Acceptance of Seasonal Influenza Vaccine Following COVID-19 Vaccination: A Survey among Israel Defense Forces Soldiers.

Data regarding the contribution of COVID-19 vaccine rollouts to real-world uptake of influenza vaccination remains unclear. This cross-sectional survey-based study among Israel Defense Forces (IDF) soldiers aimed to assess the impact of the COVID-19 pandemic and specifically, previous COVID-19 vaccines uptake, on the intention to vaccinate for influenza during 2021-2022 season. Participants engaged in an online survey addressing vaccination history and current vaccine-related preferences. The survey was delivered prior to the initiation of the IDF's annual influenza immunization campaign. A multinomial logistic regression model was applied to analyze factors correlated with unwillingness to receive influenza vaccine. Overall, 825 invitations to participate in the survey were distributed and the overall response rate was 78.5%. Among the 648 participants who replied (61.6% males, median age of 20 years), 51.9% were willing to receive the upcoming influenza vaccine. Factors associated with vaccine reluctance included being female, not receiving the previous season's influenza vaccine, not having a previous diagnosis of COVID-19, and having decreased uptake of COVID-19 vaccines. Among participants not intending to receive an influenza vaccine, 50.3% stated that they are healthy and have no need for the vaccine and 36.2% stated they received too many vaccines over the previous year. The results of this study may suggest that influenza vaccination rates in the post-COVID-19 vaccine era may be reduced due to a perceived "vaccine saturation" phenomenon, owing to the density of COVID-19 vaccine administration. Future interventions such as campaigns related to maximizing influenza vaccination coverage should address repeated doses of COVID-19 vaccine administration.

Exercise-induced albuminuria increases over time in individuals with impaired glucose metabolism.

BACKGROUND: Exercise induced albuminuria (EiA) is elevated in patients with metabolic dysfunction and diabetes, and may serve as an early biomarker for endothelial dysfunction and "kidney reserve". However, the change in EiA levels over time and its interaction with metabolic dysfunction and glucose metabolism has never been studied. Therefore, we sought to determine EiA levels over time in a cohort of individuals attending a routine annual health survey. METHODS: We prospectively enrolled 412 patients attending an annual healthy survey at our Medical Center. We collected urine samples for albumin and creatinine measurements before and immediately after completing an exercise stress test, along with multiple physiologic and metabolic parameters. Participants returned to a second follow up visit after a mean follow up period of 3 years (± 1.7 SD). RESULTS: Patients with diagnosed diabetes and subjects with HbA1c ≥ 6.5% significantly increased their EiA over time (median [IQR] change between visits = 19.5 [- 10.4-56.1] vs. - 1.1 [- 12.7-4.9] (p = 0.049) for diabetics vs non-diabetics respectively). Moreover, a diabetes diagnosis was significantly associated with a high increase in EiA over time (top 10th percentile) even after adjusting for age, BMI, eGFR, METs, self-reported history of heart disease, systolic and diastolic blood pressure; OR = 4.4 (1.01-19.3 95% CI) (p = 0.049). Finally, elevated fasting blood glucose (≥ 100 mg/dl) was the strongest and only significant predictor for a greater increase in EiA over time after adjusting for all five metabolic syndrome components; blood glucose, waist circumference, blood triglycerides, HDL cholesterol, and BP criteria; OR = 4.0 (1.6-9.8 95% CI) (p < 0.01). CONCLUSIONS: Patients with diabetes and/or elevated fasting blood glucose increase their exercise-induced urinary albumin excretion over time. The ability of EiA to predict major clinical outcomes in patients with and without diabetes needs to be determined in future studies.

Exercise capacity and body mass index - important predictors of change in resting heart rate.

BACKGROUND: Resting heart rate (RHR) is an obtainable, inexpensive, non-invasive test, readily available on any medical document. RHR has been established as a risk factor for cardiovascular morbidity, is related to other cardiovascular risk factors, and may possibly predict them. Change in RHR over time (∆RHR) has been found to be a potential predictor of mortality. METHODS: In this prospective study, RHR and ∆RHR were evaluated at baseline and over a period of 2.9 years during routine check-ups in 6683 subjects without known cardiovascular disease from the TAMCIS: Tel-Aviv Medical Center Inflammation Survey. Multiple linear regression analysis with three models was used to examine ∆RHR. The first model accounted for possible confounders by adjusting for age, sex and body mass index (BMI). The 2nd model included smoking status, baseline RHR, diastolic blood pressure (BP), dyslipidemia, high-density lipoprotein (HDL) and metabolic equivalents of task (MET), and in the last model the change in MET and change in BMI were added. RESULTS: RHR decreased with age, even after adjustment for sex, BMI and MET. The mean change in RHR was - 1.1 beats/min between two consecutive visits, in both men and women. This ∆RHR was strongly correlated with baseline RHR, age, initial MET, and change occurring in MET and BMI (P < 0.001). CONCLUSIONS: Our results highlight the need for examining individual patients' ∆RHR. Reinforcing that a positive ∆RHR is an indicator of poor adherence to a healthy lifestyle.

