How effective is topical miconazole or amorolfine for mild to moderately severe onychomycosis in primary care: the Onycho Trial - a randomised double-blind placebo-controlled trial.

OBJECTIVES: To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis. DESIGN: Randomised, double-blind, placebo-controlled trial, with computer-generated treatment allocation at a 1:1:1 ratio. SETTING: Primary care, recruitment from February 2020 to August 2022. PARTICIPANTS: 193 patients with suspected mild to moderately severe onychomycosis were recruited via general practices and from the general public, 111 of whom met the study criteria. The mean age of participants was 51 (SD 13.1), 51% were female and onychomycosis was moderately severe (mean OSI 12.1 (SD 8.0)). INTERVENTIONS: Once-daily miconazole 20 mg/g or once-weekly amorolfine 5% nail lacquer solution was compared with placebo (denatonium benzoate solution). MAIN OUTCOME MEASURES: Complete, clinical and mycological cure at 6 months. Secondary outcomes were clinical improvement, symptom burden, quality of life, adverse effects, compliance, patient-perceived improvement and treatment acceptability. RESULTS: Based on intention-to-treat analysis, none of the participants receiving miconazole or amorolfine reached complete cure compared with two in the placebo group (OR not estimable (n.e.), p=0.493 and OR n.e., p=0.240, respectively). There was no evidence of a significant difference between groups regarding clinical cure (OR n.e., p=0.493 and OR 0.47, 95% CI 0.04 to 5.45, p=0.615) while miconazole and amorolfine were less effective than placebo at reaching both mycological cure (OR 0.25, 95% CI 0.06 to 0.98, p=0.037 and OR 0.23, 95% CI 0.06 to 0.92, p=0.029, respectively) and clinical improvement (OR 0.26, 95% CI 0.08 to 0.91, p=0.028 and OR 0.25, 95% CI 0.07 to 0.85, p=0.021, respectively). There was no evidence of a significant difference in disease burden, quality of life, adverse reactions, compliance, patient-perceived improvement or treatment acceptability. CONCLUSIONS: Topical miconazole and amorolfine were not effective in achieving a complete, clinical or mycological cure of mild to moderately severe onychomycosis, nor did they significantly alleviate the severity or symptom burden. These treatments should, therefore, not be advised as monotherapy to treat onychomycosis. TRIAL REGISTRATION NUMBER: WHO ICTRP NL8193.

Tailoring remote patient management in cardiovascular risk management for healthcare professionals using panel management: a qualitative study.

BACKGROUND: While remote patient management (RPM) has the potential to assist in achieving treatment targets for cardiovascular risk factors in primary care, its effectiveness may vary among different patient subgroups. Panel management, which involves proactive care for specific patient risk groups, could offer a promising approach to tailor RPM to these groups. This study aims to (i) assess the perception of healthcare professionals and other stakeholders regarding the adoption and (ii) identify the barriers and facilitators for successfully implementing such a panel management approach. METHODS: In total, nineteen semi-structured interviews and two focus groups were conducted in the Netherlands. Three authors reviewed the audited transcripts. The Consolidated Framework for Implementation Strategies (CFIR) domains were used for the thematic analysis. RESULTS: A total of 24 participants (GPs, nurses, health insurers, project managers, and IT consultants) participated. Overall, a panel management approach to RPM in primary care was considered valuable by various stakeholders. Implementation barriers encompassed concerns about missing necessary risk factors for patient stratification, additional clinical and technical tasks for nurses, and reimbursement agreements. Facilitators included tailoring consultation frequency and early detection of at-risk patients, an implementation manager accountable for supervising project procedures and establishing agreements on assessing implementation metrics, and ambassador roles. CONCLUSION: Panel management could enhance proactive care and accurately identify which patients could benefit most from RPM to mitigate CVD risk. For successful implementation, we recommend having clear agreements on technical support, financial infrastructure and the criteria for measuring evaluation outcomes.

Association between onychomycosis and ulcerative complications in patients with diabetes: a longitudinal cohort study in Dutch general practice.

