Data-Driven Assessment of Adolescents' Mental Health During the COVID-19 Pandemic.

OBJECTIVE: Adolescents' mental health was severely compromised during the COVID-19 pandemic. Longitudinal real-world studies on changes in the mental health of adolescents during the later phase of the pandemic are limited. We aimed to quantify the effect of COVID-19 pandemic on adolescents' mental health outcomes based on electronic health records. METHOD: This was a retrospective cohort study using the computerized database of a 2.5 million members, state-mandated health organization in Israel. Rates of mental health diagnoses and psychiatric drug dispensations were measured among adolescents 12 to 17 years of age with and without pre-existing mental history, for the years 2017 to 2021. Relative risks were computed between the years, and interrupted time series (ITS) analyses evaluated changes in monthly incidence rates of psychiatric outcomes. RESULTS: The average population size was 218,146 in 2021. During the COVID-19 period, a 36% increase was observed in the incidence of depression (95% CI = 25-47), 31% in anxiety (95% CI = 23-39), 20% in stress (95% CI = 13-27), 50% in eating disorders (95% CI = 35-67), 25% in antidepressant use (95% CI = 25-33), and 28% in antipsychotic use (95% CI = 18-40). A decreased rate of 26% (95% CI = 0.80-0.88) was observed in ADHD diagnoses. The increase of the examined outcomes was most prominent among youth without psychiatric history, female youth, general secular Jewish population, youth with medium-high socioeconomic status, and those 14 to 15 years of age. ITS analysis confirmed a significantly higher growth in the incidence of psychiatric outcomes during the COVID-19 period, compared to those in previous years. CONCLUSION: This real-world study highlights the deterioration of adolescents' mental health during the COVID-19 pandemic and suggests that youth mental health should be considered during health policy decision making. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study.

OBJECTIVES: To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status. DESIGN: Retrospective nationwide cohort study. SETTING: Electronic medical records from an Israeli nationwide healthcare organisation. POPULATION: 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021. MAIN OUTCOME MEASURES: Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection. RESULTS: Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients. CONCLUSIONS: This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.

Immediate side effects of Comirnaty COVID-19 vaccine: A nationwide survey of vaccinated people in Israel, December 2020 to March 2021.

BackgroundCOVID-19 vaccine safety is of major interest worldwide, since there is no prior experience with it. Israel was one of the first countries to widely use the Comirnaty vaccine.AimWe aimed to assess the vaccine's short-term side effects directly from a large population and to predict influencing factors for self-reporting side effects.MethodsIn a retrospective cohort study, we investigated self-reported systemic vaccine side-effects using electronic surveys sent to vaccinated individuals between 20 December 2020 and 11 March 2021, within 3 days following administration of the first and second dose. We determined predictors for reporting systemic side effects by logistic regression.ResultsA total of 1,213,693 patients received at least one vaccine dose and 301,537 (24.8%) answered at least one survey. Among them, 68,162 (30.4%) and 89,854 (59.9%) individuals filled the first and the second dose surveys, respectively, and reported one or more side effects. Most common side effects were fatigue, headache and myalgia. Several respondents reported facial paraesthesia after first and second dose, respectively (n = 1,675; 0.7% and n = 1,601; 1.1%). Individuals younger than 40 years and women reported side effects more frequently than others, but pregnant women reported less. Pregnancy was a weak predictor for reporting any side effect in general and in particular fatigue, myalgia, headache, chills and fever.ConclusionsWe found further support for minor short-term side effects, within 3 days of receiving the Comirnaty vaccine. These findings from vaccine recipients in general and pregnant women in particular can improve vaccine acceptance.

Reactogenicity of a third BNT162b2 mRNA COVID-19 vaccine among immunocompromised individuals and seniors - A nationwide survey.

