Adherence to metformin and the onset of rheumatoid arthritis: a population-based cohort study.

Objective: The aim of this retrospective cohort study was to examine whether adherence to metformin treatment may be associated with lower onset of rheumatoid arthritis (RA).Method: Using the computerized databases of a 2.3-million state-mandated health services organization in Israel, we identified incident RA cases among a cohort of 113 749 adult patients who initiated metformin therapy between 1998 and 2014. Adherence was assessed by calculating the mean proportion of follow-up days covered (PDC) with metformin.Results: During the 18 year study period, there were 558 incident RA cases (61 per 100 000 person-years). Adherence to metformin treatment was associated with a lower risk of developing RA, with the lowest risk recorded among patients with a PDC of 40-59% [adjusted hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.45-0.84] compared with non-adherent patients (PDC < 20%). A mean daily metformin dose of 2550 mg or more was also associated with a lower risk of developing RA (adjusted HR 0.62, 95% CI 0.46-0.84) compared to a daily dose of 850 mg or less. In stratified analyses by gender, the negative association between adherence and the risk of RA was limited to women alone.Conclusions: Adherence to metformin treatment is associated with a reduced risk of developing RA in women. Further studies are needed to assess the effect of metformin on RA development in other patient populations.

Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members.

OBJECTIVE: Endometriosis constitutes a significant burden on the quality of life of women, their families and healthcare systems. The objective of this study is to describe the real-world epidemiology of endometriosis in an unselected low-risk population in Israel. DESIGN: Retrospective population-based study. SETTING AND SAMPLE: The computerised databases of Maccabi Healthcare Services (MHS), a 2-million-member healthcare provider representing a quarter of the Israeli population. METHODS: The crude point prevalence (31 December 2015; diagnosed since 1998) and annual incidence (2000-2015) rates of diagnosed endometriosis (ICD-9-CM 617.xx) were assessed among women aged 15-55 years. Prevalent patients were characterised in terms of sociodemographic and clinical characteristics, including validated MHS infertility and chronic disease registries. MAIN OUTCOME MEASURES: Prevalence and incidence of diagnosed endometriosis in MHS. RESULTS: The point prevalence of endometriosis [n = 6146, mean age 40.4 ± 8.0 years (SD)] was 10.8 per 1000 (95% CI 10.5-11.0). Women aged 40-44 years had the highest prevalence rate of 18.6 per 1000 (95% CI 17.7-19.5). Infertility was documented in 37% of patients. A total of 6045 patients were included in the cohort of newly-diagnosed endometriosis (mean age 34.0 ± 8.1 years), corresponding to an average annual incidence rate of 7.2 per 10 000 (95% CI 6.5-8.0). CONCLUSIONS: We observed a substantially lower prevalence of diagnosed endometriosis compared with previous reports in high-risk populations, in line with population-based estimates from European databases (range 0.8-1.8%). Further characterisation of this cohort may help to understand what affects the prevalence of endometriosis in Israel, and to promote earlier diagnosis and improve management in clinical practice. TWEETABLE ABSTRACT: Endometriosis diagnosed in 1% of women, according to a large population-based study in a community setting.

Sustained virological response to ombitasvir/paritaprevir/ritonavir and dasabuvir treatment for hepatitis C: Real-world data from a large healthcare provider.

Treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin (OPrD ± RBV), was the first interferon-free direct-acting antiviral for hepatitis C virus (HCV) introduced to Israel's national basket of health services in February 2015. Patients with HCV genotype 1 (GT1) and advanced fibrosis (F3-F4) were eligible for treatment in 2015. This study aimed to characterize patients initiating OPrD ± RBV and assess sustained virological response (SVR). A retrospective cohort study was performed using the database of Maccabi Healthcare Services (MHS), a 2-million-member health plan in Israel. The study population included adults who initiated OPrD ± RBV through December 2015 per health basket criteria. A gap in medication fills (>14 days between a fill's run-out and the next fill) was used to estimate adherence. SVR was defined by the viral tests at least 12-week post-treatment. The study population consisted of 403 patients (56.3% male), with a mean age of 60.7 years (SD 11.0). Overall, 71.0% were naïve to prior HCV treatment, and 95.6% were treated with a 12-week regimen. A total of 348 patients (86.4%) completed the regimen in the usual time frame (highly adherent), whereas 8.2% completed with a gap, and 4.7% purchased less than the recommended dose. SVR rates overall and among highly adherent patients were 395/403 (98.0%; 95% CI 96.1-99.1) and 346/348 (99.4%; 95% CI 97.9-99.9), respectively. GT1b patients on 12-week regimens attained SVR rates of 194/196 (fibrosis F3) and 170/176 (cirrhosis). After a first year of provision of OPrD ± RBV with good adherence, high SVR rates were achieved in various patient subgroups and comorbidities.

