Receipt of prescription opioid medication is associated with increased mortality in an Israeli population.

BACKGROUND: Despite Israel's increased use of prescription opioids, reported deaths resulting or associated with opioids have decreased, in fact dramatically, since 2005. This contrast is unique and difficult to explain. We sought to examine whether higher prescribed opioid dosages among adults without oncologic diagnoses were associated with higher all-cause mortality rates. METHODS: A historical cohort study in Clalit Health Services, using a data repository including all adult patients prescribed opiates between 2010 and 2020, excluding patients with oncologic diagnoses. Patients were classified into three groups according to opioid use: below 50 Morphine milligram equivalents (MME) per day, 50 to 90 MME per day, and above 90 MME per day. Sex, Charlson comorbidity score, age and socioeconomic status were recorded. Mortality rates were compared between the dosage groups and compared to age-standardized mortality rates in the general population. RESULTS: On multivariate analysis, patients receiving 90 or more MME per day were 2.37 (95%CI 2.1 to 2.68) more likely to have died compared to patients receiving below 50 MME per day. The respective hazard ratio among patients receiving between 50 and 90 MME per day was 2.23 (2.01 to 2.46). Among patients aged 18 to 50, standardized mortality ratios (SMRs) compared to the general population ranged between 5.4 to 8.6 among women, receiving between 50 and 90 MME per day, and between 8.07 and 10.7 among women receiving 90 or more MME per day. The respective SMRs among men were 1.2 to 3.8 and 2.7 to 5.4. CONCLUSION: Increased opioid use is independently associated with increased all-cause mortality among non-oncological patients. This result is most notable among young adults with little or no known comorbidities. These findings are consistent with results in other countries and seem more credible than previous Israeli reports. Healthcare regulators and providers should, therefore, act to curtail the increasing opioid prescriptions and devise and enhance controls in the healthcare system, which, until 2020, had very limited mechanisms in place.

Serological follow-up after syphilis diagnosis in Israel.

The global incidence of syphilis is increasing. Continuity of care challenges the control of sexually transmitted diseases. In this study, we assessed the follow-up and serological decline differences between community- and hospital-diagnosed patients in Israel. A historical cohort study was conducted using the Israel National Syphilis Center (NSC) repository. Patients with a positive non-specific Venereal Disease Research Laboratory (VDRL) test between 2011 and 2020 were included. Rates of serological follow-up and serological titre decreases were compared between hospital- and community-diagnosed patients. The study included 4,445 patients, 2,596 (58.4%) were diagnosed in community clinics and 1,849 (41.6%) in hospitals. Of community-diagnosed patients, 1,957 (75.4%) performed follow-up testing, compared with 834 (51.2%) hospital-diagnosed patients (p < 0.001). On multivariate analysis, the odds ratio of serology follow-up among community-diagnosed patients was 2.8 (95 per cent confidence interval (95% CI): 2.2-3.5) that of hospital-diagnosed patients. There were 1,397 (71.4%) community-diagnosed patients with serological titre decrease, compared with 626 (74.9%) hospital-diagnosed patients (p = 0.03). On multivariate analysis, this difference diminished. Serological follow-up testing is suboptimal and was performed more often among patients initially diagnosed in the community compared to hospitals. Continuity of care should be improved to promote successful patient care and prevent disease spread.

A retrospective cohort analysis of treatment outcomes of patients with tuberculosis who used substances in Tel Aviv, Israel.

AIMS: To outline the demographic, clinical, laboratory characteristics, and treatment outcomes of tuberculosis (TB) patients who used substances. METHODS: This retrospective cohort study compared 50 TB patients who used substances with a matched random sample of 100 TB patients who did not use substances between 2007 and 2017. Treatment failure was defined as a sputum smear or culture that tested positive after 5 months of treatment, loss to follow-up, unevaluated patients, or death. RESULTS: TB patients who used substances were typically younger, experienced homelessness, smokers, and had fewer chronic diseases than those who did not use substances. They also were hospitalized for longer periods, their treatment durations were longer, had higher rates of multidrug resistant strains, increased rates of treatment failure, and higher mortality. Individuals whose treatment failed predominantly originated from the former Soviet Union, experienced homelessness, and had chronic diseases compared with those whose treatment was successful. In the multivariate analysis, homelessness [odds ratios (OR) = 6.7], chronic diseases (OR = 12.4), and substance use (OR = 4.0) were predictors of treatment failures. CONCLUSIONS: TB patients who used substances were more likely to have treatment failure. Targeted interventions, including early diagnosis and enhanced support during treatment, are essential to achieve treatment success in this vulnerable population, in addition to TB-alcohol/drug collaborative activities.

