BACKGROUND:
The beneficial effects of statins in rheumatoid arthritis (RA) have been suggested previously, but it is unclear whether statins may prevent its development. The aim of this retrospective cohort study was to explore whether persistent use of statins is associated with onset of RA.

METHODS AND FINDINGS:
The computerized medical databases of a large health organization in Israel were used to identify diagnosed RA cases among adults who began statin therapy between 1998 and 2007. Persistence with statins was assessed by calculating the mean proportion of follow-up days covered (PDC) with statins for every study participant. To assess the possible effects of healthy user bias, we also examined the risk of osteoarthritis (OA), a common degenerative joint disease that is unlikely to be affected by use of statins. A total of 211,627 and 193,770 individuals were eligible for the RA and OA cohort analyses, respectively. During the study follow-up period, there were 2,578 incident RA cases (3.07 per 1,000 person-years) and 17,878 incident OA cases (24.34 per 1,000 person-years). The crude incidence density rate of RA among nonpersistent patients (PDC level of <20%) was 51% higher (3.89 per 1,000 person-years) compared to highly persistent patients who were covered with statins for at least 80% of the follow-up period. After adjustment for potential confounders, highly persistent patients had a hazard ratio of 0.58 (95% confidence interval 0.52-0.65) for RA compared with nonpersistent patients. Larger differences were observed in younger patients and in patients initiating treatment with high efficacy statins. In the OA cohort analysis, high persistence with statins was associated only with a modest decrement in risk ratio (hazard ratio = 0.85; 0.81-0.88) compared to nonadherent patients.

CONCLUSIONS:
The present study demonstrates an association between persistence with statin therapy and reduced risk of developing RA. The relationship between continuation of statin use and OA onset was weak and limited to patients with short-term follow-up.

PURPOSE:
In recent years, there is a growing body of evidence suggesting that statins may have anti-inflammatory effects; consequently, it was hypothesized that statins may have a preventive effect against cataract.
METHODS:
The study was carried out on a retrospective cohort of 180,291 new statin users in a large health organization in Israel. Study participants were followed between 1998 and 2007 for incident cataract or cataract extraction.
RESULTS:
During the study period 27,301 cataracts were diagnosed and 6,976 cataract extractions were performed among study participants. Persistence with statins was associated significantly (P < 0.001) with a reduced risk of cataract in men and women aged 45 to 74. Men aged 45-54 with a high (>80%) proportion of follow-up days covered with statins had an adjusted hazard ratio of 0.62 (95% confidence interval: 0.54-0.72), compared with patients with low persistence with statins. In elderly patients, no relationship or a positive relationship was observed.
CONCLUSIONS:
Persistent statin use was significantly protective for the incidence of cataract in men and women under 75 years of age.

BACKGROUND:
The beneficial effects of statins on cardiovascular mortality in secondary prevention have been established in several long-term, placebo-controlled trials. However, the value of statin therapy in reduction of overall mortality in patients without coronary heart disease (CHD) is questionable. This study evaluated the effect of statin therapy in subjects with no indication of cardiovascular disease (primary prevention) and patients with known CHD (secondary prevention).

METHODS:
This retrospective cohort study included 229 918 adult enrollees in a health maintenance organization in Israel who initiated statin treatment from 1998 through 2006 (mean age, 57.6 years; 50.8% female). Proportion of days covered (PDC) with statins was measured by the number of dispensed statin prescriptions during the interval between the date of the first statin prescription and the end of follow-up.

Results:
During the study period 27,301 cataracts were diagnosed and 6,976 cataract extractions were performed among study participants. Persistence with statins was associated significantly (P < 0.001) with a reduced risk of cataract in men and women aged 45 to 74. Men aged 45-54 with a high (>80%) proportion of follow-up days covered with statins had an adjusted hazard ratio of 0.62 (95% confidence interval: 0.54-0.72), compared with patients with low persistence with statins. In elderly patients, no relationship or a positive relationship was observed.

RESULTS:
During a mean of 4.0 and 5.0 years of follow-up, there were 4259 and 8906 deaths among the primary prevention and secondary prevention cohorts, respectively. In both cohorts, continuity of treatment with statins (PDC, > or =90%) conferred at least a 45% reduction in risk of death compared with patients with a PDC of less than 10%. A stronger risk reduction was calculated among patients with high baseline low-density lipoprotein cholesterol level and patients initially treated with high-efficacy statins.

CONCLUSIONS:
Better continuity of statin treatment provided an ongoing reduction in mortality among patients with and without a known history of CHD. The observed benefits from statins were greater than expected from randomized clinical trials.

BACKGROUND:
Extensive research has been carried out to quantify the efficacy and immunologic responses to influenza immunization, however, only little was reported on whether the timing of vaccine administration affects its effectiveness. The study aims were to compare post-immunization hospitalization and mortality rates among high-risk patients who were vaccinated against influenza in different periods of autumn.

METHODS:
Data for the current population-based historical prospective study were obtained from a large health organization in Israel insuring 1,600,000 members. Study population (n = 68,166) included high-risk patients aged 55 and above, who were immunized against influenza between October and November 2003.

RESULTS:
Although at baseline, individuals vaccinated in late November (12-25/11/2003) were significantly younger and had lower burden of illness compared to those vaccinated in early October (1-13/10/2003), they had higher hospitalization rates and longer hospital stay during the following winter (December to March). They also had an increased risk for all-cause mortality (RR = 1.78; 95%CI: 1.13-2.80). No such differences were observed during the following summer (April-August).

CONCLUSIONS:
In countries where influenza generally peaks between December and early March, vaccines administered after mid-November might be less beneficial.

BACKGROUND:
The effectiveness of health promotion campaigns is hard to measure due to complex outcome and external factors. This study presents a method to evaluate a mass women's health promotion campaign held in a large health maintenance organization (HMO) in Israel.

METHODS:
This population-based study used administrative and medical databases to examine whether postal invitation to 120,231 HMO-female members increased adherence with certain preventive medicine recommendations (LDL-C, bone density test, and mammography breast cancer screening). A comparison was made using three different reference data: pre- and post-campaign periods (1998-2003), HMO-male members who were not targeted by the campaign, and rates of urine tests, which were also not targeted by the campaign.

RESULTS:
During the 2 months following the campaign, adherence with mammography (3.8%) and LDL-C (12.5%) reached their maximum rates in 5 years. Adherence with bone density test increased from 2.3% in 2000 to 2.8% in the campaign period. No similar trends were observed for urine or LDL-C tests among men.

CONCLUSIONS:
The use of multiple reference groups through the analysis of administrative and medical databases supports the association between the campaign and improved adherence with screening tests. A similar methodology may be adopted for the analysis of mass health promotion campaigns in large HMOs.

BACKGROUND:
Upper respiratory tract illnesses have been associated with an increased risk of morbidity and mortality.

OBJECTIVE:
To assess the influence of vaccination against influenza on the risk of hospitalization in internal medicine and geriatric wards, and the risk of death from all causes during the 2000-2001 influenza season.

METHODS:
A historical cohort study was conducted using computerized general practitioner records on patients aged 65 years and above, members of "Maccabi Healthcare Services"--the second largest health maintenance organization in Israel with 1.6 million members. The patients were divided into high and low risk groups corresponding to coexisting conditions, and were studied. Administrative and clinical data were used to evaluate outcomes.

RESULTS:
Of the 84,613 subjects in the cohort 42.8% were immunized. At baseline, vaccinated subjects were sicker and had higher rates of coexisting conditions than unvaccinated subjects. Vaccination against influenza was associated with a 30% reduction in hospitalization rates and 70% in mortality rates in the high risk group. The NNT (number needed to treat) measured to prevent one hospitalization was 53.2 (28.2 in the high risk group and 100.4 in the low risk group). When referring to length of hospitalization, one vaccine was needed to prevent 1 day of hospitalization among the high risk group. Analyses according to age and the presence or absence of major medical conditions at baseline revealed similar findings across all subgroups.