Association of gastrointestinal events and osteoporosis treatment initiation in newly diagnosed osteoporotic Israeli women.

BACKGROUND: The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan. METHODS: This retrospective analysis of claims records included women aged ≥ 55 years with ≥ 1 osteoporosis diagnosis (date of first diagnosis was index date). Osteoporosis treatment initiation was defined as use of osteoporosis therapy (oral bisphosphonates or other) during 12 months postindex. GI events (diagnosis of GI conditions) were reported for 12 months preindex and postindex (from index to treatment initiation or 1 year postindex, whichever occurred first). The association of postindex GI events (yes/no) with the initiation of osteoporosis treatment (yes/no) and with type of therapy initiated (oral bisphosphonate vs. other) were examined with logistic regression and Cox proportional hazard regression (as sensitivity analysis). RESULTS: Among 30,788 eligible patients, 17.5% had preindex GI events and 13.0% had postindex GI events. About 70.6% of patients received no osteoporosis therapy within 1 year of diagnosis, 24.9% received oral bisphosphonates and 4.5% received other medications. Postindex GI events were associated with lower odds of osteoporosis medication initiation (85-86% reduced likelihood; p < 0.01). Upon treatment initiation, postindex GI was not significantly associated with the type of osteoporosis therapy initiated, controlling for baseline GI events and patient characteristics. CONCLUSIONS: Among newly diagnosed osteoporotic women from a large Israeli health plan, 70.6% did not receive osteoporosis treatment within 1 year of diagnosis. The presence of GI events was associated with reduced likelihood of osteoporosis treatment initiation.

Adherence to statins and the risk of psoriasis: a population-based cohort study.

BACKGROUND: Statins have been shown to downregulate immune mechanisms activated in psoriasis. However, previous studies on their potential role in preventing psoriasis have yielded conflicting results. OBJECTIVES: To assess the relationship between adherence to statins and the risk of psoriasis. METHODS: This retrospective cohort study included 205,820 health plan enrollees in Israel (mean age 55 years; 54·1% women) who initiated statin treatment from January 1998 through to September 2009. Adherence to statins, measured by the proportion of days covered (PDC), throughout the entire follow-up period (mean 6·2 years) was recorded. Diagnosis codes of psoriasis were assigned by a dermatologist or rheumatologist, or at discharge from hospital. RESULTS: During 1·28 million person-years (PY) of follow-up (median 5·74 years per person; interquartile range 3·78-8·36), 5615 cases of psoriasis (incidence density rate 4·4 per 1000 PY) were recorded. Compared with patients who did not adhere to statins (PDC < 20%), patients covered by statins for 40-59% of the time had a significantly lower risk of psoriasis (P < 0·05), with hazard ratios (HRs) of 0·84 and 0·74 among men and women, respectively. Among patients who adhered better to statins (PDC ≥ 80%), HRs were 0·88 (95% CI 0·79-0·98) and 1·00 (95% CI 0·90-1·11) among men and women, respectively. CONCLUSIONS: The results of the current study suggest that high and long-term adherence to statins is not associated with a meaningful reduction in the risk of developing psoriasis.

Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-11.

BACKGROUND: The incidence of melanoma and keratinocyte cancers (KCs) is rising worldwide. Squamous cell carcinomas (SCCs) and basal cell carcinoma (BCCs) are the most common of all cancers. OBJECTIVES: To determine trends in the incidence of melanoma, BCC and SCC among 1·7 million members of Maccabi Healthcare Services (MHS) from 2006 to 2011. METHODS: Data on patients newly diagnosed with melanoma, SCC and BCC were collected from the MHS Cancer Registry and based on histology reports from the centralized pathology laboratory. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating average annual percentage change (AAPC). RESULTS: During the 6-year study period, 16,079 patients were diagnosed with at least one BCC, 4767 with SCC and 1264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100,000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among men and primarily affected the elderly. BCC rates were stable throughout the study period [AAPC -0·7%, 95% confidence interval (CI) -4·5 to 3·2], while the incidence of SCC increased significantly (AAPC 15·5%, 95% CI 2·6-30·0). In contrast, melanoma rates continuously decreased (AAPC -3·0%, 95%CI -4·5 to -0·1). CONCLUSIONS: The incidence of KC in Israel is high. The disparities in incidence trends between SCC, BCC and melanoma allude to their different aetiologies. These findings underscore the importance of continuous monitoring, education and prevention programmes in a growing high-risk population.

