Huntington's Disease in Israel: A Population-Based Study Using 20 Years of Routinely-Collected Healthcare Data.

BACKGROUND: Huntington's disease (HD) is a rare, genetic, neurodegenerative disease. Obtaining population-level data on epidemiology and disease management is challenging. OBJECTIVE: To investigate the epidemiology, clinical manifestations, treatment, and healthcare utilization of patients with HD in Israel. METHODS: Retrospective population-based cohort study, including 20 years of routinely collected data from Maccabi Healthcare Services, an insurer and healthcare provider for one-quarter of the Israeli population. RESULTS: The study cohort included 109 adult patients (aged ≥18 years) diagnosed with HD, with mean age of 49.9 years and 56%females. The most common HD-related conditions were anxiety (40%), behavioral problems (34%), sleep disorders (21%), and falls (13%). Annual incidence rates for HD ranged from 0.17 to 1.34 per 100,000 from 2000 to 2018; the 2018 crude prevalence in adults was 4.36 per 100,000. Median survival from diagnosis was approximately 12 years (95%CI: 10.4-15.3). The most frequent symptomatic treatments were antidepressants (69%), antipsychotics (63%), and tetrabenazine (63%), the only drug approved for the treatment of HD chorea in Israel during the examined period. Patterns of healthcare utilization changed as disease duration increased, reflected by increased frequency of emergency department visits and home visits. CONCLUSION: This retrospective population-based study provides insights into the prevalence, incidence, clinical profile, survival, and resource utilization of patients with HD in ethnically diverse Israel. The findings in this study are generally consistent with the international literature and demonstrate the value of routinely collected healthcare data as a complementary resource in HD research.

Comparison of text processing methods in social media-based signal detection.

PURPOSE: Adverse event (AE) identification in social media (SM) can be performed using various types of natural language processing (NLP) and machine learning (ML). These methods can be categorized by complexity and precision level. Co-occurrence-based ML methods are rather basic, as they identify simultaneous appearance of drugs and clinical events in a single post. In contrast, statistical learning methods involve more complex NLP and identify drugs, events, and associations between them. We aimed to compare the ability of co-occurrence and NLP to identify AEs and signals of disproportionate reporting (SDR) in patient-generated SM. We also examined the performance of lift in SM-based signal detection (SD). METHODS: Our examination was performed in a corpus of SM posts crawled from open online patient forums and communities, using the spontaneously reported VigiBase data as reference data set. RESULTS: We found that co-occurrence and NLP produce AEs, which are 57% and 93% consistent with VigiBase AEs, respectively. Among the SDRs identified both in SM and in VigiBase, up to 55.3% were identified earlier in co-occurrence, and up to 32.1% were identified earlier in NLP-processed SM. Using lift in SM SD provided performance similar to frequentist methods, both in co-occurrence and in NLP-processed AEs. CONCLUSION: Our results indicate that using SM as a data source complementary to traditional pharmacovigilance sources should be considered further. Various levels of SM processing may be considered, depending on the preferred policies and tolerance for false-positive to false-negative balance in routine pharmacovigilance processes.

Challenges of post-authorization safety studies: Lessons learned and results of a French study of fentanyl buccal tablet.

PURPOSE: Recruiting and retaining participants in real-world studies that collect primary data are challenging. This article illustrates these challenges using a post-authorization safety study (PASS) to assess adverse events (AEs) experienced with fentanyl buccal tablet (FBT) over 3 months of treatment. METHODS: This was an observational, prospective, multicenter study in France conducted over 1 year. The study employed primary data collection in FBT-treated patients and their treating physicians via a site qualification questionnaire and patient log completed by physicians and a questionnaire and pain diary completed by patients. Strategies to increase participation included reminders, newsletters, frequent follow-up telephone calls, and reducing the extent of data collected. RESULTS: Of the 1118 physicians contacted who returned the participation form or responded to a telephone call, only 128 expressed willingness to participate. Key reasons for non-participation were lack of interest (69.7%) and FBT not being used in practice by the contacted physician (25.1%). Overall, 224 patients were screened by 31 physicians, and 97 were enrolled. Key reasons for patient non-inclusion were unwillingness or inability to complete the patient AE diary or questionnaire (40.9% [52/127]) and patients' decision (33.9% [43/127]). CONCLUSIONS: Despite efforts to increase participation, enrollment in this study was low. Recruitment and retention methods are limited in their capacity to optimally execute a primary data collection in a PASS. For a PASS to provide reliable and valid information on medication use, involvement from health care agencies, regulators, and pharmaceutical companies is needed to establish their importance, drive study participation, and reduce patient withdrawal.

