Clinical Guidelines Research Articles

Allergic Contact Dermatitis in Pediatric Practice.

Allergic contact dermatitis (ACD) is prevalent among pediatric population, adolescent and young adults. Patients with ACD experience a lot of sociopsychological and qualityof- life (QoL) difficulties. Children and their caregivers alike are vulnerable to the burden of ACD. We have, in this paper, provided an overview of ACD and discussed common and unusual causes of ACD. We performed an up-to-date literature review in the English language on "allergic contact dermatitis" via PubMed Clinical Queries, using the keywords "allergic contact dermatitis" in August 2022. The search included meta-analyses, randomized controlled trials, clinical trials, casecontrol studies, cohort studies, observational studies, clinical guidelines, case series, case reports, and reviews. The search was restricted to English literature and children. ACD may be acute or chronic and it affects more than 20% of children and adults with significant quality-of-life impairments. ACD is manifested by varying degrees of cutaneous edema, vesiculation, and erythema. The hypersensitivity reaction is one of the most prevalent forms of immunotoxicity in humans. Localized acute ACD lesions can be managed with high-potency topical steroids; if ACD is severe or extensive, systemic corticosteroid therapy is often required to provide relief within 24 hours. In patients with more severe dermatitis, oral prednisone should be tapered over 2-3 weeks. Rapid discontinuation of corticosteroids can result in rebound dermatitis. Patch testing should be performed if treatment fails and the specific allergen or diagnosis remains unknown. ACD is common and can be a physically, psychologically, and economically burdensome disease. Diagnosis of ACD is primarily based on history (exposure to an allergen) and physical examination (morphology and location of the eruption). Skin patch test can help determine the causative allergen. Allergen avoidance is the cornerstone of management. Topical mid- or highpotency corticosteroids are the mainstay of treatment for lesions on less than 20% of the body area. Severe cases of ACD may require treatment with systemic corticosteroids.

Respiratory Vaccination Rates in People Living With Spinal Cord Injury/Disorder in Switzerland: A Descriptive Analysis of Coverage and Vaccine Hesitancy.

The aim of the study is to provide a population-based evaluation of vaccination coverage to prevent respiratory complications from SARS-COV-2, influenza, and pneumococcus, among community-dwelling persons with spinal cord injury/disease. This is a cross-sectional survey conducted in 2022, utilizing questionnaires administered to persons with spinal cord injury/disease living in Switzerland. Main outcomes were ever-vaccination rates for SARS-COV-2, influenza, and pneumococcus. Secondary outcomes included demographics, lesion and education levels, as well as respiratory and cardiovascular conditions. Vaccine hesitancy was additionally assessed for all three vaccines in nonvaccinated persons through questions on reasons for not getting vaccinated. A total of 1158 persons participated in this survey. Overall vaccination rates were highest for SARS-COV-2 86.5% (95% CI = 84.4-88.3), followed by influenza 44.6 (41.7-47.6) and pneumococcus: 7.5% (6.0-9.3). The most prominent reasons for not being vaccinated were doubt on effectiveness (72.7%) and potential side effects (60%) for SARS-COV-2, patients did not feel at risk for influenza (57%) and insufficient information from the physician (52.4%) for pneumococcus vaccination. In individuals with spinal cord injury/disease, vaccination coverage is notably low for influenza and especially pneumococcus. Vaccine hesitancy varies between vaccination types and is associated with vaccine-specific reasons. These findings underscore the imperative for updated clinical vaccination guidelines, improved public health information, and targeted intervention programs for specific patient groups.

Effectiveness of immune checkpoint inhibitors and other treatment modalities in patients with advanced mucosal melanomas: a systematic review and individual patient data meta-analysis

