Dahlia Weitzman

A population based study of the epidemiology of Herpes Zoster and its complications

OBJECTIVESnTo assess the incidence of Herpes Zoster (HZ) and its complications in the Israeli general population and specifically in immune-compromised individuals, and to identify risk factors for developing HZ and post-herpetic neuralgia (PHN).nnnMETHODSnA retrospective database search for newly diagnosed cases of HZ and of PHN during 2006-2010 was conducted using the comprehensive longitudinal database of Maccabi Health Services. Cox-proportional hazards models were used to assess associations between risk factors and HZ and PHN.nnnRESULTSnDuring 2006-2010 there were 28,977 newly diagnosed cases of HZ and 1508 newly diagnosed cases of PHN. Incidence density rate of HZ was 3.46 per 1000 person-years in the total population and 12.8 per 1000 person-years in immune-compromised patients. HZ and PHN incidence increased sharply with age. 12.4% and 3.1% of elderly HZ patients (≥ 65 years) developed PHN or ophthalmic complications, respectively. In multivariable analyses, HZ and PHN were associated with female sex, higher socioeconomic status, diabetes mellitus, cancer history, and HIV treatment.nnnCONCLUSIONSnExtrapolating to the entire Israeli population, we estimate over 24,000 new cases of HZ and 1250 new cases of PHN each year. Cost-effectiveness analysis should be performed to determine the threshold age for vaccination against HZ.

Prevalence and Factors Associated With Resistant Hypertension in a Large Health Maintenance Organization in Israel

Previous assessments of the prevalence of resistant hypertension (RH) in uncontrolled blood pressure (BP) have ranged from 3% to 30%. Using real-world data, our aim was to estimate the prevalence of RH in patients belonging to the Maccabi Healthcare Services, a 2-million-member health organization in Israel. From 2010 to 2011, all hypertensive patients with ≥2 recorded BP measurements during a minimum period of 6 months were identified. Patients were considered uncontrolled if their most recent BP during the study period and their mean systolic BP or diastolic BP during a preceding period of ≥6months were systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg in chronic kidney disease or diabetes mellitus. Uncontrolled patients taking diuretics and ≥2 antihypertensive therapy classes at their maximal recommended dose were regarded as resistant hypertensives. A total of 172 432 patients were eligible for the study. Uncontrolled BP was found in 35.9% (n=65 710). Overall, 2.2% of the uncontrolled patients (n=1487) were resistant hypertensives. Patients with RH were characterized by a significantly (P<0.01) older age, higher body mass index, and multicomorbidity (including dyslipidemia, diabetes mellitus, and impaired renal function) compared with patients with controlled hypertension receiving equivalent treatment. The results of this large population-based study indicate a substantially lower prevalence of RH than previously reported. Most patients with uncontrolled BP took less than the maximal recommended antihypertensive treatment.

Red blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study.

Red blood cell distribution width (RDW) has been shown to predict cardiovascular mortality in various populations, but studies were less conclusive regarding cardiovascular morbidity. We aimed at evaluating the prognostic effect of RDW on cardiovascular morbidity and all-cause mortality in the largest community cohort to date.We utilised the computerised database of a large community based healthcare maintenance organization (HMO) in Israel to identify a cohort of 225,006 eligible patients aged 40 or above who performed a blood count during 2006. We evaluated the relationship between 1% increments of RDW values and major cardiovascular events and all-cause mortality over a period of five years. A total of 21,939 incident cases of a major cardiovascular event and 4,287 deaths were documented during a total of six years of follow up, respectively. In comparison with patients with RDW level <13%, the hazard ratio for total mortality gradually increased to 4.57 (95% confidence interval [CI]: 3.35-6.24, p<0.001) among male patients and to 3.26 (95% CI: 2.49-4.28, p<0.001) among female patients with a RDW of 17% or above. Similar results were evident in anaemic and non-anaemic populations. RDW above 17% was also associated with a modest increased risk of major cardiovascular events in females 1.26 (95% CI: 1.03-1.52, p=0.021), while in men it was not significant, 1.08 (95% CI: 0.82-1.41, p=NS). In conclusion, increasing RDW levels significantly increased risk of cardiovascular morbidity and all-cause mortality. Our observation is evident in both anaemic and non-anaemic patients.