BACKGROUND: Since July 13, 2021, a third SARS-CoV-2 vaccine BNT162b2 was approved in Israel to immunocompromised and seniors 60 years of age or older. We aimed to evaluate vaccine's reactogenicity. METHODS: A retrospective cohort, using electronic surveys sent to booster vaccine recipients, during July 20-August 10, 2021. RESULTS: 17,820 participated in the survey, with a response rate of 30.2%. 3195 (17.9%) were immunocompromised. Fatigue, myalgia and fever were the most frequent systemic side effects reported (19.6%, 9.2% and 8.1% respectively among immunocompromised; 21.3%, 9.9% and 9.2% respectively among seniors). 67.3% of immunocompromised and 62% of seniors reported experiencing a better or a similar response to the third dose, compared to the second. CONCLUSIONS: Local and systemic reactions after third BNT162b2 vaccine, reported by immunocompromised and seniors, were similar to those observed following previous vaccines and mostly self-resolved. These findings may aid promoting confidence among vaccine providers and recipients.

Development and efficacy of a computerized decision support system for osteoporosis management in the community.

Computerized alerts for primary care physicians, provided during visits of patients who met treatment guidelines based on their electronic medical records, are an efficient method to raise awareness to many otherwise missed cases, especially after fracture. PURPOSE: Measure the efficacy of an automated real-time alert which was developed to assist osteoporosis management in the community. METHODS: The study population included treatment naïve patients with T-score ≤ - 2.5 or hip or vertebral fracture in a 2 million member Israeli health fund. On each ambulatory visit to a primary care physician or endocrinologist, a pop-up screen reminded the caregiver to consider treatment initiation. A follow-up "smart-set" screen conveniently gathered links to common actions (namely, (a) issue first line therapy prescription, (b) referral to nutritionist consultation, (c) laboratory tests relevant for osteoporosis, and (d) printing an information page for the patient). Time till treatment initiation was compared between the 3 years prior to and following the intervention. RESULTS: Within 2 years since alert activation, a total of n = 21,070 cases were alerted, 52% of which were long standing cases: untreated for over 6 months since the event. During this period, a total of 30% initiated treatment purchases. As compared with the 3 years prior to the intervention, time till treatment initiation decreased following the intervention with HR = 1.05, 1.94, 1.29 (p values = 0.020, < 0.001, 0.005) for T-score, hip, and vertebral cases respectively. Initiation rates within 6 months increased from 52.0 to 59.8%, from 12.3 to 27.7%, and from 17.4 to 27.1% among T-score, hip, and vertebral cases, respectively (p value < 0.001). Male sex, nursing home residence, having diabetes or a cardiovascular disease and age younger than 60 or older than 80 were associated with lower treatment rates. CONCLUSIONS: A computerized decision support system can efficiently raise attention to many otherwise missed high-risk osteoporotic cases, particularly those after fractures.

Can commercial low-cost sensor platforms contribute to air quality monitoring and exposure estimates?

The emergence of low-cost, user-friendly and very compact air pollution platforms enable observations at high spatial resolution in near-real-time and provide new opportunities to simultaneously enhance existing monitoring systems, as well as engage citizens in active environmental monitoring. This provides a whole new set of capabilities in the assessment of human exposure to air pollution. However, the data generated by these platforms are often of questionable quality. We have conducted an exhaustive evaluation of 24 identical units of a commercial low-cost sensor platform against CEN (European Standardization Organization) reference analyzers, evaluating their measurement capability over time and a range of environmental conditions. Our results show that their performance varies spatially and temporally, as it depends on the atmospheric composition and the meteorological conditions. Our results show that the performance varies from unit to unit, which makes it necessary to examine the data quality of each node before its use. In general, guidance is lacking on how to test such sensor nodes and ensure adequate performance prior to marketing these platforms. We have implemented and tested diverse metrics in order to assess if the sensor can be employed for applications that require high accuracy (i.e., to meet the Data Quality Objectives defined in air quality legislation, epidemiological studies) or lower accuracy (i.e., to represent the pollution level on a coarse scale, for purposes such as awareness raising). Data quality is a pertinent concern, especially in citizen science applications, where citizens are collecting and interpreting the data. In general, while low-cost platforms present low accuracy for regulatory or health purposes they can provide relative and aggregated information about the observed air quality.