Mucosal melanomas (MM) are an aggressive subtype of melanoma. Given the rarity of this disease, the conduct of clinical trials is challenging and has been limited. Current treatment options have been extrapolated from the more common cutaneous melanoma even though MM is distinct in pathogenesis, etiology and prognosis. This is the first meta-analysis to comprehensively assess the efficacy of immune checkpoint inhibitors (anti-PD1 and anti-CTLA4) and other treatment modalities (targeted therapy such as KIT inhibitors and VEGF inhibitors, as well as radiotherapy) on survival outcomes in MM to develop clinical guidelines for evidence-based management. The protocol was prospectively registered on PROSPERO (PROSPERO ID: CRD42023411195). PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Google Scholar were searched from inception until 25 July 2024, for all cohort and observational studies. Eligible studies included those with five or more participants with locally advanced or metastatic MM treated with anti-PD1, anti-CTLA4, VEGF inhibitors and/or KIT inhibitors. Titles and abstracts of potential articles were screened and full texts of all potentially eligible studies were retrieved and reviewed by two independent reviewers. Individual patient data (IPD) from published Kaplan-Meier curves were reconstructed using a graphical reconstruction method and pooled as a one-stage meta-analysis. A sensitivity analysis using a two-stage meta-analysis approach was conducted. Extracted outcomes included overall survival (OS) and progression-free survival (PFS). For each treatment arm, median survival time and 12-month survival proportion were estimated. Data from double-arm trials was pooled to estimate hazard ratios (HRs), ratios of restricted mean time lost (RMTL) and restricted mean survival time (RMST). From a total of 7402 studies, 35 eligible studies comprising a total of 2833 participants were included. Combined anti-PD1 and anti-CTLA4 therapy had the highest 12-month OS and 12-month PFS at 71.8% (95% CI: 67.6%, 76.2%, n=476) and 35.1% (95% CI: 30.5%, 40.4%, n=401) respectively, followed by anti-PD1 therapy alone (OS: 64.0% (95% CI: 61.4%, 66.7%, n=1399); PFS: was 28.3% (95% CI: 25.8%, 31.2%, n=1142), anti-PD1 and VEGF inhibitor combination therapy (OS: 57.1% (95% CI: 51.0%, 63.9%)), KIT inhibitors (OS: 48.2% (95% CI: 37.6%, 61.8%); PFS: 8.3% (95% CI: 3.7%, 18.7%)) and anti-CTLA4 therapy alone (OS: 33.3% (95% CI: 28.4%, 39.1%); PFS: 9.8% (95% CI: 5.9%, 16.5%)). In the double-arm studies, combination therapy with anti-PD1 and anti-CTLA4 had similar OS and PFS with anti-PD1 alone (OS: HR 0.856 (95% CI: 0.704, 1.04); RMTL ratio 0.932 (95% CI: 0.832, 1.044, P=0.225); RMST ratio 1.102 (95% CI: 0.948, 1.281, P=0.204); PFS: HR 0.919 (95% CI: 0.788, 1.07); RMTL ratio 0.936 (95% CI: 0.866, 1.013, P=0.100); RMST ratio 1.21 (95% CI: 0.979, 1.496, P=0.078)), however, anti-PD1 therapy alone had significantly better PFS than anti-CTLA4 alone (HR 0.548 (95% CI: 0.376, 0.799); RMTL ratio 0.715 (95% CI: 0.606, 0.844, P<0.001); RMST ratio 1.659 (95% CI: 1.316, 2.092, P<0.001)). Anti-PD1 therapy with radiotherapy versus anti-PD1 alone showed no significant difference (OS: HR 0.854 (95% CI: 0.567, 1.29); RMTL ratio 0.855 (95% CI: 0.675, 1.083, P=0.193); RMST ratio 1.194 (95% CI: 0.928, 1.536, P=0.168; PFS: HR 0.994 (95% CI: 0.710, 1.39); RMTL ratio 1.006 (95% CI: 0.87, 1.162, P=0.939); RMST ratio 0.984 (95% CI: 0.658, 1.472, P=0.939)). For the systemic treatment of MM, anti-PD1 is the best monotherapy. While combining anti-PD1 with other treatment options such as anti-CTLA4, VEGF inhibitors or radiotherapy might achieve better outcomes, these improvements did not reach statistical significance when evaluated by HR, RMTL and RMST ratios. This work was supported by theNational Medical Research CouncilTransition Award (TA20nov-0020),SingHealthDuke-NUSOncology Academic Clinical Programme (08/FY2020/EX/67-A143 and 08/FY2021/EX/17-A47), the Khoo Pilot Collaborative Award (Duke-NUS-KP(Coll)/2022/0020A), theNational Medical Research CouncilClinician Scientist-Individual Research Grant-New Investigator Grant (CNIGnov-0025), the Terry Fox Grant (I1056) and the Khoo Bridge Funding Award (Duke-NUS-KBrFA/2024/0083I).

Behavioral Nudges to Encourage Appropriate Antimicrobial Use Among Health Professionals in Uganda

Background/Objectives: Antimicrobial resistance (AMR) is a global public health concern exacerbated by inappropriate antimicrobial prescribing practices, particularly in low-resource settings such as Uganda. The research aimed to develop a culturally sensitive behavioral intervention, leveraging a “nudge” strategy, to improve healthcare provider adherence to the 2016 Uganda Clinical Guidelines (UCG 2016) in five Ugandan hospitals. This intervention formed part of broader antimicrobial stewardship initiatives led by the United States Agency for International Development Medicines, Technologies, and Pharmaceutical Services Program. Methods: This study employed a mixed-methods approach, combining formative research and behavioral intervention. Guided by the Deloitte Behavioral Insights Framework, the research team conducted key informant interviews to identify prescribing barriers and motivators and developed three suitable behavioral interventions: perceived monitoring, ward leaderboards, and educational workshops. The study evaluated the interventions’ impact through point prevalence surveys (PPS), using the World Health Organization PPS methodology at three stages: pre-intervention, immediate post-intervention, and one-month post-intervention. Results: Key behavioral themes across individual, social, environmental, and organizational elements informed the intervention design and implementation. The behavioral intervention package increased antimicrobial prescription compliance with the UCG 2016 from 27% at baseline to 50% immediately post-intervention, though these effects diminished at one-month post-intervention. Conclusions: Our study addresses an existing gap in behavioral nudges-based operational research on antimicrobial prescribing in low- and middle-income countries. These results showed an immediate improvement in adherence to the UCG 2016 among healthcare providers in Ugandan hospitals, though the effect was attenuated at one-month follow-up. Despite the attenuation, behavior change presents a feasible, cost-effective, and sustainable approach to improving antimicrobial prescribing practices and addressing AMR.

Challenges to Implementing Clinical Guidelines for Preparticipation Physical Evaluations in Youth Sports.

Challenges to Implementing Clinical Guidelines for Preparticipation Physical Evaluations in Youth Sports.

