Using population-level incidence of hepatitis C virus and immigration status for data-driven screening policies: a case study in Israel.

BACKGROUND: Most studies estimate hepatitis C virus (HCV) disease prevalence from convenience samples. Consequently, screening policies may not include those at the highest risk for a new diagnosis. METHODS: Clalit Health Services members aged 25-74 as of 31 December 2009 were included in the study. Rates of testing and new diagnoses of HCV were calculated, and potential risk groups were examined. RESULTS: Of the 2 029 501 included members, those aged 45-54 and immigrants had lower rates of testing (12.5% and 15.6%, respectively), higher rates of testing positive (0.8% and 1.1%, respectively), as well as the highest rates of testing positive among tested (6.1% and 6.9%, respectively). DISCUSSION: In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases.

Influenza Vaccine Effectiveness Against Hospitalization in Fully and Partially Vaccinated Children in Israel: 2015-2016, 2016-2017, and 2017-2018.

BACKGROUND: Influenza vaccine effectiveness (VE) varies by season, circulating influenza strain, age, and geographic location. There have been few studies of influenza VE among hospitalized children, particularly in Europe and the Middle East. METHODS: We estimated VE against influenza hospitalization among children aged 6 months to 8 years at Clalit Health Services hospitals in Israel in the 2015-2016, 2016-2017, and 2017-2018 influenza seasons, using the test-negative design. Estimates were computed for full and partial vaccination. RESULTS: We included 326 influenza-positive case patients and 2821 influenza-negative controls (140 case patients and 971 controls from 2015-2016, 36 case patients and 1069 controls from 2016-2017, and 150 case patients and 781 controls from 2017-2018). Over all seasons, VE was 53.9% for full vaccination (95% confidence interval [CI], 38.6%-68.3%), and 25.6% for partial vaccination (-3% to 47%). In 2015-2016, most viruses were influenza A(H1N1) and vaccine lineage-mismatched influenza B/Victoria; the VE for fully vaccinated children was statistically significant for influenza A (80.7%; 95% CI, 40.3%-96.1%) but not B (23.0%; -38.5% to 59.4%). During 2016-2017, influenza A(H3N2) predominated, and VE was (70.8%; 95% CI, 17.4%-92.4%). In 2017-2018, influenza A(H3N2), H1N1 and lineage-mismatched influenza B/Yamagata cocirculated; VE was statistically significant for influenza B (63.0%; 95% CI, 24.2%-83.7%) but not influenza A (46.3%; -7.2% to 75.3%). CONCLUSIONS: Influenza vaccine was effective in preventing hospitalizations among fully vaccinated Israeli children over 3 influenza seasons, but not among partially vaccinated children. There was cross-lineage protection in a season where the vaccine contained B/Victoria and the circulating strain was B/Yamagata, but not in a season with the opposite vaccine-circulating strain distribution.

Influenza Vaccine Effectiveness in Preventing Influenza-associated Hospitalizations During Pregnancy: A Multi-country Retrospective Test Negative Design Study, 2010-2016.

BACKGROUND: To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. METHODS: The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. RESULTS: Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%-59%) against influenza-associated hospitalization during pregnancy. CONCLUSION: Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs.

Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive disease and hospital-treated pneumonia among people aged ≥65 years: a retrospective case-control study.

BACKGROUND: Streptococcus pneumoniae contributes considerably to the burden of pneumonia and invasive pneumococcal disease (IPD), with the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for preventing all-cause pneumonia still undetermined. The aim of this study was to control for common biases and confounders associated with previous observational studies and to assess PPSV23 vaccine effectiveness in preventing IPD and the most resource-intensive type of community-acquired pneumonia, hospital-treated pneumonia (HTP). METHODS: This was a retrospective case-control study nested in a population-based cohort, with age-, sex-, and risk-matched controls as the base case. Demographic information, laboratory data, and diagnoses were extracted from the chronic disease registry and from inpatient and outpatient records in the Clalit Health Services database. Vaccine effectiveness for PPSV23 was assessed using multivariable conditional logistic regression. Subgroup, sensitivity, and secondary analyses were conducted to validate findings. RESULTS: A total of 470 070 individuals aged ≥65 years were members of Clalit Health Services during the study period (1 January 2007 through 31 December 2010). The case cohort consisted of 212 participants with IPD and 23 441 with HTP. The adjusted association between vaccination and IPD was protective (odds ratio [OR], 0.58; 95% confidence interval [CI], .41-.81), whereas there was no demonstrated protective effect between vaccination and HTP (OR, 1.01; 95% CI, .97-1.04). The sensitivity analysis and all but 1 subgroup analysis provided consistent results to the base case. CONCLUSIONS: The PPSV23 vaccine is effective against the most severe invasive forms of pneumococcal disease, but the lack of effectiveness of PPSV23 in protecting against all-cause HTP should be considered for future vaccine policies.