Uptake of Pap smears among women in a large Israeli HMO between 2006 and 2008.

OBJECTIVES: The Papanicolaou (Pap) smear test is used in many countries as a screening procedure for cervical cancer and precancerous lesions. The actual uptake of this screening test among women at risk for cervical cancer is unknown. The aim of this study was to estimate the percentage of women who are screened by Pap smears from the relevant population at risk, and to detect factors that are independently associated with uptake of cervical screening. STUDY DESIGN: Retrospective database study. METHODS: This study was undertaken at Maccabi Healthcare Services (MHS), the second largest publicly funded health maintenance organization in Israel. The study population consisted of Israeli women aged 21-59 years who were insured by MHS between 2006 and 2008. Logistic regression analyses were used to determine the independent relationships between immigration and socio-economic status and cervical screening. RESULTS: The study population included 489,663 women who had a total of 313,602 Pap smears between 2006 and 2008. Fifty-four percent of the women did not have a Pap smear during the study period, 32% had at least one smear, and 14% had at least two smears. Living in a low socio-economic neighbourhood and recent immigration were independently and negatively associated with screening uptake. CONCLUSION: Despite the clinical guidelines and the low costs, many Israeli women who are at risk for cervical cancer are not screened.

The long term risk of myelodysplastic syndromes among anemia patients: a population-based study.

We have utilized the computerized data of a nationwide health plan to elucidate several epidemiologic aspects and risk factor of myelodysplastic syndromes (MDS) in Israel. The annual incidence rate (IR) of reported MDS was of 3.32 per 100,000. Among anemic patients aged 40+, the risk of reported MDS was 56.7 per 100,000. Only 44% of the reported MDS cases had an indication of bone marrow examination. In a multivariable model, older age, hemoglobin level <9 g/dl, white blood cell count of less than 3500/mm(3), and platelet count of less than 100×10(9)/L were associated with a significantly higher risk of MDS. The mean lag period from the first demonstration of anemia to the final diagnosis of MDS was 3.5 years. Our study results could be helpful for improving the detection of patients with high MDS risk, therapeutic decision-making, and designing interventional trials in the future.

Reconsidering the connection between vitamin D levels and age-related macular degeneration.

PURPOSE: Recent evidence has suggested a correlation between reduced vitamin D levels and delayed angiogenesis and reduced inflammatory response, which are known to have a major role in the development and progression of age-related macular degeneration (AMD). DESIGN: Cross-sectional study. PARTICIPANTS: Members of the Maccabi Healthcare Services (MHS, one of the four largest Israeli Health Maintenance Organization) aged ≥60 years, whose vitamin D levels were taken as part of routine examinations between 2000 and 2008. METHODS: All data for this study were obtained from MHS databases that include medical information on 1.8 million subscribers. MAIN OUTCOME MEASURES: Serum 25-OH vitamin D levels. RESULTS: The total study population comprised of 1045 members diagnosed as having AMD, and 8124 as non-AMD, for whom there was information on vitamin D levels. The mean±SD level of 25-OH vitamin D was 24.1±9.41 ng/ml (range 0.8-120) for the AMD patients and 24.13±9.50 ng/ml (range 0.0-120) for the controls (P=ns). One-third (33.6%) of the AMD patients and 32.86% of the controls had a 25-OH vitamin D level <16 ng/ml, and the proportions of tests in which the 25-OH vitamin D level was >74 ng/ml were 0.19 and 0.14%, respectively (P=ns). CONCLUSIONS: No association was detected between vitamin D levels and the presence of AMD in this cross-sectional study. These results raise some doubt about an association between reduced vitamin D levels and the prevalence of AMD.

A retrospective study of the incidence of diagnosed Type 1 diabetes among children and adolescents in a large health organization in Israel, 2000-2008.

