Willingness to pay for an mRNA-based anti-cancer treatment: results from a contingent valuation study in Israel.

BACKGROUND: mRNA technology is currently being investigated for a range of oncology indications. We assessed the willingness to pay (WTP) of the general population in Israel for a hypothetical novel mRNA-based treatment for oncology indications. METHODS: We used a contingent valuation methodology to elicit WTP using a web-based questionnaire. A sample of adult participants were presented with a hypothetical scenario in which an mRNA-based intervention increased the likelihood of a cure for various cancer types from 20% to 40% (half of the sample), or 60% (the other half of the sample). RESULTS: 531 respondents completed the questionnaire. The mean, median and mode WTP for the proposed hypothetical treatment in both scenarios were ILS65,000 (± ILS114,000), ILS20,000 and ILS50,000, respectively (1USD = 3.4ILS). The WTP was skewed towards zero, and 9.6% of the respondents were not willing to pay any amount. WTP higher amounts was significantly associated with higher income (p < 0.01), self-reported good health (p < 0.05), supplementary health insurance (p < 0.05), Jews compared to other populations (p < 0.01), interest in technology (p < 0.001) and a tendency to adopt medical innovations (p < 0.001). No statistical difference between the 40% vs. the 60% potential cure scenarios was found. Logistic and OLS regressions indicated that age, religion, income, and interest in adopting medical innovations were the best predictors of respondents' WTP. CONCLUSION: Despite the scientific breakthroughs in oncology treatment over the last few decades, many types of cancer are still incurable. Given the expected development of innovative mRNA-based treatments for cancer, these results should inform policymakers, the pharmaceutical industry and other stakeholders on the future coverage and reimbursement of these technologies incorporating patients' and societal views. To date, WTP considerations have not been given much weight in prioritization of drug reimbursement processes, neither in Israel nor in other countries. As a pioneer in adoption of the mRNA technology, Israel can also lead the incorporation of WTP considerations in this field.

Maternal diabetes following gestational diabetes: Does multiple gestation multiply the risk?

OBJECTIVE: To assess whether the risk for future diabetes is higher among women diagnosed with gestational diabetes (GD) during twin versus singleton gestations. METHOD: A retrospective cohort study was performed including all women who delivered at a tertiary medical center between the years 1991 and 2021 and had at least one GD diagnosis. The first GD diagnosis per women was defined as the index pregnancy. Women diagnosed with GD during multiple gestations were compared with women diagnosed with GD during singleton gestations. The outcomes included first hemoglobin A1C (Hba1C) level > 6.4 mg/dL post partum, and the highest level measured during the follow-up period of up to 30 years. Multivariable logistic and Cox proportional analysis were used to compare the risk between the two groups while adjusting for confounding variables. RESULTS: The current study included 13 770 mothers, with 458 patients (3.3%) diagnosed with GD during twin gestations and 13 312 (96.7%) during singleton gestations. The mean follow-up was 12.25 ± 9.3 years. Mothers of both groups did not differ in age at index pregnancy; however, mothers of twins were more likely to conceive following fertility treatments. Incidence of diabetes and prediabetes (defined as Hba1C > 6.4 and >5.7, respectively) were lower among the twin-gestation group, both during the 6-month postpartum period (for diabetes: 15.5% vs 22.1%; odds ratio [OR], 0.65 [95% confidence interval (CI), 0.46-0.91]) and during the long-term follow-up (for diabetes: 31.8% vs 40.7%; OR, 0.68 [95% CI, 0.52-0.88]). These results remained significant in the multivariable analysis, while accounting for age, ethnicity, and fertility treatments. CONCLUSION: GD diagnosis during multiple versus singleton gestations is associated with a lower risk for future diabetes.

Inequalities in intimate partner violence screening and receiving information among diverse groups of women: an online survey during COVID-19 lockdowns.