Correlative study to assess the predictive power of the ICOS HF calculator in the prediction of development of HER-2 antagonist induced cardiac dysfunction in a single center in Saudi Arabia in 2023

Abstract Background Over the past 3 decades, there has been a significant increase in cancer survivors supported by the major advances in cancer therapies. However, most of those therapies are cardio-toxic. In 2022, the European Society of cardiology had published, for the first time, a clinical guideline that describes how to manage this cohort of patients, and endorsed the utilization of a risk calculator to predictor likelihood of development of cancer therapy cardiac dysfunction (CRTCD). We did retrospective review of all consecutive patients that have received Trstuzumab (HER-2 antagonist) in the year 2023 in a single tertiary cardiac center. We assessed their demographics and co-morbidities, incidence of CRTCD, evaluated their ICOS-HF score and looked for any CRTCD in this cohort to assess whether the calculated stratification correlated with development of CRTCD. The objective is to assess the utilization of this tool in our patient population. Methods 369 unique individuals were identified from the hospital databas that had received HER-2 antagonists. Basic patient demographics were extracted from the information system along with their clinical, laboratory, and echocardiographic data. Their risk profiles were stratified using the ICOS-HF calculator. Follow up echocardiogrphic studies were reviewed to assess the incidence of CRTCD in patients receiving HER-2 antagonists and the correlation between the risk strata using the ICOS-HF and actual development of CRTCD. Results The average age was 53+/- 11 years. 96.8% were females. At baseline, 20% were diabetic, 26.8% were hypertensive, 10.8% were dyslipidemic, 1.9% had prior cardiomyopathy or heart failure, 1.3% had IHD, 1.1% were smoker, 33.3% were obese, and 3.8% had CKD. Overall, in the year 2023, the incidence of HER-2 induced cardiac dysfunction was 10.6%. At baseline, using the ICOS-HF calculator, 57.9% were stratified as low risk, 21% as moderate risk 14.6% as high risk, and 6.5% as very high risk. Approximately 5% of the patients with low to moderate risk developed CRTCD, which rose to 18.5% in the high risk, and significantly rose to 58% in the very high risk population. Conclusion The risk stratification using the ICOS-HF calculator in consecutive patients receiving Trastuzumab correlated directly with the likelihood of developing CRTCD. 58% of all of the patients in the very high risk category developed CRTCD. This retrospective analysis validates the use of this tool in our patient population and will aid in the identification of patients that would require to have a more aggressive preemptive management, especially in the high and very high risk population using a multidisciplinary cardio-oncology team to optimize their surveillance and reduce their likelihood of cardiac dysfunction.

Aortic valve replacement and mortality with left ventricular hypertrophy in setting of normal LVEF

Abstract Background Without symptoms, indications for aortic valve replacement (AVR) in severe aortic stenosis (AS) differ for individuals with normal vs. low/decreasing left ventricular ejection fraction (LVEF). Conceptually, the development of left ventricular hypertrophy (LVH) could also indicate ventricular injury and potential benefit with earlier AVR. However, little is known about the comparative effectiveness of AVR in individuals with LVH. As such, unlike low or dropping LVEF, development of LVH is not in itself an indication for AVR in clinical guidelines. Methods Initially, 1,232,492 echocardiography reports from 12 hospitals were identified from 1 January 2000 to 22 November 2022, and previously validated natural language processing modules were then applied to identify aortic gradients, LVEF, and presence of LVH. These reports were linked to mortality data, key comorbidities with a 2-year lookback covariate window, and date of any AVR. We then isolated echocardiograms demonstrating normal flow severe AS, LVEF ≥ 55% and LVH. Chart reviews were conducted to reduce missing data and outcomes were censored on the date of the chart review (October 4, 2023). To assess the association between AVR and mortality, Cox proportional hazards models considering treatment status (ie, AVR or not) were used with the index echocardiogram as time zero. Covariates used in risk-adjustment were chosen a priori based on conditions and laboratory values used in cardiac surgery mortality risk-adjustment, since those variables could plausibly confound the treatment decision. To address immortal time bias, AVR was considered a time-varying covariate. Multiple additional approaches with propensity scores were performed as sensitivity analyses. Results After application of inclusion and exclusion criteria, 4856 unique patients remained for analysis. Of those, 2043 (42.1%) received AVR with 841/2043 (41.2%) receiving surgical AVR and 1202/2043 (58.8%) receiving transcatheter AVR. Patients who received AVR had lower unadjusted mortality than those who did not receive AVR (33.6% vs. 47.1%, p &amp;lt; 0.001). After adjustment, and accounting for time-dependence of AVR, AVR was associated with reduced mortality (HR 0.81, 95% CI 0.73-0.89, p &amp;lt; 0.0001). The sensitivity analyses were all consistent with the primary analysis. Conclusions AVR was associated with reduced mortality for patients with severe AS, preserved LVEF, and LVH. This association persisted even after accounting for time-dependence, which tends to reduce the observed effectiveness of procedures in observational data. With over a million echocardiograms over more than 20 years, this is the largest known analysis of AVR outcomes in individuals with severe AS and LVH. Our findings suggest LVH may be a high-risk phenotype of individuals with AS, similar to dropping LVEF. As such, these results raise the potential of more proactive AVR clinical guidelines in individuals with LVH, even when LVEF is normal.Survival in AVR Vs No AVR

Characteristics of fatal COVID-19 among pregnant women admitted to hospitals in Kazakhstan