AIMS: To determine the incidence and examine temporal trends of Type 1 diabetes among children aged < 18 years, in a large Israeli health organization. METHODS: All incident Type 1 diabetes cases diagnosed between 2000 and 2008 were ascertained from an automated diabetes registry based on members' electronic records and validated by comparison with the Israel Juvenile Diabetes Register. RESULTS: During the study period, a total of 648 incident cases of Type 1 diabetes were identified. The average annual age-and-sex-standardized incidence was 11.09 per 100,000 person-years. There was an annual 5.82% (95% CI 1.80-9.98%) rise in incidence, with a greater relative increase in toddlers under 5 years of age. Incidence increased with age and demonstrated seasonal variation. Mean age at onset of diabetes significantly (P = 0.07) decreased from 10.21 years (SD = 4.48) in 2000-2002 to 9.25 years (SD = 4.54) in 2006-2008. Among very young patients (< 5 years), average blood glucose values at diagnosis dropped from 32.4 mmol/l (SD = 9.5) to 19.5 mmol/l (SD = 11.0) over the study period, with little change in average glucose for older children. CONCLUSIONS: Incidence of diagnosed Type 1 diabetes continues to increase in Israel at a rate that is high compared with similar American and European populations. At the same time, the clinical presentation of children is changing.

The risk of overt diabetes mellitus among women with gestational diabetes: a population-based study.

AIMS: To determine the incidence of postpartum diabetes mellitus in the years following a diagnosis of gestational diabetes mellitus (GDM) and to determine whether the severity of GDM, represented by the magnitude of the deviation of diagnostic tests from the normal values or requirement for medications, is associated with the development of diabetes. METHODS: A retrospective cohort study was performed among 185 416 pregnant women who had glucose challenge test or 3 h oral glucose tolerance test (OGTT) in a large health maintenance organization in Israel. Subsequent diagnosis of diabetes was ascertained by using an automated patient registry. RESULTS: A total of 11 270 subjects were diagnosed with GDM, comprising 6.07% of the cohort. During a total follow-up period of 1 049 334 person-years there were 1067 (16.9 per 1000 person-years) and 1125 (1.1 per 1000 person-years) diagnoses of postpartum diabetes among GDM and non-GDM women, respectively. The cumulative risk of incident diabetes in GDM patients with up to 10 years of follow-up was 15.7%, compared with 1% among the non-GDM population. Gestational diabetes mellitus was associated with nearly an eightfold higher risk of postpartum diabetes after adjusting for important confounders, such as socioeconomic status and body mass index. Among women with a history of GDM, the number of abnormal OGTT values and use of insulin were associated with a substantially higher risk for developing diabetes. CONCLUSIONS: Three or four abnormal OGTT values and GDM requiring insulin or oral hypoglycaemic medications are important predictors of postpartum diabetes risk in women with a history of GDM.

Long-term trends in hepatitis A incidence following the inclusion of Hepatitis A vaccine in the routine nationwide immunization program.

For many years hepatitis A was one of the most common vaccine preventable diseases in Israel. In 1999, Israel became the first country to introduce an inactivated hepatitis A vaccine into its national childhood vaccination program. The objectives of the present study were to study trends in disease incidence after the implementation of the new vaccination policy and to assess vaccination coverage among children and adults in Israel. We used the databases of the second largest HMO in Israel (1.7 million members) to identify patients who had evidence of hepatitis A in 1998 and 2007 and to collect information on all subjects who received at least one dose of hepatitis A vaccine during the study period. Hepatitis A vaccination coverage in children <5 years and 5-14 years of age increased from 9% and 15% in 1998 to 89% and 68% in 2007, respectively. During this period the annual incidence of hepatitis A dropped from 142.4 per to 7.6 per 100 000. The most prominent reduction in the age-specific annual incidence rates was calculated in children <5 years from 239.4 per 100 000 in 1998 to 2.2 per 100 000 in 2007 and from 310.3 per 100 000 to 3.0 per 100 000 in children aged 5-14 years. In endemic areas, vaccination of infants and children against hepatitis A can greatly reduce the total burden of the disease.

Diabetes as a risk factor for herpes zoster infection: results of a population-based study in Israel.

BACKGROUND: Studies showed that diabetes mellitus (DM) is often accompanied by impaired cell-mediated immunity, which potentially may increase the risk for infectious diseases, including herpes zoster (HZ). However, data on the relation between DM and HZ are scarce. This case-control study explored the association between DM and HZ. PATIENTS AND METHODS: This study was nested within a cohort of all members of a large health maintenance organization (HMO) in Israel. Cases totaled 22,294 members who were diagnosed with HZ between 2002 and 2006. Controls (n=88,895) were randomly selected from the remaining HMO population using frequency-matched age, sex, and duration of follow-up. Personal data on history of DM, lymphoma, leukemia, or AIDS, were obtained from computerized medical records. RESULTS: Adjusted analyses showed that the risk of HZ was associated with history of leukemia, lymphoma, use of steroids or antineoplastic medications, and AIDS, particularly among patients below 45 years of age. In a multivariate analysis, DM was associated with an increased risk of HZ (OR=1.53; 95% CI: 1.44-1.62). CONCLUSIONS: The data suggest that individuals with DM are at increased risk of HZ. Well-designed cohort studies may help to clarify the nature of this association.