Towards a subsiding diabetes epidemic: trends from a large population-based study in Israel.

BACKGROUND: With increasing diabetes prevalence worldwide, an impending diabetes "pandemic" has been reported. However, definitions of incident cases and the population at risk remain varied and ambiguous. This study analyzed trends in mortality and screening that contribute to diabetes prevalence and incidence, distinguishing between new incident cases and newly detected cases. METHODS: In an integrated provider-and-payer-system covering 53% of Israel's population, a composite diabetes case-finding algorithm was built using diagnoses, lab tests, and antidiabetic medication purchases from the organization's electronic medical record database. Data were extracted on adult members aged 26+ each year from January 1, 2004 through December 31, 2012. Rates of diabetes prevalence, incidence, screening, and mortality were reported, with incidence rates evaluated among the total, "previously-screened," and "previously-unscreened" at-risk populations. RESULTS: There were 343,554 diabetes cases in 2012 (14.4%) out of 2,379,712 members aged 26+. A consistent but decelerating upward trend in diabetes prevalence was observed from 2004-2012. Annual mortality rates among diabetics decreased from 13.8/1000 to 10.7/1000 (p = 0.0002). Total population incidence rates declined from 13.3/1000 in 2006 to 10.8/1000 in 2012 (p < 0.0001), with similar incidence trends (13.2/1000 to 10.2/1000; p = 0.0007) among previously-screened at-risk members, and a rise in testing rates from 53.0% to 66.7% (p = 0.0004). The previously-unscreened group decreased 28.6%, and the incidence rates within this group remained stable. CONCLUSIONS: The increase in diabetes prevalence is decelerating despite declining mortality and increasing testing rates. A decline in previously-screened incident cases and a shrinking pool of previously-unscreened members suggests that diabetes trends in Israel are moving toward equilibrium, rather than a growing epidemic.

Online health information seeking among Jewish and Arab adolescents in Israel: results from a national school survey.

This study examined patterns and determinants of seeking online health information among a nationally representative sample of 7,028 Jewish and Arab 7th- through 12th-grade students in 158 schools in Israel. Nearly all respondents (98.7%) reported Internet access, and 52.1% reported having sought online health information in the past year. Arab students (63%) were more likely than Jewish students (48%) to seek online health information. Population-group and sex differences in health topics sought online were identified, although fitness/exercise was most common across groups. Multivariate regression models revealed that having sought health information from other sources was the strongest independent correlate of online health information-seeking among Jews (adjusted odds ratio = 8.93, 95% CI [7.70, 10.36]) and Arabs (adjusted odds ratio = 9.77, 95% CI [7.27, 13.13]). Other factors associated with seeking online health information common to both groups were level of trust in online health information, Internet skill level, having discussed health/medical issues with a health care provider in the past year, and school performance. The most common reasons for not seeking online health information were a preference to receive information from a health professional and lack of interest in health/medical issues. The closing of the digital divide between Jews and Arabs represents a move toward equality. Identifying and addressing factors underpinning online health information-seeking behaviors is essential to improve the health status of Israeli youth and reduce health disparities.

Behavioral surveillance of knowledge about HIV/AIDS transmission and perceived need for additional knowledge in a national sample of young israeli men and women between 1993 and 2005.

The study examines trends in knowledge about HIV/AIDS prevention, perceived need for more information, and knowledge sources among 20,619 Israeli army releasees between 1993 and 2005. HIV/AIDS knowledge was strongly associated with education, lower religiosity and receiving information via the media in both genders, changing non-linearly over time. Need for more information was associated with low knowledge level among men (OR= 2.14; CI: 1.84-2.49; P < .0001) and women (OR 1.48; CI: 1.21-1.81; P < .0001). The findings underscore the need to reach those groups whose knowledge remains low over time utilizing the media, the preferred knowledge source, recognizing that a segment believes they do not need more information despite having low HIV/AIDS knowledge.

A multi-country investigation of influenza vaccine coverage in pregnant individuals, 2010-2016.