BACKGROUND: Research shows violence against women likely increases during emergencies. COVID-19's emergence exacerbated intimate partner violence (IPV), suggesting that healthcare services (HCS) should have increased IPV screening efforts and referrals of victims to support services. However, little is known about the prevalence of IPV screening and information provision during COVID-19 lockdowns. METHODS: We examined prevalence of 'ever been screened' (ES) for IPV and 'receiving information about support services' (RI) in HCS during COVID-19 lockdowns and compared these among non-immigrant Jewish women, immigrant Jewish and other women, and Palestinian women citizens in Israel. We collected data during Israel's second and third COVID-19 lockdowns (October 2020-February 2021) using a structured, online, self-administrated Arabic-language and Hebrew-language questionnaire. Eligibility criteria included women ≥18 years old, citizens of Israel, in a current intimate relationship (permanent or occasional) who used social media or smartphones. In total, 519 women completed the survey: 73 Palestinian, 127 Jewish immigrants and others, and 319 non-immigrant Jewish. RESULTS: Overall, 37.2% of women reported any IPV, of whom just 26.9% reported ES, 39.4% reported RI and 13.5% reported both (ES&RI). Palestinian women reported higher IPV rates (49.3%) compared with non-immigrant Jewish (34.2%) and immigrant Jewish and other (37.8%) women; however, they reported lower ES (OR 0.64, 90% CI (0.34 to 1.86) and RI 0.29 (0.17 to 0.50). CONCLUSIONS: In a survey during COVID-19 lockdowns, only about one-quarter of women who reported IPV were ES for IPV, or RI about support services, suggesting strengthened IPV screening is needed in HCS during emergencies, particularly targeting minority women, who report higher IPV but receive fewer services.

The impact of maternal hyperemesis gravidarum on early childhood respiratory morbidity.

BACKGROUND: Lung maldevelopment due to in-utero events may potentially cause respiratory morbidity during childhood. Maternal nutritional status during pregnancy is critical for lung development. This study is contributing to the understanding of the interplay between maternal nutrition status during pregnancy, fetal lung development and the risk for respiratory diseases in early life. RESEARCH QUESTION: To investigate the association between maternal hyperemesis gravidarum (HG) during pregnancy and respiratory morbidity in the offspring's early childhood. STUDY DESIGN AND METHODS: This is a retrospective population-based cohort study that included all singleton term deliveries at Soroka University Medical Center (SUMC) between 1991 and 2021. Preterm deliveries (<37 gestational week), perinatal deaths, multiple gestations, and children with congenital malformations or chromosomal abnormalities were excluded. The main outcomes measured were offspring's hospitalizations due to pneumonia, acute bronchiolitis, asthma, or wheezing. RESULTS: Overall 232,476 deliveries were included in the study, of which 3227 women (1.4%) were diagnosed with HG. Offspring in the HG group exhibited significantly higher rates of respiratory morbidity, including asthma (OR = 1.36, 95% CI 1.22-1.36, p < .001), acute bronchiolitis (OR = 1.38, 95% CI 1.21-1.59, p < .001), and pneumonia (OR = 1.2, 95% CI 1.12-1.48, p < .001). An inverse correlation between multivariate adjusted-hazard ratios for asthma and pneumonia with offspring's age was noted. INTERPRETATION: This study provides evidence of a potential association between maternal HG during pregnancy and increased risk of respiratory morbidity in offspring's early childhood. Maternal nutritional status during pregnancy plays a crucial role in lung development, affecting respiratory health in childhood.

Recurrent preterm delivery following twin versus singleton preterm delivery: A retrospective cohort.

OBJECTIVE: The main risk factor for preterm delivery (PTD; <37 gestational weeks) is having a history of PTD. The aim of this research was to compare the risk for recurrent PTD following twin versus singleton gestation PTD. METHODS: A retrospective population-based cohort study was performed, including all women who had two consecutive pregnancies, the first of which ended with PTD. The incidence of PTD recurrence was compared between women with PTD in twin versus singleton gestation. Multivariable logistic models were used to study the association between twinning status and PTD recurrence, and specifically by gestational age of the first PTD, inter-pregnancy interval (IPI), and mode of conception. RESULTS: The study population included 15 590 women, of whom 1680 (10.8%) had twins in their index pregnancy and 13 910 (89.2%) had singletons. The incidence of recurrent PTD was 10.5% (n = 177) following twin PTD versus 21.9% (n = 3044) following singleton PTD (adjusted odds ratio = 0.50, 95% confidence interval 0.32-0.76, while controlling for confounding variables). The results were consistent while stratifying by IPI, gestational age of the first PTD, or mode of conception. CONCLUSIONS: Women with PTD in twin gestations are at lower risk for recurrent PTD compared with women with singleton PTD.