Outcome of contemporary acute coronary syndrome complicated by ventricular tachyarrhythmias.

AIM: To evaluate the incidence and prognostic implications of ventricular tachyarrhythmias (VTAs) complicating acute myocardial infarction (MI). METHODS AND RESULTS: We evaluated 7669 MI patients [ST elevation (n = 3573) and non-ST-elevation acute coronary syndrome (ACS) (n = 4096)] from the Acute Coronary Syndrome Israeli Survey for the incidence of VTA. Ventricular tachyarrhythmia occurred in 3.8% of patients [2.1% early (≤ 48 h) and 1.7% late (>48 h) VTA]. In-hospital mortality rates were higher for patients with VTA when compared with patients with no VTA (P < 0.001). Consistent with these findings, multivariable analysis demonstrated that early and late VTAs were associated with increased risk of in-hospital death [hazard ratio (HR) = 3.84; 95% confidence interval (CI) 1.77-6.78, P < 0.001, and HR = 8.23; 95% CI 4.84-13.98, P < 0.001, respectively]. In contrast, post-discharge outcomes demonstrated that only late VTA was independently associated with a significant increased risk of 30-day mortality (HR = 5.17; 95% CI 1.54-17.27, P = 0.007) with a trend towards an increased 1-year mortality risk (HR = 1.69; 95% CI 0.79-3.62, P = 0.17). The long-term risk associated with in-hospital VTA was driven by sustained ventricular tachycardia (VT) (HR = 3.28; 95% CI 1.92-5.60, P < 0.001) but not ventricular fibrillation (HR = 1.27; 95% CI 0.65-2.49, P = 0.47). CONCLUSIONS: Our findings suggest that in patients with ACS, both early and late VTAs are associated with an increased risk of in-hospital mortality. However, only late VTA, mostly sustained VT, is associated with long-term adverse outcome.

The impact of inflammatory rheumatic diseases on the presentation, severity, and outcome of acute coronary syndrome.

Patients with inflammatory rheumatic diseases (IRD) have a high burden of cardiovascular disease (CVD), leading to increased mortality and morbidity. However, it is not clear whether increased CVD mortality in IRD is due to a higher incidence or worse outcome of cardiovascular events (higher case fatality). In this observational case-control study, we assessed the outcome of acute coronary syndrome (ACS) in patients with IRDs compared to matched controls without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS), a large, national, real-life registry detailing the extent, severity, and outcome of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified with IRD, including 11 patients with rheumatoid arthritis, five patients with systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis (AS), and one patient with psoriatic arthritis (PsA). The study patients were compared to 120 matched control patients (adjusted for age and risk factors for CVD) without IRD. Compared to controls, IRD patients had similar clinical presentation and similar type of ACS and received identical initial treatment at the ER. The two groups had comparable rates of complications including major adverse cardiovascular events (death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis) (10 vs. 11.7% in the study and control group, respectively, p > 0.05), re-hospitalization (20 vs. 21.1%, respectively, p > 0.05), and severe congestive heart failure (7.7 vs. 6.9%, respectively, p > 0.05) within 30 days. The outcome and prognosis of ACS in patients with IRD is not worse than that of control, supporting the higher prevalence of CVD in this population as the cause for their excess mortality.

Characteristics and management of patients with acute coronary syndrome and normal or non-significant coronary artery disease: results from Acute Coronary Syndrome Israeli Survey (ACSIS) 2004-2010.

