Maternal hybrid immunity and risk of infant COVID-19 hospitalizations: national case-control study in Israel.

Hybrid immunity, acquired through vaccination followed or preceded by a COVID-19 infection, elicits robust antibody augmentation. We hypothesize that maternal hybrid immunity will provide greater infant protection than other forms of COVID-19 immunity in the first 6 months of life. We conducted a case-control study in Israel, enrolling 661 infants up to 6 months of age, hospitalized with COVID-19 (cases) and 59,460 age-matched non-hospitalized infants (controls) between August 24, 2021, and March 15, 2022. Infants were grouped by maternal immunity status at delivery: Naïve (never vaccinated or tested positive, reference group), Hybrid-immunity (vaccinated and tested positive), Natural-immunity (tested positive before or during the study period), Full-vaccination (two-shot regimen plus 1 booster), and Partial-vaccination (less than full three shot regimen). Applying Cox proportional hazards models to estimate the hazard ratios, which was then converted to percent vaccine effectiveness, and using the Naïve group as the reference, maternal hybrid-immunity provided the highest protection (84% [95% CI 75-90]), followed by full-vaccination (66% [95% CI 56-74]), natural-immunity (56% [95% CI 39-68]), and partial-vaccination (29% [95% CI 15-41]). Maternal hybrid-immunity was associated with a reduced risk of infant hospitalization for Covid-19, as compared to natural-immunity, regardless of exposure timing or sequence. These findings emphasize the benefits of vaccinating previously infected individuals during pregnancy to reduce COVID-19 hospitalizations in early infancy.

Maternal third dose of BNT162b2 mRNA vaccine and risk of infant COVID-19 hospitalization.

Infants are at a higher risk of Coronavirus Disease 2019 (COVID-19)-related hospitalizations compared to older children. In this study, we investigated the effect of the recommended third maternal dose of BNT162b2 COVID-19 vaccine during pregnancy on rates of infant COVID-19-related hospitalizations. We conducted a nationwide cohort study of all live-born infants delivered in Israel between 24 August 2021 and 15 March 2022 to estimate the effectiveness of the third booster dose versus the second dose against infant COVID-19-related hospitalizations. Data were analyzed for the overall study period, and the Delta and Omicron periods were analyzed separately. Cox proportional hazard regression models estimated hazard ratios and 95% confidence intervals (CIs) for infant hospitalizations according to maternal vaccination status at delivery. Among 48,868 live-born infants included in the analysis, rates of COVID-19 hospitalization were 0.4%, 0.6% and 0.7% in the third-dose, second-dose and unvaccinated groups, respectively. Compared to the second dose, the third dose was associated with reduced infant hospitalization with estimated effectiveness of 53% (95% CI: 36-65%). Greater protection was associated with a shorter interval between vaccination and delivery. A third maternal dose during pregnancy reduced the risk of infant hospitalization for COVID-19 during the first 4 months of life, supporting clinical and public health guidance for maternal booster vaccination to prevent infant COVID-19 hospitalization.

Postexposure-vaccine-prophylaxis against COVID-19.

During the COVID-19 pandemic, postexposure-vaccine-prophylaxis is not a practice. Following exposure, only patient isolation is imposed. Moreover, no therapeutic prevention approach is applied. We asked whether evidence exists for reduced mortality rate following postexposure-vaccine-prophylaxis. To estimate the effectiveness of postexposure-vaccine-prophylaxis, we obtained data from the Israeli Ministry of Health registry. The study population consisted of Israeli residents aged 12 years and older, identified for the first time as PCR-positive for SARS-CoV-2, between December 20th, 2020 (the beginning of the vaccination campaign) and October 7th, 2021. We compared "recently injected" patients-that proved PCR-positive on the same day or on 1 of the 5 consecutive days after first vaccination (representing an unintended postexposure-vaccine-prophylaxis)s-to unvaccinated control group. Among Israeli residents identified PCR-positive for SARS-CoV-2, 11 687 were found positive on the day they received their first vaccine injection (BNT162b2) or on 1 of the 5 days thereafter. In patients over 65 years, 143 deaths occurred among 1412 recently injected (10.13%) compared to 255 deaths among the 1412 unvaccinated (18.06%), odd ratio (OR) 0.51 (95% confidence interval [CI]: 0.41-0.64; p < 0.001). A significant reduction in the death toll was observed among the 55-64 age group, with 8 deaths occurring among the 1320 recently injected (0.61%) compared to 24 deaths among the 1320 unvaccinated control (1.82%), OR 0.33 (95% CI: 0.13-0.76; p = 0.007). Postexposure-vaccine-prophylaxis is effective against death in COVID-19 infection.

Effectiveness of a third BNT162b2 mRNA COVID-19 vaccination during pregnancy: a national observational study in Israel.

The Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses' vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy during two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022). Time-dependent Cox proportional-hazards regression models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,659 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83-96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26-99%), and 48% (95% CI 37-57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes.

