Predictive modeling of medication adherence in post myocardial infarction patients: a bayesian approach using beta-regression.

AIMS: Predicting medication adherence in post myocardial infarction (MI) patients has the potential to improve patient outcomes. Most adherence prediction models dichotomize adherence metrics and status. This study aims to develop medication adherence prediction models that avoid dichotomizing adherence metrics and to test whether a simplified model including only 90-days adherence data would perform similarly to a full multivariable model. METHODS: Post MI adult patients were followed for 1-year post the event. Data from pharmacy records were used to calculate proportion of days covered (PDC). We used Bayesian beta-regression to model PDC as a proportion, avoiding dichotomization. For each medication group, statins, P2Y12 inhibitors and aspirin, two prediction models were developed, a full and a simplified model. RESULTS: 3692 patients were included for model development. The median (Inter quartile range) PDC at 1-year for statins, P2Y12 inhibitors and aspirin was 0.8 (0.33, 1.00), 0.79 (0.23, 0.99) and 0.79 (0.23, 0.99), respectively. All models showed good fit to the data by visual predictive checks. Bayesian R2 for statins, P2Y12 inhibitors and aspirin models were 61.4%,71.2% and 55.2%, respectively. The simplified models showed similar performance compared with full complex models as evaluated by cross validation. CONCLUSIONS: We developed Bayesian multilevel models for statins, P2Y12 inhibitors and aspirin in post MI patients that handled 1-year PDC as a proportion using the beta-distribution. In addition, simplified models, with 90-days adherence as single predictor, had similar performance compared with full complex models.

High rates of mood disorders in patients with chronic idiopathic eosinopenia.

Background: Mood disorders (MD) are multifactorial disorders. Identifying new biomarkers for the early diagnosis of MD and predicting response to treatment is currently a significant research topic. Both eosinopenia and MD are associated with increased activity of the hypothalamic-pituitary-adrenal axis. The present study, therefore, used a clear definition of chronic idiopathic eosinopenia (CIE) to determine the rate of MD in a large cohort of individuals with CIE. Methods: This retrospective population-based, case-control study uses data of seven consecutive years from the database of Leumit Health Services (LHS) - a nationwide health maintenance organization in Israel. Results: Participants were 13928 LHS members with CIE and 27858 negative controls. The CIE group exhibited significantly higher rates of MD than the control group throughout the whole study period, except for atypical depressive disorder at baseline. Conclusions: CIE might be associated with a higher prevalence of MD. Further basic research should elucidate the pathophysiologic mechanisms linking CIE and MD.

How to overcome information and communication barriers in Human Papillomavirus vaccination? A SWOT analysis based on the opinions of European family doctors in contact with young people and their parents.

BACKGROUND: Family doctors (FDs)/General practitioners (GPs) are the key contact points for young people and their parents regarding Human Papillomavirus (HPV) vaccination. However, their recommendations are influenced by communication skills. OBJECTIVES: Under the EU4Health project, PROTECT-EUROPE, WONCA Europe led a task to identify and analyse strategies for clinicians' interpersonal communication skills when discussing HPV and its vaccination with young people and their parents. METHODS: Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis using qualitative data focused on HPV vaccine acceptance and communication with the target population. FDs/GPs, members of WONCA Europe, were recruited using convenience and snowball sampling through surveys at conferences and emails. RESULTS: 223 FDs/GPs from 36 countries participated. Strengths included face-to-face communication, extensively used to promote the HPV vaccine. Weaknesses involved financial constraints, limited knowledge about gender-neutral vaccination, safety concerns, and time pressure during the consultations. Opportunities included confidentiality, open dialogue, trusting relationship between FDs/GPs and the target population, continuing medical education, school training, and questions & answers sessions to increase vaccine communication. Threats included social norms and cultures, stigmas against HPV, and anti-vaccination movements hindering discussions on HPV vaccination. CONCLUSION: It is crucial to train FDs/GPs to address knowledge gaps, enhance communication skills, and maintain a trusting relationship with patients when discussing HPV vaccination. Overcoming financial barriers and ensuring gender-neutral vaccination programs are accessible across Europe are also essential. Providing accurate information through the web- and school-based channels and developing community-oriented approaches targeting sociocultural factors and different needs to eliminate HPV vaccine stigmas should be considered when recommending the vaccine.

