The epidemiology of sleep disorders in Israel: results from a population-wide study.

BACKGROUND: Studies on the prevalence of sleep disorders have found great variability due to different data collection methods and case definitions. We aimed at assessing the prevalence of sleep disorders in a large, unselected population using validated clinical patient records. To the best of our knowledge, this is the first large clinically based study on sleep disorders. METHODS: This retrospective study used the computerized data of 2.3 million members of Maccabi Healthcare Services (MHS) public mandated health provider. Among enrolled MHS members alive in June 2018, electronic medical records were searched from January 2010 for sleep disorders using diagnosis codes, sleep medications, and recorded sleep studies. RESULTS: A total of 195,201 patients (9% of the total MHS population) were identified. Patients were 48.3% men and the average age at diagnosis was 50.4 years (SD = 20.9). Prevalence increased with age; 3.2% in children under 10 years, 5.2% in young adults, and 22.3% among seniors aged 75 or older. The two most prevalent disorders were insomnia (7.4%), and sleep-related breathing disorders (2%). Less prevalent disorders included central disorders of hypersomnolence (100 per 100,000), circadian rhythm sleep-wake disorders (49 per 100,000), parasomnias (140 per 100,000), and sleep-related movement disorders (20 per 100,000). CONCLUSIONS: The overall prevalence of sleep disorders including insomnia and sleep related breathing disorders in Israel were similar to other western countries despite stressful life events of ongoing war and terrorism. The large sample size allowed us to calculate the prevalence of more rare sleep disorders, which have been generally less known.

Fracture incidence after denosumab discontinuation: Real-world data from a large healthcare provider.

BACKGROUND: Vertebral fractures (VF) upon Denosumab (DMAB) discontinuation were first described as a distinct phenomenon in 2015, yet the magnitude of this event remains undetermined. OBJECTIVES: To estimate fracture risk after DMAB discontinuation, in a real-world setting. METHODS: The computerized database of a 2.3-million members' state-mandated health organization was utilized to detect osteoporotic patients with at least two DMAB dispenses. Treatment discontinuation was defined as a refill gap of 3 months or more, while the discontinuation date was defined as an anticipated missed purchase date. Fractures were identified by an osteoporosis registry and individually adjudicated by an expert's review. Fractures occurring within one year from discontinuation among DMAB discontinuers (DD) and from the 2nd year of treatment onwards for persistent users (PU) were included. RESULTS: A total of 1500 DD (92% females, mean ±â€¯SD age = 71.8 ±â€¯9.5y), and 1610 PU (91%, 71.7 ±â€¯8.8) were identified. At baseline, the groups were comparable in fracture- history, bisphosphonate exposure, smoking, and bone density. Multiple VF occurred in 12 (0.8%) DD vs. 2 (0.1%) PU (p = 0.006). The overall rate of fractures per 100 patient-years of follow-up was significantly higher in DD than PU (RR 3.2, 95% CI 2.2-4.8), as well as the rate of VF (RR 4.7, 95% CI 2.3-9.6) and multiple VF (RR 14.6, 95% CI 3.3-65.3, effect size 1.06). CONCLUSIONS: Patients who discontinue DMAB are at greater risk of major OP fractures than those who persist with treatment. Same is true for clinical multiple vertebral fractures, yet the incidence of the latter was low. These findings demonstrate a need for greater awareness and thoughtful management of DMAB discontinuation.

Comparison of Mortality and Comorbidity Rates Between Holocaust Survivors and Individuals in the General Population in Israel.

Importance: Previous studies have suggested that Holocaust survivors may experience different chronic comorbidities more often than the general population. However, the mortality hazard among these individuals has not been addressed. Objective: To assess the overall mortality rate and comorbidities of a cohort of Holocaust survivors compared with an age-matched control group. Design, Setting, and Participants: This cross-sectional study included all Holocaust survivors insured by Maccabi Healthcare Services in Israel who were born between 1911 and 1945 in Europe and control individuals born in Israel during the same years and insured by the same service. Data were collected from January 1, 1998, through December 31, 2017. Outcomes and Measures: Rates of morbidities and mortality rates adjusted for sex, socioeconomic status, and body mass index using logistic regression, Cox regression, and Kaplan-Meier analysis. Results: The 38 597 Holocaust survivors included 22 627 women (58.6%) and had a mean (SD) age of 81.7 (5.4) years, and the 34 931 individuals in the control group included 18 615 women (53.3%) and had a mean (SD) age of 77.7 (5.3) years. The Holocaust survivors had higher rates than control individuals of reported hypertension (32 038 [83.0%] vs 23 285 [66.7]), obesity (12 838 [33.3%] vs 9254 [26.5]), chronic kidney disease (11 929 [30.9%] vs 6927 [19.8]), cancer (11 369 [29.5%] vs 9721 [27.8]), dementia (6389 [16.6%] vs 3355 [9.6]), ischemic heart disease, nonmyocardial infarction (5729 [14.8%] vs 4135 [11.8]), myocardial infarction (3641 [9.4%] vs 2723 [7.8]), and osteoporotic fractures among women (6429 [28.4%] vs 4120 [22.1]). In contrast, the overall mortality rate was lower among Holocaust survivors (25.3%) compared with the control group (41.1%). After adjustment for confounders, mean age at death was significantly higher in the survivor group compared with the control group. Conclusions and Relevance: The findings showed higher rates of comorbidities and lower mortality among Holocaust survivors, which may be associated with a combination of improved health literacy and unique resilience characteristics among Holocaust survivors. More research is needed to explore the biologic and psychosocial basis for these results.

