To determine the prevalence of impaired fasting glucose (IFG) and increased glycated hemoglobin A1c (HbA1c) among Israeli children and adolescents without diabetes. A retrospective cohort study of children aged 5–18 years from three central Israeli districts from 2010 to 2020 was conducted. Data retrieved from the electronic patient medical files included age, sex, sector, socioeconomic status (SES), body mass index (BMI), fasting plasma glucose, and HbA1c levels. IFG was defined as fasting glucose 100–125 mg/dL; increased HbA1c as 5.7–6.4

We evaluated the effect of infrared thermography (IRT) on the clinical assessment of bacterial and viral pharyngitis and its impact on the predictive value of the McIsaac score algorithm for streptococcal pharyngitis in children. We also investigated if IRT could distinguish between bacterial and viral pharyngitis. The study included children aged 2-17 years presenting with sore throat and fever over 38°C from November 1, 2021, to April 30, 2022. Of the 76 assessed children, 16 were excluded due to missing data or technical issues, leaving 60 children (32 males, 28 females) divided into three groups: Group A with streptococcal pharyngitis (N = 30), viral pharyngitis (N = 16), and healthy controls (N = 14). McIsaac score and IRT imaging showed a 90% positive predictive value for streptococcal pharyngitis. While IRT alone could not distinguish between bacterial and viral infections, it significantly increased the predictive value when combined with the McIsaac score.

OBJECTIVE:To describe the impact of migraine on functioning based on comprehensive data collection, analysis, and reporting of patients' experiences. BACKGROUND:Qualitative research conducted to understand patients' perspectives on living with migraine has often focused on narrow topics or specific groups of patients or has been selectively reported. METHODS:Qualitative interviews with 71 participants were conducted during two concept elicitation studies as part of the Migraine Clinical Outcome Assessment System (MiCOAS) project, an FDA grant-funded program designed to develop a core set of patient-centered outcome measures for migraine clinical trials. Participants self-reported being diagnosed with migraine by a healthcare professional and participated in semi-structured qualitative interviews about their experiences with the symptoms and impacts of migraine. Interview transcripts were coded to identify and define concepts, which were then grouped into broad domains based on conceptual similarities. RESULTS:A total of 66 concepts were identified: 12 for physical functioning, 16 for cognitive functioning, 10 for social role functioning, 19 for emotional and psychological functioning, and 9 related to migraine management. Participants described a complex and varied relationship between migraine attack symptoms and impacts on functioning. Impacts from migraine were further influenced by numerous contextual factors, such as people's individual social environments and the level of day-to-day demand for functioning they face. CONCLUSION:Findings showed that migraine impacted individual functioning in multiple ways and the nature of these impacts was dependent on social-contextual factors. The results are being used in the development of core measures designed to improve our understanding of the burden of migraine and the efficacy of migraine therapies. The results also offer new insights and raise new questions about migraine experience that can be used to guide future research.

OBJECTIVE:To better understand the breadth and frequency of symptoms across the phases of the migraine cycle using data captured from qualitative patient interviews conducted through the Migraine Clinical Outcome Assessment System (MiCOAS) project. BACKGROUND:People living with migraine experience a range of symptoms across the pre-headache, headache, post-headache, and interictal phases of the migraine cycle. Although clinical diagnostic criteria and clinical trial endpoints focus largely on cardinal symptoms or monthly migraine days, migraine symptom profiles are far more complex. As a part of the MiCOAS project, semi-structured qualitative interviews were undertaken to better understand the migraine-related symptomology from the patient's viewpoint. METHODS:This concept elicitation study used iterative purposeful sampling to select 40 people with self-reported medical diagnosis of migraine for interviews that were conducted via audio-only web conferencing. Key topics related to migraine symptoms, including mood/emotion symptoms, were identified using content analysis. Interview transcripts were also coded to reflect the phase of migraine under discussion, so that patient experiences could be compared by phase. RESULTS:Forty participants (50%, n = 20 episodic migraine; 50%, n = 20 chronic migraine), aged from 21 to 70 years old reported a total of 60 unique symptoms, which were categorized into 30 broader symptom categories. Participants reported between 7 and 22 unique symptom categories across all phases. During pre-headache and headache, participants reported a median of 7.5 (interquartile range [IQR] = 5.5) and 8 (IQR = 4.0) different symptom categories compared to 4 (IQR = 3.0) and 1.5 (IQR = 2.5) for the post-headache and interictal periods, respectively. Head pain during the headache phase was the only universally reported symptom (100%, n = 40). Pooling across all phases, the next most reported symptoms were light sensitivity (93%, n = 37), nausea (88%, n = 35), irritability/impatience (83%, n = 24), sound sensitivity (80%, n = 32), and fatigue/exhaustion (80%, n = 32). One or more interictal symptoms were reported by 73% (n = 29) of participants and included mood/emotion symptoms, such as anxiety (30%, n = 12), depression (18%, n = 7), and anger (15%, n = 6), as well as cardinal symptoms, such as light sensitivity (13%, n = 5) and nausea (13%, n = 5). CONCLUSIONS:Patients experience a range of symptoms across the phases of the migraine cycle. Results often aligned with clinical expectations, but non-cardinal migraine-related symptoms were reported both inside and outside the headache phase, including between attacks. These discoveries highlight the importance of assessing a range of symptoms and timing when developing patient-reported outcome measures for migraine clinical trials.