Face-to-face, trust-based communication is a strength and opportunity for FDs/GPs to promote the HPV vaccine in all countries.The lack of free-of-charge, nationally implemented gender-neutral vaccination represents a policy weakness needing improvement.Stigma and vaccine hesitancy pose major threats, which FDs/GPs must proactively address, supported by robust public health policies.

Dermatological Comorbidities in Patients with Familiar Mediterranean Fever.

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Acute urticaria and cardiovascular diseases.

BACKGROUND: Acute urticaria (AU), characterized by sudden skin wheals, has been associated with various triggers. While chronic urticaria's cardiovascular comorbidities have been studied, AU's associations remain largely unexplored. OBJECTIVE: This study aimed to identify prevalent cardiovascular comorbidities in AU patients and assess their clinical significance. METHODS: A retrospective cohort study used data from Leumit Health Services, matching AU patients with controls. Demographic, clinical, and laboratory data were analyzed. Statistical analyses included Fisher's Exact Test and Mann-Whitney U test. RESULTS: The AU group (72,851 individuals) showed no sex/ethnic distribution differences from controls (291,404 individuals). Systolic blood pressure, weight, BMI, glucose, hemoglobin A1c, C-reactive protein, eosinophil counts, total IgE levels were higher in AU (p < 0.001). Several cardiovascular comorbidities showed significant associations with AU, including valvular heart diseases (aortic regurgitation, mitral regurgitation, and pulmonary valve stenosis), cardiac arrhythmias (atrial fibrillation and others), deep vein thrombosis, diseases of capillaries, peripheral artery disease, cerebrovascular disease, coronary artery disease, and inflammatory heart diseases (pericarditis, heart failure, and hypertension) (p < 0.05). Medications, including antihistamines and glucocorticoids, were more prevalent in the AU group (p < 0.001). CONCLUSION: This study's findings underscore the importance of recognizing cardiovascular comorbidities in AU patients and considering their implications for management. The observed associations provide insight into potential shared mechanisms between AU and cardiovascular diseases, though further research is needed to validate and expand upon these findings.

Understanding the Barriers to Prostate Cancer Population-Based Early Detection Programs: The PRAISE-U BEST Survey.

In 2022, the European Commission updated its recommendation on cancer screening, inviting the Member States (MSs) to explore the feasibility of stepwise implementation of population-based screening for prostate cancer (PCa). In line with this recommendation, the PRAISE-U (Prostate Cancer Awareness and Initiative for Screening in the European Union (EU)) project was initiated. As part of the PRAISE-U, we aim to understand the current practice towards early detection in the EU MSs, the barriers to implementing or planning population-based screening programmes, and potential solutions to overcome these barriers. METHODS: We adapted the Barriers to Effective Screening Tool (BEST) survey to the PCa context. However, it has not been validated in this context. We translated it into all spoken languages in the EU27 and disseminated it to different stakeholders across the EU using a snowballing approach. RESULTS: We received 410 responses from 55 countries, of which 301 (73%) were from the 27 EU MSs. The most represented stakeholder group was urologists (218 (54%)), followed by general practitioners (GPs) (83 (21%)), patient representatives (35 (9%)), policy stakeholders (27 (7%)), researchers (23 (6%)), oncologists, pathologists, radiologists, nurses, and others (16 (4%)) and one industry representative. Among all respondents, 286 (69%) reported the absence of a population-based screening programme, mainly attributed to resource limitations and a lack of political and medical society support. Out of these 286 respondents, 196 (69%) indicated that opportunistic screening is being applied in their country, and 199 (70%) expressed their support for population-based screening programmes (which was highest amongst patient representatives and urologists and lowest amongst GPs and policy stakeholders). The highest scored barriers were lack of political support, insufficient operational resources, and inadequate participation. Suggested solutions to overcome these included awareness campaigns, consensus meetings, political lobbying and European guidelines (to overcome political support barriers), compatible IT systems (to overcome operational barriers), and easy access (to overcome participation barriers). CONCLUSIONS: Participants have noted the presence of opportunistic screening, and particularly urologists and patient representatives expressed their support for the establishment of a population-based PCa screening programme. Nevertheless, successful implementation of population-based screening programmes is complex; it requires political and medical society support, operational resources and capacity, awareness campaigns, as well as the development of protocols, guidelines, and legal frameworks.