Are intelligent people more likely to get vaccinated? The association between COVID-19 vaccine adherence and cognitive profiles.

INTRODUCTION: Since vaccination adherence is crucial in reducing morbidity and mortality during a pandemic, we characterized the association between demographic, intelligence, and personal attributes and COVID-19 vaccination adherence among young adults. METHODS: Cohort study including vaccination data of 185,061 personnel, collected during 13 months of COVID-19 vaccination campaign, while a wide array of vaccination incentives were offered. The effect of demographic data (age, gender and socioeconomic status), military medical fitness - fit for combat service, administrative service, or unfit (volunteering), general intelligence score (GIS) and military social score (MSS) assessing social abilities, on vaccine adherence (allocating by IMOH guidelines) was examined. RESULTS: Adherent (vs. nonadherent) personnel presented higher GIS (mean 5.68 ± 1.84 vs. 4.72 ± 1.91) and MSS (median 26 (IQR 23-29) vs. 24 (IQR 19-26)), p < 0.001 for both. Higher intelligence was the strongest predictor for vaccine adherence (OR = 5.38, 95 %CI 5.11-5.67, p < 0.001). The probability for vaccine adherence increased in association with escalating GIS scores, with highest GIS females more likely to adhere to vaccination than same-level males (OR = 5.66, 95 %CI 5.09-6.28 vs. OR = 3.69, 95 %CI 3.45-3.94, respectively, p < 0.001 for both). Medically fit service-members were approximately three times as likely to be adherent than volunteering personnel (OR = 2.90 (95 %CI 2.65-3.17) for administrative and OR = 2.94 (95 %CI 2.70-3.21) for combative fitness, p < 0.001 for both). CONCLUSIONS: During a COVID-19 vaccination campaign, addressing vaccine hesitancy contributing factors and providing wide vaccine availability, GIS and physical fitness had the strongest association with vaccination adherence among young adults. When planning future vaccination campaigns, implementing these insights should be considered to improve adherence.

B.1.1.7 Variant Outbreak in an Air Force Military Base-Real-World Data.

OBJECTIVE: To assess the clinical features and infectivity of variant B.1.1.7 among healthy young adults in a military setting. MATERIALS AND METHODS: Positive cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a single military base (March 23, 2020 and February 16, 2021) were included. An epidemiological investigation conducted via phone included questions regarding symptoms, exposure history, smoking status, list of contacts, and recently visited places. Symptoms surveyed included fever, cough, shortness of breath, sore throat, loss of smell or taste, gastrointestinal symptoms (GI), headache, chest pain, and constitutional symptoms. Cases were divided before B.1.1.7 first reported case in Israel (December 23, 2020) (period 1) and after its identification (period 2). Symptom distribution and the risk of a contact to be infected were compared between the periods, using a chi-square test, and a negative binominal regression model, respectively. RESULTS: Of 293 confirmed cases, 89 were reported in the first period and 204 in the second. 56.0% were men with a median age of 19.5 years (interquartile range 18.6-20.5). GI symptoms, loss of taste or smell, headache, fever, and chills were more prevalent in the first period (P < .001, P = .026, P = .034, P = .001, and P < .001, respectively), while fatigue was more common in the second period (P = .008). The risk of a contact to be infected was three times higher in the second period (relative risk = 3.562 [2.414-5.258]). CONCLUSION: An outbreak of SARS-CoV-2 in young healthy adults, during a period with high national-wide B.1.1.7 variant prevalence, is characterized by decreased prevalence of fever, loss of taste or smell and GI symptoms, increased reports of fatigue, and more infected contacts for each index case.

Germline CDKN1B variant type and site are associated with phenotype in MEN4.