INTRODUCTION: Diabetic foot ulcers are feared complications of diabetes mellitus (DM), requiring extensive treatment and hospital admissions, ultimately leading to amputation and increased mortality. Different factors contribute to the development of foot ulcers and related complications. Onychomycosis, being more prevalent in patients with diabetes, could be an important risk factor for developing ulcers and related infections. However, the association between onychomycosis and diabetic complications has not been well studied in primary care. RESEARCH DESIGN AND METHODS: To determine the impact of onychomycosis on ulcer development and related complications in patients with diabetes in primary care, a longitudinal cohort study was carried out using routine care data from the Extramural Leiden University Medical Center Academic Network. Survival analyses were performed through Cox proportional hazards models with time-dependent covariates. RESULTS: Data from 48 212 patients with a mean age of 58 at diagnosis of DM, predominantly type 2 (87.8%), were analysed over a median follow-up of 10.3 years. 5.7% of patients developed an ulcer. Onychomycosis significantly increased the risk of ulcer development (HR 1.37, 95% CI 1.13 to 1.66), not affected by antimycotic treatment, nor after adjusting for confounders (HR 1.23, 95% CI 1.01 to 1.49). The same was found for surgical interventions (HR 1.54, 95% CI 1.35 to 1.75) and skin infections (HR 1.48, CI 95% 1.28 to 1.72), again not affected by treatment and significant after adjusting for confounders (HR 1.32, 95% CI 1.16 to 1.51 and HR 1.27, 95% CI 1.10 to 1.48, respectively). CONCLUSIONS: Onychomycosis significantly increased the risk of ulcer development in patients with DM in primary care, independently of other risk factors. In addition, onychomycosis increased the risk of surgeries and infectious complications. These results underscore the importance of giving sufficient attention to onychomycosis in primary care and corresponding guidelines. Early identification of onychomycosis during screening and routine care provides a good opportunity for timely recognition of increased ulcer risk.

Severe drug eruption from oral terbinafine for mild onychomycosis-A case report from family practice and literature review: "Just an innocent little pill?"

Onychomycosis is the most prevalent nail disease and is frequently encountered in clinical practice. Despite having multiple therapeutic options, of which systemic antifungals are the most effective, treatment is not always mandatory in all patients. Especially when considering systemic treatment, the risk of adverse reactions may outweigh the potential benefits of treatment. In this case report, we present a clinical case of a 49-year-old male patient with a blank past medical history who experienced a severe drug eruption from terbinafine prescribed for mild onychomycosis that required discontinuation of terbinafine, additional evaluation, and treatment of this adverse reaction.

[Loss of contact between doctor and patient: early signaling can prevent escalation]. / Verbroken arts-patiëntcontact.

A good therapeutic relationship leads to better outcomes. In the event of an imminent break in contact, discussing the alliance rupture can be helpful. Optimal use of the countertransference also contributes. Metacommunication can be useful. In this article, some cases illustrating these concepts, are being discussed.

Chronic care for heart failure patients: Who to refer back to the general practitioner?-Experiences of the Dutch integrated heart failure care model.

OBJECTIVE: The number of patients with heart failure (HF) and corresponding burden of the healthcare system will increase significantly. The Dutch integrated model, 'Transmural care of HF Patients' was based on the European Society of Cardiology (ESC) guidelines and initiated to manage the increasing prevalence of HF patients in primary and secondary care and stimulate integrated care. It is unknown how many HF patients are eligible for back-referral to general practitioners (GPs), which is important information for the management of chronic HF care. This study aims to evaluate clinical practice of patients for whom chronic HF care can be referred from the cardiologist to the GP based on the aforementioned chronic HF care model. DESIGN AND METHODS: A retrospective case record-based study was conducted, which included all chronic HF patients registered in the cardiology information systems of two different hospitals. Subsequently, 200 patients were randomly selected for evaluation. The following patients were considered eligible for referral to the GP: 1/Stable HF patients with reduced left ventricular ejection fraction (LVEF), 2/Stable HF patients with a recovered LVEF and 3/Stable HF patients with a preserved LVEF, 4/HF, palliative setting. RESULTS: Of the 200 patients, 17% was considered eligible for referral to the GP. This group consisted of 5% patients with a reduced LVEF, 10.5% patients with recovered LVEF and 1.5% patients with a preserved LVEF. Main indicators for HF care by cardiologists were active cardiac disease other than HF (39.5%), recent admission for HF (29.5%) or a recent adjustment in HF medication (7.5%). CONCLUSION: Applying the chronic HF care model of the 'Transmural care of HF patients' and the ESC-guidelines, results in an important opportunity to further optimise HF integrated care and to deal with the increasing number of HF patients referred to the hospital.