Abstract Background The factors contributing to the fatal outcome of COVID-19 in pregnant women remain not entirely clear. We compared the prevalence rates of comorbidities and laboratory test results in pregnant survivors and non-survivors. Methods This retrospective study relied on clinical and laboratory data obtained from medical records of pregnant women with COVID-19 admitted to three hospitals of the Republic of Kazakhstan from 16.07.2021 to 31.01.2022. Overall, we obtained data on 157 pregnant women with COVID-19, of whom 95.9 % survived and 4.1 % died in the hospitals. Results Arterial hypertension was present in 50% of non-survivors vs. 7.9% of survivors (P = 0.001), diabetes mellitus was diagnosed in 16.7% of non-survivors vs. 2.3% of survivors (P = 0.044), and the rate of hyperglycemia was 40% and 7.2%, respectively (P = 0.009). Heart rhythm disturbance was present in 50% of non-survivors vs. 6.4% of survivors (P &amp;lt; 0.001), and already at the time of admission to the hospital, the non-survivors had significantly higher heart and respiratory rates. Laboratory tests showed that non-survivors had higher erythrocytes sedimentation rate, C-reactive protein, leukocyte count, and D-dimer levels (P = 0.001, P &amp;lt; 0.001, P = 0.038, P = 0.014, respectively). The creatinine level was within the normal range in both study groups, but it was relatively higher in the deceased pregnant women (71.3; IQR: 66-251.75) vs. 52; IQR: 43-63; P = 0.001). Finally, a higher proportion of those who died presented with abnormal chest CT as compared with the survivors (33.3% vs. 4.2%, P &amp;lt; 0.001). Conclusions The deceased had a higher rate of comorbidities. Given the vulnerability of pregnant women to COVID-19, it is essential to plan a prospective study to provide insights into the factors that contribute to severe COVID-19 outcomes in pregnant women. Key messages • Determining risk factors for fatal COVID-19 is crucial for effective medical care of pregnant women. • Identifying potential risk factors of fatal COVID-19 among pregnant women could help inform public health policies and clinical guidelines.

Comorbidity neural network model for personalised recommendations in cardiometabolic risk factor management: towards early precision medicine in routine clinical practice

Abstract Background and Aims Hypertension and hypercholesterolaemia often develop in tandem to confer a risk of cardiovascular disease that may be more than additive. The present study explored early comorbid therapeutic intervention, i.e., beyond individual disease silos, while minimising data bias to provide clinical decision support tools that are portable across clinics. Methods A neural network was created to reproduce UK national clinical guidelines with an accuracy higher than 95%. Relying on real-world evidence from the UK primary care Clinical Practice Research Datalink electronic health record resource, a transfer learning methodology was then applied to achieve recommended risk factor goal attainment after two years. Shapley values derived from game theory were used to define similar digital twin cohorts, and to evaluate individualised recommendations that deviated from national clinical guidelines by rejecting a no-benefit hypothesis retrospectively in a classical proportion test. The methodology was ported to an independent hold-out dataset with anonymized records from six primary care clinics in the South of England. Results The adult patient population (n=469,496, mean+SD age 61+11yr; M 56% vs F 44%; primary 84% vs secondary prevention 16%) included 101,255 diagnosed for hypertension and 112,180 for cholesterol management. While a majority of the 52,504 therapeutic decisions in a test set agree with single morbidity guidelines, for 4639 deviations from the guidance, a significant minority was identified for whom alternative therapy was recommended. Rejecting a no-clinical benefit hypothesis at the 95% confidence level in a retrospective analysis, 1367 decisions showed statistically significant better outcomes over guidelines, for example by escalating anti-hypertensive therapies for patients receiving statin therapy (1085) or by complementing anti-hypertensive therapy with a statin (158). Similar findings were obtained when tested in a hold-out dataset with 13,725 decisions for 6531 patients. Conclusions The results support the contention that machine learning can identify patient subgroups for whom comorbid intervention deviating from clinical guidelines may be appropriate. A novel aspect of the study is the demonstration of clinically portable and actionable application of machine learning in the context of comorbid cardiometabolic diseases. The results represent practical steps towards personalised precision medicine for cardiovascular comorbidity in routine clinical practice.

Sub-Saharan Africa's contribution to clinical trials in international acute coronary syndromes and heart failure guidelines

Abstract Introduction There is a growing burden of acute coronary syndrome (ACS) and heart failure (HF) in sub-Saharan Africa (SSA), yet outcomes remain poor compared to high-income countries (HICs). Global clinical guidelines are pivotal to the delivery of evidence based cardiovascular care, however their applicability to populations in SSA remains unclear. Purpose To evaluate the extent to which populations from SSA contribute to pharmacotherapeutic randomised clinical trials informing international ACS and HF clinical guidelines. Methods We extracted details on pharmacotherapeutic randomised control trials (RCTs) contributing to Class I or II guideline recommendations from the 2023 European Society of Cardiology (ESC) guidelines for ACS and the 2021 ESC guidelines for HF. Data on RCTs contributing to these guidelines were extracted from the ClinicalTrials.gov or published articles. We analysed the proportion of RCTs which had a contribution from countries in each World Bank income group. Then we specifically assessed the contribution of SSA countries to clinical trials and analysed temporal trends. Results Of 119 RCTs from the ESC HF guidelines and the 343 pharmacotherapy RCTs from the ESC ASC guidelines 75.9% were exclusively conducted in high-income countries, 22.2% of the trials included at least one site from a middle-income country and none included sites from a low-income country (figure 1). The global distribution of HF (figure 2a) and ACS (figure 2b) pharmacotherapy guidelines is demonstrated in figure 2. The only country represented from SSA was South Africa which is an upper middle-income country. A site from South Africa was included in 17 (14.2%) HF RCTs and 28 (8.2%) ACS RCTs. There has been a significant increase in the proportion HF RCTs conducted in SSA, increasing from 2.6% between 1990 and 1999 to 50% since 2020 (OR 28.8, 95% CI 2.6 – 983.4, p-value for trend&amp;lt; 0.0001). For ACS RCTs, the proportion of trials conducted in SSA increased from 1.8% pre 1990 to 23.4% during 2000-2009 (OR 15.9, 95% CI 4.2 - 112.9, p value for trend = 0.003) then declined to 11.3% from 2010-2019. Conclusions There is a marked under-representation of SSA countries in ACS and HF pharmacotherapy RCTs, despite the region's escalating cardiovascular disease burden. South Africa is the sole contributor from the region, with all other SSA countries absent. This finding could potentially affect the applicability and generalisability of global guidelines to populations in SSA with distinct clinical presentations and healthcare challenges.Figure 1 Figure 2