Statin Therapy: Diabetes Mellitus Risk and Cardiovascular Benefit in Primary Prevention.

BACKGROUND: The salutary effects of statin therapy in patients with cardiovascular disease (CVD) are well established. Although generally considered safe, statin therapy has been reported to contribute to induction of diabetes mellitus (DM). OBJECTIVES: To assess the risk-benefit of statin therapy, prescribed for the prevention of CVD, in the development of DM. METHODS: In a population-based real-life study, the incidence of DM and CVD were assessed retrospectively among 265,414 subjects aged 40-70 years, 17.9% of whom were treated with statins. Outcomes were evaluated according to retrospectively determined baseline 10 year cardiovascular (CV) mortality risks as defined by the European Systematic COronary Risk Evaluation, statin dose-intensity regimen, and level of drug adherence. RESULTS: From 2010 to 2014, 5157 (1.9%) new cases of CVD and 11,637 (4.4%) of DM were observed. Low-intensity statin therapy with over 50% adherence was associated with increased DM incidence in patients at low or intermediate baseline CV risk, but not in patients at high CV risk. In patients at low CV risk, no CV protective benefit was obtained. The number needed to harm (NNH; incident DM) for low-intensity dose regimens with above 50% adherence was 40. In patients at intermediate and high CV risk, the number needed to treat was 125 and 29; NNH was 50 and 200, respectively. CONCLUSIONS: Prescribing low-dose statins for primary prevention of CVD is beneficial in patients at high risk and may be detrimental in patients at low CV risk. In patients with intermediate CV risk, our data support current recommendations of individualizing treatment decisions.

Challenges in defining the rates of ADHD diagnosis and treatment: trends over the last decade.

BACKGROUND: There is a global trend of large increases in the prevalence and incidence of Attention Deficit Hyperactivity Disorder (ADHD). This study aimed to address potential causes of these major changes. METHODS: The authors used a large cohort to analyze data employing patients' electronic medical records, with physicians' diagnosis of ADHD, including records of medication purchases. RESULTS: The prevalence of ADHD diagnoses rose twofold from 6.8% to 14.4% between 2005 and 2014 (p < 0.001), while the ratio of males to females with ADHD decreased from 2.94 in 2005 to 1.86 in 2014 (p < 0.001). The incidence increased, peaking in 2011 before declining in 2014. ADHD medication usage by children and adolescents was 3.57% in 2005 and 8.51% by 2014 (p < 0.001). CONCLUSIONS: We report a dramatic increase in the rate of ADHD diagnoses. One of the leading factors to which we attribute this increase is the physicians' and parents' changed attitude towards diagnosing attention/hyperactivity problems, with more parents appear to consider ADHD diagnosis and treatment as a means to improve their child's academic achievements, commonly with the aid of medications. This change in attitude may also be associated with the dramatic increase in female ADHD diagnosis prevalence.

Maccabi proactive Telecare Center for chronic conditions - the care of frail elderly patients.

BACKGROUND: In 2012, Maccabi Healthcare Services founded Maccabi Telecare Center (MTC), a multi-disciplinary healthcare service providing telemedical care to complex chronic patients. The current paper describes the establishment and operation of the MTC center, from the identification of the need for the service, through the design of its solution elements, to outcomes in several areas of care. We analyze the effects of the program on elderly frail patients, a growing population with complex and costly needs. METHODS: Observational quasi-experimental analyses using propensity score matching was used to assess the effect of MTC's operation on utilization outcomes including direct costs. RESULTS: Results for frail elderly patients with complex chronic conditions show significant reductions in hospitalization days and hospitalization costs. MTC interventions also entailed lower overall average monthly costs in frail patients. CONCLUSION: We conclude that a proactive telehealth service for complex chronic patients using education, empowerment to self-management, and coordination of care is a cost-effective means of improving quality care and health outcomes in frail elderly patients.