Molluscum contagiosum survey - common approach and attitude towards treatment and research in Dutch general practice.

BACKGROUND: Molluscum contagiosum (MC) can cause significant burden in children. So far, pharmacological treatment has not been proven beneficial. More rigorous interventions have not been well studied. Current guidelines advise a "wait and see" policy. However, children and their parents frequently visit their GP requesting intervention. Therefore, the aim of this study was to gain insight into the approach to MC by GPs and parents' expectations and to investigate willingness to participate in an interventional study. METHODS: A survey study was carried out among GPs and parents using a questionnaire for each group inquiring about MC and potential study participation. Descriptive statistics were used to analyze results and logistical regression to investigate factors influencing participation. RESULTS: The majority of GPs (88%) preferred an expectative approach; only 21% were willing to participate in a trial as proposed. GPs estimating ≥ 50% of parents would request treatment, were more likely to participate. Most responding parents did or would visit their GP requesting treatment. In contrast to GPs, 58% were willing to participate. Parents preferring cryotherapy or curettage were more likely to participate. CONCLUSION: Our study demonstrated that the majority of GPs preferred a conservative approach, adhering to current guidelines. However, most parents preferred treatment to resolve MC and symptoms. Parents' willingness to participate was much higher than GP's, reflecting parents' desire for treatment. These findings underscore the need for continued therapeutic research. Careful preparation and selection of GPs and patients will be essential to ensure the feasibility of such an endeavor. TRIAL REGISTRATION: This survey study was not part of a clinical trial.

Home-based initiatives for acute management of COVID-19 patients needing oxygen: differences across The Netherlands.

OBJECTIVE: During the COVID-19 pandemic new collaborative-care initiatives were developed for treating and monitoring COVID-19 patients with oxygen at home. Aim was to provide a structured overview focused on differences and similarities of initiatives of acute home-based management in the Netherlands. METHODS: Initiatives were eligible for evaluation if (i) COVID-19 patients received oxygen treatment at home; (ii) patients received structured remote monitoring; (iii) it was not an 'early hospital discharge' program; (iv) at least one patient was included. Protocols were screened, and additional information was obtained from involved physicians. Design choices were categorised into: eligible patient group, organization medical care, remote monitoring, nursing care, and devices used. RESULTS: Nine initiatives were screened for eligibility; five were included. Three initiatives included low-risk patients and two were designed specifically for frail patients. Emergency department (ED) visit for an initial diagnostic work-up and evaluation was mandatory in three initiatives before starting home management. Medical responsibility was either assigned to the general practitioner or hospital specialist, most often pulmonologist or internist. Pulse-oximetry was used in all initiatives, with additional monitoring of heart rate and respiratory rate in three initiatives. Remote monitoring staff's qualification and authority varied, and organization and logistics were covered by persons with various backgrounds. All initiatives offered remote monitoring via an application, two also offered a paper diary option. CONCLUSIONS: We observed differences in the organization of interprofessional collaboration for acute home management of hypoxemic COVID-19 patients. All initiatives used pulse-oximetry and an app for remote monitoring. Our overview may be of help to healthcare providers and organizations to set up and implement similar acute home management initiatives for critical episodes of COVID-19 (or other acute disorders) that would otherwise require hospital care.

[Acute chest pain in out-of-hours primary care]. / Acute pijn op de borst op de huisartsenpost.

Out-of-hours primary care (OOH-PC) facilities act as a first point of contact in acute care in the Netherlands, including acute chest pain. The facilities perform initial triage to assess the patient's urgency using standardized triage protocols (Netherlands Triage Standard). The performance of the current protocol for chest pain assessment was recently evaluated and showed only moderate discriminatory properties. Although final triage decision-making is improved by the clinical experience of triage assistants and general practitioners, substantial over- and under-triage persists. Improving the care of patients with chest pain in OOH-PC should primarily be sought in improving the triage software, followed by the use of innovative diagnostic tools (such as troponine measurements).