Development and implementation of a guideline-based decision support system for etiological diagnosis of Sustained Monomorphic Ventricular Tachycardia (SMVT)

Abstract Background Guideline (GL)-based decision support systems (DSSs) play a significant role in supporting physicians in their decision-making processes by providing structured clinical guidance. While these systems have shown significant success in enhancing practitioner performance and patient outcomes in general practice, their application in the context of ventricular arrhythmias remains limited. Moreover, the clinical etiological diagnosis of ventricular arrhythmias presents various challenges for healthcare professionals, such as adherence to updated diagnostic criteria and understanding of complex arrhythmia mechanisms. Purpose In this study, we aim to design, implement, and evaluate a guideline-based decision support systems for etiological diagnosis of sustained monomorphic ventricular tachycardia (SMVT), which could potentially address critical challenges associated with the disease diagnosis and management. Methods To comprehensively capture the semantics embedded in clinical guidelines, we first developed a dedicated knowledge graph tailored to the clinical decision-making. This involved extracting entities and relationships pertinent to key decision procedures from ESC guidelines for ventricular arrhythmias, clinical textbooks or literatures. Subsequently, we translated instances within the knowledge graph into archetypes within openEHR, amplifying the interoperability of clinical information. To enhance the interpretability of the DSS, we established executable diagnostic and treatment processes to offer visual representation of clinical steps in diagnosis and treatment. Ultimately, we constructed a decision support engine to implement the GL-DSS, and its effectiveness was evaluated with anonymous real-world data. Results The proposed GL-DSS was found to be quite feasible and could provide etiological diagnosis for SMVT. The knowledge base for the constructed GL-DDS included more than 2000 entities and relations, which played a vital role in representing disease pathogenesis. The proposed system can map the clinical entities to a set of openEHR archetypes, thus mitigate the interoperability issues of the hospital information systems and CDSS data integration. Also, this module improved system usability and ensured that guidelines could be easily translated and updated into decision support tools. Real-word medical records from 20 patient were collected for model evaluation, the results showed that the GL-DSS covered most of the entities and relations between diseases and diagnostic evidence recorded in clinical texts and achieved a diagnosis accuracy of 80%. Conclusions The results demonstrated that our proposed GL-DSS could completely and accurately capture the diagnostic information under the concrete EHR data. Thus, the implement decision support system could have the potential to improve clinical decision-making, patient care, and outcomes in this specialized medical domain.

Seeing and believing: behavioural insights from implementing an artificial intelligence-enabled stethoscope in primary care

Abstract Background • Early detection and treatment of cardiovascular disease (CVD) improves survival, quality of life and health economic outcomes (1) • Despite evidence of effectiveness, health systems fail to implement technologies for early detection of CVD sustainably, limiting their public health impact (2). This challenge may limit the full potential of artificial intelligence (AI) in healthcare (3). • An AI-enabled stethoscope can detect reduced left ventricular ejection fraction (LVEF), atrial fibrillation (AF) and structural cardiac murmurs during fifteen seconds of conventional cardiac examination (4) • The determinants of uptake, sustained use and clinical impact of implementing the AI-stethoscope in primary care are unknown. Purpose • To implement the AI-stethoscope in a UK primary care system • To measure rates of utilisation and their association with potential disease detection • To characterise the adoption patterns of an AI technology in primary care Methods • TRICORDER is a cluster randomised controlled trial and implementation study. • Clinicians in the intervention arm receive in-person training in use of the AI-stethoscope and are remunerated for this training time. • Clinicians using the AI-stethoscope in routine care are supported by a clinical guideline and data privacy approvals from the regional health service executive board. • GP practices are not remunerated for using the AI-stethoscope • Anonymised utilisation and AI disease detection rates were extracted from the manufacturer’s cloud database from 31st October 2023 to 25th February 2024. We performed linear regression to characterise use over time. Results • 59 practices were randomised and onboarded to the intervention arm between 31st October and 3rd December 2023, all using the stethoscope at least once, for a total of 1,555 unique patient examinations (3,253 total recordings), over a median of 90 days. • The mean (±SD) number of recordings per practice per week was 5.45 (±5.68). • There were 32 practices with utilisation data for at least 12 weeks. There was a weakly positive utilisation trend (r = 0.042; P= &amp;gt;0.05, Figure 1A), with no significant difference in rates of utilisation at 4, 8 and 12 weeks (Figure 1B). • There were 159 (4.88%), 89 (2.74%) and 102 (3.13%) abnormal AI flags for reduced LVEF, AF and structural murmurs, respectively. • We characterised three groups by patterns of use (Table 1). There were no significant differences between mean rates of abnormal AI findings between groups (ANOVA p = 0.43). Conclusions • Implementation of an AI-stethoscope in primary care is feasible and was associated with stable utilisation. • The proportion of abnormal AI findings are consistent with modelled detection gap of the target conditions in the UK, and would not consequentially overwhelm downstream health services. •The proportion of abnormal AI findings did not significantly differ between low and high-utilisation groups.Table 1Figure 1