Costs of Managing Patients with Diabetes in a Large Health Maintenance Organization in Israel: A Retrospective Cohort Study.

INTRODUCTION: The aim of this study was to evaluate the direct costs of patients with diabetes ensured in a large health maintenance organization, Maccabi Health Services (MHS), in order to compare the medical costs of these patients to the medical costs of other patients insured by MHS and to assess the impact of poorly controlled diabetes on medical costs. METHODS: A retrospective analysis of patients insured in MHS during 2012 was performed. Data were extracted automatically from the electronic database. A glycated hemoglobin (HbA1c) level of >9% (75 mmol/mol) was considered to define poorly controlled diabetes, and that of <7% (53 mmol/mol) and <8% (64 mmol/mol) to define controlled diabetes for patients aged <75 and ≥75 years, respectively. Multivariate analysis analyses were done to assess factors affecting cost. RESULTS: Data on a total of 99,017 patients with diabetes were obtained from the MHS database for 2012. Of these, 54% were male and 72% were aged 45-75 years. The median annual cost of treating diabetes was 4420 cost units (CU), with hospitalization accounting for 56% of the total costs. The median annual cost per patient in the age groups 35-44 and 75-84 years was 2836 CU and 7033 CU, respectively. Differences between costs for patients with diabetes and those for patients without diabetes was 85% for the age group 45-54 years but only 24% for the age group 75-84 years. Medical costs increased similarly with age for patients with controlled diabetes and those with poorly controlled diabetes costs, as did additional co-morbidities. Costs were significantly impacted by kidney disease. The costs for patients with an HbA1c level of 8.0-8.99% (64-74 mmol/mol) and 9.0-9.99% (75-85 mmol/mol) were 5722 and 5700 CU, respectively. In a multivariate analysis the factors affecting all patients' costs were HbA1C level, male gender, chronic diseases, complications of diabetes, disease duration, and stage of kidney function. CONCLUSIONS: The direct medical costs of patients with diabetes were significantly higher than those of patients without diabetes. The main drivers of these higher costs were hospitalizations and renal function. In poorly controlled patients the effect of HbA1c on costs was limited. These findings suggest that it is cost effective to identify patients with diabetes early in the course of the disease. FUNDING: The work was sponsored by internal funds of the authors. Article processing charges for this study was funded by Novo Nordisk.

Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial.

PURPOSE: A link between poor sleep quality and Alzheimer's disease (AD) has recently been suggested. Since endogenous melatonin levels are already reduced at preclinical AD stages, it is important to ask whether replenishing the missing hormone would be beneficial in AD and whether any such effects would be related to the presence of sleep disorder in patients. PATIENTS AND METHODS: The effects of add-on prolonged-release melatonin (PRM) (2 mg) to standard therapy on cognitive functioning and sleep were investigated in 80 patients (men [50.7%], women [49.3%], average age 75.3 years [range, 52-85 years]) diagnosed with mild to moderate AD, with and without insomnia comorbidity, and receiving standard therapy (acetylcholinesterase inhibitors with or without memantine). In this randomized, double-blind, parallel-group study, patients were treated for 2 weeks with placebo and then randomized (1:1) to receive 2 mg of PRM or placebo nightly for 24 weeks, followed by 2 weeks placebo. The AD Assessment Scale-Cognition (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), sleep, as assessed by the Pittsburgh Sleep Quality Index (PSQI) and a daily sleep diary, and safety parameters were measured. RESULTS: Patients treated with PRM (24 weeks) had significantly better cognitive performance than those treated with placebo, as measured by the IADL (P=0.004) and MMSE (P=0.044). Mean ADAS-Cog did not differ between the groups. Sleep efficiency, as measured by the PSQI, component 4, was also better with PRM (P=0.017). In the comorbid insomnia (PSQI ≥6) subgroup, PRM treatment resulted in significant and clinically meaningful effects versus the placebo, in mean IADL (P=0.032), MMSE score (+1.5 versus -3 points) (P=0.0177), and sleep efficiency (P=0.04). Median ADAS-Cog values (-3.5 versus +3 points) (P=0.045) were significantly better with PRM. Differences were more significant at longer treatment duration. PRM was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSION: Add-on PRM has positive effects on cognitive functioning and sleep maintenance in AD patients compared with placebo, particularly in those with insomnia comorbidity. The results suggest a possible causal link between poor sleep and cognitive decline.