"A day in the life" - telemedicine in family medicine and its relationship with practicing physicians' satisfaction: a cross-sectional study.

BACKGROUND: Telemedicine has expanded rapidly in recent years, and many encounters that were conducted in person now take place remotely. This study aimed to assess primary care physicians' (PCPs) attitudes towards the different modalities of patient care. METHODS: This is a cross-sectional nationwide descriptive study conducted in Israel. We asked PCPs to document an entire workday and answer a short questionnaire after each visit. The questions addressed the type of visit (face-to-face, remote synchronous [telephone/video], or remote asynchronous [online requests]), the perceived quality of the visit, and the physicians' feelings at the end of each visit. Before documenting their working day, we asked the participants to answer a questionnaire about their general attitudes toward different modalities of medical visits and how they affect their well-being and burnout. RESULTS: Sixty physicians documented 2,025 visits, of which 39% took place in person, 36% stemmed from online patient requests, 18% were telephone meetings, < 1% were video meetings, and 6% consisted of other types of contact. Mixed effects logistic regressions were used to model the visits' evaluation. The odds ratios (ORs) for perceived medical quality of visits focused on medical tasks were lower for non-face-to-face visits: OR = 0.39, 95% CI 0.25-0.59 for remote synchronous, and OR = 0.14, 95% CI 0.09-0.23 for remote asynchronous. The perceived medical quality of visits focused on administrative tasks was lower for remote asynchronous than for face-to-face visits (OR = 0.31, 95% CI 0.14-0.65). We found no association between medical quality and patients, physicians, or clinic characteristics. The inappropriateness of the visit modality was also associated with lower medical quality (OR = 0.13, 95% CI 0.09-0.18). We found a correlation between perception of medical quality and physicians' feelings at the end of the visits, Spearman's r = 0.82 (p < 0.001). CONCLUSIONS: A substantial portion of the visits was dedicated to administrative tasks and remote medicine. In comparison, physicians rated face-to-face visits' quality higher than remote visits. Policymakers should intervene to minimize administrative work, reduce PCPs' administrative workload, and direct patients to the optimal visit modality for their complaints. These steps would increase medical quality, reduce burnout, and mitigate the shortage of PCPs.

The Use of COVID-19 Mobile Apps in Connecting Patients with Primary Healthcare in 30 Countries: Eurodata Study.

BACKGROUND: The COVID-19 pandemic has necessitated changes in European healthcare systems, with a significant proportion of COVID-19 cases being managed on an outpatient basis in primary healthcare (PHC). To alleviate the burden on healthcare facilities, many European countries developed contact-tracing apps and symptom checkers to identify potential cases. As the pandemic evolved, the European Union introduced the Digital COVID-19 Certificate for travel, which relies on vaccination, recent recovery, or negative test results. However, the integration between these apps and PHC has not been thoroughly explored in Europe. OBJECTIVE: To describe if governmental COVID-19 apps allowed COVID-19 patients to connect with PHC through their apps in Europe and to examine how the Digital COVID-19 Certificate was obtained. METHODOLOGY: Design and setting: Retrospective descriptive study in PHC in 30 European countries. An ad hoc, semi-structured questionnaire was developed to collect country-specific data on primary healthcare activity during the COVID-19 pandemic and the use of information technology tools to support medical care from 15 March 2020 to 31 August 2021. Key informants belong to the WONCA Europe network (World Organization of Family Doctors). The data were collected from relevant and reliable official sources, such as governmental websites and guidelines. MAIN OUTCOME MEASURES: Patient's first contact with health system, governmental COVID-19 app (name and function), Digital COVID-19 Certification, COVID-19 app connection with PHC. RESULTS: Primary care was the first point of care for suspected COVID-19 patients in 28 countries, and 24 countries developed apps to complement classical medical care. The most frequently developed app was for tracing COVID-19 cases (24 countries), followed by the Digital COVID-19 Certificate app (17 countries). Bulgaria, Italy, Serbia, North Macedonia, and Romania had interoperability between PHC and COVID-19 apps, and Poland and Romania's apps considered social needs. CONCLUSIONS: COVID-19 apps were widely created during the first pandemic year. Contact tracing was the most frequent function found in the registered apps. Connection with PHC was scarcely developed. In future pandemics, connections between health system levels should be guaranteed to develop and implement effective strategies for managing diseases.