Implementation of a group-based lifestyle intervention programme (Healthy Heart) in general practices in The Netherlands: a mixed-methods study.

BACKGROUND: Lifestyle intervention programmes target behavioural risk factors that contribute to cardiovascular diseases (CVDs). Unfortunately, sustainable implementation of these programmes can be challenging. Gaining insights into the barriers and facilitators for successful implementation is important for maximising public health impact of these interventions. The Healthy Heart (HH) programme is an example of a combined lifestyle intervention programme. AIM: To analyse the reach, adoption, and implementation of the HH programme. DESIGN & SETTING: A mixed-methods study conducted in a general practice setting in The Netherlands. METHOD: Quantitative data were collected from the Healthy Heart study (HH study), a non-randomised cluster stepped-wedge trial to assess the effect of the HH programme on patients at high risk of developing CVDs at practice level. Qualitative data were obtained through focus groups. RESULTS: Out of 73 approached general practices, 55 implemented the HH programme. A total of 1082 patients agreed to participate in the HH study, of whom 64 patients were referred to the HH programme and 41 patients participated. Several barriers for participation were identified such as time investment, lack of risk perception, and being confident in changing lifestyle on their own. Important barriers for healthcare providers (HCPs) to refer a patient were time investment, lack of information to sufficiently inform patients, and preconceived notions regarding which patients the programme was suitable for. CONCLUSION: This study has offered insights from a patient and HCP perspective regarding barriers and facilitators for implementation of the group-based lifestyle intervention programme. The identified barriers and facilitators, and the suggested improvements, can be used by others who wish to implement a similar programme.

Added Predictive Value of Female-Specific Factors and Psychosocial Factors for the Risk of Stroke in Women Under 50.

BACKGROUND AND OBJECTIVES: Female-specific factors and psychosocial factors may be important in the prediction of stroke but are not included in prediction models that are currently used. We investigated whether addition of these factors would improve the performance of prediction models for the risk of stroke in women younger than 50 years. METHODS: We used data from the Stichting Informatievoorziening voor Zorg en Onderzoek, population-based, primary care database of women aged 20-49 years without a history of cardiovascular disease. Analyses were stratified by 10-year age intervals at cohort entry. Cox proportional hazards models to predict stroke risk were developed, including traditional cardiovascular factors, and compared with models that additionally included female-specific and psychosocial factors. We compared the risk models using the c-statistic and slope of the calibration curve at a follow-up of 10 years. We developed an age-specific stroke risk prediction tool that may help communicating the risk of stroke in clinical practice. RESULTS: We included 409,026 women with a total of 3,990,185 person-years of follow-up. Stroke occurred in 2,751 women (incidence rate 6.9 [95% CI 6.6-7.2] per 10,000 person-years). Models with only traditional cardiovascular factors performed poorly to moderately in all age groups: 20-29 years: c-statistic: 0.617 (95% CI 0.592-0.639); 30-39 years: c-statistic: 0.615 (95% CI 0.596-0.634); and 40-49 years: c-statistic: 0.585 (95% CI 0.573-0.597). After adding the female-specific and psychosocial risk factors to the reference models, the model discrimination increased moderately, especially in the age groups 30-39 (Δc-statistic: 0.019) and 40-49 years (Δc-statistic: 0.029) compared with the reference models, respectively. DISCUSSION: The addition of female-specific factors and psychosocial risk factors improves the discriminatory performance of prediction models for stroke in women younger than 50 years.

The efficacy of aspirin to inhibit platelet aggregation in patients hospitalised with a severe infection: a multicentre, open-label, randomised controlled trial.