Multiple endocrine neoplasia 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome clinically hallmarked by primary hyperparathyroidism (PHPT), pituitary adenoma (PitAd), and neuroendocrine tumors (NET), clinically overlapping MEN1. The underlying mutated gene - CDKN1B, encodes for the cell-cycle regulator p27. Possible genotype-phenotype correlations in MEN4 have not been thoroughly assessed. Prompted by the findings in three Israeli MEN4 kindreds, we performed a literature review on published and unpublished data from previously reported MEN4/CDKN1B cases. Univariate analysis analyzed time-dependent risks for developing PHPT, PitAd, or NET by variant type and position along the gene. Overall, 74 MEN4 cases were analyzed. PHPT risk was 53.4% by age 60 years (mean age at diagnosis age 50.6 ± 13.9 years), risk for PitAd was 23.2% and risk for NET was 16.2% (34.4 ± 21.4 and 52.9 ± 13.9 years, respectively). The frameshift variant p.Q107fs was the most common variant identified (4/41 (9.7%) kindreds). Patients with indels had higher risk for PHPT vs point mutations (log-rank, P = 0.029). Variants in codons 94-96 were associated with higher risk for PHPT (P < 0.001) and PitAd (P = 0.031). To conclude, MEN4 is clinically distinct from MEN1, with lower risk and older age for PHPT diagnosis. We report recurrent CDKN1B frameshift variants and possible genotype-phenotype correlations.

Characterization of Meningitis and Meningoencephalitis in the Israeli Defense Forces From 2004 to 2015: A Population-Based Study.

Background: Meningitis and meningoencephalitis (MME) are potential medical emergencies. Mandatory reporting of all MME cases in the Israel Defense Force (IDF) allows accurate characterization of MME incidence and course. In the present study, we described the epidemiology of MME in soldiers. Methods: Medical charts of 860,000 combat and non-combat soldiers serving during the years 2004-2015, accounting for 2,256,060 patient years, were retrospectively evaluated. The diagnosis of MME was based on signs of meningeal irritation and a count of > 5 white blood cells (WBC) in the cerebrospinal fluid (CSF). Data on the diagnosis of bacterial or aseptic MME, significant sequelae, and associated mortality were collected. Results: Approximately 273 cases of MME were diagnosed. Overall, MME incidence was 12.1/100,000 patient-years. Bacterial and viral pathogens were identified in 31/273 (11.4%) and 52/273 (19%) cases, respectively. Combat soldiers had higher incidence of bacterial meningitis [14/40 (35%) vs. 31/212 (14.6%); p = 0.002] and meningoencephalitis [13/40 (32.5%) vs. 33/212 (15.6%); p = 0.023] compared to non-combat soldiers. Their clinical presentation was more severe, including confusion [10/40 (25%) vs. 22/212 (10.4%); p = 0.018], focal neurological deficits [12/40 (30%) vs. 11/212 (5.2%); p < 0.0001], and status epilepticus [3/40 (7.5%) vs. 0/212 (0.0%); p < 0.01]. Mortality among combat soldiers was higher [5/40 (15%) vs. 1/212 (0.5%); p < 0.001]. N. meningitidis was the most frequently isolated bacteria, despite universal preventative vaccination. Conclusion: The incidence of bacterial MME in the IDF is higher than in the civilian population. Combat soldiers present with higher incidence of meningoencephalitis and bacterial meningitis.

Association between SARS-CoV-2 infection and the physical fitness of young-adult cadets: a retrospective case-control study.

OBJECTIVES: To determine the association of symptomatic and asymptomatic mild COVID-19 and the SARS-CoV-2 viral load with the physical fitness of army cadets. DESIGN: A retrospective case-control study. SETTING: Officers' Training School of the Israel Defense Forces. PARTICIPANTS: The study included all cadets (age, 20.22±1.17 years) in the combatant (n=597; 514 males, 83 females; 33 infected, all males) and non-combatant (n=611; 238 males, 373 females; 91 infected, 57 females, 34 males) training courses between 1 August 2020 and 28 February 2021. COVID-19 outbreaks occurred in September 2020 (non-combatants) and January 2021(combatants). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were the aerobic (3000 m race) and anaerobic (combatant/non-combatant-specific) physical fitness mean score differences (MSDs) between the start and end of the respective training courses in infected and non-infected cadets. Secondary outcome measures included aerobic MSD associations with various COVID-19 symptoms and SARS-CoV-2 viral loads. RESULTS: SARS-CoV-2 infection led to declined non-combatant and combatant aerobic fitness MSD (14.53±47.80 vs -19.19±60.89 s; p<0.001 and -2.72±21.74 vs -23.63±30.92 s; p<0.001), but not anaerobic. The aerobic physical fitness MSD decreased in symptomatic cadets (14.69±44.87 s) and increased in asymptomatic cadets (-3.79±31.07 s), but the difference was statistically insignificant (p=0.07). Symptomatic cadets with fever (24.70±50.95 vs -0.37±33.87 s; p=0.008) and headache (21.85±43.17 vs 1.69±39.54 s; p=0.043) had more positive aerobic physical fitness MSD than asymptomatic cadets. The aerobic fitness decline was negatively associated with viral load assessed by the RNA-dependent RNA polymerase (n=61; r = -0.329; p=0.010), envelope (n=56; r = -0.385; p=0.002) and nucleus (n=65; r = -0.340; p=0.010) genes. CONCLUSIONS: SARS-CoV-2 infection was associated with a lingering decline in aerobic, but not anaerobic, fitness in symptomatic and asymptomatic young adults, suggesting possible directions for individualised symptom-dependent and severity-dependent rehabilitation plans' optimisation.