CONCLUSIONS:
In the elderly, vaccination against influenza is associated with a reduction in both the total risk of hospitalization and in the risk of death from all causes during the influenza season. These findings compel the rationale to increase compliance with recommendations for annual influenza vaccination among the elderly.

BACKGROUND: Despite the availability of a wide selection of effective antihypertensive treatments and the existence of clear treatment guidelines, many patients with hypertension do not have controlled blood pressure. We conducted a qualitative study to explore beliefs and perceptions regarding hypertension and gain an understanding of barriers to treatment among patients with and without diabetes.

METHODS: Ten focus groups were held for patients with hypertension in three age ranges, with and without diabetes. The topic guides for the groups were: What will determine your future health status? What do you understand by "raised blood pressure"? How should one go about treating raised blood pressure?

RESULTS: People with hypertension tend to see hypertension not as a disease but as a risk factor for myocardial infarction or stroke. They do not view it as a continuous, degenerative process of damage to the vascular system, but rather as a binary risk process, within which you can either be a winner (not become ill) or a loser. This makes non-adherence to treatment a gamble with a potential positive outcome. Patients with diabetes are more likely to accept hypertension as a chronic illness with minor impact on their routine, and less important than their diabetes. Most participants overestimated the effect of stress as a causative factor believing that a reduction in levels of stress is the most important treatment modality. Many believe they "know their bodies" and are able to control their blood pressure. Patients without diabetes were most likely to adopt a treatment which is a compromise between their physician's suggestions and their own understanding of hypertension.

CONCLUSION: Patient denial and non-adherence to hypertension treatment is a prevalent phenomenon reflecting a conscious choice made by the patient, based on his knowledge and perceptions regarding the medical condition and its treatment. There is a need to change perception of hypertension from a gamble to a disease process. Changing the message from the existing one of "silent killer" to one that depicts hypertension as a manageable disease process may have the potential to significantly increase adherence rates.

BACKGROUND:
Guidelines recommend that LDL-C level should be <100mg/dl among diabetes mellitus (DM) and coronary heart disease (CHD) patients.

OBJECTIVE:
To evaluate how patients with DM and CHD differ in attaining the target level and to examine the association between goal achievement, demographic and clinical parameters.

METHODS:
The study was conducted in Maccabi Healthcare Services, the second largest health maintenance organization in Israel. All patients with DM (n=54,261), CHD (n=24,083) or DM and CHD (n=15,370) who were listed in the computerized database and had at least one LDL-C level measurement between January 1, 2007 and July 15, 2008 were eligible. The percentage of patients who attained LDL-C level <100mg/dl and its association with demographic and clinical parameters were analyzed.

RESULTS:
The rate of reaching the LDL-C target level was higher among the CHD and CHD and DM patients than DM ones (67% vs. 57% vs. 50%, p<0.001, respectively). Male gender; 5th socioeconomic status quintile; underlying disease i.e. CHD, CHD and DM; high statins compliance; and revascularization by percutaneous coronary intervention predicted for reaching target level. DM; absence of renal function evaluation; hospitalizations; HbA1C>7% or missing its measurements had a negative predictive value.

CONCLUSIONS:
The rate of reaching LDL-C target level should be increased in all high risk patients, mainly diabetic ones. Efforts should include educational programs to physicians and patients regarding the importance, the need to adhere and to intensify the cholesterol lowering treatment.

We examined the uptake of rotavirus vaccine and its effectiveness in preventing acute gastroenteritis (AGE) in the community. Data on rotavirus vaccines purchases and AGE were extracted from the computerized database of a large health maintenance organization in Israel. The incidence of AGE requiring a physician visit during 2008-09 rotavirus season among vaccinated and non-vaccinated children were compared, and vaccine effectiveness was calculated as: (1-Relative Risk)×100. During the study period, the uptake of rotavirus vaccine (mostly monovalent) reached 55.1% (N=19,108) of the studied cohort. The risk of AGE requiring a physician visit was 23.2% and 46.4% among vaccinated and unvaccinated children, respectively, yielding an effectiveness of 50.1% (95% CI: 47.5%, 52.6%). Rotavirus monovalent vaccine was highly effective in preventing AGE in the community.

The association between rotavirus gastroenteritis (RVGE)-associated hospitalization and rotavirus vaccine receipt was examined, and vaccine effectiveness was estimated in a case-control study conducted between 11/2007 and 12/2009 among Israeli children age eligible for rotavirus vaccination. Cases (n=111) were hospitalized children with diarrhea testing positive for rotavirus by immunochromatography. Controls (n=216) were hospitalized children with diarrhea testing negative for rotavirus. Among controls 36 (16.7%) children were vaccinated against rotavirus compared with two children (1.8%) among cases (p < 0.001). Rotavirus immunization was associated with lower risk of RVGE-associated hospitalization; adjusted OR 0.106 (95% CI 0.024, 0.481), yielding a vaccine effectiveness of 89.4% (95% CI 51.9%, 97.6%) in preventing hospitalization. These data demonstrate high effectiveness of rotavirus vaccines in a high income country

BACKGROUND:
Trials of hormone replacement therapy (HRT) for prevention of chronic disease in postmenopausal women have suggested that the risks of treatment outweigh the benefits. The publication in 2002 of the Women's Health Initiative (WHI) study sparked a rapid decline in HRT purchases among American women.

OBJECTIVE:
To examine the impact of the WHI findings on patterns of HRT use in Israeli women.

METHODS:
We linked purchases of estrogen preparations from 1998 to 2007 by female Israeli health maintenance organization members aged 45 years and older to membership data. For each year, we calculated total annual purchases and rate of HRT utilization, characterized new users by age and mode of therapy, and examined rates of switching between modes of therapy.

RESULTS:
Twenty percent of women aged 45 years and older purchased estrogen products in 2001, versus 10% in 2007 (p < 0.001; chi(2)). Vaginally administered products accounted for a rising percentage of purchases, from 5% in 1999 to 18% in 2007. An increasing percentage of new users aged 55 years and older started with a vaginal product (62% in 1999, 82% in 2007). After 2002, new users of oral therapy discontinued use more quickly than those who started oral therapy before 2002. Tibolone accounted for an increasing percentage of oral drugs purchased (12% in 2003, 29% in 2007).

CONCLUSIONS:
The WHI findings had a rapid and sustained impact on HRT utilization in a large population of Israeli women, including a sharp decrease in the rate of use, particularly of oral preparations, as well as reduced duration of therapy and increased use of vaginal preparations and tibolone as first choices for treatment.

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.

OBJECTIVES:
To compare death rates of diabetic men and women relative to the general population and to identify sex-specific risk factors for all-cause mortality.

STUDY DESIGN AND SETTINGS:
In the current historical prospective cohort study, standardized mortality ratios (SMRs) were calculated for 19,657 men and women with diabetes in a large Israeli health care organization compared to the mortality in the general population from 1999 to 2003. In addition, sex-specific survival analyses were performed for men and women separately using baseline data obtained between 1995 and 1999.

RESULTS:
During the study follow-up (90,899 person-years), 2,924 deaths were identified. The SMR for diabetic women (1.40; 95% confidence interval [CI]: 1.33, 1.47) was significantly (P<0.01) higher than for diabetic men (1.20; 95% CI: 1.14, 1.26). Age, glycated hemoglobin, serum creatinine, low-density lipoprotein, high-density lipoprotein, dialysis, use of angiotensin-converting enzyme inhibitors, and insulin were similarly associated with mortality in both sexes. Residing in the south of Israel was related with higher risk among men but with decreased risk among women.

CONCLUSIONS:
The study indicates that diabetes seems to eliminate the relative protection against death usually seen in women. It also suggests that most risk factors are comparable between the sexes, underlining the importance of similarly intensive disease management in diabetic women and in diabetic men.