Patients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether hyperaggregation occurs during infection, and whether aspirin inhibits this. In this multicentre, open-label, randomised controlled trial, patients hospitalised due to acute infection were randomised to receive 10 days of aspirin treatment (80 mg 1dd or 40 mg 2dd) or no intervention (1:1:1 allocation). Measurements were performed during infection (T1; days 1-3), after intervention (T2; day 14) and without infection (T3; day > 90). The primary endpoint was platelet aggregation measured by the Platelet Function Analyzer® closure time (CT), and the secondary outcomes were serum and plasma thromboxane B2 (sTxB2 and pTxB2). Fifty-four patients (28 females) were included between January 2018 and December 2020. CT was 18% (95%CI 6;32) higher at T3 compared with T1 in the control group (n = 16), whereas sTxB2 and pTxB2 did not differ. Aspirin prolonged CT with 100% (95%CI 77; 127) from T1 to T2 in the intervention group (n = 38), while it increased with only 12% (95%CI 1;25) in controls. sTxB2 decreased with 95% (95%CI - 97; - 92) from T1 to T2, while it increased in the control group. pTxB2 was not affected compared with controls. Platelet aggregation is increased during severe infection, and this can be inhibited by aspirin. Optimisation of the treatment regimen may further diminish the persisting pTxB2 levels that point towards remaining platelet activity. This trial was registered on 13 April 2017 at EudraCT (2016-004303-32).

Ruling out acute coronary syndrome in primary care with a clinical decision rule and a capillary, high-sensitive troponin I point of care test: study protocol of a diagnostic RCT in the Netherlands (POB HELP).

INTRODUCTION: Chest pain is a common reason for consultation in primary care. To rule out acute coronary syndrome (ACS), general practitioners (GP) refer 40%-70% of patients with chest pain to the emergency department (ED). Only 10%-20% of those referred, are diagnosed with ACS. A clinical decision rule, including a high-sensitive cardiac troponin-I point-of-care test (hs-cTnI-POCT), may safely rule out ACS in primary care. Being able to safely rule out ACS at the GP level reduces referrals and thereby alleviates the burden on the ED. Moreover, prompt feedback to the patients may reduce anxiety and stress. METHODS AND ANALYSIS: The POB HELP study is a clustered randomised controlled diagnostic trial investigating the (cost-)effectiveness and diagnostic accuracy of a primary care decision rule for acute chest pain, consisting of the Marburg Heart Score combined with a hs-cTnI-POCT (limit of detection 1.6 ng/L, 99th percentile 23 ng/L, cut-off value between negative and positive used in this study 3.8 ng/L). General practices are 2:1 randomised to the intervention group (clinical decision rule) or control group (regular care). In total 1500 patients with acute chest pain are planned to be included by GPs in three regions in The Netherlands. Primary endpoints are the number of hospital referrals and the diagnostic accuracy of the decision rule 24 hours, 6 weeks and 6 months after inclusion. ETHICS AND DISSEMINATION: The medical ethics committee Leiden-Den Haag-Delft (the Netherlands) has approved this trial. Written informed consent will be obtained from all participating patients. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. TRIAL REGISTRATION NUMBERS: NL9525 and NCT05827237.

Artificial intelligence in mobile health for skin cancer diagnostics at home (AIM HIGH): a pilot feasibility study.

Background: Artificial intelligence (AI)-based mobile phone apps (mHealth) have the potential to streamline care for suspicious skin lesions in primary care. This study aims to investigate the conditions and feasibility of a study that incorporates an AI-based app in primary care and evaluates its potential impact. Methods: We conducted a pilot feasibility study from November 22nd, 2021 to June 9th, 2022 with a mixed-methods design on implementation of an AI-based mHealth app for skin cancer detection in three primary care practices in the Netherlands (Rotterdam, Leiden and Katwijk). The primary outcome was the inclusion and successful participation rate of patients and general practitioners (GPs). Secondary outcomes were the reasons, facilitators and barriers for successful participation and the potential impact in both pathways for future sample size calculations. Patients were offered use of an AI-based mHealth app before consulting their GP. GPs assessed the patients blinded and then unblinded to the app. Qualitative data included observations and audio-diaries from patients and GPs and focus-groups and interviews with GPs and GP assistants. Findings: Fifty patients were included with a median age of 52 years (IQR 33.5-60.3), 64% were female, and 90% had a light skin type. The average patient inclusion rate was 4-6 per GP practice per month and 84% (n = 42) successfully participated. Similarly, in 90% (n = 45 patients) the GPs also successfully completed the study. GPs never changed their working diagnosis, but did change their treatment plan (n = 5) based on the app's assessments. Notably, 54% of patients with a benign skin lesion and low risk rating, indicated that they would be reassured and cancel their GP visit with these results (p < 0.001). Interpretation: Our findings suggest that studying implementation of an AI-based mHealth app for detection of skin cancer in the hands of patients or as a diagnostic tool used by GPs in primary care appears feasible. Preliminary results indicate potential to further investigate both intended use settings. Funding: SkinVision B.V.

