BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting.

BACKGROUND: As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel's largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. METHODS: All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19-related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan-Meier estimator. RESULTS: Each study group included 596,618 persons. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions. CONCLUSIONS: This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19-related outcomes, a finding consistent with that of the randomized trial.

The interplay between vaccination and social distancing strategies affects COVID19 population-level outcomes.

Social distancing is an effective population-level mitigation strategy to prevent COVID19 propagation but it does not reduce the number of susceptible individuals and bears severe social consequences-a dire situation that can be overcome with the recently developed vaccines. Although a combination of these interventions should provide greater benefits than their isolated deployment, a mechanistic understanding of the interplay between them is missing. To tackle this challenge we developed an age-structured deterministic model in which vaccines are deployed during the pandemic to individuals who do not show symptoms. The model allows for flexible and dynamic prioritization strategies with shifts between target groups. We find a strong interaction between social distancing and vaccination in their effect on the proportion of hospitalizations. In particular, prioritizing vaccines to elderly (60+) before adults (20-59) is more effective when social distancing is applied to adults or uniformly. In addition, the temporal reproductive number Rt is only affected by vaccines when deployed at sufficiently high rates and in tandem with social distancing. Finally, the same reduction in hospitalization can be achieved via different combination of strategies, giving decision makers flexibility in choosing public health policies. Our study provides insights into the factors that affect vaccination success and provides methodology to test different intervention strategies in a way that will align with ethical guidelines.

Newborn Auditory Brainstem Responses in Children with Developmental Disabilities.

We integrated data from a newborn hearing screening database and a preschool disability database to examine the relationship between newborn click evoked auditory brainstem responses (ABRs) and developmental disabilities. This sample included children with developmental delay (n = 2992), speech impairment (SI, n = 905), language impairment (n = 566), autism spectrum disorder (ASD, n = 370), and comparison children (n = 128,181). We compared the phase of the ABR waveform, a measure of sound processing latency, across groups. Children with SI and children with ASD had greater newborn ABR phase values than both the comparison group and the developmental delay group. Newborns later diagnosed with SI or ASD have slower neurological responses to auditory stimuli, suggesting sensory differences at birth.

Association of opioid use disorder with healthcare utilization and cost in a public health system.

AIM: To quantify the healthcare costs associated with opioid use disorder among members in a public healthcare system and compare them with healthcare costs in the general population. DESIGN: Retrospective cohort study. SETTING: Inpatient and outpatient care settings of Israel's largest public healthcare provider (that covers 4.7 million members). PARTICIPANTS: Participants included 1173 members who had a diagnosis of opioid use disorder in the years between 2013 and 2018. Each patient was matched with 10 controls based on age and sex. MEASUREMENTS: The main outcome was monthly healthcare costs. FINDINGS: The mean monthly healthcare cost of members with opioid use disorder was $1102 compared with $211 among controls (5.2-fold difference; 95% CI, 4.6-6.0). After excluding members with heroin related diagnoses before the index date (to focus on prescription opioids), this healthcare cost ratio did not substantially change (4.6-fold; 95% CI, 3.9-5.4). Members with opioid use disorder under the age of 65 years had a cost difference of 6.1-fold (95% CI, 5.2-7.1), whereas those 65 years and older experienced cost difference of 3.4-fold (95% CI, 2.6-4.5), compared with controls. The category with the highest cost for members with opioid use disorder was inpatient services, which was 8.7-fold (95%CI, 7.2-10.4) greater than among controls. CONCLUSIONS: Healthcare costs among individuals with opioid use disorder in Israel's public health system are substantially higher than among controls, at least partially attributable to prescription opioid use disorder. Differences are greater among individuals under 65 years.

Trends in the Volume and Types of Primary Care Visits during the Two Years of the COVID-19 Pandemic in Israel.