BACKGROUND:
Previous reports demonstrated an association between psoriasis and other diseases including heart failure and diabetes mellitus.

OBJECTIVES:
Our aim was to describe the association between psoriasis, diabetes mellitus, and atherosclerosis in Israel.

METHODS:
A cross-sectional study was performed utilizing the database of Maccabi Healthcare Services (MHS), a large health provider organization in Israel. Case patients were defined as subjects who were diagnosed with psoriasis. Patients with diabetes and atherosclerosis were identified by using the MHS diabetes and cardiovascular registries, respectively. The control group included MHS enrollees without psoriasis. The proportion of diabetes and atherosclerosis among case and control groups was compared. Chi-square tests were used to compare categorical parameters. Logistic regression models were used for multivariate analyses.

RESULTS:
The study included 46,095 patients with psoriasis (case patients) and 1,579,037 subjects without psoriasis (control patients). The age-adjusted proportion of diabetes was significantly higher in psoriasis patients as compared with the control group (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.1-1.48). The age-adjusted proportion of atherosclerosis was significantly higher in psoriasis patients as compared with the control group (OR 1.28, 95% CI 1.04-1.59). In patients with psoriasis, a multivariate logistic regression model demonstrated an association between diabetes and the multiple use of very potent topical steroids (P < .05) or use of systemic medication for psoriasis (methotrexate, cyclosporine or acitretin) (P < .001). A similar model demonstrated an association between atherosclerosis and the use of phototherapy (P < .001).

LIMITATIONS:
Our study was based on a computerized database. The diagnosis of psoriasis was based on digitally transmitted data. Therefore overestimation (false-positive cases) and underestimation (false-negative cases) of psoriasis patients may exist, thereby being a source for information bias. A second limitation is selection bias that may occur due to the possibility that reporting of both psoriasis and associated illnesses is higher in individuals who are seeking medical care. A third limitation concerns the causal effect between occurrence of psoriasis and atherosclerosis or diabetes. The dataset of MHS records diagnoses only from 1997 and does not record the date of disease onset.

CONCLUSIONS:
Our study supports previous reports for an association between psoriasis and atherosclerosis and psoriasis and diabetes. Further study is needed to support this observation.

(13)C-urea breath test (UBT) for the diagnosis of Helicobacter pylori requires a high density and active bacteria and has the potential to provide a noninvasive index of bacterial growth. We describe the gender differences in delta over baseline (13)C-UBT values in 7373 patients (4531 females and 2842 males) who underwent (13)C-UBT test for the diagnosis of H. pylori infection. A significantly (P<.001) higher mean +/- SD excess delta (13)CO(2) excretion was recorded in females (24.7+/-17.4) compared to males (17.6+/-11.8) aged 10-80 years. The age-adjusted difference between sexes was 7.1 (95% confidence interval, 6.4-7.9). Our analysis demonstrates quantitatively for the first time gender associated differences in H. pylori host interaction. This study suggests that infected females have a higher bacterial load and therefore may potentially infect their children at a higher degree than males.

Diabetes is one of the most prevalent non-communicable disease globally and it is one of the leading cause for death in most developed countries. The current population-based study aim was to describe to the epidemiology of diabetes in Israel by using our HMO's automated medical databases. All diabetic patients appearing in the diabetes registry among 1.6 million insured members in the second largest HMO in Israel were selected for epidemiological analysis. We identified 39,768 diabetic patients (crude prevalence rate of 2.6%). Higher age-specific prevalence rates were recorded among males. The highest age-specific prevalence rate of diabetes was calculated for men aged 75 and above (18.1%). A rise in the prevalence and mortality rates was recorded between 1999 and 2001 female (from 1.9 to 2.8 per 100,000) and for men (from 2.3 to 3.8 per 100,000). The current study demonstrates the potential of using large automated medical and administrative databases to determine the epidemiology of chronic disease, such as diabetes. The rise in the prevalence and mortality of diabetes patients has important implication for Israeli health authorities and should be seriously regarded.

INTRODUCTION: Data on utilization of ambulatory care and the impact of lifestyle on health among young adults are scarce. Israeli mandatory military service provides a unique opportunity to investigate these topics. Study objective was to analyze the utilization of health care services (HCS) during the first year of military service, and its associations with health behavior at recruitment, in order to plan health services, health classification, and health promotion activities.

METHODS: We conducted a retrospective cohort study among a representative sample of 5,751 mandatory new recruits between January 1, 2004, and December 31, 2008. Data were collected from the Israeli Defense Force computerized medical and administrative records and from an ongoing health survey among military recruits.

RESULTS: During their first year of service, recruits had, on average, more than 7 visits to the primary care clinic, more than 10 dispensed nonchronic medications, and more than 5 days of sick leave. Female sex (OR = 1.27; 1.06-1.51) and current cigarette smoking (OR = 1.57; 1.34-1.84) were significantly associated with increased use of HCS, after controlling for possible confounders.Conclusions:Our findings indicate high utilization of HCS during the first year of military service and highlight the potential effect of cigarette smoking as a risk factor for increased morbidity among apparently healthy young adults. These findings support adding smoking status to fitness assessments and could aid health promotion efforts to reduce smoking rates among adolescents.

OBJECTIVES:
The aim of this study was to assess the direct medical cost of treating major chronic illnesses in Maccabi Healthcare Services, a 1.8 million member health maintenance organization in Israel.

METHODS:
Direct medical costs were calculated for each member in 2006. We used multiple linear regression models to evaluate the overall costs of chronic conditions (cardiovascular diseases, diabetes mellitus, hypertension, female infertility treatments, and cancer), pregnancy and treatments for female infertility.

RESULTS:
According to the study model, hypertension was associated with the largest direct medical costs in both sexes. Cardiovascular diseases accounted for 9.5% of the total direct medical costs in men, but only 5.9% in women. Diabetes mellitus accounted for 3.5% of the total medical costs both in men and women and is comparable to the total pregnancy-related costs in women.

CONCLUSIONS:
The findings indicate that hypertension, diabetes mellitus and female infertility treatments impose a considerable economic burden on public healthcare services in Israel which is comparable with the costs of cancer and cardiovascular diseases.

BACKGROUND:
Rotavirus is a common cause of acute gastroenteritis in children under 5 years of age. Two effective vaccines against rotavirus gastroenteritis were recently licensed in many countries throughout the world. The study aimed to investigate the cost effectiveness of vaccinating an Israeli birth cohort of 143 500 children.

METHODS:
The cost-effectiveness analysis was determined using a decision analytical model, based on evidence-based estimates of the medical burden of rotavirus gastroenteritis in Israel.

RESULTS:
According to our model, a routine rotavirus immunization program using Rotarix and RotaTeq would prevent 17,801 and 13,288 office visits and 645 and 535 hospitalizations every year, respectively. When direct healthcare costs and societal costs are taken into account, the incremental cost-effectiveness ratio per gained QALY for Rotarix and RotaTeq are $10,995 and $30,674, respectively.

CONCLUSION:
Rotavirus vaccination can be considered a cost-effective intervention in Israel, depending on the precise vaccine price.

OBJECTIVE:
Although transmission of VZV is recognized as an important cause for morbidity in health care workers (HCWs), there is no general agreement on the recommended immunization policy. This study aimed to evaluate several of such prevention policies in economic terms.

SETTINGS:
Analysis of the cost per avoided future varicella cases among HCWs in Israel.

METHODS:
A cost-effectiveness analysis was performed by comparing the cost per avoided case of varicella among a theoretical cohort of 63,353 physician and nurses aged less than 45 years in Israel. Four policies were examined: (a) do nothing (status quo); (b) vaccination of susceptible workers using VZV serotesting; with (c) or without anamnestic history of chickenpox; and (d) presumptive mass vaccination of all eligible workers. A Markov-based model was developed using data from our recent seroepidemiological study in target population and from the literature.