The accuracy of clinical diagnosis of onychomycosis in Dutch general practice: a diagnostic accuracy study.

BACKGROUND: Onychomycosis, the most common cause of nail dystrophy, is generally diagnosed by clinical examination. Current guidelines for Dutch general practice advise confirmatory testing only in cases of doubt or insufficient response to treatment. However, making a correct diagnosis can be challenging given the wide variety of clinical features and differential diagnosis. AIM: To establish accuracy of clinical diagnosis of onychomycosis by GPs. DESIGN & SETTING: A diagnostic accuracy study based on GPs' clinical diagnosis of primary care patients suspected of onychomycosis. METHOD: Using 137 complete datasets from the Onycho Trial, diagnostic accuracy of clinical diagnosis as the index test was compared with confirmatory testing as the reference test. A sensitivity analysis was performed to determine diagnostic values for different combinations of index and reference test. Logistical regression was used to assess which clinical characteristics were associated with the positive predictive value (PPV) of the index test. RESULTS: Clinical accuracy, that is the PPV of the index test, was 74.5%. Sensitivity analysis showed no significant difference in diagnostic values. Male sex and a history of any previous treatment significantly increased clinical accuracy with an odds ratio (OR) of 3.873 (95% confidence interval [CI] = 1.230 to 12.195, P = 0.021) and OR 4.022 (95% CI = 1.075 to 15.040, P = 0.039), respectively. CONCLUSION: The study demonstrated that the GPs' clinical diagnosis of onychomycosis was insufficiently accurate to initiate treatment without confirmatory testing. Further research is needed to investigate how to increase clinical accuracy and reduce potentially unnecessary exposure to treatment.

The Effect and Cost-Effectiveness of Offering a Combined Lifestyle Intervention for the Prevention of Cardiovascular Disease in Primary Care: Results of the Healthy Heart Stepped-Wedge Trial.

OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of offering the combined lifestyle programme "Healthy Heart", addressing overweight, diet, physical activity, smoking and alcohol, to improve lifestyle behaviour and reduce cardiovascular risk. DESIGN: A practice-based non-randomised stepped-wedge cluster trial with two-year follow-up. Outcomes were obtained via questionnaires and routine care data. A cost-utility analysis was performed. During the intervention period, "Healthy Heart" was offered during regular cardiovascular risk management consultations in primary care in The Hague, The Netherlands. The period prior to the intervention period served as the control period. RESULTS: In total, 511 participants (control) and 276 (intervention) with a high cardiovascular risk were included (overall mean ± SD age 65.0 ± 9.6; women: 56%). During the intervention period, 40 persons (15%) participated in the Healthy Heart programme. Adjusted outcomes did not differ between the control and intervention period after 3-6 months and 12-24 months. Intervention versus control (95% CI) 3-6 months: weight: ß -0.5 (-1.08-0.05); SBP ß 0.15 (-2.70-2.99); LDL-cholesterol ß 0.07 (-0.22-0.35); HDL-cholesterol ß -0.03 (-0.10-0.05); physical activity ß 38 (-97-171); diet ß 0.95 (-0.93-2.83); alcohol OR 0.81 (0.44-1.49); quit smoking OR 2.54 (0.45-14.24). Results were similar for 12-24 months. Mean QALYs and mean costs of cardiovascular care were comparable over the full study period (mean difference (95% CI) QALYs: -0.10 (-0.20; 0.002); costs: EUR 106 (-80; 293)). CONCLUSIONS: For both the shorter (3-6 months) and longer term (12-24 months), offering the Healthy Heart programme to high-cardiovascular-risk patients did not improve their lifestyle behaviour nor cardiovascular risk and was not cost-effective on a population level.

Cardiovascular Risk Prediction in Men and Women Aged Under 50 Years Using Routine Care Data.