OptiHeart: determinants and prognostic importance of optimal medical treatment in patients with heart failure discharged from the heart failure clinic

Abstract Background Heart failure (HF) is an increasing health problem globally. Current guidelines are based on studies with primarily male patients. Females are less likely to receive target dose of HF medication as recommended by the clinical guidelines. The reason for this is uncertain, but it has led to the question whether females might not need as high dosages as the males to achieve the beneficial effects of the HF medication. Aim To assess baseline predictors for achieving optimal medical treatment (OMT) and the prognostic importance of OMT for male and female patients who have attended a HF clinical program (HFCP). Methods OPTIHEART included 870 patients with left ventricular ejection fraction (LVEF) &amp;lt;45% leaving HFCP in 2018, 2019 or 2020 and followed in registers for a mean of 1083(SD 11.3) days. OMT was defined as receiving an angiotensin-converting-enzyme-inhibitor (ACEi), angiotensin-receptor blocker (ARB) or angiotensin-II-receptor blocker and nephrylisin-inhibitor (ARNI) AND a betablocker both in doses &amp;gt; 50% of target dose. Association between baseline data at referral and OMT at end of HFCP were calculated using logistic regression. The association between OMT and a 5-point Major Adverse Cardiovascular Event (a 5-Point MACE consisting of cardiovascular mortality, non-fatal acute myocardial infarction, non-fatal stroke, coronary revascularization, worsening of heart failure (both hospitalisation and re-referral to HFC)), were calculated and adjusted for other cardiovascular risk factors using multiple Cox-regression analyses. Results Achieving OMT was associated with male sex (OR: 2.05 95%CI 1.44-2.97; P&amp;lt;0.0001) independently of younger age, higher diastolic blood pressure (DBP), and lower creatinine at referral. A lower rate of 5-point MACE was associated achieved OMT (HR: 0.67 95%CI 0.50-0.89; P=0.006) independently of female sex (HR: 0.62 95%CI 0.47-0.82; P=0.002), younger age, never smoking and NYHA≤2. The beneficial effect of OMT was more pronounced in patients with BMI&amp;lt;26.5kg/m2 (HR=0.41[0.23-0.72] vs. HR=0.84[0.58-1.21], Pinteraction= 0.02), and insignificantly more pronounced in patients with male sex, older age, higher creatinine, and lower DBP. Conclusion OMT was more frequently achieved in patients with male sex independently of lower age, higher DBP, and lower creatinine. Achieving OMT was associated with less 5-point MACE independently of female sex, younger age, never smoking and NYHA≤2 and especially in patients with BMI&amp;lt;26.5kg/m2.Hazard RatioMedical treatment

A survey of availability and affordability of polypills for primary and secondary prevention of cardiovascular diseases in selected countries

Abstract Background/Introduction The recent inclusion of polypills—fixed-dose combinations of two or more antihypertensive drugs and statin with or without aspirin—in the World Health Organization’s Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for primary or secondary prevention of cardiovascular diseases (CVDs). Although there exists extensive evidence on efficacy, safety, and acceptability of polypills, there is no research to-date assessing the "real world" availability and affordability of polypills globally. Purpose We conducted a cross-sectional survey of public and private sector facilities in 13 countries from around the world to evaluate the availability and affordability of polypills. Methods In the surveyed countries, we first ascertained whether any polypill was authorized for marketing and/or included in the national EMLs and clinical guidelines. The facility survey employed a modified WHO/Health Action International methodology. In each country, we collected retail and price data for polypills from at least one public sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable in a given country if the lowest paid worker spends more than a days’ wage to purchase monthly supply. Results Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius, and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. Further, none of the surveyed public pharmacies in any of the four countries stocked any polypills. Among the surveyed private sector facilities, availability ranged from 0% in India (out-of-stock on the survey day but listed for sale) to 100% in Argentina and Spain. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Although not in stock, India had a wider range of various combinations (n=5). Many combinations (63%) found in this survey were affordable in the local context, but these were limited to India and Spain. A lowest paid government worker would spend between 0.2 (India)–2.8 (Mauritius) days’ wages to pay the price for one month’s supply of the polypills. Polypills were likely to be affordable in countries that locally manufactured them. Further, two-pill combinations (one antihypertensive and a statin) were stocked by private pharmacies in Argentina, Bangladesh, Cameroon, India, Nepal, and Spain, with affordability ranging from 0.2 (India)–7.1 (Cameroon) days’ wages. Conclusion Low availability and affordability of polypills in both public and private sectors suggest that the implementation and overall uptake of polypills remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

Traditional medicine use to manage hypercholesterolemia, hyperglycaemia and hypertension in Ecuador