Trends in Israeli community-based opioid prescribing, 2010-2020, an observational study of the country's largest HMO.

BACKGROUND: Prescription opioids are widely used for pain control and palliative care but have been associated with a variety of untoward effects, including opioid use disorder, addiction, and increased mortality. Patterns of opioid use in Israel are to date poorly described. METHODS: Using a community-based database, the authors performed a retrospective analysis of filled opioid prescriptions of Israeli HMO members 18 years of age or older during the years of 2010-2020 that filled at least one opioid prescription. Morphine milligram equivalent (MME) calculations were stratified by presence or absence of oncology diagnosis and by specific opioid medication. RESULTS: The percentage of HMO members who filled at least one opioid prescription increased every year from 2.1% in 2010 to 4.2% in 2020. There was an increase in the MME per prescription (44.2%), daily MME per capita (142.1%) and MME per prescription-filling patient (39%) from 2010 to 2020. Increased prescription opioid use is driven by a small group of non-oncological patients, which is less than 1.5% of opioid-prescribed patients and 0.1% of the adult population, primarily owing to fentanyl use. CONCLUSION: Supervision and control of opioid prescriptions in Israel should be a focused effort directed at patients prescribed uniquely high dosages rather than a population-wide strategy that focuses on all patients prescribed opioids. This should be complemented by improved physician training and access to non-opioid therapies, as well as improved data collection and analysis.

Hepatitis C Virus Elimination Program among Prison Inmates, Israel.

The Israeli Prison Services implemented a hepatitis C virus (HCV) elimination program in 2020. Inmates considered high risk for HCV were offered serology; HCV-seropositive participants were offered HCV RNA testing. Among participants, 7.0% had detectable HCV RNA and were offered antiviral drug therapy. This program reduced HCV burden among incarcerated persons.

COVID-19 Booster Vaccination Among Individuals With Schizophrenia in Israel.

Importance: Individuals with schizophrenia are at higher risk for severe COVID-19 illness and mortality. Previous reports have demonstrated vaccination gaps among this high-risk population; however, it is unclear whether these gaps have continued to manifest with the booster dose. Objective: To assess gaps in first, second, and booster vaccinations among individuals with schizophrenia. Design, Setting, and Participants: This was a matched, controlled, retrospective cohort study conducted in November 2021, and included follow-up data from March 2020, to November 2021. The study used the databases of Clalit Health Services, the largest health care management organization in Israel. Individuals with a diagnosis of schizophrenia at the onset of the pandemic and matched controls were included in the analysis. Main Outcomes and Measures: Rates of first, second, and booster vaccinations and time to reach vaccination. Results: The study included 34 797 individuals (mean [SD] age, 50.8 [16.4] years; 20 851 men [59.9%]) with schizophrenia and 34 797 matched controls (mean [SD] age, 50.7 [16.4] years; 20 851 men [59.9]) for a total of 69 594 individuals. A total of 6845 of 33 045 individuals (20.7%) with schizophrenia were completely unvaccinated, compared with 4986 of 34 366 (14.5%) in the control group (odds ratio [OR], 0.65; 95% CI, 0.62-0.67, P < .001). Once vaccinated, no significant differences were observed in the uptake of the second vaccine. Gaps emerged again with the booster vaccine, with 18 469 individuals (74.7%) with schizophrenia completing the booster, compared with 21 563 (77.9%) in the control group (OR, 0.83; 95% CI, 0.80-0.87, P < .001). Kaplan-Meier analyses indicated significant differences in time to reach vaccination, although gaps were lower compared with those reported in the first vaccination (log-rank test, 601.99 days; P < .001 for the first vaccination, compared with log-rank test, 81.48 days, P < .001 for the booster). Multivariate Cox regression analyses indicated that gaps in the first and booster vaccine were sustained even after controlling for demographic and clinical variables (first vaccine: hazard ratio [HR], 0.80; 95% CI, 0.78-0.81; P < .001 and booster: HR, 0.88; 95% CI, 0.87-0.90; P < .001) but were not significant for the second vaccine. Conclusions and Relevance: Results of this cohort study of Israeli adults found lower rates of COVID-19 vaccination among individuals with schizophrenia compared with a control group without schizophrenia, especially during the vaccine initiation phase. Countries worldwide should adopt strategies to mitigate the persistence of vaccination gaps to improve health care for this vulnerable population.

Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance.

Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus. The quantitation method was validated using data from vaccination with bivalent oral polio vaccine (bOPV). The method was then applied to infer the weekly number of excreters in a large, sustained, asymptomatic outbreak of wild type 1 poliovirus in Israel (2013) in a population where >90% of the individuals received three doses of inactivated polio vaccine (IPV). Evidence-based intervention strategies were based on the short TAT for direct quantitative detection. Furthermore, a TAT shorter than the duration of poliovirus excretion allowed resampling of infected individuals. Finally, the method documented absence of infections after successful intervention of the asymptomatic outbreak. The methodologies described here can be applied to outbreaks of other excreted viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where there are (1) significant numbers of asymptomatic infections; (2) long incubation times during which infectious virus is excreted; and (3) limited resources, facilities, and manpower that restrict the number of individuals who can be tested and re-tested.

Nationwide seroprevalence of antibodies against SARS-CoV-2 in Israel.

The first local spread of COVID-19 in Israel was detected in March 2020. Due to the diversity in clinical presentations of COVID-19, diagnosis by RT-PCR alone might miss patients with mild or no symptoms. Serology testing may better evaluate the actual magnitude of the spread of infection in the population. This is the first nationwide seroprevalence study conducted in Israel. It is one of the most widespread to be conducted thus far, and the largest per-country population size. The survey was conducted between June 28 and September 14, 2020 and included 54,357 patients who arrived at the Health Maintenance Organizations to undergo a blood test for any reason. A patient was considered seropositive after two consecutive positive results with two different kits (Abbott and DiaSorin).The overall seroprevalence was 3.8% (95%CI 3.7-4.0), males higher than females [4.9% (95%CI 4.6-5.2) vs. 3.1% (95%CI 2.9-3.3) respectively]. Adolescents had the highest prevalence [7.8% (95%CI 7.0-8.6)] compared to other age groups. Participants who had undergone RT-PCR testing had a tenfold higher risk to be seropositive. The prevalence-to-incidence ratio was 4.5-15.7. Serology testing is an important complimentary tool for assessing the actual magnitude of infection and thus essential for implementing policy measures to control the pandemic. A positive serology test result was recently accepted in Israel as being sufficient to define recovery, with possible far-reaching consequences, such as the deploying of employees to ensure the maintenance of a functional economy.

Lower rates of neural tube defects in Israel following folic acid supplementation policy.

Neural tube defects (NTDs) are common and disabling congenital malformations that remain a public health challenge despite prevention efforts. In 2000, The Israeli Ministry of Health published recommendations on daily folic acid (FA) supplementation for women of reproductive age and established a national NTD registry. This study aims to evaluate the long-term impact of the FA supplementation policy on NTD rates in Israel and the need for further intervention. In this descriptive report, we present the rate of NTD-affected pregnancies recorded in the registry between 2000 and 2012, their subtype (anencephaly, spina bifida or other), outcome (live birth, stillbirth or pregnancy termination), ethnic group (Jewish, Bedouin and non-Bedouin Muslim) and years of maternal education. The final analysis included 2374 NTD cases reported between 2000 and 2012, compared with 1,668,073 live births. During this period NTD rates decreased from 20.3 to 11.2 cases per 10,000 live births, a 45% reduction. Reductions were seen in rates of spina bifida, anencephaly and encephalocele. NTD rates decreased in all pregnancy outcomes and in all ethnic groups, though rates among Bedouins remain high. Women with higher levels of education tended to have lower NTD rates, and were more prone to choose termination of an affected pregnancy. Following the institution of FA supplementation in Israel, a substantial reduction was seen in NTD rates. Nonetheless, Israeli NTD rates remain higher than in other developed countries. FA interventions should continue to be vigorously implemented, especially in vulnerable populations. The global success of mandatory fortification of grain strongly advocates its consideration in Israel.

No-shows in ambulatory clinics and non-utilized appointments for elective operations in selected surgical departments at a tertiary hospital in Israel.