Background Prediction models for risk of cardiovascular events generally do not include young adults, and cardiovascular risk factors differ between women and men. Therefore, this study aimed to develop prediction models for first-ever cardiovascular event risk in men and women aged 30 to 49 years. Methods and Results We included patients aged 30 to 49 years without cardiovascular disease from a Dutch routine care database. Outcome was defined as first-ever cardiovascular event. Our reference models were sex-specific Cox proportional hazards models based on traditional cardiovascular predictors, which we compared with models using 2 predictor subsets with the 20 or 50 most important predictors based on the Cox elastic net model regularization coefficients. We assessed the C-index and calibration curve slopes at 10 years of follow-up. We stratified our analyses based on 30- to 39-year and 40- to 49-year age groups at baseline. We included 542 141 patients (mean age 39.7, 51% women). During follow-up, 10 767 cardiovascular events occurred. Discrimination of reference models including traditional cardiovascular predictors was moderate (women: C-index, 0.648 [95% CI, 0.645-0.652]; men: C-index, 0.661 [95%CI, 0.658-0.664]). In women and men, the Cox proportional hazard models including 50 most important predictors resulted in an increase in C-index (0.030 and 0.012, respectively), and a net correct reclassification of 3.7% of the events in women and 1.2% in men compared with the reference model. Conclusions Sex-specific electronic health record-derived prediction models for first-ever cardiovascular events in the general population aged <50 years have moderate discriminatory performance. Data-driven predictor selection leads to identification of nontraditional cardiovascular predictors, which modestly increase performance of models.

What Makes a Quality Health App-Developing a Global Research-Based Health App Quality Assessment Framework for CEN-ISO/TS 82304-2: Delphi Study.

BACKGROUND: The lack of an international standard for assessing and communicating health app quality and the lack of consensus about what makes a high-quality health app negatively affect the uptake of such apps. At the request of the European Commission, the international Standard Development Organizations (SDOs), European Committee for Standardization, International Organization for Standardization, and International Electrotechnical Commission have joined forces to develop a technical specification (TS) for assessing the quality and reliability of health and wellness apps. OBJECTIVE: This study aimed to create a useful, globally applicable, trustworthy, and usable framework to assess health app quality. METHODS: A 2-round Delphi technique with 83 experts from 6 continents (predominantly Europe) participating in one (n=42, 51%) or both (n=41, 49%) rounds was used to achieve consensus on a framework for assessing health app quality. Aims included identifying the maximum 100 requirement questions for the uptake of apps that do or do not qualify as medical devices. The draft assessment framework was built on 26 existing frameworks, the principles of stringent legislation, and input from 20 core experts. A follow-up survey with 28 respondents informed a scoring mechanism for the questions. After subsequent alignment with related standards, the quality assessment framework was tested and fine-tuned with manufacturers of 11 COVID-19 symptom apps. National mirror committees from the 52 countries that participated in the SDO technical committees were invited to comment on 4 working drafts and subsequently vote on the TS. RESULTS: The final quality assessment framework includes 81 questions, 67 (83%) of which impact the scores of 4 overarching quality aspects. After testing with people with low health literacy, these aspects were phrased as "Healthy and safe," "Easy to use," "Secure data," and "Robust build." The scoring mechanism enables communication of the quality assessment results in a health app quality score and label, alongside a detailed report. Unstructured interviews with stakeholders revealed that evidence and third-party assessment are needed for health app uptake. The manufacturers considered the time needed to complete the assessment and gather evidence (2-4 days) acceptable. Publication of CEN-ISO/TS 82304-2:2021 Health software - Part 2: Health and wellness apps - Quality and reliability was approved in May 2021 in a nearly unanimous vote by 34 national SDOs, including 6 of the 10 most populous countries worldwide. CONCLUSIONS: A useful and usable international standard for health app quality assessment was developed. Its quality, approval rate, and early use provide proof of its potential to become the trusted, commonly used global framework. The framework will help manufacturers enhance and efficiently demonstrate the quality of health apps, consumers, and health care professionals to make informed decisions on health apps. It will also help insurers to make reimbursement decisions on health apps.

Non-acute chest pain in primary care; referral rates, communication and guideline adherence: a cohort study using routinely collected health data.