RESULTS:
Screening and vaccination of susceptible workers using anamnestic selection is expected to reduce future cases, within 20 years since vaccination, from 58.3 to 33.0 with an incremental cost of 23,713 US dollars per avoided cases. Using only serological tests to detect susceptible workers would prevent additional 5.7 cases with an incremental cost of 206,692 US dollars per avoided case. Vaccinating all HCWs without serotesting, raises the costs markedly, with almost identical effectiveness, resulting in an incremental cost of 10.4 million US dollars per avoided case. Sensitivity analyses do not alter the ranking of the options.

CONCLUSION:
From the employer's perspective, routine varicella vaccination program for HCWs with or without selection of susceptible workers is extremely expensive compared to other high-cost practiced approaches. Substantial reduction in cost of vaccination may alter this conclusion.

Diabetes mellitus is an important chronic disease with a growing prevalence that absorbs an ever increasing investment of resources. This population-based study evaluated the direct medical costs of diabetes mellitus in an HMO setting. We evaluated both the total cost of diabetic patients and their added cost in comparison to other HMO members (diabetes-related costs). Data were obtained for the years 1999-2001 in a cohort of 24,632 diabetic patients followed up for 3 years drawn from the computerized medical administrative database of a large HMO in Israel, insuring around 25% of the population. The mean direct cost of the medical treatment of a diabetic patient rose 29% from US $2,017 in 1999 to $2,601 in 2001 (in 2001 terms) in comparison to a 19.7% rise (from $1,246 to $1,492). Hospitalizations, medication, and physician visits account for 39%, 29%, and 21% of the total diabetic patient costs, respectively. Dialysis, insulin intake, impaired creatinine, and elevated HbA1c were associated with increased expenditures. According to our results, the total national medical cost of diabetes alone in 2001 was $317 million and that of diabetic patients was $564 million, 6.9% and 12.4% of the total Israeli HMO budget, respectively. The study presents the use of a population-based computerized database to comprehensively assess the economic burden of disease and the potential savings from prevention. The study data suggest a rise in the cost of diabetes which has implications for prevention and treatment policies.

BACKGROUND:
Trials of hormone replacement therapy (HRT) for prevention of chronic disease in postmenopausal women have suggested that the risks of treatment outweigh the benefits. The publication in 2002 of the Women's Health Initiative (WHI) study sparked a rapid decline in HRT purchases among American women.

OBJECTIVE:
To examine the impact of the WHI findings on patterns of HRT use in Israeli women.

METHODS:
We linked purchases of estrogen preparations from 1998 to 2007 by female Israeli health maintenance organization members aged 45 years and older to membership data. For each year, we calculated total annual purchases and rate of HRT utilization, characterized new users by age and mode of therapy, and examined rates of switching between modes of therapy.

RESULTS:
Twenty percent of women aged 45 years and older purchased estrogen products in 2001, versus 10% in 2007 (p < 0.001; chi(2)). Vaginally administered products accounted for a rising percentage of purchases, from 5% in 1999 to 18% in 2007. An increasing percentage of new users aged 55 years and older started with a vaginal product (62% in 1999, 82% in 2007). After 2002, new users of oral therapy discontinued use more quickly than those who started oral therapy before 2002. Tibolone accounted for an increasing percentage of oral drugs purchased (12% in 2003, 29% in 2007).

CONCLUSIONS:
The WHI findings had a rapid and sustained impact on HRT utilization in a large population of Israeli women, including a sharp decrease in the rate of use, particularly of oral preparations, as well as reduced duration of therapy and increased use of vaginal preparations and tibolone as first choices for treatment.

BACKGROUND:
Although discontinuing lipid-lowering treatment can cause preventable morbidity, previously published reports have indicated considerable variability in persistence with statin use. In general, such reports have been limited by short follow-up periods and modest study populations.

OBJECTIVES:
The aims of this study were to assess long-term persistence with statins and to identify the sociodemographic, clinical, and pharmacotherapy-related factors associated with long-term persistence with statin treatment in first-time users in Israel.

METHODS:
This retrospective cohort study used data from adult enrollees of a not-for-profit health maintenance organization and from death certificates in Israel. Eligible patients initiated statin treatment between 1998 and 2006. Persistence was assessed separately in patients with no indication of a cardiovascular disease (primary prevention) or coronary artery disease (secondary prevention). Treatment persistence and proportion of days covered (PDC) were measured using the interval between the date of the first prescription dispensation (index date) and the point of discontinuation.

RESULTS:
Data from 229,918 patients were included (primary prevention, 136,052; secondary prevention, 93,866). The PDC was significantly higher in the secondary-prevention group compared with the primary-prevention group (59% vs 45%; P < 0.001). In both cohorts, persistence continually diminished from the index date through follow-up, with > or = 75% of patients discontinuing statin therapy by 2 years. Baseline predictors of discontinuation of statin treatment included younger age, female sex, lower socioeconomic status (SES), absence of diabetes or hypertension, no concurrent use of beta-blockers or angiotensin-converting enzyme inhibitors, and less health service utilization. New immigrants and patients in the primary-prevention group who had a baseline low-density lipoprotein cholesterol concentration <130 mg/dL were at increased risk for treatment discontinuation.

CONCLUSION:
In this study in these patients receiving first-time statin treatment in Israel, we found poor persistence with statins among both the primary- and secondary-prevention cohorts, especially among new immigrants and patients with low SES despite low out-of-pocket prescription costs and free access to health services.

BACKGROUND:
Adverse reactions related to the upper gastrointestinal tract (UGIT) that are associated with generic alendronate formulations may differ from those associated with the brand drug.

OBJECTIVE:
To test the hypothesis that adverse UGIT effects of alendronate formulations may differ between generic and brand products.

METHODS:
We conducted a database health resource utilization analysis of UGIT outcomes in patients who started treatment with generic or brand alendronate formulations during 2001-2005. We included 6962 patients who were treated continuously for 3 months with 1 of 4 alendronate formulations: brand 10 mg/day (Merck, Sharpe & Dohme, n = 1418), generic A 10 mg/day (Teva, Israel, n = 650), generic B 10 mg/day (Unipharm, Israel, n = 628), and brand 70 mg/wk (n = 4266). In these patients, who had neither filled a prescription for alendronate nor had any gastrointestinal problems in the year preceding the study, we compared incidence rates of new use of gastric medications (H2-blockers, proton-pump inhibitors, or antacids), gastroenterology visits, endoscopies, and hospital admissions.

RESULTS:
Incident rate ratios (IRR) for treatment discontinuation were higher with both daily generic products (IRR 1.3; 95% CI 1.04 to 1.63). Adherence (medication possession ratio [MPR] >80%) was better with brand 10 mg/day (IRR 1.19; 95% CI 1.11 to 1.27). All comparisons were adjusted for use of concurrent corticosteroids, nonsteroidal antiinflammatory drugs, and potassium supplements. Hospitalization rates (2.7-3.2%) were similar in all groups. New use of gastric medications (3.4-4.9%) was lower with brand 10 mg/day (IRR 0.71; 95% CI 0.53 to 0.95). Rates of UGIT endoscopy (n = 49) in patients receiving 10 mg were 0.6% (brand), 1.1% (generic A), and 1.6% (generic B), with generic B higher (IRR 2.88; 95% CI 1.14 to 7.29) in the entire cohort, but not among new users (n = 273) of gastric drugs (IRR 2.46; 95% CI 0.55 to 11.05). Endoscopic findings were normal in 22 patients, hiatal hernia with no mucosal lesion was present in 10 patients, and there was mild-to-moderate esophagitis or gastritis in 17 patients; there were no significant differences among the formulations.