Continuation of Statin Therapy and Primary Prevention of Nonfatal Cardiovascular Events

Although the beneficial effect of statins in secondary prevention of cardiac events is well established, their effectiveness in primary prevention is questionable when most evidence derives from randomized controlled trials and not real-life data. To evaluate the association between persistent use of statins and risk of acute nonfatal cardiovascular events in primary prevention patients in community settings, we retrospectively analyzed a cohort of 171,535 adults 45 to 75 years old with no indication of cardiovascular disease who began statin therapy from 1998 to 2009 in a large health maintenance organization in Israel. Persistence with statins was measured by the proportion of days covered with dispensed prescriptions of statins during the follow-up period. Main outcome measurements were occurrence of myocardial infarction or performance of a cardiac revascularization procedure. Incidence of acute cardiovascular events during the follow-up period (993,519 person-years) was 10.22 per 1,000 person-years. Persistence with statins was associated with a lower risk of incident cardiac events (p for trend <0.01). The most persistent users (covered with statins for ≥80% of their follow-up time) had a hazard ratio of 0.58 (95% confidence interval 0.55 to 0.62) compared to nonpersistent users (proportion of days covered <20%). Similar results were found when analyses were limited to patients with >5 years of follow-up. Treatment with high efficacy statins was associated with a lower risk of cardiac events. In conclusion, our large and unselected community-based study supports the results of randomized controlled trials regarding the beneficial effect of statins in the primary prevention of acute cardiac events.

Thrombosis following acute cytomegalovirus infection: a community prospective study

Infection might be associated with increased risk of venous thromboembolism (VTE) and arterial thrombosis. Specific hypotheses have been raised regarding the procoagulant response induced by acute cytomegalovirus (CMV) infection. Accordingly, we investigated the 6-month incidence of VTE and/or arterial thrombosis in patients that had been tested positive for CMV-IgM antibodies in a large health maintenance organization. Logistic regression analysis was used to identify independent risk factors for VTE and arterial thrombosis. Among 90,515 patients eligible for the VTE analysis and 90,805 patients eligible for the arterial thrombosis analysis, 6,205 (6.9xa0%) and 6,222 (6.9xa0%) patients were tested positive for CMV-IgM antibodies, respectively. During 6xa0months of follow-up from index date, the incidence rates per 1,000 capita of VTE among CMV-IgM seropositive and CMV-IgM seronegative patients were 3.06 (19 patients) and 1.36 (115 patients), respectively (odds ratio (OR) 2.25; 95xa0% confidence intervals (95xa0% CI) 1.38–3.66; pu2009=u20090.003). CMV-IgM seropositivity was independently associated with VTE appearance (OR 2.49; 95xa0% CI 1.53–4.06; pu2009<u20090.0001) following adjustment for age, sex, and other confounders. The incidence rates per 1,000 capita of arterial thrombosis among CMV-IgM seropositive and CMV-IgM seronegative patients were 1.12 (7 patients) and 1.06 (90 patients), respectively (OR 1.06; 95xa0% CI 0.49–2.28; pu2009=u20090.840). CMV-IgM seropositivity was not associated with arterial thrombosis. We conclude that acute CMV infection might be associated with an increased short-term VTE risk. To the best of our knowledge, this is the largest study ever to confirm this association.

Hemoglobin nonrecovery following acute myocardial infarction is a biomarker of poor outcome: a retrospective database study.