Sub-cutaneous Pfizer/BioNTech COVID-19 vaccine administration results in seroconversion among young adults.

Route of vaccine administration plays a role in extent and quality of immunogenicity. 790 military personnel accidentally received the first of two doses of Pfizer/BioNTech mRNA anti Covid-19 vaccine using a needle intended for subcutaneous administration. A serological blood test (on day 21, prior to the second intramuscular dose) was performed, analyzing whether immunological response was elicited. 98.2% demonstrated seroconversion. IgG titers were negatively correlated with age and did not correlate with BMI. Our results could help reassure providers confronted with a similar mistake and may even imply a possibly new and effective administration route.

Stuttering and Incident Type 2 Diabetes: A Population-Based Study of 2.2 Million Adolescents.

PURPOSE: To investigate the association between stuttering in adolescence and incident type 2 diabetes in young adulthood. METHODS: This nationwide population-based study included 2 193 855 adolescents of age 16 to 20 years who were assessed for military service between 1980 and 2013. Diagnoses of stuttering in adolescence were confirmed by a speech-language pathologist. Diabetes status for each individual as of December 31, 2016, was determined by linkage to the Israeli National Diabetes Registry. Relationships were analyzed using regression models adjusted for socioeconomic variables, cognitive performance, coexisting morbidities, and adolescent body mass index. RESULTS: Analysis was stratified by sex (Pinteraction = 0.035). Of the 4443 (0.4%) adolescent men with stuttering, 162 (3.7%) developed type 2 diabetes, compared with 25 678 (2.1%) men without stuttering (adjusted odds ratio [OR] 1.3; 95% CI, 1.1-1.6). This relationship persisted when unaffected brothers of men with stuttering were used as the reference group (adjusted OR = 1.5; 95% CI, 1.01-2.2), or when the analysis included only adolescents with unimpaired health at baseline (adjusted OR = 1.4; 95% CI, 1.1-1.7). The association was stronger in later birth cohorts, with an adjusted OR of 2.4 (1.4-4.1) for cases of type 2 diabetes before age 40. Of the 503 (0.1%) adolescent women with stuttering 7 (1.4%) developed type 2 diabetes, compared with 10 139 (1.1%) women without stuttering (OR = 2.03; 95% CI, 0.48-2.20). CONCLUSIONS: Adolescent stuttering is associated with an increased risk for early-onset type 2 diabetes among men.

The ability of the wide range CRP assay to classify individuals with low grade inflammation into cardiovascular risk groups.

BACKGROUND: High sensitivity C-reactive protein (hsCRP) has become a routine assessment tool to discriminate between patients at low, intermediate or high risk for cardiovascular events using the threshold values of 1 and 3mg/L, respectively. Over the past years, several studies have proposed the wide range C-reactive protein (wrCRP) as an alternative to the hsCRP in various clinical scenarios. However, the potential use of wrCRP in assessing the cardiovascular risk has not yet been evaluated. METHODS: Both wrCRP and hsCRP were evaluated in 15,780 apparently healthy individuals who underwent a routine annual checkup in the Tel Aviv Sourasky Medical Center. Individuals with CRP levels >5mg/L were excluded. Agreement between the two methods was observed using the Bland-Altman method and the concordance correlation coefficient. Deming regression was used to build a calibration equation. Reclassification of individuals' risk level was observed and Cohen's kappa was used to evaluate risk agreement. RESULTS: A high correlation (r=0.98) along with a significant difference (p<0.001) between hsCRP and wrCRP raised the need for calibration. A simple calibration equation (Adjusted wrCRP=0.3136+0.8803×wrCRP) led to high agreement which enabled 8.4% reclassification of the risk group. A change in the intermediate risk threshold value from 1 to 0.9mg/L led to an almost perfect agreement (kappa=0.87, p<0.001) and a low reclassification rate (7.6%), with under 0.05% of the population undergoing a major reclassification (from high to low risk or vice versa). CONCLUSIONS: In the era of limited financial resources, wrCRP assay may be used as a reasonable routine assay to evaluate the cardiovascular risk in patients undergoing a routine annual checkup.