CONCLUSIONS:
We found insufficient evidence to indicate major differences in UGIT adverse effects related to use of daily generic, as compared with brand, alendronates.

In October 2006, four deaths occurred in Israel shortly after influenza immunization, resulting in a temporary halt to the vaccination campaign. After an epidemiologic investigation, the Ministry of Health concluded that these deaths were not related to the vaccine itself and the campaign resumed; however, vaccine uptake was markedly reduced. Estimates of true background mortality in this high-risk population would aid in public education and quell unnecessary concerns regarding vaccine safety. We used data from a large HMO to estimate mortality in influenza vaccine recipients aged 55 and over during four consecutive winters (2003, 2004, 2005 and 2006). Date of immunization was ascertained from patient treatment files, vital status through Israeli National Insurance Institute data. We calculated crude death rates within 7, 14 and 30 days of influenza immunization, and used a Cox Proportional Hazards Model to estimate the risk of death within 14 days of vaccination, adjusting for age and comorbid conditions (age over 75, history of diabetes or cardiovascular disease, status as homebound patient) in 2006. The death rate among influenza vaccine recipients ranged from 0.01 to 0.02% within 7 days and 0.09-0.10% at 30 days. Influenza immunization was associated with a decreased risk of death within 14 days after adjustment for comorbidities (Hazard ratio, 0.33, 95% CI, 0.18-0.61). Our findings support the assumption that influenza vaccination is not associated with increased risk of death in the short term.

BACKGROUND:
The varicella vaccine Varilrix (GlaxoSmithKline) was introduced in Israel in June 2000 as an optional vaccination for children.

METHODS:
We used the database of a single health maintenance organization that serves 25% of the population in Israel to assess the effectiveness of the vaccine retrospectively. Incidence and complications of varicella were derived from the database from January 1, 1998 until December 31, 2002.

RESULTS:
Since licensure >30000 individuals younger than 10 years in this health maintenance organization have been immunized with the vaccine. Annual incidence of disease per 1000 in the study population was 86.6 in 1998, 74.6 in 1999, 74.0 in 2000, 37.1 in 2001 and 44.6 in 2002. This declining trend in incidence of disease was statistically significant. Complications of varicella occurred in approximately 1% of patients throughout the 5-year study period, but there was a parallel decline in the number of patients with complications corresponding to the decline in disease incidence. Vaccine effectiveness for prevention of clinical disease in this population was 92% (95% confidence interval, 91.0 to 92.7). There were varying rates of utilization within communities of varied socioeconomic class, so that in the higher socioeconomic class there was an increased utilization and a corresponding decrease of attack rate; whereas in communities where there were lower utilization rates, corresponding increased numbers of varicella cases were seen.

CONCLUSION:
This database enables long term follow-up of the effectiveness of this vaccine in a large population.

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.

BACKGROUND: Human papillomavirus (HPV) infection is mostly associated with cervical cancer (CC). However, it can cause other illnesses as well, all of which impact on people's wellbeing and consume healthcare resources. Measures for prevention or early detection of these conditions differ in their effectiveness and cost. An informative evaluation of the projected benefit of these measures depends on understanding the current unmet need, not only limited to CC.

OBJECTIVE: To evaluate the burden of HPV-related conditions in Israel, including CC, cervical precancerous lesions and genital warts.

METHODS: A retrospective database analysis was conducted for the second largest health management organization (HMO) in Israel, covering approximately 1.8 million people. Records were drawn following a search for key words indicative of related diagnoses, lab results, medications, or procedures for the time period of 2006-2008. Prevalence, incidence and resource utilization were analysed. Findings were extrapolated to the whole Israeli population using age and gender incidence rates.

RESULTS: Incidence of CC was found to be 5 per 100,000 females. Incidences of cervical intraepithelial neoplasia (CIN) grades 1, 2 and 3 were 74, 27 and 36 per 100,000 females, respectively. Incidence of genital warts was 239 and 185 per 100,000 for men and women, respectively. The overall annual economic burden was calculated to be $US48,838,058 (year 2010 values).

CONCLUSIONS: HPV poses a significant burden in terms of health (clinical and quality of life) and in monetary terms, even for conditions that are sometimes regarded as benign, such as CIN1 or genital warts. Current findings should be used for proper evaluation of measures to reduce HPV-related morbidity and mortality, such as regular screening and vaccination.

BACKGROUND: Chronic urticaria (CU) is a common disease in which most cases were considered to be idiopathic. Recent evidence indicates that at least a subset of cases of chronic idiopathic urticaria are autoimmune in origin.

OBJECTIVE: We aimed to characterize the association between CU, autoimmune diseases, and autoimmune/inflammatory serologic markers in a large unselected population.

METHODS: Data on 12,778 patients given a diagnosis of CU by either allergy or dermatology specialists during 17 years in a large health maintenance organization in Israel were collected. For each patient, we collected information on diagnosis of major, well-defined autoimmune diseases and autoimmunity- and inflammatory-related serologic markers. Similar data were collected for a control group comprised of 10,714 patients who visited dermatologists, family physicians, or allergy specialists and had no indication of CU.

RESULTS: Having CU was associated with an increased odds ratio for hypothyroidism, hyperthyroidism, and antithyroid antibodies. Female patients with CU had a significantly higher incidence of rheumatoid arthritis, Sjögren syndrome, celiac disease, type I diabetes mellitus, and systemic lupus erythematosus, mostly diagnosed during the 10 years after the diagnosis of CU. High mean platelet volume, positive rheumatoid factor, and antinuclear antibodies were all significantly more prevalent in patients with CU.

CONCLUSIONS: A strong association was found between CU and major autoimmune diseases. A common pathogenic mechanism is implied by the high prevalence of autoantibodies and the existence of a chronic inflammatory process expressed by the high mean platelet volume. These findings have implications for the diagnosis, management, and prognosis of patients with CU

PURPOSE: Maccabi Healthcare Services, a large health maintenance organization (HMO) operating in Israel, has recently constructed a computerized registry of patients with severe mental illnesses (SMI). In the present study, we aimed to use this registry to investigate the epidemiology of schizophrenia and bipolar affective disorder among adults, and to assess their comorbidity and mortality compared to the general population.

METHODS: In this historical cohort study, we investigated the age- and sex-specific prevalence and incidence rates of HMO members diagnosed with schizophrenia or bipolar affective disorder between 2003 and 2009. We compared their medical comorbidity and mortality to the general HMO population.

RESULTS: A total of 8,848 and 5,732 patients were diagnosed with bipolar (crude prevalence rate of 5 per 1,000) and schizophrenia (3 per 1,000), respectively. The annual incidence rates were 4.2 and 2.4 per 1,000 for schizophrenia and bipolar disorder, respectively. On average, schizophrenic men were diagnosed 4-5 years earlier than schizophrenic women. Compared to the general population, schizophrenia and bipolar disorder patients had a 12- and 9-year shorter life expectancy, respectively. They were also more likely to be diagnosed with diabetes mellitus (odds ratio of 1.9 and 1.6, respectively).

CONCLUSIONS: The current study demonstrates the potential use of automated medical databases to characterize the epidemiology of SMI in the community. The increased comorbidity and mortality among these patients has important implication for health authorities for prevention and delivery of health-care services.

In this paper we report the use of the open source Spatiotemporal Epidemiological Modeler (STEM, www.eclipse.org/stem) to compare three basic models for seasonal influenza transmission. The models are designed to test for possible differences between the seasonal transmission of influenza A and B. Model 1 assumes that the seasonality and magnitude of transmission do not vary between influenza A and B. Model 2 assumes that the magnitude of seasonal forcing (i.e., the maximum transmissibility), but not the background transmission or flu season length, differs between influenza A and B. Model 3 assumes that the magnitude of seasonal forcing, the background transmission, and flu season length all differ between strains. The models are all optimized using 10 years of surveillance data from 49 of 50 administrative divisions in Israel. Using a cross-validation technique, we compare the relative accuracy of the models and discuss the potential for prediction. We find that accounting for variation in transmission amplitude increases the predictive ability compared to the base. However, little improvement is obtained by allowing for further variation in the shape of the seasonal forcing function.