BACKGROUNDnAnemia on admission and during hospitalization is associated with poor short and long term prognosis among patients with acute coronary syndrome (ACS). Our objective was to examine the prognostic implications of longitudinal hemoglobin (Hb) levels following a first acute myocardial infarction (AMI).nnnMETHODSnWe utilized data obtained from the computerized database of a large community based health care maintenance organization to identify patients who survived for at least 6 months following a first AMI, during the years 2003-2010. Hazard ratios were calculated using Cox proportional regression models with various Hb measurements as dependent variables, and net reclassification improvement (NRI) was applied to evaluate the prognostic usefulness of these Hb measurements.nnnRESULTSnLast Hb measurement during a 6-24 month follow-up period was found to have the highest prognostic power. In males, Hb levels below 13 g/dL were gradually associated with a higher risk of events, reaching a HR of 4.13 at Hb levels <11 g/dL. In females, only Hb levels lower than 11 g/dL were significantly associated with a higher event rate (HR=2.42, p=0.003). Hb decrease was significantly associated with an increased risk in both genders, even among non-anemic patients at baseline.nnnCONCLUSIONSnAnemia and Hb decrement following a first AMI are associated with worse prognosis and elevated risk of combined all cause mortality and recurrent cardiac events.

No male predominance in offspring of women with rheumatoid arthritis or systemic lupus erythematosus

To assess the proportion of male versus female offspring of women diagnosed with SLE or RA, disorders in which female predominance is well known and PsA a disease in which female dominance is less established. The study population encompassed all females aged 16–46, who were members of the Maccabi Health Services (MHS) throughout the period of 2000–2011 and had at least one pregnancy. Data were retrieved from the computerized database of MHS, a 2-million enrollee health maintenance organization operating in Israel. The database was also used to collect data on patients with RA, SLE, and PsA. A total of 182,073 women had at least one indication of pregnancy during the study period. Among them, 546, 270, and 170 were diagnosed with RA, SLE, and PsA, respectively. The proportion of live-born males in 380,472 offspring of women free of these diseases was 51.5xa0% (95xa0% CI 51.4–51.7xa0%). The proportion (95xa0% CIs) of male offspring born to mothers diagnosed with of RA, SLE, and PsA were 46.3xa0% (42.3–50.3xa0%), 51.8xa0% (46.6–57.0xa0%), and 50.6xa0% (42.8–58.5xa0%), respectively. Our findings support the primary contribution of the hormonal phenotype rather than the genetic phenotype on autoimmunity. Neither patients with SLE or RA differ from the general population by the sex of their offspring.

Comprehensive healthcare resource use among newly diagnosed congestive heart failure

BackgroundCongestive heart failure (CHF) is among the most common causes of hospital admissions and readmissions in the Western world. However, the burden of ambulatory care has not been as well investigated. The objective of this study was to assess the relative burden and direct medical costs of CHF including inpatient and outpatient care.MethodsWe used longitudinal clinical data from a two-million member health organization in Israel (Maccabi Healthcare Services) to identify adults with newly diagnosed CHF between January 2006 and December 2012, either in the in- or outpatient setting. Adults without CHF were age- and sex-matched to CHF patients and healthcare utilization and all modes of healthcare costs were compared among them, excluding those in their last year of life.ResultsThe burden posed by 6592 CHF patients was significantly (pu2009<u20090.001) larger than that of 32,960 matched controls. CHF patients had significantly higher rates of baseline comorbidity and healthcare utilization compared to non-CHF controls. This was evident in all categories of healthcare services and expenses, including in- and outpatient visits, laboratory expenses, medication costs, among younger and older, men and women. Among those who incurred any healthcare costs, younger (45-64y) and older (65u2009+u2009y) subjects with CHF were observed to have about 3.25 (95% CI: 2.96–3.56) and 2.08 (95% CI: 1.99–2.17) times the healthcare costs, respectively, compared to subjects without CHF after adjusting for patient characteristics.ConclusionCHF is associated with an overall two- to three-fold higher cost of healthcare services depending on patient age, accounting for over half of all healthcare costs incurred by elderly CHF patients, and more than two-thirds of all costs among younger CHF patients. Observations of the large burden posed on one of the youngest societies in the developed world are profound, implicative of great opportunities to control the costs of CHF. Further research to understand how resource use impacts health outcomes and quality of care is warranted.