Exploring the accessibility of primary health care data in Europe's COVID-19 response: developing key indicators for managing future pandemics (Eurodata study).

BACKGROUND: Primary Health Care (PHC) plays a crucial role in managing the COVID-19 pandemic, with only 8% of cases requiring hospitalization. However, PHC COVID-19 data often goes unnoticed on European government dashboards and in media discussions. This project aims to examine official information on PHC patient care during the COVID-19 pandemic in Europe, with specific objectives: (1) Describe PHC's clinical pathways for acute COVID-19 cases, including long-term care facilities, (2) Describe PHC COVID-19 pandemic indicators, (3) Develop COVID-19 PHC activity indicators, (4) Explain PHC's role in vaccination strategies, and (5) Create a PHC contingency plan for future pandemics. METHODS: A mixed-method study will employ two online questionnaires to gather retrospective PHC data on COVID-19 management and PHC involvement in vaccination strategies. Validation will occur through focus group discussions with medical and public health (PH) experts. A two-wave Delphi survey will establish a European PHC indicators dashboard for future pandemics. Additionally, a coordinated health system action plan involving PHC, secondary care, and PH will be devised to address future pandemic scenarios. ANALYSIS: Quantitative data will be analysed using STATA v16.0 for descriptive and multivariate analyses. Qualitative data will be collected through peer-reviewed questionnaires and content analysis of focus group discussions. A Delphi survey and multiple focus groups will be employed to achieve consensus on PHC indicators and a common European health system response plan for future pandemics. The Eurodata research group involving researchers from 28 European countries support the development. DISCUSSION: While PHC manages most COVID-19 acute cases, data remains limited in many European countries. This study collects data from numerous countries, offering a comprehensive perspective on PHC's role during the pandemic in Europe. It pioneers the development of a PHC dashboard and health system plan for pandemics in Europe. These results may prove invaluable in future pandemics. However, data may have biases due to key informants' involvement and may not fully represent all European GP practices. PHC has a significant role in the management of the COVID-19 pandemic, as most of the cases are mild or moderate and only 8% needed hospitalization. However, PHC COVID-19 activity data is invisible on governments' daily dashboards in Europe, often overlooked in media and public debates.

Influence of cytochrome P450 2D6*10/*10 genotype on the risk for tramadol associated adverse effects: a retrospective cohort study.

Background: Tramadol is primarily metabolized by the highly polymorphic CYP2D6 enzyme, leading to a large spectrum of adverse events and clinical response. Ample evidence pointed a reduced CYPD26 activity score in individuals harboring the CYP2D6*10/*10 genotype, nevertheless, there is scarce studies on the impact of CYP2D6*10/*10 genetic polymorphism on long-term tramadol's adverse effects. Aim: To test the correlation between CYP2D6*10/*10 expression and the risk for tramadol-associated adverse effects. Method: Using a database of Leumit Healthcare Services in Israel, we retrospectively assessed the occurrence of adverse events in patients who were prescribed tramadol. A binary logistic regression model was applied to model the relationship between CYP2D6*10/*10 genotype and the occurrence of adverse effects. Results: Data from four hundred ninety-three patients were included in this study. Only 25 (5.1%) patients were heterozygous for the CYP2D6*10 variant, while 56 patients (11%) were tested positive to the CYP2D6*10/*10 genotype. Compared to carriers of other variants, patients with the CYP2D6*10/*10 variant exhibited a higher occurrence of adverse events (odds ratio [OR] = 6.14, 95% confidence interval 3.18-11.83); the odds ratio for central nervous system adverse events and gastrointestinal adverse events were 5.13 (95% CI 2.84-9.28), and 3.25 (95% CI 1.78-5.93), respectively. Conclusion: Among the different CYP2D6 genotypes, CYP2D6*10/*10 genotype carries the higher risk of tramadol related adverse events. Appreciating the frequency of this specific allele it seems prudent to pharmacogenetically screen patients considered for long term tramadol treatment for better tolerability and efficacy outcomes.