BACKGROUND: The outbreak of the COVID-19 pandemic led to a decrease in primary health care in-person visits and a simultaneous increase in virtual encounters. OBJECTIVE: To quantify the change in the total volume of primary care visits and mix of visit types during the two years of the pandemic in Israel. DESIGN: Cross-sectional study. PARTICIPANTS: All primary care visits by members of the largest healthcare organization in Israel, during three one-year periods: the pre-COVID-19 year (March 2019-February 2020), the first year of COVID-19 (March 2020-February 2021), and the second year of COVID-19 (March 2021-February 2022). MAIN MEASURES: Total volume of primary care visits and mix of visit types. RESULTS: More than 112 million primary care visits were included in the study. The total visit rate per 1000 members did not change significantly between the pre-COVID year (19) and the first COVID year (19.8), but was 21% higher in the second COVID-19 year (23). The rate of in-person visits per 1000 members decreased from 12.0 in the pre-COVID year to 7.7 in the first COVID year and then increased to 9.6 in the second. The rate of phone visits and asynchronous communication increased from 0.7 and 6.3, respectively, in the pre-COVID year, to 4.1 and 8, respectively, in the first COVID year, and remained unchanged in the second. There was substantial variation across age groups and sectors in the adoption of virtual platforms. CONCLUSIONS: The rapid introduction of virtual encounters in primary care tended to displace in-person visits in the first year of the pandemic, but they appear to have been additive in the second. This transition should be monitored, with the goal of ensuring appropriate planning efforts and resource allocation to deal with the potential added burden on medical staff. Efforts should be invested in encouraging the use of virtual platforms in patient groups that currently underutilize it, such as minorities.

Effect of Socioeconomic and Ethnic Characteristics on COVID-19 Infection: the Case of the Ultra-Orthodox and the Arab Communities in Israel.

BACKGROUND: During infectious disease outbreaks, the weakest communities are more vulnerable to infection and its deleterious effects. In Israel, the Arab and Ultra-Orthodox Jewish communities have unique demographic and cultural characteristics that place them at higher risk of infection. OBJECTIVE: To examine socioeconomic and ethnic differences in rates of COVID-19 testing, confirmed cases and deaths, and to analyze patterns of transmission in ethnically diverse communities. METHODS: A cross-sectional ecologic study design was used. Consecutive data on rates of COVID-19 diagnostic testing, lab-confirmed cases, and deaths collected from March 31 through May 1, 2020, in 174 localities across Israel (84% of the population) were analyzed by socioeconomic ranking and ethnicity. RESULTS: Tests were performed on 331,594 individuals (4.29% of the total population). Of those, 14,865 individuals (4.48%) were positive for COVID-19 and 203 died (1.37% of confirmed cases). Testing rate was 26% higher in the lowest SE category compared with the highest. The risk of testing positive was 2.16 times higher in the lowest socioeconomic category, compared with the highest. The proportion of confirmed cases was 4.96 times higher in the Jewish compared with the Arab population. The rate of confirmed cases in 2 Ultra-Orthodox localities increased relatively early and quickly. Other Jewish and Arab localities showed consistently low rates of confirmed COVID-19 cases, regardless of socioeconomic ranking. CONCLUSIONS: Culturally different communities reacted differently to the COVID-19 outbreak and to government measures, resulting in different outcomes. Socioeconomic and ethnic variables cannot fully explain communities' reaction to the pandemic. Our findings stress the need for a culturally adapted approach for dealing with health crises.

Prolonged Auditory Brainstem Response in Universal Hearing Screening of Newborns with Autism Spectrum Disorder.

Previous studies report prolonged auditory brainstem response (ABR) in children and adults with autism spectrum disorder (ASD). Despite its promise as a biomarker, it is unclear whether healthy newborns who later develop ASD also show ABR abnormalities. In the current study, we extracted ABR data on 139,154 newborns from their Universal Newborn Hearing Screening, including 321 newborns who were later diagnosed with ASD. We found that the ASD newborns had significant prolongations of their ABR phase and V-negative latency compared with the non-ASD newborns. Newborns in the ASD group also exhibited greater variance in their latencies compared to previous studies in older ASD samples, likely due in part to the low intensity of the ABR stimulus. These findings suggest that newborns display neurophysiological variation associated with ASD at birth. Future studies with higher-intensity stimulus ABRs may allow more accurate predictions of ASD risk, which could augment the universal ABR test that currently screens millions of newborns worldwide. LAY SUMMARY: Children with autism spectrum disorder (ASD) have slow brain responses to sounds. We examined these brain responses from newborns' hearing tests and found that newborns who were later diagnosed with autism also had slower brain responses to sounds. Future studies might use these findings to better predict autism risk, with a hearing test that is already used on millions of newborns worldwide.