Trends in statin therapy initiation during the period 2000–2010 in Israel

PurposeThe aim of this population-based study is to describe trends in the characteristics and treatment patterns of statin initiators over the first decade of the 21st century.MethodsNew statin use was studied retrospectively using the database of Maccabi Healthcare Services (MHS), a large Israeli health maintenance organization. Statin initiators were defined as MHS members aged ≥30xa0years who first purchased statins between 2000 and 2010. The starting dose was calculated in simvastatin equivalents based on the World Health Organization’s daily defined dose index. Persistence was calculated as the percentage of days covered (PDC) with statins during the first year of therapy.ResultsStatin initiation peaked in 2005 and decreased from 38.6 to 18.6 per 1,000 in the period 2005–2010. The average age at therapy initiation decreased from 58.9 (±12.0) to 54.5 (±11.7) years, and the average (SD)xa0baseline low-density lipoprotein cholesterol (LDL-C) decreased from 4.2 (±1.1) to 4.0 (±0.9) mmol/l during the study period. Women were on average 3 years older than men at treatment initiation, with a higher baseline LDL-C. Among statin initiators, the prevalence of ischemic heart disease (IHD) decreased from 17.8 to 6.7xa0%, and diabetes prevalence increased from 8.6 to 15.7xa0%, peaking in 2008 (18.0xa0%). The PDC with statins ranged between 52.9 and 57.7xa0%. Simvastatin use at initiation increased from 27.5xa0% in 2000 to >90xa0% since 2002. Starting dose increased from 18.5 (±8.9) to 24.3 (±13.7) mg simvastatin equivalent.ConclusionsAmong the study population, statin initiators were increasingly characterized by a lower cardiovascular risk—namely, younger individuals without IHD and with a lower baseline LDL-C. These trends underscore the important shift towards statin initiation for primary prevention, as well as the need to balance between benefits and the potential side effect of statins.

Characterization of adherence and persistence profile in a real‐life population of patients treated with adalimumab

AIMSnPublished data on long-term adherence and persistence with adalimumab (Humira® ) in clinical practice are scarce and often limited to selected patient populations. This study assessed adherence with adalimumab across different indications and identified correlates and outcomes of poor adherence.nnnMETHODSnWe analysed data originating from the electronic database of Maccabi Healthcare Services (MHS) that includes 2.1 million enrolees. We randomly selected patients with at least one dispense of adalimumab since it was included in the local health basket in Israel in 2008 until the end of 2013. Patients with the following indications (nxa0=xa01339) were included: Crohns disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriatic arthritis (PSA), ankylosing spondylitis (AS) and psoriasis. Adherence with therapy was assessed by the medication possession ratio (MPR) during the follow-up period.nnnRESULTSnGood adherence (MPRxa0≥xa080%) was observed among 80% of study patients and was associated with lower risk for ≥1 hospitalization per year of follow-up (adjusted-OR = 1.94, 95% CI:1.15-3.28). Patients with AS and CD persisted on adalimumab therapy the most, reaching median use of 27.0 and 26.7 months, respectively. Half (52.4%) of the patients discontinued treatment during a mean (SD) follow-up of 3.07 (1.71) years. High socioeconomic status was associated with lower risk for discontinuation (adjusted-HR = 0.74; 0.60-0.91). UC and concomitant prednisolone use were associated with increased risk for treatment discontinuation (HR = 1.31; 1.00-1.72, and HR = 1.40; 1.17-1.68, respectively).nnnCONCLUSIONnOur results indicate encouraging persistence and adherence with adalimumab of patients with inflammatory conditions.