Gestational diabetes and risk of incident primary cancer: a large historical cohort study in Israel.

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.

The association between socio-demographic characteristics and adherence to breast and colorectal cancer screening: analysis of large sub populations.

BACKGROUND: Populations having lower socioeconomic status, as well as ethnic minorities, have demonstrated lower utilization of preventive screening, including tests for early detection of breast and colorectal cancer. THE OBJECTIVE: To explore socio-demographic disparities in adherence to screening recommendations for early detection of cancer. METHODS: The study was conducted by Maccabi Healthcare Services, an Israeli HMO (health plan) providing healthcare services to 1.9 million members. Utilization of breast cancer (BC) and colorectal cancer (CC) screening were analyzed by socio-economic ranks (SERs), ethnicity (Arab vs non-Arab), immigration status and ownership of voluntarily supplemental health insurance (VSHI). RESULTS: Data on 157,928 and 303,330 adults, eligible for BC and CC screening, respectively, were analyzed. Those having lower SER, Arabs, immigrants from Former Soviet Union countries and non-owners of VSHI performed fewer cancer screening examinations compared with those having higher SER, non-Arabs, veterans and owners of VSHI (p < 0.001). Logistic regression model for BC Screening revealed a positive association with age and ownership of VSHI and a negative association with being an Arab and having a lower SER. The model for CC screening revealed a positive association with age and ownership of VSHI and a negative association with being an Arab, having a lower SER and being an immigrant. The model estimated for BC and CC screening among females revealed a positive association with age and ownership of VSHI and a negative association with being an Arab, having a lower SER and being an immigrant. CONCLUSION: Patients from low socio-economic backgrounds, Arabs, immigrants and those who do not own supplemental insurance do fewer tests for early detection of cancer. These sub-populations should be considered priority populations for targeted intervention programs and improved resource allocation.

Persistence with statins and onset of rheumatoid arthritis: a population-based cohort study.

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.

Diabetes and risk of incident cancer: a large population-based cohort study in Israel.

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.

Disparities in diabetes care: role of the patient's socio-demographic characteristics.

BACKGROUND: The commitment to promoting equity in health is derived from the notion that all human beings have the right to the best attainable health. However, disparities in health care are well-documented. The objectives were to explore disparities in diabetes prevalence, care and control among diabetic patients. The study was conducted by Maccabi Healthcare Services (MHS), an Israeli HMO (health care plan). METHODS: Retrospective study. The dependent variables were diabetes prevalence, uptake of follow-up examinations, and disease control. The independent variables were socio-economic rank (SER), ethnicity (Arab vs non Arab), supplementary voluntary health insurance (SVHI), and immigration from Former Soviet Union (FSU) countries. Chi Square and Logistic Regression Models were estimated. RESULTS: We analyzed 74,953 diabetes patients. Diabetes was more prevalent in males, lower SER patients, Arabs, immigrants and owners of SVHI. Optimal follow up was more frequent among females, lower SERs patients, non Arabs, immigrants and SVHI owners. Patients who were female, had higher SERs, non Arabs, immigrants and SVHI owners achieved better control of the disease. The multivariate analysis revealed significant associations between optimal follow up and age, gender (males), SER (Ranks 1-10), Arabs and SVHI (OR 1.02, 0.95, 1.15, 0.85 and 1.31, respectively); poor diabetes control (HbA1C > 9 gr%) was significantly associated with age, gender (males), Arabs, immigrants, SER (Ranks1-10) and SVHI (OR 0.96, 1.26, 1.38, 0.72, 1.37 and 0.57, respectively); significant associations with LDL control (< 100 gr%) were revealed for age, gender (males) and SVHI (OR 1.02, 1.30 and 1.44, respectively). CONCLUSION: Disparities in diabetes prevalence, care and control were revealed according to population sub-group. MHS has recently established a comprehensive strategy and action plan, aimed to reduce disparities among members of low socioeconomic rank and Arab ethnicity, sub-groups identified in our study as being at risk for less favorable health outcomes.

[Equity promotion in Maccabi Healthcare Services: from the Equality Report to an organizational action plan].