Seasonal Variation of Testosterone Levels in a Large Cohort of Men.

Objectives: The aim of the study was to evaluate in a large cohort of males with a wide range of age, metabolic status, and coexistent morbidities whether month of blood test performance was associated with total and bioavailable testosterone levels independent of age, body mass index (BMI), existing cardiovascular disease (CVD), and CVD risk factors. Methods: Cross-sectional study includes data from computerized medical records of 27,328 men aged 20-70, treated by the largest healthcare organization in Israel, who had undergone testosterone measurement. In 7,940 subjects with available sex-hormone-binding globulin levels, bioavailable testosterone was calculated. Results: Total and bioavailable testosterone levels gradually decreased with age and BMI (P < 0.001) and were significantly lower in men with diabetes, hypertension, hyperlipidemia, and known CVD, but were higher in current smokers compared with nonsmokers (P < 0.001). Hormone levels were highest in August-October declined after and lowest in March. Overall, both total and bioavailable testosterone levels were significantly lower in March compared to August-October (P < 0.001). In a linear regression analysis, age, BMI, current smoking, and month of testing were independently associated with total (P < 0.001) and bioavailable testosterone levels (P=0.002), and diabetes was associated with total testosterone (P < 0.001). Conclusion: In a large cohort of men with a wide range of age, BMI, and comorbidities, month of testing was independently associated with total and bioavailable testosterone levels. These data provide strong evidence that seasonal variation has to be considered in clinical practice.

Patterns of longitudinal medical treatment of pediatric patients ever-diagnosed with attention deficit hyperactive disorder: A community-based, retrospective, naturalistic study.

BACKGROUND: Pharmacological treatment for ADHD exhibits much variation. Longitudinal prescription-filling trajectories are interesting objects to explore. The goal of this study is to identify distinct patterns of longitudinal prescription filling among pediatric patients who were ever diagnosed with ADHD. METHODS: Longitudinal data of ADHD-specific prescription filling during 2010-2019 of children diagnosed with ADHD during 2000-2019 who were 4-17-years-old at the time of diagnosis was obtained. Clustering of prescription-filling vectors was performed using K-means. RESULTS: Analysis of 57,110 prescription vectors yields five distinct patterns: high intensity treatment, from early childhood to late teens (5.7%); moderate intensity, from early childhood to late teens (13.3%); high intensity, from late childhood to late teens (6.1%); moderate intensity, from late childhood to late teens (14.2%); and low intensity, sporadic treatment (60.7%). These patterns correspond with observed clinical presentations. CONCLUSIONS: Identifying longitudinal prescription-filling patterns substantiates and qualifies the variation in long-term efficacy of pharmacological treatment for ADHD in a treatment-as-usual community setting. Prescription-filling implies that symptoms are present, and that treatment is efficacious, as perceived by parents' and carers. Prolonged pharmacological treatment was perceived to have had a positive net value for 40% of the children, which under appropriate reservations, provides weak evidence of efficacy.

Skin exposure to UVB light induces a skin-brain-gonad axis and sexual behavior.

Ultraviolet (UV) light affects endocrinological and behavioral aspects of sexuality via an unknown mechanism. Here we discover that ultraviolet B (UVB) exposure enhances the levels of sex-steroid hormones and sexual behavior, which are mediated by the skin. In female mice, UVB exposure increases hypothalamus-pituitary-gonadal axis hormone levels, resulting in larger ovaries; extends estrus days; and increases anti-Mullerian hormone (AMH) expression. UVB exposure also enhances the sexual responsiveness and attractiveness of females and male-female interactions. Conditional knockout of p53 specifically in skin keratinocytes abolishes the effects of UVB. Thus, UVB triggers a skin-brain-gonadal axis through skin p53 activation. In humans, solar exposure enhances romantic passion in both genders and aggressiveness in men, as seen in analysis of individual questionaries, and positively correlates with testosterone level. Our findings suggest opportunities for treatment of sex-steroid-related dysfunctions.

Antibiotic prescription policy for acute otitis media: do we follow the guidelines?