PURPOSE: Gestational diabetes mellitus (GDM), a state of glucose intolerance associated with pregnancy, is increasing in prevalence. Data regarding the cancer risk associated with GDM are sparse and limited to cancers of the breast and pancreas. This study was conducted to examine the risk of incident overall and site-specific malignancies associated with prior GDM in a historical cohort of women in a large health maintenance organization in Israel.

METHODS: All pregnant women aged 15-50 years who underwent 50-g glucose challenge tests between 13 March 1995 and 27 May 2009, without history of malignancy, diabetes, and infertility, were included. Clinical and demographic parameters at index date including age, socioeconomic level, BMI, and parity were collected. Diagnosis of gestational diabetes was based on the 100-g oral glucose tolerance test using Carpenter and Coustan criteria. Cancer diagnoses were obtained from the Israel Cancer Register through linkage data.

RESULTS: Among the 185,315 women who had undergone glucose challenge during the study period, 11,264 (6.1%) were diagnosed with GDM. During a total follow-up period of 1.05 million person-years (mean = 5.19 ± 3.9, median = 4.3), 2,034 incident cases of cancer were identified. GDM was associated with a hazard ratio (HR) of 7.06 (95% CI: 1.69-29.45) for pancreatic cancer (nine cases) and a HR of 1.70 (95% CI: 0.97-2.99) for hematological malignancies (177 cases). The association between GDM and hematological malignancies was limited to women with 5 or more years of follow-up (HR = 4.53; 95% CI: 1.81-11.31).

CONCLUSION: GDM is associated with an increased risk of pancreatic cancer and hematologic malignancies.

BACKGROUND:
Fetal alcohol spectrum disorder (FASD) is a range of disabilities caused by gestational exposure of the fetus to alcohol. Alcohol consumption in Israel has increased dramatically in the last decades. Our previous study revealed limited knowledge among Israeli medical professionals of the risks and potential long-term effects of FASD.

OBJECTIVES:
To evaluate the awareness and knowledge of women regarding the current recommendations on alcohol consumption during pregnancy, evaluate how many of the women received information regarding alcohol consumption during pregnancy from medical professionals, and their personal drinking habits during pregnancy.

METHODS:
A cross-sectional sample of new mothers in 3 large hospitals in Israel were asked to complete an ad hoc questionnaire on aspects of alcohol consumption during pregnancy.

RESULTS:
A total of 3815 women of mean age 30.4 years participated in the study; 82% were Jewish. Alcohol consumption during pregnancy was reported by 14.1%, including more than 17% of the Jewish women, 11.1% of the Christian women, and none of the Muslim women. Rates were higher among nonsecular and younger women and first-time mothers. 71.6% of the sample claimed that women should not drink alcohol at all during pregnancy, and 21.4% thought that it was permissible if limited to 2 drinks per week. Seventy-five percent had received no formal information from medical professionals regarding alcohol consumption during pregnancy.

CONCLUSIONS:
Alcohol consumption is frequent among pregnant women in Israel, especially young secular Jewish women with first pregnancies. Improved educational programs on the dangers of FASD are needed for both professionals and the general public.

PURPOSE:
To examine the association between age-related macular degeneration (AMD) and the risk of myocardial infarctions (MIs) in a large health maintenance organization.

DESIGN:
A retrospective cohort study carried out at Maccabi Healthcare Services (MHS).

PARTICIPANTS:
A total of 6,546 patients aged ≥65 years who were diagnosed with AMD between April 18 1996 and June 6 2008, and 61,672 non-AMD patients frequency-matched for age and gender.

METHODS:
Participants were retrospectively followed to the day of leaving the MHS, to undergoing an MI, or to closure of the study on July 1 2008, whichever came earlier. The relative risk of MI associated with AMD was estimated using the Cox proportional hazard model.

MAIN OUTCOME MEASURES:
Incident myocardial infarction events.

RESULTS:
During the study period, there were 159 (5.1 per 1,000 person years [PY]) and 2,997 (4.2 per 1,000 PY) MIs respectively in the AMD and non-AMD patient groups. The age- and gender-adjusted hazard ratio (HR) of MI among AMD patients was 1.01 (95%CI: 0.85-1.20). Baseline medical characteristics associated with increased risk of mortality included diabetes mellitus, hypertension, older age, and male gender. The fully adjusted HR associated with AMD was 1.03 (95%CI: 0.87-1.22).

CONCLUSION:
Despite the shared risk factors associated with AMD and MIs, we found no increased risk of MI in AMD patients.

OBJECTIVE:
To investigate the association between persistent use of statins and the risk of age-related macular degeneration (AMD).

DESIGN:
A population-based retrospective cohort among adults who began statin therapy between 1998 and 2006 in a large health organization in Israel. The organization's central computerized databases were used to collect data on incident AMD cases diagnosed by ophthalmologists.

RESULTS:
A total of 108,973 individuals aged 55 or older were identified. During the study follow-up period 409,113 person-years, there were 2,732 incident AMD cases (6.68 per 1,000 person-years). The crude incidence density rate of AMD among patients at the lowest quintile of persistence with statins (7.18 per 1,000) was comparable to that of highest persistence quintile (7.13 per 1,000). After adjustment for potential confounders, patients in the highest quintile of persistence with statins had a hazard ratio of 0.99 (95% Confidence Interval: 0.78-1.26) for AMD compared with patients in the lowest proportion of days covered (PDC) quintile. In addition to age, AMD was found to associate with past smoking, asthma, diabetes and frequent visits to ophthalmologists or primary physicians prior to index date.

CONCLUSIONS:
Our study agrees with previous studies that showed no association between persistent use of statins and reduced risk of AMD. These results suggest that the early reports on a strong protective effect of statins against AMD development were probably a result of a small study effect.

At present, more than 10% of adult American women are diagnosed with diabetes mellitus (DM). As the prevalence of the disease increases, there is greater interest in the relationship between DM and other major health issues, such as cancer - one of the leading causes of death in the western world. This paper reviews the literature on the relationship between Type 2 DM and different types of cancer among women. We discuss the possible biological mechanisms that may link diabetes and cancer, important confounders, shared risk factors and a short review of the epidemiologic literature on the association between Type 2 DM and cancer of specific organs (pancreas, liver, colorectal, bladder, endometrial, non-Hodgkin's lymphoma and breast). We also examine the association between gestational diabetes, a closely related risk factor for DM in women, and subsequent risk of cancer. Cancer survival of diabetic women is also briefly discussed. The paper concludes with an agenda for future research targeting the relationship between diabetes and cancer.

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.

At present, more than 10% of adult American women are diagnosed with diabetes mellitus (DM). As the prevalence of the disease increases, there is greater interest in the relationship between DM and other major health issues, such as cancer - one of the leading causes of death in the western world. This paper reviews the literature on the relationship between Type 2 DM and different types of cancer among women. We discuss the possible biological mechanisms that may link diabetes and cancer, important confounders, shared risk factors and a short review of the epidemiologic literature on the association between Type 2 DM and cancer of specific organs (pancreas, liver, colorectal, bladder, endometrial, non-Hodgkin's lymphoma and breast). We also examine the association between gestational diabetes, a closely related risk factor for DM in women, and subsequent risk of cancer. Cancer survival of diabetic women is also briefly discussed. The paper concludes with an agenda for future research targeting the relationship between diabetes and cancer.