BACKGROUND: The prevalence of coronary artery disease is increasing due to the aging population and increasing prevalence of cardiovascular risk factors. Non-acute chest pain often is the first symptom of stable coronary artery disease. To optimise care for patients with non-acute chest pain and make efficient use of available resources, we need to know more about the current incidence, referral rate and management of these patients. METHODS: We used routinely collected health data from the STIZON data warehouse in the Netherlands between 2010 and 2016. Patients > 18 years, with no history of cardiovascular disease, seen by the general practitioner (GP) for non-acute chest pain with a suspected cardiac origin were included. Outcomes were (i) incidence of new non-acute chest pain in primary care, (ii) referral rates to the cardiologist, (iii) correspondence from the cardiologist to the GP, (iv) registration by GPs of received correspondence and; (v) pharmacological guideline adherence after newly diagnosed stable angina pectoris. RESULTS: In total 9029 patients were included during the study period, resulting in an incidence of new non-acute chest pain of 1.01/1000 patient-years. 2166 (24%) patients were referred to the cardiologist. In 857/2114 (41%) referred patients, correspondence from the cardiologist was not available in the GP's electronic medical record. In 753/1257 (60%) patients with available correspondence, the GP did not code the conclusion in the electronic medical record. Despite guideline recommendations, 37/255 (15%) patients with angina pectoris were not prescribed antiplatelet therapy nor anticoagulation, 69/255 (27%) no statin and 67/255 (26%) no beta-blocker. CONCLUSION: After referral, both communication from cardiologists and registration of the final diagnosis by GPs were suboptimal. Both cardiologists and GPs should make adequate communication and registration a priority, as it improves health outcomes. Secondary pharmacological prevention in patients with angina pectoris was below guideline standards. So, proactive attention needs to be given to optimise secondary prevention in this high-risk group in primary care.

Impact of a Machine Learning-Based Decision Support System for Urinary Tract Infections: Prospective Observational Study in 36 Primary Care Practices.

BACKGROUND: There is increasing attention on machine learning (ML)-based clinical decision support systems (CDSS), but their added value and pitfalls are very rarely evaluated in clinical practice. We implemented a CDSS to aid general practitioners (GPs) in treating patients with urinary tract infections (UTIs), which are a significant health burden worldwide. OBJECTIVE: This study aims to prospectively assess the impact of this CDSS on treatment success and change in antibiotic prescription behavior of the physician. In doing so, we hope to identify drivers and obstacles that positively impact the quality of health care practice with ML. METHODS: The CDSS was developed by Pacmed, Nivel, and Leiden University Medical Center (LUMC). The CDSS presents the expected outcomes of treatments, using interpretable decision trees as ML classifiers. Treatment success was defined as a subsequent period of 28 days during which no new antibiotic treatment for UTI was needed. In this prospective observational study, 36 primary care practices used the software for 4 months. Furthermore, 29 control practices were identified using propensity score-matching. All analyses were performed using electronic health records from the Nivel Primary Care Database. Patients for whom the software was used were identified in the Nivel database by sequential matching using CDSS use data. We compared the proportion of successful treatments before and during the study within the treatment arm. The same analysis was performed for the control practices and the patient subgroup the software was definitely used for. All analyses, including that of physicians' prescription behavior, were statistically tested using 2-sided z tests with an α level of .05. RESULTS: In the treatment practices, 4998 observations were included before and 3422 observations (of 2423 unique patients) were included during the implementation period. In the control practices, 5044 observations were included before and 3360 observations were included during the implementation period. The proportion of successful treatments increased significantly from 75% to 80% in treatment practices (z=5.47, P<.001). No significant difference was detected in control practices (76% before and 76% during the pilot, z=0.02; P=.98). Of the 2423 patients, we identified 734 (30.29%) in the CDSS use database in the Nivel database. For these patients, the proportion of successful treatments during the study was 83%-a statistically significant difference, with 75% of successful treatments before the study in the treatment practices (z=4.95; P<.001). CONCLUSIONS: The introduction of the CDSS as an intervention in the 36 treatment practices was associated with a statistically significant improvement in treatment success. We excluded temporal effects and validated the results with the subgroup analysis in patients for whom we were certain that the software was used. This study shows important strengths and points of attention for the development and implementation of an ML-based CDSS in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04408976; https://clinicaltrials.gov/ct2/show/NCT04408976.