Automatic assessment of cardiac load due to acute pulmonary embolism: Saddle vs. central and peripheral emboli distribution.

BACKGROUND: Changes in cardiac chambers' volumes in relations to different distributions of pulmonary embolism (PE) have not been investigated. OBJECTIVES: To compare cardiac chambers' volumes of patients with saddle, central or peripheral PE. METHODS: Consecutive patients with PE on computed tomography pulmonary angiography (CTPA), 1/2007-12/2010, divided according to emboli distribution. Software automatically provided the volumes of each cardiac compartment. We measured the ability of each chamber's volume and ratios between the right and left ventricles (RV/LV) and right and left atria (RA/LA) to discriminate between emboli locations. RESULTS: Among the 636 patients, 325 (51%) had peripheral, 278 (44%) central and 33 (5%) had saddle emboli. The RV/LV and RA/LA volume ratios discriminated well between saddle and central PE (AUC ≥0.74) and saddle and peripheral PE (AUC ≥0.83), but not between central and peripheral PE (AUC ≤0.6). CONCLUSION: Automatic volumetric analysis of diagnostic CTPAs provides rapid tool which can discriminate between cardiac responses in saddle, central or peripheral PE.

Prediction of Mortality in Pulmonary Embolism Based on Left Atrial Volume Measured on CT Pulmonary Angiography.

BACKGROUND: Preliminary reports suggest that a small left atrium (LA) is associated with severe acute pulmonary embolism (PE). This study used data derived from volumetric analyses of computed tomographic pulmonary angiography (CTPA) to investigate whether a reduced LA volume can predict adverse outcome in a large series of patients with acute PE. METHODS: We retrospectively analyzed 756 consecutive patients who received a diagnosis of acute PE by nongated CTPA between January 2007 and December 2010. Each CTPA was investigated with volumetric analysis software that automatically provides the volumes of the LA, right atrium, right ventricle, and left ventricle. A classification tree divided the cardiac chamber volumes and ratios into categories according to mortality. Cox regression assessed the association between these categories and 30-day mortality after adjustment for age, sex, and clinical background. RESULTS: The final study group consisted of 636 patients who had successful volumetric segmentation and complete outcome data. Eighty-four patients (13.2%) died within 30 days of PE diagnosis. There was a higher mortality rate among patients with an LA volume ≤62 mL compared with those with an LA volume >62 mL (19.6% vs 8.9%, respectively; HR, 2.44; P < .001), a left ventricle volume ≤67 mL (16.4% vs 8.3%; HR, 1.8; P = .024) and a right atrium/LA volume ratio >1.2 (17% vs 9.4%; HR, 2.1; P = .002). A reduced LA volume was the best predictor of adverse outcome. CONCLUSIONS: Decreased LA volume is associated with higher mortality and is the first among the various cardiac compartments to predict mortality in patients with acute PE.

Drug-induced Brugada syndrome: Clinical characteristics and risk factors.

BACKGROUND: Cardiac arrest may result from seemingly innocuous medications that do not necessarily have cardiac indications. The best-known example is the drug-induced long QT syndrome. A less known but not necessarily less important form of drug-induced proarrhythmia is the drug-induced Brugada syndrome. OBJECTIVE: The purpose of this study was to identify clinical and ECG risk markers for drug-induced Brugada syndrome. METHODS: Reports of drug-induced Brugada syndrome recounted by an international database (http://www.brugadadrugs.org) were reviewed to define characteristics that identify patients prone to developing this complication. For each patient with drug-induced Brugada syndrome who had an ECG recorded in the absence of drugs, we included 5 healthy controls matched by gender and age. All ECGs were evaluated for Brugada-like abnormalities. RESULTS: Seventy-four cases of drug-induced Brugada syndrome from noncardiac medications were identified: 77% were male, and drug toxicity was involved in 46%. Drug-induced Brugada syndrome from oral medications generally occurred weeks after the initiation of therapy. Mortality was 13%. By definition, all cases had a type I Brugada pattern during drug therapy. Nevertheless, their ECG in the absence of drugs was more frequently abnormal than the ECG of controls (56% vs 33%, P = .04). CONCLUSION: Drug-induced Brugada syndrome from noncardiac drugs occurs predominantly in adult males, is frequently due to drug toxicity, and occurs late after the onset of therapy. Minor changes are frequently noticeable on baseline ECG, but screening is impractical because of a prohibitive false-positive rate.