BACKGROUND: The phenomenon of a patient missing a medical appointment without notification is called a "no-show". In contrast, "non-utilized appointments" are a broader phenomenon including all appointments that didn't occur as registered - whether due to actions taken by providers or patients. Both no-shows and non-utilized appointments can lead to reduced quality of care, loss in productivity, financial losses and impaired patient outcomes. METHODS: The study was carried out between August 2016 and January 2017 in the ENT, Orthopedics and General Surgery Departments of the Jerusalem-based Shaare Zedek Medical Center. The study team sought to examine the reasons for non-utilized appointments in elective operations. The study team also interviewed no-show ambulatory care patients regarding the causes of the no-show and reviewed medical records of no-show patients to determine the nature of the missed appointments. RESULTS: The rate of non-utilization of appointments for elective operations was 6%. The leading reasons for non-utilization of these appointments were: patient health issues, patient surgery postponement and surgery schedule overload (together accounting for 52% of cases and 72% of known reasons). The no-show rate for ambulatory clinic appointments was approximately 15%. The leading reasons for ambulatory clinic no-shows were: administrative issues, illness and forgetfulness (together accounting for 58% of all reasons). The leading types of appointments missed were:post-operation follow-ups and chronic illness follow-up (together accounting for 46% of cases and 63% of known reasons). CONCLUSIONS: In this study, the non-utilized appointment rate for elective operations was found to be lower than those noted in the medical literature, while the no-show rate for ambulatory visits was found to be similar to that found in the literature. There is room to question the necessity of certain types of postoperative follow-up appointments since they are at "high risk" for no-show. One promising way to reduce the no-show rate would involve improving the hospital's information and computing systems in order to identify patients who are susceptible to a no-show incident.

Outbreak of human leptospirosis linked to contaminated water bodies in Northern Israel, June to August 2018.

We report preliminary findings of a large outbreak of human leptospirosis with 36 confirmed/probable and 583 suspected cases from June-August 2018, linked to contaminated water bodies in Northern Israel. There was a travel-associated case in Germany; additional cases are being investigated in other countries. The presumed chain of transmission, implicating wild boar and cattle, raises multiple challenges for risk assessment, risk management and risk communication currently being addressed by a public health response team.

Isolated fetal horseshoe kidney does not seem to increase the risk for abnormal chromosomal microarray results.

OBJECTIVE: To examine the risk for clinically significant chromosomal microarray analysis (CMA) among fetuses with apparently isolated horseshoe kidney. METHODS: Data from all CMA analyses performed due to isolated horseshoe kidney reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained from a computerized database. Risk estimation was performed comparing the rate of abnormal CMA findings to the general population, based on a systematic review encompassing 9272 pregnancies with normal ultrasound, and local data cohort of 5541 pregnancies undergoing CMA due to maternal request. RESULTS: Of 82 pregnancies with isolated horseshoe kidney, one loss-of-copy-number variant compatible with 16p13.11 microdeletion syndrome was demonstrated (1.2%). In addition, two variants of unknown significance (VOUS) were detected (2.4%). The relative risk for pathogenic CMA findings among pregnancies with isolated single horseshoe kidney was not significantly different from the control population (1.03-1.39%). DISCUSSION: To our best knowledge, our study is the first report describing the rate of clinically significant CMA findings in fetuses with isolated horseshoe kidney. The detection of one pathogenic CMA findings in our cohort implies that the value of CMA analysis in such pregnancies is similar to the general population.

Estimation of polio infection prevalence from environmental surveillance data.

A major obstacle to eradicating polio is that poliovirus from endemic countries can be reintroduced to polio-free countries. Environmental surveillance (ES) can detect poliovirus from sewage or wastewaters samples, even in the absence of patients with paralysis. ES is underused, in part because its sensitivity is unknown. We used two unique data sets collected during a natural experiment provided by the 2013 polio outbreak in Israel: ES data from different locations and records of supplemental immunization with the live vaccine. Data from the intersecting population between the two data sets (covering more than 63,000 people) yielded a dose-dependent relationship between the number of poliovirus shedders and the amount of poliovirus in sewage. Using a mixed-effects linear regression analysis of these data, we developed several quantitative tools, such as (i) ascertainment of the number of infected individuals from ES data for application during future epidemics elsewhere, (ii) evaluation of the sensitivity of ES, and (iii) determination of the confidence level of the termination of poliovirus circulation after an outbreak. These results will be valuable in monitoring future outbreaks with ES, and this approach could be used to certify poliovirus elimination or to validate the need for more containment efforts.

Mortality, hospital days and expenditures attributable to ambient air pollution from particulate matter in Israel.