Abstract Background Although the use of traditional medicine (TM) to manage health issues is frequently reported, clinical guidelines often overlook this practice. This study aimed to describe the frequency of TM use to control 3 cardiometabolic risk factors for non-communicable diseases (arterial hypertension, hypercholesterolemia, and hyperglycaemia, collectively referred to as CMRF here); and associated sociodemographic, economic, and clinical characteristics. Methods Descriptive cross-sectional study with a representative population of two health districts in Ecuador, one urban in southern Quito and one in a forested rural area with diverse ethnic groups in Esmeraldas. We included 602 individuals with at least one CMRF and calculated the proportion of those who reported regular use of TM (herbal or traditional remedies) to control their CMRF. We used a multivariable logistic regression model to calculate Odds Ratios for TM use according to sociodemographic, economic, and clinical characteristics. Results TM was commonly used to control CMRF in both sociocultural contexts (39.4% Esmeraldas, 31.1% Quito), often in combination with conventional medicine (CM). A notable percentage of people (33.9% Esmeraldas, 39.0% Quito) did not take any treatment for their CMRF, and the rest used CM alone. In both settings, education was significantly associated with TM use. While in Quito people with higher education were more likely to use TM (aOR 2.04, 95%CI 1.03-3.90), in Esmeraldas, it was more common among people without formal schooling (aOR 3.76; 95%CI 1.59-8.88) as well as those of younger age (aOR per year 0.97; 95%CI 0.95-0.99) and from Afro-Ecudorian ethnicity (aOR 2.13; 95%CI 1.02-4.45). Conclusions Traditional medicine is used by a significant portion of Ecuador’s population, highlighting the need for a more accessible and intercultural approach to healthcare. Key messages • The use of traditional medicine to address hypertension, hypercholesterolemia, and hyperglycaemia appears to be widespread in different sociocultural and economic contexts of Ecuador. • To promote intercultural health, understanding the diverse sociocultural patterns associated with the use of traditional medicine, often combined with conventional medicine, is crucial.

Reassessing pharmacological trials with positive composite outcome driven by reduction in nonfatal myocardial infarction: a systematic review and meta-analysis

Abstract Background Nonfatal myocardial infarction (MI) inadequately predicts cardiovascular and all-cause mortality in contemporary RCTs. The perceived efficacy of new treatments could be overstated if positivity in composite outcome is primarily attributed to reduction in nonfatal MI. Purpose This study seeks to assess pharmacological RCTs with positive results influenced by nonfatal MI reductions and scrutinize the associated clinical guideline recommendations. Methods Pharmacological RCTs focusing on mortality and nonfatal MI published from 2000 to 2023 were searched in PubMed and Web of Science, with subsequent citation tracking in Web of Science and Google Scholar for candidate RCTs referenced in English-language clinical guidelines. Main outcomes included: 1) relative risk reduction in the composite outcome excluding nonfatal MI; 2) relevant guideline recommendations based on the supporting trials. The impact of nonfatal MI on composite outcome was assessed by using the leave-one-out method. Meta-analysis utilized a random effects model. Results After reviewing 19,825 records, we identified 8 RCTs where positive composite outcomes were driven by reductions in non-fatal MI (Figure 1A). These were divided into three therapeutic groups: anti-thrombotic (3 trials), lipid-lowering (3 trials), and anti-inflammatory (2 trials). In guidelines citing these RCTs, lipid-lowering trials (IMPROVE-IT, FOURIER, CLEAR Outcomes; the latter has not been cited yet; a total of 60 recommendations across 17 guidelines; Figure 2) outperformed anti-thrombotic (27 recommendations across 15 guidelines) and anti-inflammatory trials (3 recommendations in 3 guidelines), with significantly higher Class I (45%) and IIa (33.3%) recommendations, and fewer Class IIb (21.7%) recommendations, compared to anti-thrombotic (0%, 22.2%, 66.7%) and anti-inflammatory (0%, 0%, 100%) trials (Figure 1B). In a meta-analysis of all trials on combined intensive lipid-lowering on top of maximally-tolerated statins (the ODYSSEY OUTCOMES, IMPROVE-IT, and FOURIER trials), the exclusion of nonfatal MI data sustained the negative findings (HR 0.94, 95% CI: 0.88 to 1.01). Conclusions Despite the overestimation of efficacy in certain anti-thrombotic, anti-inflammatory, and lipid-lowering RCTs due to the inclusion of nonfatal MI, lipid-lowering trials, particularly those supporting combined intensive therapy with statins, still receive disproportionately favorable guideline recommendations. This underscores the need to reassess the strength of evidence for these trials in guidelines, advocating for a more equitable and evidence-based approach to cardiovascular guideline recommendations.

A sex-related analysis on the influence of lipoprotein(a) on primary cardiovascular disease prevention and its interplay with traditional lipid markers: results from a 20-year cohort study

Abstract Introduction Elevated lipoprotein(a) [Lp(a)] levels is an established risk factor mediating cardiovascular disease. Purpose The relationship between Lp(a) and the first fatal/non-fatal CVD incident over a 20-year period in males and females without CVD was assessed. Methods A longitudinal prospective study was conducted during 2002–2022. In 2002, a total of 3,042 CVD-free adults (1,514 males and 1,528 females) were enrolled. A follow-up was carried out after 20 years, in 2022, which included 2,169 participants. Out of these, 1,988 had comprehensive data for the occurrence of CVD. The recommended threshold of 50mg/dL was used to define abnormal Lp(a) status (≥50mg/dL). Results During the 2002-2022 period, 718 (i.e. 36%) of participants had a fatal or non-fatal CVD event. Twenty-year CVD-event rate was 35.8% and 40.0% in participants with normal and abnormal Lp(a) levels, respectively. For every mg/dL increase in Lp(a), the odds of having a CVD event within 20 years increases by approximately 0.36% (Hazard ratio (HR) = 1.0036, 95% confidence interval (CI) 1.001,1.007, p=0.048). When stratified by sex the relationship remained significant only in females (HR= 1.006, 95% confidence interval (CI) 1.001,1.011, p=0.023). In the multivariate analysis, significance was lost after adjusting for low- and high-density lipoprotein (LDL-C, HDL-C) and triglycerides (HR= 1.0017, 95% confidence interval (CI) 0.998,1.005, p=0.348). Conclusion Elevated Lp(a) levels are linked to higher CVD risk, particularly in females. Despite growing efforts to clarify Lp(a) as a risk-predicting marker in CVD, clinical guidelines still require definitive evidence, particularly from a sex-focused perspective.