BACKGROUND:Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance. OBJECTIVES:To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children. METHODS:We assessed 54 children aged 2-17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification. RESULTS:The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36). CONCLUSIONS:Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.

Familial Mediterranean Fever (FMF) patients are required to adhere to a life-long treatment with colchicine, primarily for preventing amyloidosis. As some patients may be asymptomatic for long periods of time, it remains unclear whether it is possible to discontinue colchicine treatment in a selective group of patients. We aimed to identify predictive characteristics for a successful cessation of colchicine therapy. Out of 646 FMF pediatric patients followed in our referral FMF clinic, colchicine treatment was discontinued in 51 patients. In this study we compared the genetic, demographic, and clinical characteristics between patients for whom a successful cessation of therapy was made (Group 1; n = 21) and patients for whom cessation of therapy was deemed a failure (Group 2; n = 30) and consequently had to resume colchicine therapy. Patients for whom a successful cessation of therapy was achieved had no biallelic pathogenic MEFV mutations, were less likely to have “severe attacks” (two or more FMF characteristic symptoms) (24% vs 80%; P = 0.000067) and did not require higher than 1 mg/day of colchicine, prior to the drug cessation. Remission duration under colchicine treatment was significantly higher in group 1 compared with group 2 (4.36 years ±2.12 vs 2.53 years ±2; P = 0.0036). This study supports the concept of colchicine free remission in a minority of FMF patients (3%). Holding treatment, under close monitoring, may be reasonable when selecting the appropriate patients.

Objectives: To capture patients' perspectives on migraine-related cognitive symptoms during pre-headache, headache, post-headache, and interictal periods.Background: Migraine-related cognitive symptoms are reported by people with migraine both during and between attacks. Associated with disability, they are increasingly viewed as a priority target for treatment. The Migraine Clinical Outcome Assessment System (MiCOAS) project is focused on developing a patient-centered core set of outcome measures for the evaluation of migraine treatments. The project focuses on incorporating the experience of people living with migraine and the outcomes most meaningful to them. This includes an examination of the presence and functional impact of migraine related cognitive symptoms and their perceived impact on quality of life and disability.Methods: Forty individuals with self-reported medically diagnosed migraine were recruited via iterative purposeful sampling for semi-structured qualitative interviews conducted using audio only web conferencing. Thematic content analysis was performed to identify key concepts around migraine-related cognitive symptoms. Recruitment continued until concept saturation was achieved.Results: Participants described symptoms consistent with migraine-related deficits in language/speech, sustained attention, executive function, and memory that manifest during pre-headache (36/40 [90%] reported >= 1 cognitive feature), headache (35/40 [88%] reported >= 1 cognitive feature), post-headache (27/40 [68%] reported >= 1 cognitive feature), and interictal periods (13/40 [33%] reported >= 1 cognitive feature). Among participants reporting cognitive symptoms during pre-headache, 32/40 (81%) endorsed 2- 5 cognitive symptoms. Findings were similar during the headache phase. Participants reported language/speech problems consistent with, for example, impairments in receptive language, expressive language, and articulation. Issues with sustained attention included fogginess, confusion/disorientation, and trouble with concentration/focus. Deficits in executive function included difficulty processing information and reduced capacity for planning and decision-making. Memory issues were reported across all phases of the migraine attack.Conclusions: This patient level qualitative study suggests that cognitive symptoms are common for persons with migraine, particularly in the pre-headache and headache phases. These findings highlight the importance of assessing and ameliorating these cognitive problems.