BACKGROUND: Many countries recommend influenza vaccination during pregnancy. Despite this recommendation, influenza vaccine among pregnant individuals remains under-utilized and uptake varies by country. Factors associated with influenza vaccine uptake during pregnancy may also vary across countries. METHODS: As members of the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), five sites from four countries (Australia, Canada, Israel, and the United States) retrospectively identified cohorts of individuals aged 18-50 years who were pregnant during pre-defined influenza seasons. Influenza vaccine coverage estimates were calculated for the 2010-11 through 2015-16 northern hemisphere and the 2012 through 2015 southern hemisphere influenza seasons, by site. Sites used electronic health records, administrative data, and immunization registries to collect information on pregnancy, health history, demographics, and vaccination status. Each season, vaccination coverage was calculated as the percentage of individuals who received influenza vaccine among the individuals in the cohort that season. Characteristics were compared between those vaccinated and unvaccinated, by site. RESULTS: More than two million pregnancies were identified over the study period. Influenza vaccination coverage ranged from 5% to 58% across sites and seasons. Coverage increased consistently over the study period at three of the five sites (Western Australia, Alberta, and Israel), and was highest in all seasons at the United States study site (39-58%). Associations with vaccination varied by country and across seasons; where available, parity >0, presence of a high-risk medical condition, and urban residence were consistently associated with increased likelihood of vaccination. CONCLUSIONS: Though increasing, uptake of influenza vaccine among pregnant individuals remains lower than recommended. Coverage varied substantially by country, suggesting an ongoing need for targeted strategies to improve influenza vaccine uptake in this population.

High rates of serology testing for coeliac disease, and low rates of endoscopy in serologically positive children and adults in Israel: lessons from a large real-world database.

BACKGROUND: Although coeliac disease is common worldwide, little is known regarding screening patterns in unselected populations, and on real-life adherence to professional guidelines for coeliac disease diagnosis and management. OBJECTIVE: To explore current practices in the diagnosis and management of coeliac disease, using data from a large Health Maintenance Organization in Israel that covers 54% of the population. METHODS: A population-based electronic database of about 4.5 million individuals was reviewed during the period of 1 January 2008 to 31 December 2015. Rates and results of coeliac disease serology testing and endoscopy procedures were examined. Subgroup analysis was performed by age, sex, ethnicity and socioeconomic status. RESULTS: Coeliac disease serology cumulative testing rate was 17.1% and 8.9% in the paediatric and adult population, respectively. The cumulative incidence of positive coeliac disease serology was 0.45% in children and 0.17% in adults, and was associated with age, sex, ethnicity and socioeconomic status sub-groups (P-value < 0.01). Gastrointestinal endoscopies were not subsequently performed in 44.1% of children and 47.1% of adults with positive coeliac disease serology. Within the study period, 36% of children and 56% of adults never achieved coeliac disease serology normalization. CONCLUSION: In a large real-life database, screening for coeliac disease was common. However, confirmatory intestinal biopsies were under-utilized, and coeliac disease serology often remained positive over a long period time in both children and adults.

An international cohort study of birth outcomes associated with hospitalized acute respiratory infection during pregnancy.

OBJECTIVES: Findings during the 2009 pandemic suggest severe maternal infection with pandemic influenza had adverse perinatal health consequences. Limited data exist evaluating the perinatal health effects of severe seasonal influenza and non-influenza infections during pregnancy. METHODS: A retrospective cohort of pregnant women from Australia, Canada, Israel, and the United States was established using birth records to identify pregnancies and birth outcomes and hospital and laboratory testing records to identify influenza and non-influenza associated acute respiratory or febrile illness (ARFI) hospitalizations. ARFI hospitalized women were matched to non-hospitalized women (1:4) by country and season of conception. Log-binomial regression was used to estimate the relative risk (aRR) of preterm birth (PTB), small-for-gestational-age (SGA), and low birthweight (LBW) birth, adjusting for pre-existing medical conditions, maternal age, and parity. RESULTS: 950 pregnant women hospitalized with an ARFI were matched with 3,800 non-hospitalized pregnant women. Compared to non-hospitalized women, risk of PTB was greater among women hospitalized with influenza-associated ARFI (aRR: 1.57; 95% CI: 1.15-2.15) and non-influenza ARFI (aRR: 2.78; 95% CI: 2.12-3.65). Similar results were observed for LBW; there were no associations with SGA birth. CONCLUSIONS: ARFI hospitalization during pregnancy was associated with increased risk of PTB and LBW.