The association between glycemic, lipids and blood pressure control among Israeli diabetic patients.

BACKGROUND: It is recommended that in diabetes mellitus patients all risk factors for cardiovascular disease should be controlled. AIM: To evaluate the rate of reaching all glycemic, lipids and blood pressure target levels among diabetic patients in Israel and to analyze demographic and clinical parameters associated with it. DESIGN: A cross-sectional study. METHODS: The study was conducted in Maccabi Healthcare Services, Israel's second largest health maintenance organization. All patients (n = 41 936), older than 20 years, who were listed on Maccabi Healthcare Service's diabetes mellitus computerized database and had all three study parameters (HbA1c, LDL-C and blood pressure levels during 2005) were eligible for the study. The rate of reaching HbA1c <7.0%, LDL-C <100 mg/dl and blood pressure <130/85 mmHg, as well as its association with various demographic and clinical parameters were analyzed. RESULTS: Only 13% of all study patients achieved all three target levels. The parameters which were significantly associated with goal achievement were compliance to medical treatment for all three parameters (OR 1.56, 95% CI 1.44-1.69, P = 0.0001), male gender (OR 1.42, 95% CI 1.31-1.54, P = 0.0001), comorbidity with ischemic heart disease (OR 1.23, 95% CI 1.13-1.34, P = 0.0001), and >12 visits per year to family physician (OR 1.10, 95% CI 1.02-1.19, P = 0.012). CONCLUSION: Non-compliance with treatment and sub-optimal follow-up by family physicians are associated with increased risk of failure to control major risk factor among diabetic patients.

Mandatory computer field for blood pressure measurement improves screening.

METHODS: We evaluated the effectiveness of a compulsory data field in a computerized medical record (CMR) in improving blood pressure (BP) screening. RESULTS: The proportion of study patients who had their BP measured increased from 40.6% to 58.5% (P < 0.001) after the intervention. After adjusting for age, gender and number of visits, patients were 73% more likely to have their BP recorded after the introduction of the compulsory field.

Gender differences in healthcare utilization and medical indicators among patients with diabetes.

OBJECTIVE: To describe differences in healthcare utilization and health indicators of patients with diabetes, according to gender. STUDY DESIGN: A population-based outcome study conducted on 21,277 diabetic patients between the ages of 45 and 64 years who are members of the second largest health maintenance organization in Israel. METHODS: Data on healthcare utilization (process indicators) and health problems (outcome indicators) were obtained from computerized medical records that are stored routinely by the organization. The study period was the year 2002. RESULTS: Significantly (P < 0.05) lower healthcare utilization was observed in men compared with women for all indicators examined (number of visits to physicians and the performance of urine, lipids and creatinine tests). Nonetheless, men showed better health outcomes (lower low-density lipoprotein cholesterol, triglycerides, HbA1c). CONCLUSIONS: Women who suffer from diabetes use more healthcare services and have a higher morbidity rate compared with men. Future research should seek to identify the factors contributing to this observation, which can potentially make an important contribution to the development of disease management strategies that target diabetic women.

[Multimodal treatment of pancreatic cancer]. / Kombinirovannoe lechenie raka podzheludochnoi zhelezy.

The experience with combined treatment of 122 patients with pancreatic cancer in the clinic of the Institute of Clinical & Experimental Surgery for the period of from 1988 to 1990 is summarized. Radical operations were performed in 54 patients, the palliative ones--in 68. After performance of a palliative operation, the patients underwent polychemotherapy, 5--in combination with UHF-hyperthermia. To study the effect of chemotherapy on the immune system, the immunologic monitoring was carried out. It was established that under the influence of chemotherapy and hyperthermia, the indices of immunity in patients with pancreatic cancer improved. In cancer of the pancreatic head with involvement of pancreatic body, the performance of subtotal pancreatoduodenal resection with subsequent regional chemotherapy is expedient. Chemotherapy and hyperthermia in combination with creation of a shunt permit to improve the results of treatment of inoperable tumors. The use of regional chemotherapy in subtotal resection contributed to increase in 2-year survival of the patients.