ObjectiveThree aims: to elucidate determinants associated with COVID-19 vaccine uptake in children and the association with parental vaccination; to compare rates of PCR-positive SARS-CoV-2 results between vaccinated and unvaccinated children; to estimate the rate of parental COVID-19 vaccination and its association with the vaccination rate of their children.MethodsWe performed a retrospective chart review of all children aged 5–11 years registered at a central district in Israel from November 21st, 2021 to April 30th, 2022, and characterized COVID-19 vaccinated vs. unvaccinated individuals. Data retrieved from the electronic medical files included: demographics [age, gender, sector, socioeconomic status (SES)]; COVID-19 vaccination (first and second doses) and influenza vaccination status; co-morbidities; and parental vaccinations for COVID-19. We divided the population into three distinct demographic groups: non-ultra-orthodox Jews (43,889 children), ultra-orthodox Jews (13,858 children), and Arabs (4,029 children).ResultsOf the 61,776 children included in the study, 20,355 (32.9%) received at least one dose of the COVID-19 vaccine. Vaccination rates were similar amongst males and females and were higher in children aged 9–11 years compared to children aged 5–6 years. Multivariate analysis identified five independent determinants that were significantly (p < 0.001) associated with low vaccination rates: Arab and ultra-orthodox sectors (odds ratios: 0.235 and 0.617, respectively); children aged 5–8 years; children of low SES; and children who had not received previous seasonal influenza vaccination. Relatively high vaccination rates were noted amongst children with the following medical co-morbidities: treatment with biological agents (42.9%); solid tumor transplantation (42.9%); type 1 diabetes mellitus (38.5%), asthma (38.2%), and attention deficit and hyperactivity disorder (ADHD) (37.6%). Regarding the uptake of two vaccine doses among children with co-morbidities, it was highest in those with type 1 diabetes mellitus, heart failure, treatment with biological agents, asthma and obesity.ConclusionThis study highlights several pediatric sub-populations with low and high vaccine uptake. It is essential to focus on determinants associated with low vaccination rates.

We aimed to investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with community-acquired pneumonia (CAP). Antibiotic purchasing data were collected for children aged 3 months to 18 years diagnosed with CAP from November 2016 to April 2017 (pre-intervention period) and from November 2017 to April 2018 (post-intervention period). The intervention was a 1-day seminar for primary care pediatricians on the diagnosis and treatment of CAP in children according to national guidelines. There was a substantial decrease in the use of azithromycin after the intervention. In younger children, there was a 42% decrease, alongside an increased use of amoxicillin ( P < .001). In older children, there was a smaller, non-statistically significant decrease in the use of azithromycin ( P = .45). Our data demonstrate that the implementation of an ASP was associated with a reduction in the use of broad-spectrum antibiotics and macrolides and increased guideline adherence for the safe treatment of CAP.

Rapid advances in precision medicine promise dramatic reductions in morbidity and mortality for a growing array of conditions. To realize the benefits of precision medicine and minimize harm, it is necessary to address real-world challenges encountered in translating this research into practice. Foremost among these is how to choose and use precision medicine modalities in real-world practice by addressing issues related to caring for the sizable proportion of people living with multimorbidity. Precision medicine needs to be delivered in the broader context of precision care to account for factors that influence outcomes for specific therapeutics. Precision care integrates a person-centered approach with precision medicine to inform decision making and care planning by taking multimorbidity, functional status, values, goals, preferences, social and societal context into account. Designing dissemination and implementation of precision medicine around precision care would improve person-centered quality and outcomes of care, target interventions to those most likely to benefit thereby improving access to new therapeutics, minimize the risk of withdrawal from the market from unanticipated harms of therapy, and advance health equity by tailoring interventions and care to meet the needs of diverse individuals and populations. Precision medicine delivered in the context of precision care would foster respectful care aligned with preferences, values, and goals, engendering trust, and providing needed information to make informed decisions. Accelerating adoption requires attention to the full continuum of translational research: developing new approaches, demonstrating their usefulness, disseminating and implementing findings, while engaging patients throughout the process. This encompasses basic science, preclinical and clinical research and implementation into practice, ultimately improving health. This article examines challenges to the adoption of precision medicine in the context of multimorbidity. Although the potential of precision medicine is enormous, proactive efforts are needed to avoid unintended consequences and foster its equitable and effective adoption.

Objective To compare the rate of the administration of the Pfizer–BioNTech COVID-19 vaccinations between adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) and non-ADHD subjects. Method A retrospective chart review was performed on all adolescents aged 12–17 years registered at a central district in Israel from January 1st 2021 to October 31st 2021. Results Of the 46,544 subjects included in the study, 8241 (17.7%) were diagnosed with ADHD. Of them, 3% were PCR-COVID-19 positive. Among the patients with ADHD, the older adolescents were more likely to be vaccinated: 48.8% of those aged 12-15 years were vaccinated versus 59.6% of patients aged 16-17 years. The ultra-orthodox Jewish and Arab adolescents in the ADHD group were far less likely to be vaccinated (22.9% and 34.6%, respectively), compared to the adolescents with ADHD in the general population (60.5%). Girls were also somewhat more likely to be vaccinated. Conclusions Adolescents diagnosed with ADHD had a higher COVID-19 vaccination rate compared to their non-ADHD counterparts. The vaccine uptake was lower amongst Arab and ultra-orthodox Jewish populations.