BACKGROUND: Acute otitis media (AOM) is a common cause for antibiotic prescription. Most guidelines endorse abstaining from immediate antibiotic treatment ('watchful waiting', WW) in mild-moderate episodes. We studied adherence rates to the latest AOM guidelines (2013), in terms of antibiotic type and prescription options. METHODS: In this population-based study, AOM episodes were identified in Clalit Health Services-insured children aged 0-10 years between 2011 and 2018, using a data-sharing platform. After identifying the index, prescription and issuing dates for antibiotics for each AOM episode, treatment was categorized as immediate (≤2 days after diagnosis) or WW (antibiotic not prescribed/issued; prescribed ≤2 days after diagnosis but issued on Days 2-7; or prescribed/issued on Days 2-7). Guideline adherence was measured according to age. RESULTS: Of the 491 106 episodes, 361 518 (73.6%) were treated with antibiotics. Following the 2013 guidelines, the ratio of episodes in children aged ≤6 months that were adherent (immediate treatment) was higher (OR = 1.22; 95% CI 1.15-1.29; P < 0.001), whereas the adherent episode ratio for children aged 6-24 months and 2-10 years (WW) was lower (OR = 0.87; 95% CI 0.85-0.88 and OR = 0.94; 95% CI 0.92-0.96, respectively; P < 0.001). Antibiotic prescription rates after 2013 for children aged ≤6 months were not different (OR = 1.03; 95% CI 0.96-1.1; P = 0.4), but were higher in children aged 6-24 months and 2-10 years (OR = 1.07; 95% CI 1.05-1.09; P < 0.001 and OR = 1.02; 95% CI 1.01-1.04; P = 0.015, respectively). Amoxicillin was the most common antibiotic, administered in 75.6% of episodes. Azithromycin was most commonly associated with treatment failure (6.6%). CONCLUSIONS: Improved adherence to the 2013 guidelines was observed only in children aged ≤6 months and over-treatment with antibiotics was still high.

Pneumococcal Conjugated Vaccines Decreased Acute Otitis Media Burden: A Population-Based Study in Israel.

OBJECTIVE: To study time trends in all-cause acute otitis media (AOM) burden by calculating incidence rates of AOM episodes and recurrent acute otitis media (rAOM) cases in highly immunized pediatric population during the pre- and post-pneumococcal conjugated vaccine (PCV) years. STUDY DESIGN: In this population-based study, AOM episodes and rAOM cases were identified in Clalit Health Services-insured Israeli children aged 0-10 years between 2005 and 2018 by using a data-sharing platform. Because a near-sequential implementation of PCV-7/PCV-13 occurred within a 1-year period (2009/2010), we compared AOM visits before (2005-July 2009) and after (August 2009-2018) the introduction of PCVs. We focused on children younger than 2 years of age, who are the target population of PCVs and are at AOM peak age. RESULTS: We identified 805 389 AOM episodes contributed by 270 137 children. The median number of AOM episodes was 2 (IQR 1-4). A downward trend of incidence rates of AOM episodes was observed during the post-PCV years in children younger than age 9 years (P < .001). The largest decrease (21%) was observed in children younger than 1 year, from 807/1000 children during the pre-PCV years to 640/1000 during the post-PCV years (P < .001). An average annual decrease of ∼14/1000 AOM episodes was calculated in children younger than 1 year old (ß = -13.39, 95% CI -16.25 to -10.53, P < .001). Of rAOM cases, documented in 84 237 (31.2%) children, 74% were in children younger than 2 years, and 55% were in boys. The risk to develop rAOM significantly decreased during the post-PCV years in children younger than 2 years (hazard ratio 0.893, 95% CI 0.878-0.908; P < .001). CONCLUSIONS: AOM burden significantly decreased following PCVs introduction in highly immunized children.

Disparities in assessments of asthma control between children, parents, and physicians.

OBJECTIVE: Assessment of asthma control in children by physicians, patients and their parents was compared, assuming parents may underestimate symptoms in asthmatic children and exploring whether physicians tend to agree with them. DESIGN: Asthma control perception was assessed in 4- to 11-year-old asthmatic children and their parents, using C-ACT, during 2011-2012. Pediatric pulmonologists used GINA guidelines for their assessment; pediatricians, not having spirometry, used the information given in addition to physical examination. The C-ACT scores given by the children and their parents were further analyzed separately, and compared with their physicians' assessment. Statistical methods, which also measured possible influence of different variables, included kappa, Chi-square, linear-by-linear association, McNemar test and logistic regression. PATIENT SELECTION: The study comprised 354 parents and children aged 4-11 years with moderate-severe asthma; 129 (36.4%) were treated by 23 pediatricians; 225 (63.6%) by 11 pediatric pulmonologists. RESULTS: The C-ACT was generally found valid in assessing asthma control (P < 0.001; κ 0.529; CI 0.441, 0.617) and showed that in 229/354 (53%) of children the asthma was uncontrolled. Nevertheless, of the 229 children who indicated their asthma was uncontrolled, 124 (54.1%) of their parents (κ 0.245; CI 0.15, 0.34) and 96 (41.9%) of their physicians believed it to be controlled (κ 0.331; 0.24, 0.43). Comparing the physician-child discordance vis-à-vis the parents, the significant difference was when 96/229 children (41.9%) and 34/126 parents (27.0%) indicated the asthma was uncontrolled while the physician determined it controlled (OR 1.95; 1.19, 3.24). There were no significant differences between pediatric pulmonologists and pediatricians. CONCLUSIONS: In addition to increasing awareness of parents to symptoms in their asthmatic children, physicians should question the child appropriately, as well as using the children's responses to C-ACT as an information source for properly assessing asthma control.