Periodontal diseases and cardiovascular diseases, diabetes, and respiratory diseases: Summary of the consensus report by the European Federation of Periodontology and WONCA Europe.

BACKGROUND: Periodontitis is a chronic inflammatory non-communicable disease (NCD) characterised by the destruction of the tooth-supporting apparatus (periodontium), including alveolar bone, the presence of periodontal pockets, and bleeding on probing. OBJECTIVES: To outline, for family doctors, the implications of the association between periodontal and systemic diseases; to explore the role of family doctors in managing periodontitis as an ubiquitous non-communicable disease (NCD). METHODS: The consensus reports of previous focused collaborative workshops between WONCA Europe and the European Federation of Periodontology (using previously undertaken systematic reviews), and a specifically commissioned systematic review formed the technical papers to underpin discussions. Working groups prepared proposals independently, and the proposals were subsequently discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19 complications. Treatment of periodontitis has been associated with improvements in systemic health outcomes. The article also presents evidence gaps. Oral health care professionals (OHPs) and family doctors should collaborate in managing these conditions, including implementing strategies for early case detection of periodontitis in primary medical care centres and of systemic NCDs in oral/dental care settings. There is a need to raise awareness of periodontal diseases, their consequences, and the associated risk factors amongst family doctors. CONCLUSION: Closer collaboration between OHPs and family doctors is important in the early case detection and management of NCDs like cardiovascular diseases, diabetes mellitus, and respiratory diseases. Strategies for early case detection/prevention of NCDs, including periodontitis, should be developed for family doctors, other health professionals (OHPs), and healthcare funders. Evidence-based information on the reported associations between periodontitis and other NCDs should be made available to family doctors, OHPs, healthcare funders, patients, and the general population.

Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19.Periodontal treatment for optimal outcomes improves diabetes outcomes and surrogate measures of cardiovascular risk.Closer collaboration between oral health care professionals and family doctors is important in the early case detection and management of non-communicable diseases.Information on the reported associations should be made available to family doctors, oral health professionals, healthcare funders, patients, and the general population.

Primary care indicators for disease burden, monitoring and surveillance of COVID-19 in 31 European countries: Eurodata Study.

BACKGROUND: During the COVID-19 pandemic, the majority of patients received ambulatory treatment, highlighting the importance of primary health care (PHC). However, there is limited knowledge regarding PHC workload in Europe during this period. The utilization of COVID-19 PHC indicators could facilitate the efficient monitoring and coordination of the pandemic response. The objective of this study is to describe PHC indicators for disease surveillance and monitoring of COVID-19's impact in Europe. METHODS: Descriptive, cross-sectional study employing data obtained through a semi-structured ad hoc questionnaire, which was collectively agreed upon by all participants. The study encompasses PHC settings in 31 European countries from March 2020 to August 2021. Key-informants from each country answered the questionnaire. Main outcome: the identification of any indicator used to describe PHC COVID-19 activity. RESULTS: Out of the 31 countries surveyed, data on PHC information were obtained from 14. The principal indicators were: total number of cases within PHC (Belarus, Cyprus, Italy, Romania and Spain), number of follow-up cases (Croatia, Cyprus, Finland, Spain and Turkey), GP's COVID-19 tests referrals (Poland), proportion of COVID-19 cases among respiratory illnesses consultations (Norway and France), sick leaves issued by GPs (Romania and Spain) and examination and complementary tests (Cyprus). All COVID-19 cases were attended in PHC in Belarus and Italy. CONCLUSIONS: The COVID-19 pandemic exposes a crucial deficiency in preparedness for infectious diseases in European health systems highlighting the inconsistent recording of indicators within PHC organizations. PHC standardized indicators and public data accessibility are urgently needed, conforming the foundation for an effective European-level health services response framework against future pandemics.