Food-induced anaphylaxis during infancy is associated with later sleeping and eating disorders.

BACKGROUND: Accumulating evidence suggests that food-induced anaphylaxis (FIA) may induce different psychological disorders (PDs). In this study, we aimed to further evaluate the effect of FIA, specifically when occurring in early life, on subsequent PDs development. METHODS: We conducted a population-based, retrospective, matched-cohort study of pediatric patients (age ≤ 18 years) treated at the "Clalit" healthcare organization during the period 2001-2021. Children diagnosed with FIA were propensity score-matched with patients without any allergies (controls) of similar demographic parameters. Associations between FIA and different PDs were examined by multivariable regression models. RESULTS: The cohorts comprised 545 FIA patients and 4514 controls. Most patients were <3 years old [87.6% of controls (N = 3955) and 87.3% of the FIA cohort (N = 476)]. In this age group, the major food allergens were cow's milk (N = 258; 54.2%), eggs (N = 60; 12.6%), and peanuts (N = 20; 4.2%). The multivariable regression model identified an association between FIA and any PDs (p < .001), sleeping disorders (p < .001), and eating disorders (p = .050). Kaplan-Meier curves revealed that patients who experienced FIA before 3 years of age had an increased cumulative risk over the follow-up time of developing any PDs, sleeping disorders, and eating disorders. CONCLUSION: FIA during the first 3 years of life increases the risk of later developing eating and sleeping disorders, which can last into adulthood. Further attention should be focused on accurately diagnosing these children.

Syncope in pregnancy, immediate pregnancy outcomes, and offspring long-term neurologic health.

BACKGROUND: There are limited data regarding the perinatal consequences of maternal syncope during pregnancy, and even less is known about the potential long-term effect on offspring health. OBJECTIVE: This study aimed to examine perinatal outcomes as well as long-term offspring neurologic morbidity associated with prenatal maternal syncope, and the possible differential effect by trimester of first syncope episode. STUDY DESIGN: A retrospective cohort study was conducted, including all singleton deliveries occurring between 1991 and 2021 at a large tertiary medical center. Multivariable analyses were applied to study the associations between prenatal maternal syncope and various perinatal outcomes as well as offspring neurologic morbidity up to the age of 18 years, while adjusting for clinically relevant factors. Analyses were further conducted by trimester of first syncope episode. RESULTS: The study population included 232,475 pregnancies, 774 (0.3%) were affected by maternal syncope, which most frequently first occurred during the second trimester (44.5%), followed by the first trimester (31.8%) and finally the third trimester (27.7%). Maternal syncope was independently associated with increased risk for intrauterine growth restriction (adjusted odds ratio, 1.52; 95% confidence interval, 1.01-2.29), which appeared to be mainly driven by first trimester syncope occurrence; as well as with increased risk for cesarean delivery (adjusted odds ratio, 1.33; 95% confidence interval, 1.10-1.61), and for long-term offspring neurologic morbidity (adjusted hazard ratio, 1.79; 95% confidence interval, 1.65-2.08), regardless of the trimester of syncope occurrence. CONCLUSION: Prenatal maternal syncope is an independent risk factor for intrauterine growth restriction, cesarean delivery, and for long-term offspring neurologic morbidity.

Safety of monovalent and bivalent BNT162b2 mRNA COVID-19 vaccine boosters in at-risk populations in Israel: a large-scale, retrospective, self-controlled case series study.