An evaluation tool kit of air quality micro-sensing units.

Recent developments in sensory and communication technologies have made the development of portable air-quality (AQ) micro-sensing units (MSUs) feasible. These MSUs allow AQ measurements in many new applications, such as ambulatory exposure analyses and citizen science. Typically, the performance of these devices is assessed using the mean error or correlation coefficients with respect to a laboratory equipment. However, these criteria do not represent how such sensors perform outside of laboratory conditions in large-scale field applications, and do not cover all aspects of possible differences in performance between the sensor-based and standardized equipment, or changes in performance over time. This paper presents a comprehensive Sensor Evaluation Toolbox (SET) for evaluating AQ MSUs by a range of criteria, to better assess their performance in varied applications and environments. Within the SET are included four new schemes for evaluating sensors' capability to: locate pollution sources; represent the pollution level on a coarse scale; capture the high temporal variability of the observed pollutant and their reliability. Each of the evaluation criteria allows for assessing sensors' performance in a different way, together constituting a holistic evaluation of the suitability and usability of the sensors in a wide range of applications. Application of the SET on measurements acquired by 25 MSUs deployed in eight cities across Europe showed that the suggested schemes facilitates a comprehensive cross platform analysis that can be used to determine and compare the sensors' performance. The SET was implemented in R and the code is available on the first author's website.

High Prevalence of Diverse Insertion Sequences within the rRNA Operons of Mycoplasma bovis.

Insertion sequences (ISs) are widespread in the genome of Mycoplasma bovis strain PG45, but no ISs were identified within its two tandemly positioned rRNA operons (rrn1 and rrn2). However, characterization of the rrn locus in 70 M. bovis isolates revealed the presence of ISs related to the ISMbov1 (IS30 family) and ISMbov4 (IS4 family) isomers in 35 isolates. ISs were inserted into intergenic region 1 (IGR-1) or IGR-3, which are the putative promoter regions of rrn1 and rrn2, respectively, and into IGR-5, located downstream of the rrl2 gene. Seven different configurations (A to G) of the rrn locus with respect to ISs were identified, including those in five annotated genomes. The transcriptional start site for the single rrn operon in M. bovis strain 88127 was mapped within IGR-1, 60 bp upstream of the rrs gene. Notably, only 1 nucleotide separated the direct repeat (DR) for ISMbov1 and the promoter -35 element in configuration D, while in configuration F, the -35 motif was a part of the ISMbov1 DR. Relative quantitative real-time (qRT) PCR analysis and growth rate comparisons detected a significant increase (P < 0.05) in the expression of the rrs genes and in the number of viable cells during log phase growth (8, 12, and 16 h) in the strains with configuration F in comparison to strains with one or two rrn operons that did not have ISs. A high prevalence of IS elements within or close to the M. bovis rrn operon-promoter region may reflect their important role in regulation of both ribosome synthesis and function. IMPORTANCE: Data presented in this study show a high prevalence of diverse ISs within the M. bovis rrn locus resulting in intraspecies variability and diversity. Such abundance of IS elements near or within the rrn locus may offer a selective advantage to M. bovis Moreover, the fact that expression of the rrs genes as well as the number of viable cells increased in the group of strains with IS element insertion within a putative promoter -35 sequence (configuration F) in comparison to that in strains with one or two rrn operons that do not have ISs may serve as a basis for understanding the possible role of M. bovis IS elements in fundamental biological processes such as regulation of ribosome synthesis and function.

The effect of ego-motion on environmental monitoring.

Air pollution has a proven impact on public health. Currently, pollutant levels are obtained by high-priced, sizeable, stationary Air Quality Monitoring (AQM) stations. Recent developments in sensory and communication technologies have made relatively low-cost, micro-sensing units (MSUs) feasible. Their lower power consumption and small size enable mobile sensing, deploying single or multiple units simultaneously. Recent studies have reported on measurements acquired by mobile MSUs, mounted on cars, bicycles and pedestrians. While these modes of transportation inherently present different velocity and acceleration regimes, the effect of the sensors' varying movement characteristics have not been previously accounted for. This research assesses the impact of sensor's motion on its functionality through laboratory measurements and a field campaign. The laboratory setup consists of a wind tunnel to assess the effect of air flow on the measurements of nitrogen dioxide and ozone at different velocities in a controlled environment, while the field campaign is based on three cars mounted with MSUs, measuring pollutants and environmental variables at different traveling speeds. In both experimental designs we can regard the MSUs as a moving object in the environment, i.e. having a distinct ego-motion. The results show that MSU's behavior is highly affected by variation in speed and sensor placement with respect to direction of movement, mainly due to the physical properties of installed sensors. This strongly suggests that any future design of MSU must account for the speed effect from the design stage all the way through deployment and results analysis. This is the first report examining the influence of airflow variations on MSU's ability to accurately measure pollutant levels.

On the feasibility of measuring urban air pollution by wireless distributed sensor networks.

Accurate evaluation of air pollution on human-wellbeing requires high-resolution measurements. Standard air quality monitoring stations provide accurate pollution levels but due to their sparse distribution they cannot capture the highly resolved spatial variations within cities. Similarly, dedicated field campaigns can use tens of measurement devices and obtain highly dense spatial coverage but normally deployment has been limited to short periods of no more than few weeks. Nowadays, advances in communication and sensory technologies enable the deployment of dense grids of wireless distributed air monitoring nodes, yet their sensor ability to capture the spatiotemporal pollutant variability at the sub-neighborhood scale has never been thoroughly tested. This study reports ambient measurements of gaseous air pollutants by a network of six wireless multi-sensor miniature nodes that have been deployed in three urban sites, about 150 m apart. We demonstrate the network's capability to capture spatiotemporal concentration variations at an exceptional fine resolution but highlight the need for a frequent in-situ calibration to maintain the consistency of some sensors. Accordingly, a procedure for a field calibration is proposed and shown to improve the system's performance. Overall, our results support the compatibility of wireless distributed sensor networks for measuring urban air pollution at a sub-neighborhood spatial resolution, which suits the requirement for highly spatiotemporal resolved measurements at the breathing-height when assessing exposure to urban air pollution.

Acquired resistance to the 16-membered macrolides tylosin and tilmicosin by Mycoplasma bovis.

The molecular mechanism of acquired resistance to the 16-membered macrolides tylosin (Ty) and tilmicosin (Tm) was investigated in Mycoplasma bovis field isolates. Sequence analysis of domains II and V of the two 23S rRNA alleles and ribosomal proteins L4 and L22 was performed on 54 M. bovis isolates showing different minimal inhibitory concentrations (MIC). The presence of any one of the point mutations G748A, C752T, A2058G, A2059G or A2059C (Escherichia coli numbering) in one or both alleles of the 23S rRNAs was correlated with decreased susceptibility to Ty (8-1024 µg/ml) and to Tm (32 to >256 µg/ml) in 27/27 and 27/31 M. bovis isolates, respectively. Although a single mutation in domain II or V could be sufficient to cause decreased susceptibility to Ty, our data imply that a combination of mutations in two domains is necessary to achieve higher MICs (≥ 128 µg/ml). The influence of a combination of mutations in two domains II and V on enhancement of resistance to Tm was less clear. In addition, the amino acid (aa) substitution L22-Q90H was found in 24/32 representative M. bovis isolates with different MICs, but no correlation with decreased susceptibility to Ty or Tm was identified. Multiple aa substitutions were also identified in the L4 protein, including at positions 185-186 (positions 64 and 65 in E. coli) which are adjacent to the macrolide-binding site. This is the first description of the molecular mechanism of acquired resistance to the 16-membered macrolides in M. bovis.