Identifying Diabetes Related-Complications in a Real-World Free-Text Electronic Medical Records in Hebrew Using Natural Language Processing Techniques.

BACKGROUND: Studies have demonstrated that 50% to 80% of patients do not receive an International Classification of Diseases (ICD) code assigned to their medical encounter or condition. For these patients, their clinical information is mostly recorded as unstructured free-text narrative data in the medical record without standardized coding or extraction of structured data elements. Leumit Health Services (LHS) in collaboration with the Israeli Ministry of Health (MoH) conducted this study using electronic medical records (EMRs) to systematically extract meaningful clinical information about people with diabetes from the unstructured free-text notes. OBJECTIVES: To develop and validate natural language processing (NLP) algorithms to identify diabetes-related complications in the free-text medical records of patients who have LHS membership. METHODS: The study data included 2.3 million records of 41 469 patients with diabetes aged 35 or older between the years 2012 and 2017. The diabetes related complications included cardiovascular disease, diabetic neuropathy, nephropathy, retinopathy, diabetic foot, cognitive impairments, mood disorders and hypoglycemia. A vocabulary list of terms was determined and adjudicated by two physicians who are experienced in diabetes care board certified diabetes specialist in endocrinology or family medicine. Two independent registered nurses with PhDs reviewed the free-text medical records. Both rule-based and machine learning techniques were used for the NLP algorithm development. Precision, recall, and F-score were calculated to compare the performance of (1) the NLP algorithm with the reviewers' comments and (2) the ICD codes with the reviewers' comments for each complication. RESULTS: The NLP algorithm versus the reviewers (gold standard) achieved an overall good performance with a mean F-score of 86%. This was better than the ICD codes which achieved a mean F-score of only 51%. CONCLUSION: NLP algorithms and machine learning processes may enable more accurate identification of diabetes complications in EMR data.

Clinical characteristics and healthcare utilisation associated with undiagnosed cognitive impairment in elderly patients with diabetes in a primary care setting: a population-based cohort study.

OBJECTIVES: The objective of this study is to report the prevalence, clinical characteristics and healthcare utilisation of patients with type 2 diabetes (T2DM) and previously undiagnosed cognitive impairment who were identified as having a low Montreal Cognitive Assessment (MoCA) score. DESIGN: A population-based cohort study comparing clinical characteristics, medications, outpatient and inpatient care of patients with a MoCA score <19 to MoCA >26 using descriptive statistics, linear regression and multivariate logistic regression. SETTING: Electronic medical records of a large health maintenance organisation in Israel. PARTICIPANTS: 350 patients, age >65 with T2DM who participated in a cognitive function screening initiative using MoCA, and had a follow-up visit during the 12 months after screening. RESULTS: 130 (37.1%) had a MoCA score >26 and 68 (19.4%) <19. Patients with MoCA<19 had more diabetes-related complications, poorer glycaemic and lipid control, fewer visits to their main primary care physician (PCP; 3.9±3.2 vs 7.3±4.2 visits/year p=0.008), shorter duration of PCP visits (8.3±4.5 vs 4.0±3.5 min, p=0.007), fewer nutritionist and endocrinologist visits, and lower participation in diabetes or smoking cessation workshops. They were less likely to be treated with glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 inhibitor (DPP-4), or sodium-glucose transport protein 2 (SGLT-2) inhibitors and more likely to receive insulin or sulfonylurea. Moreover, they had more emergency room visits (ER; 15 (11.5%) vs 16 (23.5%), p=0.019), hospitalisations (8 (6.2%) vs 22 (32.4%), p=0.001), and longer hospital stays (4.3±3.2 vs 14.5±9.8, p=0.001). Using statistical models, MoCA<19 was identified as a risk factor for fewer and shorter PCP visits and more ER visits and hospitalisations. CONCLUSIONS: This study highlights the high prevalence of undiagnosed severe cognitive impairment in elderly patients with T2DM and its association with poor outpatient care. Appropriate interventions are needed to improve outcomes and prevent hospitalisation in this high-risk population.