City-level SARS-CoV-2 sewage surveillance.

The COVID-19 pandemic created a global crisis impacting not only healthcare systems, but also economics and society. Therefore, it is important to find novel methods for monitoring disease activity. Recent data have indicated that fecal shedding of SARS-CoV-2 is common, and that viral RNA can be detected in wastewater. This suggests that wastewater monitoring is a potentially efficient tool for both epidemiological surveillance, and early warning for SARS-CoV-2 circulation at the population level. In this study we sampled an urban wastewater infrastructure in the city of Ashkelon (Ì´ 150,000 population), Israel, during the end of the first COVID-19 wave in May 2020 when the number of infections seemed to be waning. We were able to show varying presence of SARS-CoV-2 RNA in wastewater from several locations in the city during two sampling periods, before the resurgence was clinically apparent. This was expressed with a new index, Normalized Viral Load (NVL) which can be used in different area scales to define levels of virus activity such as red (high) or green (no), and to follow morbidity in the population at the tested area. The rise in viral load between the two sampling periods (one week apart) indicated an increase in morbidity that was evident two weeks to a month later in the population. Thus, this methodology may provide an early indication for SARS-CoV-2 infection outbreak in a population before an outbreak is clinically apparent.

Auditory brainstem response in infants and children with autism spectrum disorder: A meta-analysis of wave V.

Infants with autism spectrum disorder (ASD) were recently found to have prolonged auditory brainstem response (ABR); however, at older ages, findings are contradictory. We compared ABR differences between participants with ASD and controls with respect to age using a meta-analysis. Data sources included MEDLINE, EMBASE, Web of Science, Google Scholar, HOLLIS, and ScienceDirect from their inception to June 2016. The 25 studies that were included had a total of 1349 participants (727 participants with ASD and 622 controls) and an age range of 0-40 years. Prolongation of the absolute latency of wave V in ASD had a significant negative correlation with age (R2 = 0.23; P = 0.01). The 22 studies below age 18 years showed a significantly prolonged wave V in ASD (Standard Mean Difference = 0.6 [95% CI, 0.5-0.8]; P < 0.001). The 3 studies above 18 years of age showed a significantly shorter wave V in ASD (SMD = -0.6 [95% CI, -1.0 to -0.2]; P = 0.004). Prolonged ABR was consistent in infants and children with ASD, suggesting it can serve as an ASD biomarker at infancy. As the ABR is routinely used to screen infants for hearing impairment, the opportunity for replication studies is extensive. Autism Res 2018, 11: 355-363. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: Our analysis of previous studies showed that infants and children with autism spectrum disorder (ASD) have a slower brain response to sound, while adults have a faster brain response to sound. This suggests that slower brain response in infants may predict ASD risk. Brain response to sound is routinely tested on newborns to screen hearing impairment, which has created large data sets to afford replication of these results.

Prolonged auditory brainstem responses in infants with autism.

Numerous studies have attempted to identify early physiological abnormalities in infants and toddlers who later develop autism spectrum disorder (ASD). One potential measure of early neurophysiology is the auditory brainstem response (ABR), which has been reported to exhibit prolonged latencies in children with ASD. We examined whether prolonged ABR latencies appear in infancy, before the onset of ASD symptoms, and irrespective of hearing thresholds. To determine how early in development these differences appear, we retrospectively examined clinical ABR recordings of infants who were later diagnosed with ASD. Of the 118 children in the participant pool, 48 were excluded due to elevated ABR thresholds, genetic aberrations, or old testing age, leaving a sample of 70 children: 30 of which were tested at 0-3 months, and 40 were tested at toddlerhood (1.5-3.5 years). In the infant group, the ABR wave-V was significantly prolonged in those who later developed ASD as compared with case-matched controls (n = 30). Classification of infants who later developed ASD and case-matched controls using this measure enabled accurate identification of ASD infants with 80% specificity and 70% sensitivity. In the group of toddlers with ASD, absolute and interpeak latencies were prolonged compared to clinical norms. Findings indicate that ABR latencies are significantly prolonged in infants who are later diagnosed with ASD irrespective of their hearing thresholds; suggesting that abnormal responses might be detected soon after birth. Further research is needed to determine if ABR might be a valid marker for ASD risk. Autism Res 2016, 9: 689-695. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.