Use of prescription opioids in Israel and socio-economic correlations between 2010 and 2020.

BACKGROUND: The use of opioids has increased dramatically over the past several years in Israel. The aim of this study was to explore the trends of opioid consumption in Israel over a decade (2010-2020) stratified by socioeconomic status (SES), residence in the periphery, and ethnic background. METHODS: This cross-sectional study included all adult Maccabi Healthcare Services (MHS) patients who filled at least one prescription for opioids during the past decade. In order to standardize dosages and compare different opioid medications, we used the Morphine Milligram Equivalent (MME) conversion factor. We performed The Mann-Kendall test with autocorrelation correction to assess each trend. We then checked the differences between the trends with the Mann-Whitney test (for periphery) and the Kruskal Wallis (for SES and ethnic background). RESULTS: Between the years 2010-2020, 261,270 MHS members met the study's inclusion criteria. The proportions of opioids consumption were 23.9/1000 patients in 2010 and 27.6/1000 patients in 2020, representing a 15% increase. The average daily consumption of opioids was 4.6 and 10.5 MME in 2010 and 2020, respectively, an increase of 227%. The daily MME during 2020 was higher for residents of the periphery compared to non-periphery residents (daily MME of 14.0 compared to 10.1, respectively). Average daily MME increased gradually during the study period for all levels of SES; the values were highest for the low SES group and the lowest for the high SES group (daily MME in 2020 for the lowest, middle, and high SES groups were 15.2 vs. 11.8 vs. 6.7 respectively). CONCLUSIONS: This study highlights that the primary concern in the increase of opioid use is the increasing dosages. The increase in the number of patients using opioids is also significant but to a minor extent. These phenomena disproportionately impact vulnerable populations. Education programs should be offered to physicians regarding the possible harms of long-term use of opioids. These programs should emphasize the risk factors associated with the development of opioid use disorder (OUD) and the caution needed when increasing dosages or switching to higher-potency drugs. Pain clinics and centers for rehabilitation for patients with chronic pain or OUD should be available, not only in central areas but also in the periphery of the country. These clinics and centers should use a holistic approach and a multidisciplinary team that includes specialists in pain and addiction. They should be financially accessible for patients from low SES group and provide solutions in multiple languages.

Short term safety of BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine among children aged 5-11 years, a nationwide parental survey.

PURPOSE: SARS-CoV-2 vaccine safety is of major interest worldwide, and transparent information about potential side effects is essential to decrease vaccine hesitancy. The aim of this study was to assess SARS-CoV-2 BNT162b2 vaccine short-term side effects among children aged 5-11 years. METHODS: An observational, cross sectional study of vaccine side-effects using electronic surveys sent to parents one week post administration of BNT162b2 vaccine to their child in a large health maintenance organization in Israel. RESULTS: First dose and second dose surveys were filled for 5,842 and 6,126 children, respectively, with a response rate of 32.1% and 24.8%. Local side effects were reported by 68.7% and 69.1% of the first and second survey respondents, and general side effects were reported by 20.8% and 34.5% of them. The symptoms most frequently reported were fatigue, headache and myalgia. Duration of symptoms lasted three days or less among 86.5% and 81.5% of first and second dose survey respondents. Most respondents (92%) reported that their child did not need any medical consultation following vaccination. CONCLUSIONS: We found further support for the BNT162b2 SARS-CoV-2 vaccine short- term safety among children aged 5-11 years. With ongoing pandemic and future booster COVID-19 vaccines, these findings can encourage vaccine confidence for parents and providers.

Common Bacterial Infections during the 3-Month Period after SARS-CoV-2 Infection: A Retrospective Cohort Study.

INTRODUCTION: Correlations between SARS-CoV-2 and bacterial infections have mainly been studied in hospitals, and these studies have shown that such interactions may be lethal for many. In the context of community flora, less is known of the trends and consequences of viral infections relative to subsequent bacterial infections. PURPOSE: This study aims to explore the prevalence and characteristics of bacterial infections in the three months following SARS-CoV-2 infections, in a community, real-world setting. METHODS: In this retrospective cohort study, we compared patients who completed a polymerase chain reaction (PCR) test or an antigen test for SARS-CoV-2 during January 2022, the peak of the Omicron wave, and examined bacterial infections following the test. We searched these cases for diagnoses of the following four bacterial infections for three months following the test: Group A Streptococcus (GAS) pharyngitis, pneumonia, cellulitis, and urinary tract infections (UTI). RESULTS: During January 2022, 267,931 patients tested positive and 261,909 tested negative for SARS-CoV-2. Test-positive compared to test-negative patients were significantly younger (42.5 years old vs. 48.5 years old, p < 0.001), smoked less, and had fewer comorbidities (including ischemic heart disease, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, and chronic renal failure). In the multivariable analysis, test-positive patients had an increased risk for GAS pharyngitis (adjusted odds ratio [aOR] = 1.25, 95% CI 1.14-1.38, p-value < 0.001) and pneumonia (aOR = 1.25, 95% CI 1.15-1.35, p-value < 0.001), a trend towards an increased prevalence of UTI (aOR = 1.05, 95% CI 0.99-1.12, p-value = 0.092), and lower risk for cellulitis (aOR = 0.92, 95% CI 0.86-0.99, p-value < 0.05). CONCLUSIONS: A history of SARS-CoV-2 infection in the past three months increased susceptibility to respiratory tract bacterial infections and the prevalence of UTI.

Smoking cessation - better together: A retrospective cohort study.

INTRODUCTION: Smoking is the leading preventable cause of death and illness globally. There is conflicting evidence regarding the association between quitting rates and partners' smoking status. It is thought that spouses influence one another's health habits, including smoking. This study aims to evaluate this association in patients who made a smoking cessation attempt with pharmacotherapy. METHODS: For this Israeli nationwide retrospective cohort study, we randomly selected patients who filled a prescription for varenicline as part of their smoking cessation process and were partnered. The participants were asked to complete a questionnaire 26-52 weeks after the first varenicline purchase. The independent variables were the partner's smoking status at the beginning of the smoking cessation process and while answering the questionnaire. The outcome was a success in the quitting process. RESULTS: In all, 226 (50%) participants had partners who smoked at the beginning of the quitting process, and 230 (50%) had non-smoking partners; 178 (39%) participants reported successful smoking cessation. There was a significant difference in success rates depending on partners' smoking status at the end of the process, with success rates of 39% with a non-smoking partner, 76% with a partner who also stopped smoking, and 31% with a partner who continued smoking (p<0.001). Multivariate analysis showed that having a partner who stopped smoking during the quitting process was associated with higher odds of quitting compared with having a non-smoking partner (OR=4.73; 95% CI: 1.86-12.05). CONCLUSIONS: This study showed that both partners quitting was associated with increased odds of successful quitting. Health providers should make efforts to engage both partners in smoking cessation.

Risk Stratification Model for Severe COVID-19 Disease: A Retrospective Cohort Study.

BACKGROUND: Risk stratification models have been developed to identify patients that are at a higher risk of COVID-19 infection and severe illness. Objectives To develop and implement a scoring tool to identify COVID-19 patients that are at risk for severe illness during the Omicron wave. METHODS: This is a retrospective cohort study that was conducted in Israel's second-largest healthcare maintenance organization. All patients with a new episode of COVID-19 between 26 November 2021 and 18 January 2022 were included. A model was developed to predict severe illness (COVID-19-related hospitalization or death) based on one-third of the study population (the train group). The model was then applied to the remaining two-thirds of the study population (the test group). Risk score sensitivity, specificity, and positive predictive value rates, and receiver operating characteristics (ROC) were calculated to describe the performance of the model. RESULTS: A total of 409,693 patients were diagnosed with COVID-19 over the two-month study period, of which 0.4% had severe illness. Factors that were associated with severe disease were age (age > 75, OR-70.4, 95% confidence interval [CI] 42.8-115.9), immunosuppression (OR-4.8, 95% CI 3.4-6.7), and pregnancy (5 months or more, OR-82.9, 95% CI 53-129.6). Factors that were associated with a reduced risk for severe disease were vaccination status (patients vaccinated in the previous six months OR-0.6, 95% CI 0.4-0.8) and a prior episode of COVID-19 (OR-0.3, 95% CI 0.2-0.5). According to the model, patients who were in the 10th percentile of the risk severity score were considered at an increased risk for severe disease. The model accuracy was 88.7%. CONCLUSIONS: This model has allowed us to prioritize patients requiring closer follow-up by their physicians and outreach services, as well as identify those that are most likely to benefit from anti-viral treatment during the fifth wave of infection in Israel, dominated by the Omicron variant.

Long COVID symptoms in Israeli children with and without a history of SARS-CoV-2 infection: a cross-sectional study.

OBJECTIVES: To estimate the prevalence of long COVID symptoms in children with and without a history of SARS-CoV-2 infection and to evaluate factors associated with long COVID. DESIGN: A nationwide cross-sectional study. SETTING: Primary care. PARTICIPANTS: 3240 parents of children aged 5-18 with and without SARS-CoV-2 infection completed an online questionnaire (11.9% response rate); 1148 and 2092 with/without a history of infection, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the prevalence of long COVID symptoms in children with/without a history of infection. Secondary outcomes were the factors associated with the presence of long COVID symptoms and with failure to return to baseline health status in children with a history of infection including gender, age, time from illness, symptomatic illness and vaccine status. RESULTS: Most long COVID symptoms were more prevalent in children with a history of SARS-CoV-2 infection: headaches (211 (18.4%) vs 114 (5.4%), p<0.001), weakness (173 (15.1%) vs 70 (3.3%), p<0.001), fatigue (141 (12.3%) vs 133 (6.4%), p<0.001) and abdominal pain (109 (9.5%) vs 79 (3.8%), p<0.001). Most long COVID symptoms in children with a history of SARS-CoV-2 infection were more prevalent in the older age group (12-18) compared with the younger age group (5-11). Some symptoms were more prevalent in children without a history of SARS-CoV-2 infection, including attention problems with school malfunctioning (225 (10.8%) vs 98 (8.5%), p=0.05), stress (190 (9.1%) vs 65 (5.7%), p<0.001), social problems (164 (7.8%) vs 32 (2.8%)) and weight changes (143 (6.8%) vs 43 (3.7%), p<0.001). CONCLUSION: This study suggests that the prevalence of long COVID symptoms in children with a history of SARS-CoV-2 infection might be higher and more prevalent in adolescents than in young children. Some of the symptoms, mainly somatic symptoms, were more prevalent in children without a history of SARS-CoV-2 infection, highlighting the impact of the pandemic itself rather than the infection.

Association Between AZD7442 (Tixagevimab-Cilgavimab) Administration and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, Hospitalization, and Mortality.

BACKGROUND: Intramuscular AZD7442 (tixagevimab-cilgavimab [Evusheld; AstraZeneca]) has been found effective among immunocompromised individuals (ICIs) in reducing SARS-CoV-2 infection and severe disease in ICIs. We evaluated the association between AZD7442 administration and SARS-CoV-2 infection and severe disease (COVID-19 hospitalization and all-cause mortality) among selected ICIs, during a fifth Omicron-dominated wave of COVID-19 (December 2021-April 2022) in Israel. METHODS: ICIs aged ≥12 years identified in the Maccabi HealthCare Services database were invited by SMS/e-mail to receive AZD7442. Demographic information, comorbidities, coronavirus vaccination, and prior SARS-CoV-2 infection and COVID-19 outcome data (infection, severe disease) were extracted from the database. Rates of infection and severe disease were compared between those administered AZD7442 and those who did not respond to the invitation over a 3-month period. RESULTS: Of all 825 ICIs administered AZD7442, 29 (3.5%) became infected with SARS-CoV-2 compared with 308 (7.2%) of 4299 ICIs not administered AZD7442 (P < .001). After adjustment, the AZD7442 group was half as likely to become infected with SARS-CoV-2 than the nonadministered group (OR: .51; 95% CI: .30-.84). One person in the AZD7442 group (0.1%) was hospitalized for COVID-19 compared with 27 (0.6%) in the nonadministered group (P = .07). No mortality was recorded among the AZD7442 group compared with 40 deaths (0.9%) in the nonadministered group (P = .005). After adjustment, ICIs administered AZD7442 were 92% less likely to be hospitalized/die than those not administered AZD7442 (OR: .08; 95% CI: .01-.54). CONCLUSIONS: AZD7442 among ICIs may protect against Omicron variant infection and severe disease and should be considered for pre-exposure prophylactic AZD7442.

Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals, a prospective longitudinal cohort study.

PURPOSE: As protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion. METHODS: A prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster. RESULTS: Among 110 participants,56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25-11.67) folds and 2.40 (95 %CI 1.90-3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5-79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1-34.7) fold in and immunocompetent group, was observed. CONCLUSION: A third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.

How compassionate use enabled Israel to deliver the Pfizer-BioNTech COVID-19 vaccination to vulnerable children aged 12-15 years before regulatory approval.

AIM: This paper describes the emergency, compassionate use of the COVID-19 vaccination for high-risk adolescents aged 12-15 years prior to approval by the American Food and Drugs Administration in May 2021. The target audience had underlying health conditions associated with severe disease and multisystem inflammatory syndrome in children (MIS-C) or severely immunosuppressed household members. METHODS: An orderly approval system was established in Israel for adolescents aged 12-15 years, based on a professional position paper and compassionate treatment regulations. From 12 February 2021, eligible adolescents were referred to the Israeli Ministry of Health for permission to vaccinate, via four health maintenance organisations. Data were collected about adverse events after vaccinations and the incidence of any cases of COVID-19. RESULTS: By 15 March 2021, the vaccine had been approved for 607 adolescents: 333 had received one dose, and 92 had received two doses. The median age was 14.6 years, and the major indication was obesity. Only one child tested positive for the virus, 4 days after vaccination, and no adverse effects were recorded. CONCLUSION: The emergency use of COVID-19 vaccination for 333 adolescents aged 12-15, 92 of them with 2 doses, based on a position paper and compassionate treatment regulations, did not result in any adverse effects. Since 27 July 2021, the same process was further applied in Israel among younger children, aged 5-11, preceding formal release of the clinical trial.