BACKGROUND: COVID-19 continues to be a major health threat, particularly among at-risk groups, including individuals aged 60 years or older and people with particular medical conditions. Nevertheless, the absence of sufficient vaccine safety information is one of the key contributors to vaccine refusal. We aimed to assess the short-term safety profile of the BNT162b2 mRNA COVID-19 vaccine booster doses. METHODS: In this self-controlled case series study, we used a database of members of the largest health-care organisation in Israel. We analysed the medical records of individuals at risk of COVID-19 complications who had received two doses of the monovalent BNT162b2 mRNA COVID-19 vaccine (tozinameran, Pfizer-BioNTech) as their primary course of vaccination and then also received BNT162b2 mRNA COVID-19 vaccine boosters between July 30, 2021, and Nov 28, 2022, as a monovalent first or second booster, or as a bivalent first, second, or third booster, or a combination of these. We included individuals who had active membership of the health-care organisation and who were alive (excluding COVID-19 deaths) throughout the entire study period. We excluded individuals who, during the study period, were either not active Clalit Health Services members or died of non-COVID-19 causes, and those who were infected with COVID-19 during the 7-day period after vaccination. Individuals' at-risk status was assessed on the day before the baseline period started. The primary outcome was non-COVID-19 hospitalisation for 29 adverse events that might be associated with vaccination. For each adverse event, we compared the risk difference of hospitalisation during a 28-day pre-vaccination baseline period versus during a 28-day post-vaccination period, using a non-parametric percentile bootstrap method. FINDINGS: Of the 3 574 243 members of the health-care organisation, 1 073 110 received a first monovalent booster, 394 251 received a second monovalent booster, and 123 084 received a bivalent first, second, or third booster. Overall, we found no indication of an elevated risk of non-COVID-19 hospitalisation following administration of any of the booster vaccines (risk difference in events per 100 000 individuals: first monovalent booster -37·1 [95% CI -49·8 to -24·2]; second monovalent booster -37·8 [-62·2 to -13·2]; and bivalent booster -18·7 [-53·6 to 15·4]). Except for extremely rare elevated risks after the first monovalent booster-of myocarditis (risk difference 0·7 events per 100 000 individuals [95% CI 0·3-1·3]), seizures (2·2 [0·4-4·1]), and thrombocytopenia (2·6 [0·7-4·7])-we found no safety signals in other adverse events, including ischaemic stroke. INTERPRETATION: This study provides the necessary vaccine safety assurances for at-risk populations to receive timed roll-out booster vaccinations. These assurances could reduce vaccine hesitancy and increase the number of at-risk individuals who opt to become vaccinated, and thereby prevent the severe outcomes associated with COVID-19. FUNDING: Israel Science Foundation and Israel Precision Medicine Partnership programme.

Twins vs singletons-Long-term health outcomes.

INTRODUCTION: Multiple gestations are a risk factor for most pregnancy complications. The current study aimed to study whether offspring born after twin pregnancies are at increased risk for long-term health complications. MATERIAL AND METHODS: A retrospective cohort study was conducted in a large medical center, including all offspring born between the years 1991-2021, which were followed-up until 18 years of age. Hospital-based diagnoses of the offspring were categorized into main groups of morbidities: cardiac, respiratory, infectious, neurological, malignancy, and metabolic. Incidence of hospitalization with diagnoses from each main group was compared between twins and singletons, as well as time to first hospitalization. Cox proportional hazard models were used to study the association between twins vs singletons and hospitalizations by grouped morbidities, while adjusting for maternal age, ethnicity and gender, besides maternal recurrence in the cohort. RESULTS: A total of 369 478 offspring were included in the analysis; of these 11 986 (3.2%) were twins and 357 492 (96.8%) were singletons. Twins were more likely to be delivered preterm (odds ratio = 17.65, 95% CI: 16.74-18.60), by cesarean delivery and following infertility treatments. Incidence of hospitalizations with all morbidity groups was slightly, some significantly, higher among twins, including cardiac: 1.9% vs 1.5%, respiratory; 8.4% vs 7.1%, neurological: 7.7% vs 7.4%, infectious: 26.0% vs 24.1%, and malignancies: 0.7% vs 0.4%. The risk remained higher in the multivariable analyses (adjusted hazard ratios ranging between 1.09-1.75). When stratifying by gestational age at delivery, the risk for most morbidities was lower among twins vs singletons born in similar gestational ages. CONCLUSIONS: Twins as compared to singletons are at increased risk for most morbidities due to their risk of being born earlier.

The association between normal 50-g glucose challenge test results and risk for future metabolic morbidities: A retrospective cohort study.

OBJECTIVE: To study the association between normal glucose challenge test (GCT) results during pregnancy and the incidence of future maternal metabolic morbidities. METHOD: This was a population-based retrospective cohort study conducted between the years 2005 and 2020. The study included all women aged 17-55 years who underwent GCT as part of the routine prenatal care at the Central District of Clalit Health Services, Israel. The highest GCT result per woman was categorized into five study groups: <120 (reference), 120-129, 130-139, 140-149, and ≥150 mg/dL. Adjusted hazard ratios of the study groups for metabolic morbidities were calculated with Cox proportional survival analysis models. RESULTS: Among a total of 77 568 women participants, 53%, 12.3%, and 10.3% had normal GCT results of <120, 120-129, and 130-139 mg/dL, respectively. During the study period of 6.07 ± 4.35 years, 13 151 (17.0%) cases of metabolic morbidities were documented. High-normal GCT results of 120-129 and 130-139 mg/dL were significantly associated with increased risk for future metabolic morbidity compared with <120 mg/dL (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.08-1.22 and aHR 1.32, 95% CI 1.24-1.41, respectively). CONCLUSION: Although GCT is only recommended as a screening tool for gestational diabetes mellitus, high results, even within the normal range, may point to maternal increased risk for future metabolic morbidity.

Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study.

BACKGROUND: In late 2022, the SARS-CoV-2 omicron (B.1.1.529) BA.5 sublineage accounted for most of the sequenced viral genomes worldwide. Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the omicron BA.4 and BA.5 sublineages. Since September, 2022, a single bivalent mRNA vaccine booster dose has been recommended for adults who have completed a primary SARS-CoV-2 vaccination series and are at high risk of severe COVID-19. We aimed to evaluate the effectiveness of a bivalent mRNA vaccine booster dose to reduce hospitalisations and deaths due to COVID-19. METHODS: We did a retrospective, population-based, cohort study in Israel, using data from electronic medical records in Clalit Health Services (CHS). We included all members of CHS who were aged 65 years or older and eligible for a bivalent mRNA COVID-19 booster vaccination. We used hospital records to identify COVID-19-related hospitalisations and deaths. The primary endpoint was hospitalisation due to COVID-19, which we compared between participants who received a bivalent mRNA booster vaccination and those who did not. A Cox proportional hazards regression model with time-dependent covariates was used to estimate the association between the bivalent vaccine and hospitalisation due to COVID-19 while adjusting for demographic factors and coexisting illnesses. FINDINGS: Between Sept 27, 2022, and Jan 25, 2023, 569 519 eligible participants were identified. Of those, 134 215 (24%) participants received a bivalent mRNA booster vaccination during the study period. Hospitalisation due to COVID-19 occurred in 32 participants who received a bivalent mRNA booster vaccination and 541 who did not receive a bivalent booster vaccination (adjusted hazard ratio 0·28, 95% CI 0·19-0·40). The absolute risk reduction for hospitalisations due to COVID-19 in bivalent mRNA booster recipients versus non-recipients was 0·089% (95% CI 0·075-0·101), and the number needed to vaccinate to prevent one hospitalisation due to COVID-19 was 1118 people (95% CI 993-1341). INTERPRETATION: Participants who received a bivalent mRNA booster vaccine dose had lower rates of hospitalisation due to COVID-19 than participants who did not receive a bivalent booster vaccination, for up to 120 days after vaccination. These findings highlight the importance of bivalent mRNA booster vaccination in populations at high risk of severe COVID-19. Further studies with longer observation times are warranted. FUNDING: None.

Randomised clinical trial: Psychological intervention improves work productivity and daily activity by reducing abdominal pain and fatigue in Crohn's disease.

BACKGROUND: Chronic abdominal pain and fatigue are characteristics of Crohn's disease (CD) and contribute to functional impairments. AIMS: To examine whether CD-tailored cognitive-behavioural and mindfulness intervention (COBMINDEX) is effective in reducing abdominal pain and fatigue in patients with CD and whether changes in abdominal pain and fatigue mediate any beneficial effects of COBMINDEX on impairments in work productivity and daily activities. METHODS: This is a secondary analysis of a parallel-group multicentre randomised controlled trial. Patients with mild-to-moderate CD (n = 142) were randomised into either intervention group receiving COBMINDEX, or control group receiving treatment-as-usual for 3 months followed by COBMINDEX. Complete data were collected from 120 patients (34.0 ± 10.7 years, 62.5% female, intervention = 60, control = 60). Analysis of covariance assessed group differences in 3-month follow-up scores, controlling for baseline scores. Multiple parallel mediation analysis assessed the proposed mechanisms for the entire sample. RESULTS: The intervention group demonstrated significantly lower levels of abdominal pain (F = 17.46, p < 0.001, η2 p  = 0.13), fatigue (F = 7.26, p = 0.008, η2 p  = 0.06) and impairments at work (F = 4.82, p = 0.032, η2 p  = 0.07) and daily activities (F = 6.26, p = 0.014, η2 p  = 0.05), compared with treatment-as-usual. Moreover, changes in abdominal pain and fatigue significantly mediated the beneficial effects of COBMINDEX on patients' work productivity (b = -9.90, SE = 2.86, 95% CI: -16.11 to -4.94) and daily activities (b = -9.65, SE = 1.91, 95% CI: -13.77 to 6.35), independent of changes in disease activity. CONCLUSIONS: COBMINDEX is effective at reducing abdominal pain and fatigue in patients with CD, which in turn leads to improvement in functioning. Clinicians should incorporate screening for severe abdominal pain and fatigue and consider offering cognitive-behavioural and mindfulness training. CLINICALTRIALS: gov, Number: NCT05085925. Ministry of Health in Israel (https://my.health.gov.il/CliniTrials/Pages/MOH_2020-02-24_008721.aspx).