Type 2 diabetes mellitus has been associated with an increased risk of a variety of cancers in observational studies, but few have reported the relationship between diabetes and cancer risk in men and women separately. The main goal of this retrospective cohort study was to evaluate the sex-specific risk of incident overall and site-specific cancer among people with DM compared with those without, who had no reported history of cancer at the start of the follow-up in January 2000. During an average of 8 years of follow-up (SD = 2.5), we documented 1,639 and 7,945 incident cases of cancer among 16,721 people with DM and 83,874 free of DM, respectively. In women, DM was associated with an adjusted hazard ratio of 1.96 (95% CI: 1.53-2.50) and 1.41 (95% CI: 1.20-1.66) for cancers of genital organs and digestive organs, respectively. A significantly reduced HR was observed for skin cancer (0.38; 95% CI: 0.22-0.66). In men with DM, there was no significant increase in overall risk of cancer. DM was related with a 47% reduction in the risk of prostate cancer. These findings suggest that the nature of the association between DM and cancer depends on sex and specific cancer site.

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.

OBJECTIVES:
In 1999 Israel became the first country to introduce immunization against hepatitis A to its national childhood vaccination program. The study objectives were to assess the uptake of hepatitis A vaccine following the new policy and to examine the incidence of hepatitis A and the number of prevented cases.

METHODS:
Data on incidence of hepatitis A and vaccination rates were obtained from a large health maintenance organization in Israel covering 1.6 million members. We identified all members that were diagnosed by a primary care physician as suffering from hepatitis A, had a positive hepatitis A virus-IgM test result, or were hospitalized due to hepatitis A between 1998 and 2004.

RESULTS:
The results indicate that 5 years following its inclusion in the national childhood immunization program, vaccination coverage levels with at least one dose of hepatitis A vaccine for children aged under 5 years and 5-14 years were 87% and 51%, respectively. During this period the annual incidence rates declined by 88% from 142.4 to 17.3 per 100,000. The most significant reduction in morbidity was observed among children.

CONCLUSIONS:
In endemic areas, vaccination of infants and children against hepatitis A may be efficient to greatly reduce the total burden of the disease.

PURPOSE:
To investigate the effect of season on birth weight and whether it is expressed also in fluctuations of proportions of extreme birth weights.

METHODS:
Information about 225,545 singletons born during 1998 to 2004 was obtained from a large health maintenance organization in Israel. We conducted a linear regression analysis of the weight with month and year of birth, sex, maternal age, diabetes, and several meteorological factors as independent variables, which were also incorporated into multivariate logistic regression models to examine the effect of season of birth on the frequency of low birth weight (LBW, <2500 g) or macrosomia (>4000 g).

RESULTS:
A significant (P < .001) seasonal pattern in birth weights was observed, with a peak in July and a trough in January. Babies born in summer had an OR of 1.12 (95% CI; 1.07 to 1.18) for macrosomia compared with those born in the winter. No such pattern was found for LBW.

CONCLUSIONS:
While in regions of mid-latitude, summer is associated with relatively lower birth weight, possibly because of exposure to cold temperature during early or mid-pregnancy, our data suggest that in Israel, the peak birth weight is in summer, possibly because of increased exposure to sunlight in the last weeks of the pregnancy.

Because the absolute numbers of both community-acquired and nosocomial rotavirus gastroenteritis (RVGE) vary, we studied the percentage of hospitalizations for RVGE that were transmitted nosocomially as an indicator of in-hospital acquisition of the infection. In a 4-year prospective study, the percentage of nosocomial RVGE declined steadily, from 20.3% in 2003 to 12.7% in 2006 (P = .001). Concomitantly, the rate of compliance with hand hygiene increased from 33.7% to 49% (P = .012), with a significant (P < .0001) inverse association noted between the two trends.

OBJECTIVE:
To explore the possibility that mild inflammatory changes exist in asymptomatic adults during bouts of acute respiratory tract infections in the general population, and may mediate atherothrombotic events.

METHODS:
An epidemiological study that enrolled 5315 males and 2795 females attending a routine screening health program between the years 2003 and 2007. We correlated the concentrations of high sensitivity C-reactive protein (hs-CRP) and quantitative fibrinogen in completely asymptomatic and non-inflamed adults to the weekly epidemiological data for the incidence of acute respiratory tract infections in the community.

RESULTS:
Significant seasonal variations in the inflammatory variables were found for both genders. The population's weekly rates of acute respiratory tract infection had a significant epidemiological influence on the inflammatory biomarkers in the asymptomatic cohort. The magnitude of this influence could reach as much as 12% (3-22%) in hs-CRP concentrations in women and 0.30 micromol/L (0.20-0.41) in fibrinogen concentrations in men, for the change between the mean August and the mean January population's respiratory illness burden.

CONCLUSION:
Increase in the concentrations of two inflammation-sensitive biomarkers can occur in completely asymptomatic adults at times of increased burden of acute respiratory tract infection in the general population. The possibility exists that these inflammatory changes represent occult and asymptomatic infections that could by themselves trigger acute atherothrombotic events.

OBJECTIVE:
MTX hepatotoxicity is considered to occur more frequently in patients with psoriasis than in patients with RA. However, toxicity guidelines are based on reports from studies with small sample sizes and limited follow-up periods. The current study's objective was to examine the long-term risk of MTX hepatotoxicity based on a database review of patients with RA or psoriasis, and to examine whether the two populations differed.

METHODS:
We conducted a retrospective cohort review among members of a large health maintenance organization (HMO) in Israel who were diagnosed with either RA (n = 119) or psoriasis (n = 690) and who had purchased at least one dose of MTX. Liver function analyses were performed serially in these patients during the follow-up. All abnormal assays were recorded in the computerized database of the HMO.

RESULTS:
Both groups had hepatic enzyme elevation; the pre-disposing factors predictive of liver damage were female gender and a higher cumulative dose of MTX (hazard ratios, 1.46 and 1.07, respectively, P < 0.001). Age, concurrent diseases and type of disease had no influence on susceptibility to liver damage. No statistically significant difference was detected in any abnormal liver function test among patients with either RA or psoriasis.

CONCLUSION:
Our study did not corroborate previous findings of significant differences between psoriasis patients and RA patients concerning susceptibility to hepatotoxicity from MTX therapy. The only significant factor predicting a higher risk of hepatic damage was female gender.

OBJECTIVE:
To determine whether medication use is associated with the development of a pemphigus variant.

DESIGN:
Population-based case-cohort study.

SETTING:
Health maintenance organization in Israel.

METHODS:
All incident pemphigus variant cases diagnosed from January 1, 1997, through December 31, 2001, among 1.5 million members were identified. A cohort of 150,000 was randomly selected from the health maintenance organization population as the control group. Data on case patients and control subjects, including all medication purchased during the 6 months before the diagnosis, were obtained using the health maintenance organization's central database.

RESULTS:
We identified a total of 363 case patients diagnosed as having pemphigus during the 5-year study (6,961,853 person-years of follow-up). The mean age at diagnosis was 49.8 (SD, 22.7) years, and 53% of the cases were women. Results of a multivariate analysis showed that increased risk for pemphigus was associated with purchasing penicillin during the 6 months before the diagnosis (odds ratio, 2.03; 95% confidence interval, 1.56-2.64). Compared with individuals with no penicillin purchases, we calculated increased risks of 1.84 (95% CI, 1.36-2.49) and 3.02 (95% CI, 1.41-6.49) in those with 1 and 3 or more purchases, respectively. None of the other examined medications, including cephalosporins, angiotensin-converting enzyme inhibitors, dipyrone, anticonvulsants, and nonsteroidal anti-inflammatory drugs, showed similar risks.

CONCLUSIONS:
To our knowledge, the present research is one of the largest published epidemiological studies on pemphigus variant. The use of computerized medical and administrative databases allowed the detection of case patients in the community, resulting in a higher calculated incidence rate than previously reported. The findings suggest a relationship between the use of penicillin and pemphigus variant. Further studies to assess the nature of this statistical association are warranted.