A socio-ecological analysis of Ethiopian immigrants' interactions with the Israeli healthcare system and its policy and service implications.

OBJECTIVE: Despite receiving full medical care and many social services, many Ethiopian immigrants in Israel feel frustrated, and even alienated, by the care they receive. This study uses a qualitative approach to explore the obstacles Ethiopian immigrants face regarding effective health seeking behavior and optimal interactions with healthcare providers in Israel. DESIGN: We gained a three-cornered perspective by conducting semi-structured interviews with healthcare providers, immigrants, and interpreters who mediate between the two. An ecological system or socio-ecological model guided the data analysis. It allowed organizing the varied and complex relationship between the factors that influence healthcare delivery and receipt among this population. RESULTS: The advanced analysis of our results delineated four themes which we grouped into two domains: the cultural divide and the interpreters. Within each of these themes, we explored influences on health or healthcare at each level of the socio-ecological model. We demonstrated that the problems surrounding health seeking behaviors and receiving treatment stem mainly from a cultural divide. This cultural incongruity and its effects are apparent at multiple levels of the ecological model and must be recognized and addressed programmatically at these levels. CONCLUSIONS: Necessary program and service modifications include that cultural mediation become an integral part of health personnel's training for healthcare delivery and a necessary criterion for good practices. We recommend that professionals from within the health system be trained to act as interpreters. Lastly, the integration of traditional healers into the allopathic health system should be considered. These modifications require a system-wide change in policy, structure of services, and practices.

Development of a risk score for predicting the benefit versus harm of extending dual antiplatelet therapy beyond 6 months following percutaneous coronary intervention for stable coronary artery disease.

BACKGROUND: Decisions on dual antiplatelet therapy (DAPT) duration should balance the opposing risks of ischaemia and bleeding. Our aim was to develop a risk score to identify stable coronary artery disease (SCAD) patients undergoing PCI who would benefit or suffer from extending DAPT beyond 6 months. METHODS: Retrospective analysis of a cohort of patients who completed 6 months of DAPT following PCI. Predictors of ischaemic and bleeding events for the 6-12 month period post-PCI were identified and a risk score was developed to estimate the likelihood of benefiting from extending DAPT beyond 6 months. Incidence of mortality, ischaemic and bleeding events for patients treated with DAPT for 6 vs. 6-12 months, was compared, stratified by strata of the risk score. RESULTS: The study included 2,699 patients. Over 6 months' follow up, there were 78 (2.9%) ischaemic and 43 (1.6%) bleeding events. Four variables (heart failure, left ventricular ejection fraction ≤30%, left main or three vessel CAD, status post (s/p) PCI and s/p stroke) predicted ischemic events, two variables (age>75, haemoglobin <10 g/dL) predicted bleeding. In the lower stratum of the risk score, 6-12 months of treatment with DAPT resulted in increased bleeding (p = 0.045) with no decrease in ischaemic events. In the upper stratum, 6-12 months DAPT was associated with reduced ischaemic events (p = 0.029), with no increase in bleeding. CONCLUSION: In a population of SCAD patients who completed 6 months of DAPT, a risk score for subsequent ischaemic and bleeding events identified patients likely to benefit from continuing or stopping DAPT.

Estimating Vaccine Effectiveness Against Hospitalized Influenza During Pregnancy: Multicountry Protocol for a Retrospective Cohort Study.