BACKGROUND: Worldwide, ambient air pollution accounts for around 3.7 million deaths annually. Measuring the burden of disease is important not just for advocacy but also is a first step towards carrying out a full cost-utility analysis in order to prioritise technological interventions that are available to reduce air pollution (and subsequent morbidity and mortality) from industrial, power generating and vehicular sources. METHODS: We calculated the average national exposure to particulate matter particles less than 2.5 µm (PM2.5) in diameter by weighting readings from 52 (non-roadside) monitoring stations by the population of the catchment area around the station. The PM2.5 exposure level was then multiplied by the gender and cause specific (Acute Lower Respiratory Infections, Asthma, Circulatory Diseases, Coronary Heart Failure, Chronic Obstructive Pulmonary Disease, Diabetes, Ischemic Heart Disease, Lung Cancer, Low Birth Weight, Respiratory Diseases and Stroke) relative risks and the national age, cause and gender specific mortality (and hospital utilisation which included neuro-degenerative disorders) rates to arrive at the estimated mortality and hospital days attributable to ambient PM2.5 pollution in Israel in 2015. We utilised a WHO spread-sheet model, which was expanded to include relative risks (based on more recent meta-analyses) of sub-sets of other diagnoses in two additional models. RESULTS: Mortality estimates from the three models were 1609, 1908 and 2253 respectively in addition to 184,000, 348,000 and 542,000 days hospitalisation in general hospitals. Total costs from PM2.5 pollution (including premature burial costs) amounted to $544 million, $1030 million and $1749 million respectively (or 0.18 %, 0.35 % and 0.59 % of GNP). CONCLUSIONS: Subject to the caveat that our estimates were based on a limited number of non-randomly sited stations exposure data. The mortality, morbidity and monetary burden of disease attributable to air pollution from particulate matter in Israel is of sufficient magnitude to warrant the consideration of and prioritisation of technological interventions that are available to reduce air pollution from industrial, power generating and vehicular sources. The accuracy of our burden estimates would be improved if more precise estimates of population exposure were to become available in the future.

Modeling the spread of polio in an IPV-vaccinated population: lessons learned from the 2013 silent outbreak in southern Israel.

BACKGROUND: Polio eradication is an extraordinary globally coordinated health program in terms of its magnitude and reach, leading to the elimination of wild poliovirus (WPV) in most parts of the world. In 2013, a silent outbreak of WPV was detected in Israel, a country using an inactivated polio vaccine (IPV) exclusively since 2005. The outbreak was detected using environmental surveillance (ES) of sewage reservoirs. Stool surveys indicated the outbreak to be restricted mainly to children under the age of 10 in the Bedouin population of southern Israel. In order to curtail the outbreak, a nationwide vaccination campaign using oral polio vaccine (OPV) was conducted, targeting all children under 10. METHODS: A transmission model, fitted to the results of the stool surveys, with additional conditions set by the ES measurements, was used to evaluate the prevalence of WPV in Bedouin children and the effectiveness of the vaccination campaign. Employing the parameter estimates of the model fitting, the model was used to investigate the effect of alternative timings, coverages and dosages of the OPV campaign on the outcome of the outbreak. RESULTS: The mean estimate for the mean reproductive number was 1.77 (95 % credible interval, 1.46-2.30). With seasonal variation, the reproductive number maximum range was between zero and six. The mean estimate for the mean infectious periods was 16.8 (8.6-24.9) days. The modeling indicates the OPV campaign was effective in curtailing the outbreak. The mean estimate for the attack rate in Bedouin children under 10 at the end of 2014 was 42 % (22-65 %), whereas without the campaign the mean projected attack rate was 57 % (35-74 %). The campaign also likely shortened the duration of the outbreak by a mean estimate of 309 (2-846) days. A faster initiation of the OPV campaign could have reduced the incidence of WPV even if a lower coverage was reached, at the risk of prolonging the outbreak. CONCLUSIONS: OPV campaigns are essential for interrupting WPV transmission, even in a developed country setting with a high coverage of IPV. In this setting, establishing ES of WPV circulation is particularly crucial for early detection and containment of an outbreak.

The Israeli national population program of genetic carrier screening for reproductive purposes.

PURPOSE: The Israeli population genetic screening program for reproductive purposes, launched in January 2013, includes all known, nationally frequent severe diseases (carrier frequency 1:60 and/or disease frequency 1 in 15,000 live births). The carrier screening program is free of charge and offers testing for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy for nearly the entire population, according to disease frequency among the different groups within the population. We report the results of the first year of the program. METHODS: Data on the tests performed over a 12-month period were collected from laboratories nationwide. RESULTS: More than 62,000 individuals were examined. The carrier frequency was within the expected range for most of the diseases. The few exceptions included lower carrier rates for cystic fibrosis among Muslim Arabs (1:236) and Druze (1:1,021) and Niemann-Pick type A among Muslim Arabs in a delineated region of Israel (1:229). CONCLUSION: The national population genetic carrier screening is aimed toward providing couples with knowledge of the existing options for the prevention of serious genetic conditions when it is relevant for them. It is still too early to determine whether this aim has been achieved.