Factors associated with COVID-19 vaccination likelihood during pregnancy.

OBJECTIVE: To identify maternal background, medical and gynecological characteristics associated with COVID-19 vaccination likelihood, in the context where COVID-19 vaccination rates among pregnant women are significantly lower than the general population. METHODS: In a retrospective cohort study, including all women who delivered between January and September 2021, background and medical history, including current and previous pregnancies diagnoses, were compared between vaccinated and unvaccinated women. Multivariable logistic models were used to identify factors associated with vaccination for the entire population, and for the two distinctive populations included in the study (Bedouin Arabs and Jewish women). RESULTS: The study population included 7017 women, of whom 1925 (27.4%) were vaccinated during pregnancy. According to the multivariable analysis, unvaccinated mothers were younger with lower socioeconomic score. They were more likely to be Bedouin Arabs, have a poor obstetrical history or recurrent pregnancy loss, and insufficient prenatal care. Additional risk factors were inconsistent between the two ethnicities included in the study. CONCLUSIONS: Ethnicity, insufficient prenatal care, and having a poor obstetric history were consistently associated with lower vaccination among pregnant women. These factors should be considered in future plans aimed at increasing vaccination among pregnant women.

Risk factors for hospitalization at the pediatric intensive care unit among infants and children younger than 5 years of age diagnosed with infectious diseases.

BACKGROUND: Children hospitalized with infectious diseases may develop severe, life-threatening conditions, often requiring admission to pediatric intensive care unit (PICU). The objectives of this study were to identify independent risk factors for PICU hospitalization with an infectious disease in children <5 years of age. METHODS: In southern Israel, two populations live side by side: the middle-high income Jewish population and the low-income Bedouin population, both receiving equal and free medical care at the only tertiary medical center in the area. The study population included all children born in southern Israel and hospitalized at PICU with an infectious disease during 1991-2012. Risk factors for PICU hospitalizations were retrospectively studied by Kaplan-Meier and Cox proportional hazard survival analyses. RESULTS: 9951 Jewish children and 18,002 Bedouin children were enrolled; overall, 1135 episodes of PICU hospitalizations with an infectious disease were recorded (879, 77.4% Bedouin and 256, 22.6% Jewish patients). Bedouin children had a higher risk for PICU hospitalization with an infectious disease compared with Jewish children (adjusted Hazard Ratio [adj. HR] 1.7, 95% CI 1.5-2.0); maternal multiparity and low-birth weight (<2500 g) were additional risk factors for PICU hospitalization with an infectious disease compared to firstborns (adj. HR = 1.2, 95% CI 1.0-1.5) or to children with a birth weight ≥2500 g (adj. HR = 1.5, 95% 1.2-1.9). Older age was a protective factor for PICU hospitalization (adj. HR = 0.98, 95% CI 0.97-0.99). Children hospitalized with a central nervous system infection had the highest risk of PICU hospitalization (adj. HR 6.8, 95% CI 5.5-8.4), followed by those with urinary tract infections (UTI, adj. HR 3.1, 95% CI 2.5-3.8) and those with lower respiratory tract infections (LRTI, adj. HR 2.9, 95% CI 2.4-3.4). CONCLUSION: Bedouin ethnicity, low birth weight, maternal multiparity and younger age were significant risk factors for PICU hospitalizations with an infectious disease. Among the infectious diseases analyzed, CNS infection had the highest risk for PICU hospitalization, followed by UTI and LRTI.