BACKGROUND:
The use of computed tomography in Israel has been growing rapidly during recent decades. The major drawback of this important technology is the exposure to ionizing radiation, especially among children who have increased organ radiosensitivity and a long lifetime to potentially develop radiation-related cancer.

OBJECTIVE:
To estimate the number of excess lifetime cancer deaths related to annual CT scans performed in children in Israel.

METHODS:
We used CT scan utilization data from 1999 to 2003 obtained from the second largest health management organization in the country to project age and gender-specific CT scan use nationwide. Based on published organ doses for common CT examinations and radiation-related cancer mortality risk estimates from studies in survivors of the atomic bomb, we estimated the excess lifetime risks for cancer mortality attributed to use of CT in children and adolescents (up to 18 years old) in Israel.

RESULTS:
We estimated that 17,686 pediatric scans were conducted annually in Israel during 1999-2003. We project that 9.5 lifetime deaths would be associated with 1 year of pediatric CT scanning. This number represents an excess of 0.29% over the total number of patients who are eventually estimated to die from cancer in their lifetime.

CONCLUSIONS:
Pediatric CT scans in Israel may result in a small but not negligible increased lifetime risk for cancer mortality. Because of the uncertainty regarding radiation effects at low doses, our estimates of CT-related cancer mortality should be considered with caution. Nevertheless, physicians, CT technologists, and health authorities should work together to minimize the radiation dose for children to as low as reasonably achievable and encourage responsible use of this essential diagnostic tool.

BACKGROUND:
Concern has been raised about the potential risks related to radiation exposure from CT scans, particularly among children. However, to date, there are few data available describing the magnitude of pediatric CT utilization.

OBJECTIVE:
The aim of the study was to explore patterns of CT use in pediatric patients, with respect to time, use of multiple scans, body regions imaged, and medical diagnoses.

MATERIALS AND METHODS:
Records of 22,223 scans performed on 18,075 people aged < or =18 years over the period 1999-2003, including diagnoses recorded within 21 days after the examination, were obtained from a large Israeli Health Maintenance Organization (1,600,000 members).

RESULTS:
The highest annual CT examination rate (per 1,000) was recorded in 2001 (10.1) compared to 7.0 and 6.3 in 1999 and 2003, respectively. The lowest rate (three scans per 1,000) was found for 3-year-old children, with increasing rates with age. The head was the most frequently scanned region, both in young children (78%) and adolescents (39%). Symptoms of ill-defined conditions and injuries were documented in 22% and 10% of all scans, respectively.

CONCLUSIONS:
Although the results suggest that children comprise only 3% of all patients undergoing CT, this important modality must be carefully used because of their increased radiosensitivity

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.

We evaluated the effect of school closure on the occurrence of respiratory infection among children ages 6-12 years and its impact on health care services. During this period, there were significant decreases in the diagnoses of respiratory infections (42%), visits to physician (28%) and emergency departments (28%) and medication purchases (35%). The present study provides quantitative data to support school closure during an influenza pandemic.

BACKGROUND: The present study describes a computerized registry of cardiovascular disease patients in a large health maintenance organization in Israel. The registry is aimed to be used by health professionals to identify cardiovascular disease patients and to follow the courses of their illnesses and risk factors.

METHODS: In 1998, the registry was initiated using advanced information technology that integrated personal computerized community and hospital records, data from laboratory tests, dispensed medications, physiological signals, radiological images, and reports from investigations and procedures.

RESULTS: Between 1998 and 2007, the number of patients with cardiovascular diseases that were identified by the registry has increased from 34,144 to 80,339. During this period, the age-adjusted prevalence rates have risen from 3.7% to 5.1% and from 1.9% to 2.6%, among men and women, respectively. The percentage of ischemic heart disease patients who reached target LDL was doubled, from 21% in 2000 to 50% in 2006. The average stay in hospital declined from 11.7 to 8.6 days. Primary myocardial infarction rates declined 33% and 54% in men aged 54-65 and women aged 65-74 years, respectively.

CONCLUSIONS: The present study provides, for the first time in Israel, data on selected quality of care and clinical outcomes using a large, population-based registry of cardiovascular disease patients. It demonstrates a significant improvement in the adherence with LDL tests and achieving target LDL levels and a subsequent decline in incidence of myocardial infarction within ten years since its establishment.

BACKGROUND:
It has been demonstrated by meta analysis that if a regular review of patients is guaranteed, the standard of primary care can be as good or better than hospital outpatient care, however, empirical data suggests that compliance with diabetes clinical practice recommendations is inadequate in primary care. This study describes the reorganization of diabetes care using disease management principles in a Preferred Provider Organization (PPO) operating on a country-wide basis in which each diabetes clinic became responsible for the overall care of all patients with diabetes.

METHODS:
This descriptive pre and post change study was undertaken in a large public-funded PPO insuring over one and half million individuals. The study was possible due the use of a centralized electronic disease registry which enabled the collection of all patient data. Several markers, such as HbA1C and LDC-cholesterol levels, were used to assess the quality of care for the diabetic patients.

RESULTS:
Mean HbA1C results of the cohort showed a continuous reduction from 8.1% (S.D. = 1.55) in 1999 to 7.68% (S.D. = 1.47) in 2002 and to 7.79 (S.D. = 1.54) in 2004. Improved results were also recorded for LDL-C 126.37 (S.D. = 35.16) in 1999 to 114.74 (S.D. = 34.49) in 2002, and to 113.39 (S.D. = 33.8) in 2004. The number of diabetic patients seen by the diabetologist increased by 62% over this period, despite an increase in diabetologist work hours of only 23%.

CONCLUSION:
The reorganization of health delivery for diabetic patients within a country-wide PPO, based on the principles of disease management and supported by medical informatics improves quality of care.

PURPOSE:
Our study was designed to find whether a change in physician ordering of laboratory testing could be obtained by the simple strategy of changing the set-up of the check-box laboratory order form that is embedded in a computerized medical record.

METHODS:
This prospective intervention study was undertaken in Maccabi Healthcare Services, a Preferred Provider Organization that has used a computerized medical record since 1992. We examined data from 865 primary healthcare physicians over 3 years. In May 2005 we changed the order form and reduced the number of tests that can be ordered using a check-box form from 51 to 26. Twenty-seven tests were removed from the form and two tests were added. The total number of laboratory test orders and the median rate of test orders per visit to physician during each of the study periods were calculated separately for each test.

RESULTS:
Tests that were added to the computerized laboratory order form showed an increase of 60.7% in the first year and a further 90% increase in the following year. For the unchanged tests the percentage changes over the same periods were +18.4% and -22.4%. For the deleted tests the change was -27% and -19.2% for the respective years.

CONCLUSIONS:
Changes in format of laboratory test order forms can change physician test ordering and may be useful together with other interventions to improve appropriateness of laboratory testing. A thoughtfully built test ordering form can reinforce clinical guidelines for the performance of some preventive testing and follow-up.

More than 20% of approximately 35,000 patients filling a diuretic prescription had no potassium blood test recorded within the previous year. A laboratory reporting system used throughout Israel by Maccabi Healthcare Services physicians was modified to provide physician alerts regarding potassium testing. The physicians were experienced users of a computerized medical record (CMR) that provided online laboratory test results. A nightly batch file checked pharmacy diuretic purchases against the patient's potassium blood test status. On-screen computer-generated reminders were sent to physicians of patients lacking a recent potassium test. Reminders to clinicians increased potassium testing by 9.8% (p < 0.001). Physician age and gender played a small part in predicting compliance to the alert, but specialty and practice size did not. The time delay between the date a reminder was sent and the potassium test date decreased steadily during the intervention. The success of this reminder system encourages expansion to include more drug-laboratory interactions. Furthermore, direct alerts to patients at multiple organization/patient contact points are planned.