Maccabi Healthcare Services (MHS), the second largest HMO in Israel, has chosen to implement a multi-annual strategy to promote equality and equity in healthcare. Within the strategy's framework, MHS will maintain an ongoing process of studying the variability of its members characteristics for the purpose of adjusting service provision and improving health outcomes. MHS has recently published its first Equality Report, dedicated to defining the observed associations between its members demographic and socioeconomic characteristics and their health measures. The report identifies those sub-groups belonging to Israel's geographic and social peripheries that require focused interventions. Based on the report's recommendations, MHS has decided to designate promotion of equality as its strategic objective, a filter through which every policy decision will be reviewed. In addition it was decided to: 1. develop an organizational methodology to produce an index to assess reductions in disparities over time; 2. adjust MHS services to member's ethnic and cultural needs; 3. strengthen perceptions of community orientation based in primary care; 4. target resources to "social peripheries", beginning in 2010; 5. improve service accessibility and availability in geographically peripheral areas; 6. reduce economic barriers to healthcare. This article details the disparities as analyzed in the report in addition to the specific policy decisions made in their wake.

Use of hormone replacement therapy, 1998-2007: sustained impact of the Women's Health Initiative findings.

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.

Potential impact and cost-effectiveness analysis of rotavirus vaccination of children in Israel.

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.

Women's and men's perceptions of infertility and their associations with psychological adjustment: a dyadic approach.

OBJECTIVES: Research on illness perceptions and their associations with psychological adjustment to medical conditions has mostly focused on individuals coping with chronic diseases. The objective of the current study was to expand this research to the study of couples by examining the perceptions of infertility among couples undergoing treatment and their associations with each partner's psychological adjustment. DESIGN: The study was cross-sectional and included two samples that differed in the stage of treatment: Sample 1 included 72 couples at their first visit to an infertility clinic and Sample 2 included 49 couples at various stages of treatment. METHODS: Participants filled in the Illness Perception Questionnaire regarding the timeline, consequences and controllability of their fertility problem and Infertility-Specific Distress and Well-being Scales. Dyadic analyses were conducted on the basis of the Actor-Partner Interdependence Model (APIM). RESULTS: The partners differed in their perceptions of infertility and their distress. Partners' psychological adjustment was related to their perceptions of the fertility problem. Among couples at their first visit, perceptions of consequences of both partners were additively related to their distress whereas controllability perceptions interacted in their association with women's distress: Highest distress was reported by women who perceived low controllability whereas their partner perceived high controllability, compared with couples who reported similar (high or low) levels of controllability. CONCLUSIONS: A dyadic approach to studying illness perceptions can uncover patterns of couples at risk for poor adjustment. This is especially needed in contexts such as infertility, where both partners are involved and affected by the health threat.

Long-term persistence with statin treatment in a not-for-profit health maintenance organization: a population-based retrospective cohort study in Israel.

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.

[The physician manager--building a clinical leadership in community medicine--the Maccabi Healthcare Services (MHS) model].

Community medicine around the world is facing constant trends of changes. The need to overcome the huge burden of chronic diseases, the need to prioritize and adapt new technologies, and above all, the fact that all these must be done within a given, restricted budget, calls for advanced medical management. In this review we focused on the development of the role of the physician manager in Maccabi Healthcare Services (MHS) over the last 60 years. From what was once a reactive, utilization control-oriented administrative physician role, there has emerged a proactive, formally educated, health quality leader who is expected to lead his clinical colleagues towards achieving the organization's goals. Every organization should answer 4 basic questions in order to encourage/develop the new generation of physician managers. 1. Who am I?--What is the profile and what are the tasks of the physician manager's role? 2. What is the time allocation allotted to the physician manager by the organization to enable him to do his job? 3. What are the educational and managerial tools provided for the 'new" physician manager? 4. What are the rewards that the organization grants to its best people? By addressing the above questions MHS has successfully developed new generations of young clinical leaders who can help MHS management conduct a real dialogue with its clinical physicians in order to maximize the services that our beneficiaries are receiving from the HMO. Our conclusion is that choosing the right people, providing them with the right tools and positioning the physician manager appropriately in the organization's hierarchy will enable the medical care delivery system in Israel to achieve the level of clinical leadership that can lead us towards a better future.

[Redesign of community-based health services: the solution for decreasing the quality gap].

The quality gap is defined as the gap between the observed and the expected, evidence-based, quality indicators. Experts agree that significant reduction of the quality gap requires transformation of the current system of health care provision. Maccabi Healthcare Services has formulated a "change package" in order to redesign its community-based healthcare services. This is based on a proactive approach in primary care, which manages all aspects of health for a defined community of members. This is built on multidisciplinary team-work, led by a physician and a nurse; planned visits for the management of patients with chronic diseases; one-stop-shopping for efficient health promotion; and encouraging patient-centeredness, which ensures that patient values will guide all clinical decisions and patients will be provided with support to enable self-management. The following conditions and infrastructure were required to allow for the redesign: 1) Redesign became a focus of the organizational strategy; 2) Building a comparative performance measurement for presentation at all managerial levels; 3) Agreement on the incentives to primary care clinics, which voluntarily joined the process of change; training of "quality leaders" who will use common terms and methodology to improve the quality of care. Starting in 2005 as a "pilot project", the change process has gradually evolved to include about 50 primary care clinics towards the end of the year 2007.

Evaluation of a syndromic surveillance system using the WSARE algorithm for early detection of an unusual, localized summer outbreak of influenza B: implications for bioterrorism surveillance.

BACKGROUND: Syndromic surveillance systems have been developed for early detection of bioterrorist attacks, but few validation studies exist for these systems and their efficacy has been questioned. OBJECTIVES: To assess the capabilities of a syndromic surveillance system based on community clinics in conjunction with the WSARE algorithm in identifying early signals of a localized unusual influenza outbreak. METHODS: This retrospective study used data on a documented influenza B outbreak in an elementary school in central Israel. The WSARE algorithm for anomalous pattern detection was applied to individual records of daily patient visits to clinics of one of the four health management organizations in the country. RESULTS: Two successive significant anomalies were detected in the HMO's data set that could signal the influenza outbreak. If data were available for analysis in real time, the first anomaly could be detected on day 3 of the outbreak, 1 day after the school principal reported the outbreak to the public health authorities. CONCLUSIONS: Early detection is difficult in this type of fast-developing institutionalized outbreak. However, the information derived from WSARE could help define the outbreak in terms of time, place and the population at risk.

[Description of a diabetes disease register extracted from a central database].

OBJECTIVES: To describe the development of inclusion criteria for identifying diabetic patients using administrative, laboratory and pharmacy data on a large central electronic database. DESIGN: A descriptive study in which entry criteria were developed, validated then changed in an iterative fashion and revalidated. The final register was compared with a traditionally built diabetes register. RESULTS: The four criterion chosen were: 1) HbAlc> or = 7.25%; 2) Glucose> or = 200mg/dl (for individuals who are included in the register on this criterion alone, supporting data for the diagnosis of diabetes is required at six months. If none are found, the patient is deleted from the register); 3) Purchase of diabetic medication twice in the last two months; 4) A diagnosis of diabetes (ICD9 code) in the chart and HbA1c6.5% or Glucose > 125mg/dl. CONCLUSION: Adoption of criteria for identification of diabetic patients using data sets on central computers can provide the registers necessary for diabetes care.

The implementation of managed care for diabetes using medical informatics in a large Preferred Provider Organization.

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.

The use of medical informatics as a management tool for community health services during the 2006 Israel-Lebanon War.

BACKGROUND: During war the health management organizations have tremendous difficulty monitoring members' needs according to geographic spread. OBJECTIVES: To describe how an HMO used its health information technology in a way that enables its management to receive updated online information on the needs of the insured, according to their distribution throughout the country during the time of the war in Lebanon in July-August 2006. METHODS: Data were derived from the computerized medical records of Maccabi Healthcare Services--the second largest HMO in Israel, providing care to more than 1.7 million members nationwide. Data on healthcare utilization by northern members were compared to the geographic distribution of clinics. RESULTS: The war was characterized by the massive evacuation of citizens southwards. During this period there was an abrupt decline in the utilization of medical services by northern members in the northern region. This decline returned to normal 10 days after the ceasefire. A reciprocal increase was noted in the use of health services by citizens from the north in other regions. This increase returned to normal after the war. No such pattern was noticed during the same period in 2005. CONCLUSIONS: Real-time surveillance of trends in consumption of health services by citizens in times of regular daily living as well as during emergencies and wars is a vital management tool for medical directors responsible for providing health services.

Variability in the difficulties experienced by women undergoing infertility treatments.

OBJECTIVE: To identify the variety and extent of difficulties experienced by infertile women. DESIGN: A cross-sectional survey study. SETTING: A regional infertility clinic. PATIENT(S): Two hundred forty-two women undergoing evaluation and treatment of fertility problems, mostly at the initial stages of treatment. INTERVENTION(S): List of difficulties administered along with infertility distress and well-being scales. MAIN OUTCOME MEASURES: Infertility distress and well-being measures. RESULT(S): Twenty-two difficulties resulting from infertility and its treatment were identified. Findings show great variability among women in the extent to which they experience these difficulties. Greater experience of difficulties was related to more distress and lower well-being. Some difficulties were lower for mothers of two or more children, yet even mothers of one child experienced difficulties that were mostly at similar levels to those reported by childless women. CONCLUSION(S): It is important to be aware of the great variability among women in their experience of infertility. The list of difficulties identified here, or similar lists identified using this procedure, could assist health care providers and psychosocial counselors in identifying misperceptions of difficulties that result in communication gaps between patients and providers and between patients and spouses.

The direct medical cost of diabetes in Israel.

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.

Reduced hospitalizations and death associated with influenza vaccination among patients with and without diabetes.

OBJECTIVE: To assess whether the influenza vaccination of community-dwelling, diabetic, elderly individuals is associated with reduced rates of hospitalization and death. RESEARCH DESIGN AND METHODS: In this outcome-research study, we compared mortality and hospitalization rates of 15,556 patients aged >or=65 years followed using a diabetes registry in a large health maintenance organization to that of 69,097 members not suffering from chronic disease who were considered as a reference group. The study outcomes included all-cause death and hospitalization in internal medicine or geriatric wards for any reason over winter and summer (control) periods. RESULTS: Vaccination rates were 48.8 and 42.0% among patients with diabetes and the reference population, respectively. Influenza vaccination was associated with a 12.3% reduction in hospitalization rates for patients with diabetes compared with 23.0% in the reference group (P = 0.08). The reduction in hospitalization rates was similar in both sexes among patients with diabetes. In addition, there was a significant reduction in mortality for the vaccinated group of patients with diabetes when compared with the nonvaccinated group except for female patients aged >or=85 years. CONCLUSIONS: The study results support the use of influenza vaccine among an elderly population. However, there does not appear to be an additional benefit for patients with diabetes.

Increased warfarin doses and decreased international normalized ratio response after nationwide generic switching.

OBJECTIVE: Our objective was to examine possible changes in the effectiveness of warfarin after a nationwide generic substitution of formulations in 1998. METHODS: In the computerized records of a health maintenance organization database, we identified 975 patients who took warfarin continuously over two 6-month periods, before (period 1) and after (period 2) the generic switch. In this sample we performed a retrospective, between-period paired comparison of warfarin doses dispensed and international normalized ratio (INR) levels maintained, as well as of the apparent warfarin sensitivity index (calculated as INR/Warfarin dose [in milligrams per day]). RESULTS: Overall, for period 2, doses were 26.5% higher and INR 4.2% lower, with a 14.7% reduction in warfarin sensitivity index (P <.001). The findings were strongest in the 61 of 975 patients (6.3%) dispensed the lowest maintenance doses (<1.0 mg/d), with minimal change at greater than 3 mg/d. In 94 other patients (9.6%) in whom doses were unchanged, INR (median with 5th and 95th percentiles) dropped to subtherapeutic levels, from 2.2 (1.8, 3.0) to 1.7 (1.3, 1.8) (P <.001). There were no adverse events, expressed as no change in hospital admissions. Apparent warfarin sensitivity was reduced in period 2 by 15% to 20% (P <.001) across all period 1 INR levels. CONCLUSION: Because a general unidirectional change in INR response per unit warfarin dose cannot be explained by biologic mechanisms or confounding, we conclude that slightly reduced bioavailability (within the acceptable bioequivalence range) of the new formulation led to overestimated period 2 doses and reduced apparent warfarin sensitivity in all patient subgroups (by period 1 dose or INR), which was most prominent in those individuals with the lowest maintenance dose requirements.