The Association Between Repeated Measured Febrile Episodes During Early Childhood and Attention Deficit Hyperactivity Disorder: A Large-Scale Population-Based Study.

OBJECTIVE: We examined the association between the number, magnitude, and frequency of febrile episodes during the 0 to 4 years of life and subsequent diagnosis of ADHD. METHODS: This population-based case-control study in an Israeli HMO, Leumit Health Services (LHS), uses a database for all LHS members aged 5 to 18 years between 1/1/2002 and 1/30/2022. The number and magnitude of measured fever episodes during the 0 to 4 years were recorded in individuals with ADHD (N = 18,558) and individually matched non-ADHD controls in a 1:2 ratio (N = 37,116). RESULTS: A significant, independent association was found between the number and magnitude of febrile episodes during the 0 to 4 years and the probability of a later diagnosis of ADHD. Children who never had a measured temperature >37.5°C had a significantly lower rate of ADHD (OR = 0.834, 95% CI [0.802, 0.866], p < .0001). CONCLUSIONS: Febrile episodes during 0 to 4 years are associated with a significantly increased rate of a later diagnosis of ADHD in a doseresponse relationship.

Increased Rate of Familial Mediterranean Fever in Children With ADHD: A Population-Based Case-Control Study.

OBJECTIVE: There is growing evidence of involvement of inflammatory mechanisms in ADHD. Previous studies found significantly higher rates of ADHD among children with FMF. The present study examined the rate of exposure to FMF in children with a later (within a 5-year period) diagnosis of ADHD compared to non-ADHD children. METHODS: A population-based case-control study of all children (<18 years) registered in Leumit Health Services during 01.01.2006 to 06.30.2021. All cases met ICD-9/10 criteria for ADHD. They were matched by age, sex, and socioeconomic status on a 1:2 rate to randomly selected non-ADHD controls. RESULTS: Fifty-six (0.30%) children with ADHD (N = 18,756) were previously diagnosed with FMF compared to 65 of 37,512 controls (0.17%). A significant, independent association existed between a preceding FMF diagnosis and a later ADHD diagnosis [OR = 1.72 (95% CI 1.18-2.51); p = .003]. CONCLUSIONS: The mechanisms underlying the association w between FMF and later ADHD diagnosis merit further elucidation.

A case-control study for comorbidity and laboratory factors associated with food-induced anaphylaxis.

Background: Food-induced anaphylaxis (FIA) is a serious and potentially life-threatening allergic reaction triggered by food allergens. Objective: This case-control study aimed to investigate comorbidities and laboratory factors associated with FIA in the pediatric population of Israel. Methods: Retrospective data from the electronic health records of Leumit Health Care Services were used to identify 711 pediatric patients with FIA and 2560 subjects with food allergy and without anaphylaxis matched for age, gender, and ethnicity. Comorbidities were identified based on medical billing diagnosis codes, and laboratory characteristics were compared between the two groups. Results: The mean ± standard deviation age of patients with FIA was 4.1 ± 4.1 years, and 37.3% were girls. Laboratory analysis revealed increased eosinophil counts (p < 0.001), elevated immunoglobulin E (IgE) (p < 0.001), and IgA levels (p = 0.001) in the FIA group compared with the controls. With regard to comorbidities, the FIA group had higher prevalence rates of allergic diseases, including allergic rhinitis (odds ratio [OR] 1.72; p < 0.001), allergic conjunctivitis (OR 1.84; p = 0.001), asthma (OR 1.36; p < 0.001), angioedema (OR 6.37; p < 0.001), atopic dermatitis (OR 1.77; p < 0.001), and contact dermatitis (OR 1.42; p = 0.001). There was a trend toward significance for chronic spontaneous urticaria (p = 0.051). There was a significant negative association between helminthiases, particularly enterobiasis, and FIA (OR 0.76 [95% confidence interval, 0.59-0.98]; p = 0.029). Conclusion: This study provides valuable epidemiologic evidence on the associations among FIA, comorbidities, and laboratory factors in the pediatric population.