BACKGROUND:Many primary school children withhold urine and stool whilst at school for various reasons. Limited toilet access and the failure to provide safe, sanitary toilets are putting children at risk for toilet avoidance behavior.OBJECTIVE:We aimed to examine personal hygiene, environmental conditions, the perception of these on children, and their toilet use in primary schools.STUDY DESIGN:Children aged 6-12 and their parents were asked to complete a self-report questionnaire regarding toilet behavior and the perception of school toilet standards.RESULTS:The main findings are listed below using the data from the questionnaire.DISCUSSION:We found that 9% and 63% of the children avoided urination and defecating at school, respectively. Similar results were reported previously. The participants' perceptions regarding the environmental conditions of school toilets and conditions revealed that 34% of the children felt that the toilets were dirty or very dirty. Around one-third of them reported a lack of toilet paper sometimes or most of the time. These unsatisfying hygienic conditions of school toilets can be easily solved. Unfortunately, 46% of the children in our study experienced bullying in school toilets. These worrisome data are seldom reported in other studies. The urination habits of the girls, who mostly preferred to partially squat or stand may lead to dysfunctional voiding and incomplete bladder emptying. Our study was limited by the relatively small population, the subjectiveness of the self-reporting questionnaire, and the voiding and defecation habits of the investigated children during school hours. These hours do not necessarily reflect the children's habits after school hours and during the weekends. Despite these limitations, the discussed issues regarding personal hygiene and the environmental conditions in the sampled primary schools are extremely important.CONCLUSION:Nearly half of the school children had negative perceptions of school toilets. This should raise awareness and concern for school staff to consider and investigate potential facilities improvement in light of the impact observed here. Implementation of appropriate education and a better environment of toilet facilities and security is important for the children's well-being.

Abstract Introduction Familial Mediterranean Fever (FMF) is the most common monogentic autoinflammatory disease. FMF results from mutations in MEFV, which lead to a pro-inflammatory state and increased production of Interleukin 1 beta subunit (IL-1b) by myeloid cells. Despite the overall positive results obtained with anti-IL-1 agents in FMF patients, little is known about the long-term growth impact of these drugs in the pediatric population. Objectives To assess the long-term body weight and height trajectories in children with FMF treated with anti-IL-1 agents. Methods We conducted a retrospective analysis of 646 pediatric FMF patients followed in our center, of whom 22 were treated with either anakinra (36.3%) and/or canakinumab (90.9%). Patients were assessed for demographic, clinical and genetic characteristics and were followed for a mean of 3.05 ± 1.75 years. Data of height and weight percentiles were recorded before and after treatment. Results The most common indication for IL-1 blockers treatment was colchicine resistance (66.6%). Ninety percent of those patients had a moderate or severe disease according to the Pras score and had higher proportion of M694V homozygosity compared with patients who did not require anti IL-1 agents (95.2% vs. 30.5%, p < 0.001). Overall, anakinra and canakinumab resulted in a complete response in 80% of patients and exhibited low rates of adverse effects. We found a significant increase in height and body weight percentiles following treatment (19.6 ± 16% vs. 30.8 ± 23%, p = 0.007, and 29.5 ± 30% vs. 39.1 ± 36%, p = 0.043, respectively). Conclusion Treatment with anti-IL-1 agents in children with FMF is effective and safe and may potentiate long-term growth.

BackgroundThere is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment.ObjectivesTo obtain insights directly from people living with migraine on their priorities for treatment.MethodsA total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant-funded program to develop a core set of patient-centered outcome measures for migraine clinical trials. Interviews included a structured exercise in which participants rank-ordered pre-defined lists of potential benefits for acute and preventive migraine therapy. The 40 study participants who reported being diagnosed with migraine by a clinician ranked the benefits and explained their rationale.ResultsStudy participants consistently ranked either pain relief or absence of pain as their top priority for acute treatment. Relief/absence of other migraine symptoms and improved functioning were also prioritized. For preventive treatment, participants prioritized reductions in migraine frequency, symptom severity, and attack duration. Few differences were found between participants with episodic migraine and those with chronic migraine. However, participants with chronic migraine ranked "increased predictability of attacks" much higher than those with episodic migraine. Participants' rankings were influenced by prior expectations and experiences of migraine treatments, which caused many participants to deprioritize desired benefits as unrealistic. Participants also identified several additional priorities, including limited side-effects and reliable treatment efficacy in both acute and preventive treatments.ConclusionThe results showed the participants prioritized treatment benefits aligned with existing core clinical outcomes used in migraine research, but also valued benefits that are not typically assessed, such as predictability. Participants also deprioritized important benefits when they believed treatment was unlikely to deliver those outcomes.

Objectives: We sought to understand the knowledge, attitudes, and beliefs of emergency medicine (EM) physicians towards non-specific neurological conditions and the use of clinical decision support (CDS) to improve diagnostic accuracy. Methods: We conducted semi-structured interviews of EM physicians at four emergency departments (EDs) affiliated with a single US healthcare system. Interviews were conducted until thematic saturation was achieved. Conventional content analysis was used to identify themes related to EM physicians' perspectives on acute diagnostic neurology; directed content analysis was used to explore views regarding CDS. Each interview transcript was independently coded by two researchers using an iteratively refined codebook with consensus-based resolution of coding differences. Results: We identified two domains regarding diagnostic safety: (1) challenges unique to neurological complaints and (2) challenges in EM more broadly. Themes relevant to neurology included: (1) knowledge gaps and uncertainty, (2) skepticism about neurology, (3) comfort with basic as opposed to detailed neurological examination, and (4) comfort with non-neurological diseases. Themes relevant to diagnostic decision making in the ED included: (1) cognitive biases, (2) ED system/environmental issues, (3) patient barriers, (4) comfort with diagnostic uncertainty, and (5) concerns regarding diagnostic error identification and measurement. Most participating EM physicians were enthusiastic about the potential for well-designed CDS to improve diagnostic accuracy for non-specific neurological complaints. Conclusions: Physicians identified diagnostic challenges unique to neurological diseases as well as issues related more generally to diagnostic accuracy in EM. These physician-reported issues should be accounted for when designing interventions to improve ED diagnostic accuracy.

CF-IQ, a 23-item patient-reported outcome instrument assessing the life impacts of CF, was recently validated in people with CF aged ≥18 years. This study aimed to qualitatively evaluate the content validity of the CF-IQ in adolescents (aged 12-17 years) with CF.

BACKGROUND:On 18 March 2020, the Israeli Health Ministry issued lockdown orders to mitigate the spread of coronavirus disease 2019 (COVID-19).OBJECTIVES:To assess the association of lockdown orders on telemedicine practice and the effect of social distancing on infectious diseases in a primary care community pediatric clinic as well as the rate of referrals to emergency departments (ED) and trends of hospitalization.METHODS:Investigators performed a retrospective secondary data analysis that screened for visits in a large pediatric center from 1 January to 31 May 2020. Total visits were compared from January to December 2020 during the same period in 2019. Visits were coded during the first lockdown as being via telemedicine or in-person, and whether they resulted in ED referral or hospitalization. Month-to-month comparisons were performed as well as percent change from the previous year.RESULTS:There was a sharp decline of in-person visits (24%) and an increase in telemedicine consultations (76%) during the first lockdown (p < 0.001). When the lockdown restrictions were eased, there was a rebound of 50% in-person visits (p < 0.05). There was a profound decrease of visits for common infectious diseases during the lockdown period. Substantial decreases were noted for overall visits, ED referrals, and hospitalizations in 2020 compared to 2019.CONCLUSIONS:COVID-19 had a major impact on primary care clinics, resulting in fewer patient-doctor encounters, fewer overall visits, fewer ED referrals, and fewer hospitalizations.

The coronavirus disease 2019 (COVID‐19) pandemic is an ongoing global health crisis that has had a range of impacts on people living with migraine.

Objective: To postulate that ADHD is a potential risk factor for COVID-19 infection; to evaluate the COVID-19 risk factor on drug-treated ADHD subjects. Methods: A retrospective chart review was performed on ADHD subjects aged 6 to 18 years in Israel, who had undergone at least one COVID-19 test during the study period. Results: Of the 64,409 subjects included in the study, 6,207 (9.64%) had at least one positive COVID-19 test result, 13,300 (20.65%) were diagnosed with ADHD, and of whom 1,751 (13%) had purchased at least two ADHD medications 3 months prior to COVID-19 testing and were defined as being medically treated. Medically-treated ADHD subjects had a significantly lower likelihood to be infected with COVID-19 than untreated subjects. Conclusion: Untreated ADHD patients seem to constitute a risk group for COVID-19 infection. Drug treatment ameliorates risk of spreading COVID-19 infection within the pediatric population and secondary spread in the general population.