BACKGROUND: Although pregnant women are believed to have elevated risks of severe influenza infection and are targeted for influenza vaccination, no study to date has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy, primarily because this outcome poses many methodological challenges. OBJECTIVE: The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) was formed in 2016 as an international collaboration with the Centers for Disease Control and Prevention; Abt Associates; and study sites in Australia, Canada, Israel, and the United States. The primary goal of this collaboration is to estimate IVE in preventing acute respiratory or febrile illness (ARFI) hospitalizations associated with laboratory-confirmed influenza virus infection during pregnancy. Secondary aims include (1) describing the incidence, clinical course, and severity of influenza-associated ARFI hospitalization during pregnancy; (2) comparing the characteristics of ARFI-hospitalized pregnant women who were tested for influenza with those who were not tested; (3) describing influenza vaccination coverage in pregnant women; and (4) comparing birth outcomes among women with laboratory-confirmed influenza-associated hospitalization versus other noninfluenza ARFI hospitalizations. METHODS: For an initial assessment of IVE, sites identified a retrospective cohort of pregnant women aged from 18 to 50 years whose pregnancies overlapped with local influenza seasons from 2010 to 2016. Pregnancies were defined as those that ended in a live birth or stillbirth of at least 20 weeks gestation. The analytic sample for the primary IVE analysis was restricted to pregnant women who were hospitalized for ARFI during site-specific influenza seasons and clinically tested for influenza virus infection using real-time reverse transcription polymerase chain reaction. RESULTS: We identified approximately 2 million women whose pregnancies overlapped with influenza seasons; 550,344 had at least one hospitalization during this time. After restricting to women who were hospitalized for ARFI and tested for influenza, the IVE analytic sample included 1005 women. CONCLUSIONS: In addition to addressing the primary question about the effectiveness of influenza vaccination, PREVENT data will address other important knowledge gaps including understanding the incidence, clinical course, and severity of influenza-related hospitalizations during pregnancy. The data infrastructure and international partnerships created for these analyses may be useful and informative for future influenza studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11333.

Obesity or smoking: Which factor contributes more to the incidence of myocardial infarction?

OBJECTIVE: Comparing the contributions of smoking and obesity to the risk of myocardial infarction (MI) can help prioritize behavioral modifications. The objective of this study was to determine the relative risk of smoking, obesity and the joint burden on the risk of MI. METHODS: This is a retrospective cohort study of data accessed from electronic medical records of the largest health care organization in Israel. The study population included all 738,380 members of Clalit Health Services, with at least one smoking status and one BMI assessment recorded in 2009 or 2010, aged 40-74years, who were MI-free before 2009. Obesity was defined as BMI >30kg/m(2). New and primary MI between January 1 and December 31, 2011 were recorded. RESULTS: Rates of MI were: 0.18% for non-obese never smokers, 0.25% for obese never smokers, 0.40% for non-obese past smokers, 0.50% for obese past smokers, 0.53% for non-obese current smokers and 0.66% for obese current smokers. Among non-obese individuals, past smokers and current smokers had a greater risk of MI than did never smokers, after adjusting for age, gender and socioeconomic position (OR, 1.45; 95% CI, 1.23-1.70 and OR, 2.35; 95% CI, 2.10-2.63, respectively). The burden of obesity increased the risk of MI for never smokers but the burden of obesity did not elevate the risk of MI when combined with current or past smoking groups, after adjusting for comorbidities. CONCLUSIONS: Past and, more so, current smoking confers greater risk for MI than obesity.

Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment.

IMPORTANCE: International guidelines recommend treatment with statins for patients with preexisting ischemic heart disease to prevent additional cardiovascular events but differ regarding target levels of low-density lipoprotein cholesterol (LDL-C). Trial data on this question are inconclusive and observational data are lacking. OBJECTIVE: To assess the relationship between levels of LDL-C achieved with statin treatment and cardiovascular events in adherent patients with preexisting ischemic heart disease. DESIGN, SETTING, AND PARTICIPANTS: Population-based observational cohort study from 2009 to 2013 using data from a health care organization in Israel covering more than 4.3 million members. Included patients had ischemic heart disease, were aged 30 to 84 years, were treated with statins, and were at least 80% adherent to treatment or, in a sensitivity analysis, at least 50% adherent. Patients with active cancer or metabolic abnormalities were excluded. EXPOSURES: Index LDL-C was defined as the first achieved serum LDL-C measure after at least 1 year of statin treatment, grouped as low (≤70.0 mg/dL), moderate (70.1-100.0 mg/dL), or high (100.1-130.0 mg/dL). MAIN OUTCOMES AND MEASURES: Major adverse cardiac events included acute myocardial infarction, unstable angina, stroke, angioplasty, bypass surgery, or all-cause mortality. The hazard ratio of adverse outcomes was estimated using 2 Cox proportional hazards models with low vs moderate and moderate vs high LDL-C, adjusted for confounders and further tested using propensity score matching analysis. RESULTS: The cohort with at least 80% adherence included 31 619 patients, for whom the mean (SD) age was 67.3 (9.8) years. Of this population, 27% were female and 29% had low, 53% moderate, and 18% high LDL-C when taking statin treatment. Overall, there were 9035 patients who had an adverse outcome during a mean 1.6 years of follow-up (6.7 per 1000 persons per year). The adjusted incidence of adverse outcomes was not different between low and moderate LDL-C (hazard ratio [HR], 1.02; 95% CI, 0.97-1.07; P = .54), but it was lower with moderate vs high LDL-C (HR, 0.89; 95% CI, 0.84-0.94; P < .001). Among 54 884 patients with at least 50% statin adherence, the adjusted HR was 1.06 (95% CI, 1.02-1.10; P = .001) in the low vs moderate groups and 0.87 (95% CI, 0.84-0.91; P = .001) in the moderate vs high groups. CONCLUSIONS AND RELEVANCE: Patients with LDL-C levels of 70 to 100 mg/dL taking statins had lower risk of adverse cardiac outcomes compared with those with LDL-C levels between 100 and 130 mg/dL, but no additional benefit was gained by achieving LDL-C of 70 mg/dL or less. These population-based data do not support treatment guidelines recommending very low target LDL-C levels for all patients with preexisting heart disease.