Traffic Noise and Ambient Air Pollution Are Risk Factorsfor Preeclampsia.

Purpose: We aimed to evaluate the effect of traffic-related noise (TRN), environmental noise (EN) and traffic-related air pollution (TRAP) on preeclampsia. Methods: We followed 285 pregnant women from Maternal and Child Health Clinics who reported exposure to TRN on a scale from 0 (absence of EN) to 10 (high level of EN). EN was measured using a portable dosimeter, and NOx was calculated using the AERMOD pollutant dispersion model. Results: Using a multiple logistic regression model, adjusted for maternal age, BMI, number of births, fetal sex and maternal chronic illness, TRN (score ≥ 6 vs. score < 6) and TRAP (NOx ≥ 300 µ/m3 vs. NOx < 300 µ/m3) were noted as independent risk factors for preeclampsia, with OR = 3.07 (95% CI 0.97; 9.70, p = 0.056) and OR = 3.43 (95% CI 1.20; 9.87, p = 0.022), respectively. Joint exposure to TRN and TRAP was associated with a significant and independent risk for preeclampsia (OR of 4.11 (95% CI 1.31; 12.94, p = 0.016). Conclusions: In our population, traffic-related noise and ambient TRAP were risk factors for preeclampsia.

Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge.

BACKGROUND: The oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk, unvaccinated patients infected with the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data regarding the effectiveness of nirmatrelvir in preventing severe coronavirus disease 2019 (Covid-19) outcomes from the B.1.1.529 (omicron) variant are limited. METHODS: We obtained data for all members of Clalit Health Services who were 40 years of age or older at the start of the study period and were assessed as being eligible to receive nirmatrelvir therapy during the omicron surge. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of nirmatrelvir treatment with hospitalization and death due to Covid-19, with adjustment for sociodemographic factors, coexisting conditions, and previous SARS-CoV-2 immunity status. RESULTS: A total of 109,254 patients met the eligibility criteria, of whom 3902 (4%) received nirmatrelvir during the study period. Among patients 65 years of age or older, the rate of hospitalization due to Covid-19 was 14.7 cases per 100,000 person-days among treated patients as compared with 58.9 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.15 to 0.49). The adjusted hazard ratio for death due to Covid-19 was 0.21 (95% CI, 0.05 to 0.82). Among patients 40 to 64 years of age, the rate of hospitalization due to Covid-19 was 15.2 cases per 100,000 person-days among treated patients and 15.8 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.74; 95% CI, 0.35 to 1.58). The adjusted hazard ratio for death due to Covid-19 was 1.32 (95% CI, 0.16 to 10.75). CONCLUSIONS: Among patients 65 years of age or older, the rates of hospitalization and death due to Covid-19 were significantly lower among those who received nirmatrelvir than among those who did not. No evidence of benefit was found in younger adults.

Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years.

The rapid emergence of the B.1.1.529 (Omicron) variant of SARS-CoV-2 led to a global resurgence of coronavirus disease 2019 (COVID-19). Israeli authorities approved a fourth COVID-19 vaccine dose (second booster) for individuals aged 60 years and over who had received a first booster dose 4 or more months earlier. Evidence for the effectiveness of a second booster dose in reducing hospitalizations and mortality due to COVID-19 is warranted. This retrospective cohort study included all members of Clalit Health Services who were aged 60-100 years and who were eligible for the second booster on 3 January 2022. Hospitalizations and mortality due to COVID-19 in participants who received the second booster were compared with those for participants who received one booster dose. Cox proportional hazards regression models with time-dependent covariates were used to estimate the association between the second booster and hospitalization and death due to COVID-19 while adjusting for demographic factors and coexisting illnesses. A total of 563,465 participants met the eligibility criteria. Of those, 328,597 (58%) received a second booster dose during the 40 day study period. Hospitalization due to COVID-19 occurred in 270 of the second-booster recipients and in 550 participants who received one booster dose (adjusted hazard ratio, 0.36; 95% confidence interval (CI): 0.31-0.43). Death due to COVID-19 occurred in 92 second-booster recipients and in 232 participants who received one booster dose (adjusted hazard ratio, 0.22; 95% CI: 0.17-0.28). This study demonstrates a substantial reduction in hospitalizations and deaths due to COVID-19 conferred by a second booster in Israeli adults aged 60 years and over.