Physical Activity-Related Health Services in Germany: Relevance and Necessary Framework Conditions - a Position Paper of the DNVF Working Group Physical Activity-Related Health Services Research

Based on the relevance of an established and broad foundation of physical activity in healthcare, this position paper of the DNVF working group Physical Activity-Related Health Services research presents current conceptual approaches to physical activity-related health services in Germany and highlights the need for interprofessional and interdisciplinary approaches. Three central positions are outlined and elaborated in order to integrate the evidence on health benefits of physical activity and exercise more strongly into healthcare and to show that, against the background of the challenges in the German healthcare system, physical activity-related health services can make a cost-effective and high-quality contribution to improve healthcare. These three positions include 1) the integration of all professional groups involved in healthcare into physical activity-related health services, 2) the greater integration of physical activity professions and physical activity interventions into all healthcare contexts and 3) the systematic consideration of physical activity- and exercise-related expertise in clinical guidelines.

Mapping barriers and bottlenecks for personalized preventive approaches in health systems worldwide

Abstract Over the past decades, the growing prevalence of chronic disease globally raised the public health need to plan tailored personalized preventive approaches, mainly through big data and -omic sciences. However, a conspicuous body of literature highlighted the existence of many barriers and bottlenecks hindering their actual implementation in real-word settings. From here, this scoping review of reviews aims to map all known barriers and bottlenecks to the implementation of personalized preventive approaches in European health systems and beyond. PubMed, Web of Science, Scopus and gray literature sources were consulted from 2017 to January 2023, identified barriers and bottlenecks were analyzed against the Consolidated Framework for Implementation Research (CFIR). Out of 11,602 records, 220 were deemed eligible for full-text screening, and a final sample of 34 review studies were extracted. Studies were mainly performed in USA 15 (44%) and UK 3 (9%), followed by Canada 2 (6%), India 2 (6%) and Italy 2 (6%). From our results, the lack of evidence on clinical utility, guidelines, specialized professionals, citizen trust and cultural issues are the most frequently reported barriers to the implementation of personalized preventive approaches worldwide. These in turn affect country specific policies and the applicability of such innovations across different populations, raising the risk of increasing health inequalities and discrimination concerns. Findings confirmed that most translational challenges pertain to primary and secondary prevention levels across several chronic diseases, with particular concerns for non-European ancestry individuals. Key messages • The identification of bottlenecks are informative of future precision public health interventions. • Barriers reported in most of the studies suggest the need to establish a targeted agenda.

Temporal trends in antithrombotic therapy following transcatheter aortic valve implantation in denmark

Abstract Background A number of randomized clinical trials have examined the use of antithrombotic therapy after transcatheter aortic valve implantation (TAVI), and guidelines have changed over time. Yet, data from clinical practise patterns are lacking and it is important to evaluate adherence to guideline recommendations over time. Purpose This study aims to evaluate the temporal use of antithrombotic therapy after TAVI in Denmark. Methods A nationwide Danish cohort of patients undergoing first-time TAVI from 2008 to 2017 were identified from Danish nationwide registries. Patients were categorized into four groups according to data on prescription filling of antithrombotic therapy within a three-months period post-TAVI: i) No antithrombotic therapy, ii) single antiplatelet therapy (SAPT), iii) dual antiplatelet therapy (DAPT), or iv) anticoagulant therapy. The use of antithrombotic therapy post-TAVI was examined for each year from 2008 to 2017. Results We identified 3187 patients undergoing first-time TAVI, among whom 120 (3.8%) did not receive any antithrombotic therapy, 715 (22.4%) were prescribed SAPT, 1244 (39.0%) were on DAPT, and 1108 (34.8%) were treated with anticoagulant therapy at three months post-TAVI. Patients without antithrombotic therapy were more often men (64.2%) and were more likely to have a history of malignancy (23.3%) compared with the other treatment groups. Patients who received oral anticoagulation had a higher burden of atrial fibrillation (75.7%). The proportion of patients with atrial fibrillation remained stable over time. During the first decade of TAVI, there was a shift in the antithrombotic treatment pattern: no therapy was ranging from 1.1% to 6.6%, SAPT from 19.1% to 29.4%, while DAPT decreased from 51.0% to 31.2% and anticoagulant therapy increased from 21.6% to 39.8% (Figure 1). Conclusion During the first decade of TAVI, antithrombotic therapy patterns post-TAVI changed substantially, such that the use of dual antiplatelet therapy decreased over time, while the use of anticoagulant therapy increased. Since atrial fibrillation remained stable over time, the increase in anticoagulant therapy is most likely due to changes in guidelines for management of atrial fibrillation in 2010. These findings show the evolving treatment patterns in the first decade of TAVI, which reflects the recommendations from clinical trials and guidelines for the management of antithrombotic therapy for patients with TAVI.