Defining the role of medication adherence in poor glycemic control among a general adult population with diabetes.

AIMS: This study assesses the attributable impact of adherence to oral glucose medications as a risk factor for poor glycemic control in population subgroups of a large general population, using an objective medication adherence measure. METHODS: Using electronic health records data, adherence to diabetes medications over a two-year period was calculated by prescription-based Medication Possession Ratios for adults with diabetes diagnosed before January 1, 2010. Glycemic control was determined by the HbA1c test closest to the last drug prescription during 2010-2012. Poor control was defined as HbA1c>75 mmol/mol (9.0%). Medication adherence was categorized as "good" (>80%), "moderate" (50-80%), or "poor" (<50%). Logistic regression models assessed the role medication adherence plays in the association between disease duration, age, and poor glycemic control. We calculated the change in the attributable fraction of glucose control if the non-adherent diabetic medication population would become adherent by age-groups. RESULTS: Among 228,846 diabetes patients treated by oral antiglycemic medication, 46.4% had good, 28.8% had moderate, and 24.8% had poor adherence. Good adherence rates increased with increasing disease duration, while glycemic control became worse. There was a strong inverse association between adherence level and poor control (OR = 2.50; CI = 2.43-2.58), and adherence was a significant mediator between age and poor control. CONCLUSIONS: A large portion of the diabetes population is reported to have poor adherence to oral diabetes medications, which is strongly associated with poor glycemic control in all disease durations. While poor adherence does not mediate the poorer glycemic control seen in patients with longer-standing disease, it is a significant mediator of poor glycemic control among younger diabetes patients. A greater fraction of poorly controlled younger patients, compared to older patients, could be prevented if at least 80% adherence to their medications was achieved. Therefore, our results suggest that interventions to improve adherence should focus on this younger sub-group.

Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

BACKGROUND: Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. METHODS: Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. RESULTS: In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. CONCLUSIONS: We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international guidelines. Health care managers and policy-makers may consider the strategic potential of utilizing clinical and administrative databases for creating population-specific risk prediction models to inform vaccination campaigns.

Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies.

OBJECTIVE: To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances. DESIGN: Systematic review and meta-analysis of observational studies and randomised controlled trials. DATA SOURCES: Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators. STUDY SELECTION: Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes. DATA EXTRACTION: Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849,412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30,716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics. RESULTS: In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods. CONCLUSIONS: Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk.

Decreased serum concentrations of 25-hydroxycholecalciferol are associated with increased risk of progression to impaired fasting glucose and diabetes.

OBJECTIVE: To study the association between vitamin D status and the risk of incident impaired fasting glucose (IFG) and diabetes in a population-based cohort of diabetes-free subjects. RESEARCH DESIGN AND METHODS: In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes-free subjects aged 40-70 years with serum 25-hydroxycholecalciferol (25-OHD) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups: ≥25, 25.1-37.5, 37.6-50, 50.1-75, and >75 nmol/L. RESULTS: The baseline cohort included 117,960 adults: 83,526 normoglycemic subjects and 34,434 subjects with IFG. During follow-up, 8,629 subjects (10.3% of the normoglycemic group) developed IFG, and 2,162 subjects (1.8% of the total cohort) progressed to diabetes. A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes. The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25-OHD level ≤25 nmol/L were greater than those of subjects with a 25-OHD level >75 nmol/L [odds ratio 1.13 (95% CI 1.03-1.24), 1.77 (1.11-2.83), and 1.43 (1.16-1.76), respectively]. CONCLUSIONS: Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes.