth rate per transfer and cumulative live birth rate per retrieval.

Results
The baseline characteristics were comparable between the two groups, except for the proportion of primary infertility, which was higher in the ICSI group (17.66% vs 32.86%, p=0.000). Compared with the IVF group, the ICSI group showed higher normal fertilisation rate and lower cycle cancellation rate (65.99% vs 76.56%, p=0.002; 33.53% vs 24.41%, p=0.023). However, no significant differences were found in clinical pregnancy rate per transfer (23.86% vs 18.92%, p=0.545), miscarriage rate per fresh embryo transfer (19.05% vs 28.57%, p=0.595), live birth rate per transfer (17.05% vs 13.51%, p=0.623), cumulative clinical pregnancy rate per retrieval (12.87% vs 11.27%, p=0.576) and cumulative live birth rate per retrieval (9.28% vs 6.57%, p=0.261) between the two groups (p >0.05).

Conclusions
In non-male factor ART cycles, ICSI was not associated with improved pregnancy outcomes in older women with a low number of oocytes retrieved. Routine use of ICSI is not recommended in older women who are infertile due to non-male factors.

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Novembre 2024

Coping with cancer pain: a qualitative study to explore pain perception and self-coping strategies of patients with cancer in Sri Lanka

Pain is one of the most debilitating symptoms of cancer, substantially diminishing one’s quality of life. The level of pain experienced is eventually determined by the pain coping strategies adopted by patients individually. The awareness of the ‘self-coping methods of pain’ of individual patients would be beneficial for the multidisciplinary pain team to consider such methods when planning future interventions to manage pain.
Objectives
This study explores the pain perception and coping strategies used by patients with cancer pain in Sri Lanka.

Design
A descriptive qualitative study.

Setting
Pain management unit, Apeksha Hospital, Maharagama, Sri Lanka.

Participants
The study was conducted among purposively selected patients with cancer and registered at the pain management unit. 21 semi-structured interviews were conducted until data saturation. Data were analysed using Graneheim and Lundman’s content analysis method.

Results
Most participants were between 51 and 60 years old and identified as Sinhalese Buddhists. The study’s findings revealed two subthemes under ‘Understanding pain’, namely ‘Physical and emotional impact’ and ‘Cultural and spiritual interpretations’, and five subthemes under ‘Coping strategies for living with pain’, namely ‘Medication and self-control’, ‘Seeking spiritual support’, ‘Receiving social support’, ‘Exploring alternative treatments’ and ‘Adapting daily life’.

Conclusion
Coping strategies were adopted especially in achieving essential life aspirations and participating in preferred activities. Goals or activities were often adjusted to fall within their health limits. Acceptance and progress in life were considered more important than pain control. We recommend giving due consideration to the ‘self-coping strategies’ of individual patients in designing interventions to mitigate cancer pain.

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Novembre 2024

Pain control post total knee replacement in patients given local infiltrative analgesia combined with adductor canal block compared to either modality alone: a systematic review and meta-analysis

Objectives
Optimising postoperative pain following knee replacement is important for patients, healthcare professionals and healthcare funders. Adductor canal blocks (ACB) are widely used but there is uncertainty about their efficacy when combined with local infiltration analgesia (LIA) compared with either LIA or ACB alone.

Design
A systematic review and meta-analyses of randomised controlled. The primary outcome was pain over the first 72 hours. Secondary outcomes included morphine use, range of movement, distance walked, length of hospital stay, health economic outcomes and reported adverse events.

Data sources
MEDLINE, Embase, EB Health – KSR Evidence, Cochrane Central Register of Controlled Trials, CINAHL, International HTA database, ClinicalTrials.gov and the International Clinical Trials Registry Platform (WHO) were searched up to June 2023.

Eligibility criteria
Randomised controlled trials involving patients undergoing primary total knee replacement comparing LIA combined with ACB to either LIA or ACB alone.

Data extraction and synthesis
All eligible studies were data extracted independently by two reviewers. Studies were pooled for each outcome at each timepoint in a random effects meta-analysis.

Results
We identified 13 completed studies including 1154 participants. 12 studies compared LIA vs combination and 5 compared ACB vs combination. We identified that participants receiving the combination had lower pain scores at rest at 24 hours compared with LIA alone (SMD 0.42, 95% CI 0.20 to 0.64) or ACB alone (SMD 0.63, 95% CI 0.42 to 0.83). Pain on movement at 24 hours was also lower for patients with combination vs LIA alone (SMD 0.37, 95% CI 0.01 to 0.73) or ACB alone (SMD 0.81, 95% CI 0.35 to 1.26). We also identified that patients on combination used less morphine than on LIA alone (MD 1.06, 95% CI –0.09 to 2.20) or ACB alone (MD 5.94, 95% CI –2.41 to 14.29). The same was seen with range of motion at 24 hours with combination having a larger improvement than LIA alone (MD –5.19, 95% CI –5.55 to –4.83) or ACB alone (MD –3.80, 95% CI –4.37 to –3.23). These findings were consistent across all time points; however, there were no studies deemed to be at a low risk of bias.

Conclusions
Further well-designed and conducted randomised controlled trials are needed to confirm if a combination of LIA and ACB is superior to either option alone for patients undergoing primary total knee arthroplasty.

PROSPERO registration number
CRD42023436895.

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Novembre 2024

Abstract 4123637: Prevalence of Invasively Diagnosed Coronary Endothelial Dysfunction in Patients with Chest Pain and Normal Coronary Flow Reserve: The Systematically Missed Diagnosis on Non-invasive Testing

Circulation, Volume 150, Issue Suppl_1, Page A4123637-A4123637, November 12, 2024. Background:Invasive coronary reactivity testing (CRT) is the gold standard for comprehensive assessment of coronary endothelial and microvascular dysfunction in patients with angina and non-obstructive CAD (ANOCA). Non-invasive imaging modalities (PET and CMR) have emerged as potential alternatives. However, due to the inability to systemically administer acetylcholine, patients with normal coronary flow reserve (CFR) but abnormal endothelial function on invasive Ach testing are systemically missed on non-invasive testing. We aimed to assess the prevalence of coronary endothelial dysfunction in ANOCA patients with normal CFR.Methods:Consecutive patients undergoing CRT at our institution were included. Those with normal adenosine-based CFR ( >2.5), were further stratified as having normal coronary endothelial function (NEF, 50% increase in coronary blood flow in response to ACh) vs abnormal endothelial function (AEF, >20% epicardial coronary diameter constriction and/or

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Novembre 2024

Abstract 4145822: The Enigma of Chest Pain: Rare Presentation of ALCAPA Syndrome in a Young Adult

Circulation, Volume 150, Issue Suppl_1, Page A4145822-A4145822, November 12, 2024. Introduction:Anomalous Left Coronary Artery Arising from the Pulmonary Artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital anomaly(incidence:1 in 300,000 live births) typically presenting during infancy. Adult presentations are even rarer due to a high mortality rate of nearly 90% in the first year of life without surgical intervention. This report examines an adult patient with exercise-induced chest pain who received a delayed diagnosis of ALCAPA via multimodal imaging.Case Summary:A 21-year-old male presented to the emergency department(ED) with severe retrosternal chest pain radiating to both shoulders and arms, which began during exercise 30 minutes prior. He had a history of similar, milder episodes during exercise, previously treated as musculoskeletal pain and gastroesophageal reflux disease in the ED. His medical, social, and family histories were unremarkable. Physical examination revealed a soft, continuous murmur along the left sternal border. During this visit, An EKG done showed sinus tachycardia at 110 bpm and deep T-wave inversions in the anterolateral leads, a dynamic ST-T changes from his baseline.Serial Cardiac biomarkers and a lipid profile were within normal ranges. Initially managed for acute coronary syndrome-unstable angina with antithrombotic therapy, beta-blockers, and nitrates, he underwent urgent coronary angiography. This revealed a dilated right coronary artery (RCA) with retrograde flow to the left coronary artery (LCA) into the main pulmonary artery (PA) via collaterals, with no evidence of atherosclerosis (Figure 1).Echocardiography (Figure 2) and coronary CT angiography (Figure 3) confirmed the diagnosis of ALCAPA. The patient underwent successful surgical repair with aortic reimplantation of the LCA and was discharged in good health.Discussion:In adult ALCAPA patients, good collateral circulation may develop; however, myocardial ischemia can occur due to the “coronary steal phenomenon” and poor collateral flow regulation, leading to angina, arrhythmias, and sudden cardiac death. ALCAPA should be considered a differential diagnosis in adults presenting with exercise intolerance, as most sudden cardiac death cases occur by the fourth decade. A high index of clinical suspicion and a multimodality imaging approach is essential for the early diagnosis of this rare coronary anomaly, underscoring the critical role of early surgical intervention in preventing catastrophic, life-threatening events.

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Novembre 2024

Abstract 4144554: Revascularization of Patients with Low-Density Non-Calcified Plaque was Associated with Lower Occurrence of Acute Coronary Syndrome

Circulation, Volume 150, Issue Suppl_1, Page A4144554-A4144554, November 12, 2024. INTRODUCTION:Coronary CT angiography (CCTA) is a powerful noninvasive tool for identifying high-risk plaque, such as low-density non-calcified plaque (LD-NCP). Though, the optimal treatment of patients with LD-NCP remains unclear. This study explored the association of revascularization in the setting of LD-NCP with the occurrence of acute coronary syndrome (ACS).Methods:This was a post-hoc analysis of the ICONIC study. A subset of 234 patients that underwent CCTA with subsequent ACS were matched to 234 control patients who also underwent CCTA but did not have ACS during follow-up. Patients were also followed for occurrence of revascularization, either coronary artery bypass graft or percutaneous coronary intervention. Atherosclerosis imaging-enabled quantitative CT (AI-QCT) was used to measure diameter stenosis, and LD-NCP, non-calcified plaque, and calcified plaque volumes from each CCTA. LD-NCP was defined as plaque with -190 to 30 Hounsfield Units. Patients were stratified based on the presence of LD-NCP. Subgroup analysis was conducted to compare the occurrence of ACS with the rate of revascularization. Kaplan-Meier survival curves and extended Cox regression analysis were used to evaluate the effect size of revascularization and LD-NCP on occurrence of ACS.Results:AI-QCT was completed in 448/468 subjects (follow-up time [MEAN±SD] 2.44±2.48 years). The median of LD-NCP was 1.2 mm3for patients with >0 mm3LD-NCP. There were 85 patients with LD-NCP >1.2 mm3and 363 patients with LD-NCP ≤1.2 mm3. In patients with LD-NCP >1.2 mm3, the rate of revascularization in patients with and without ACS was 3/52 (5.8%) versus 14/33 (42.4%) (p1.2 mm3and revascularization were less likely to have ACS during follow-up (adjusted HR: 0.20 [0.07, 0.61]; p=0.005). Additionally, patients with LD-NCP >1.2 mm3who did not undergo revascularization were more likely to have ACS (adjusted HR: 1.47 [1.03, 2.12]; p=0.036). Hazard ratios were adjusted for diameter stenosis, and non-calcified and calcified plaque volume. Time-dependent coefficients were included for diameter stenosis.Conclusion:Revascularization of patients with LD-NCP >1.2 mm3identified on CCTA with AI-QCT was associated with less risk for ACS.

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Novembre 2024