BACKGROUND: An important subset of patients presenting with acute coronary syndrome (ACS) are found to have either normal coronaries (NCs) or non-obstructive coronary artery disease (NOCAD; lumen diameter narrowing <50%). OBJECTIVES: To explore the characteristics and management strategies in this population in a real-world setting. METHODS: The Acute Coronary Syndrome Israeli Survey (ACSIS) database was utilized to compare the characteristics and therapeutic approach for patients who underwent angiography for ACS and had either NC (n = 84; 2%), NOCAD (n = 79; 2%), or obstructive coronary artery disease (OCAD; n = 3523; 96%). RESULTS: Baseline characteristics were comparable, save for a younger age and a higher proportion of females in the NC group (P<.001 for both). Prior to admission, chronic anticoagulant therapy was more frequently used in the NC vs. the OCAD group (4.8% vs. 1.6%, respectively; P=.02). Recommended ACS evidence-based medications, both in-hospital and at discharge, were less frequently prescribed to patients with NC or NOCAD. CONCLUSIONS: In a real-world practice of ACS, underutilization of evidence-based medications in patients with NC or NOCAD was observed. Nonetheless, its prognostic significance is still unknown and must be explored in larger patient cohorts.

Temporal trends in all-cause mortality of smokers versus non-smokers hospitalized with ST-segment elevation myocardial infarction.

BACKGROUND/OBJECTIVES: Over the past decade, the development of novel management strategies has resulted in improved outcomes among patients hospitalized with ST-segment myocardial infarction (STEMI). The aim of the present study was to compare temporal trends in the mortality of smokers versus non-smokers admitted with STEMI in a real world setting between 2000 and 2010. METHODS: We evaluated time-dependent changes in the clinical characteristics, management strategies, and one year all-cause mortality of STEMI patients who were enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) between 2000 and 2010, categorized as smokers (n=2399) and non-smokers (n=3069). We divided the survey periods into early (2000-2004) and late (2006-2010). The primary endpoint of the study was the occurrence of one-year all-cause mortality. RESULTS: A total of 4564 STEMI patients were enrolled in the study. Compared with non-smokers, smokers were significantly younger and displayed a significantly lower rate of all-cause mortality at 30 days and 1-year. Both smokers and non-smokers who were enrolled in the late survey period received more evidence-based therapies (primary PCI and guideline-based medications) (p<0.001 for all). There was a significant reduction in the risk of 1-year all-cause mortality only among non-smokers (HR=0.664 CI 95% 0.52-0.85, p=0.0009), whereas smokers who were enrolled in more recent survey periods did not display a significant risk reduction (HR=1.08 CI 95% 0.77-1.51, p=0.67). CONCLUSION: Survival following STEMI among smokers has not improved over the past decade despite corresponding changes in management strategies. Future trials should focus on reducing the risk in smokers.

The weight of MMRV-related febrile convulsions among other clinical factors contributing to febrile convulsions in children.

BACKGROUND: It was previously demonstrated that MMRV vaccine causes a higher rate of febrile convulsions (FC) compared to the MMR vaccine. Additional risk factors for FC include age, familial tendency, day care attendance, viral diseases, complications at birth and developmental delay. OBJECTIVE: We evaluated the relative and attributable risk of FC for vaccinees' age, ethnicity, low birth weight, preterm birth and MMRV vaccination in 10-24 months old children. METHODS: Data on medical history and vaccination were extracted from data warehouses of Clalit Health Services and Israel's Ministry of Health and linked on an individual record level for 90,294 MMR- and 8344 MMRV-vaccinees. A retrospective study design was used to reveal the risk factors associated with FC in study participants. RESULTS: During the second week after immunization, an elevated relative risk of FC was demonstrated in MMRV-recipients (adjusted RR=2.16 (95%CI: 1.01; 4.64)). However, the cumulative incidence of FC during the entire 40-day observation period did not differ between the MMR and MMRV vaccinees. The MMRV-specific attributable risk of FC was not statistically significant at any point of observation period and was exceedingly low compared to other risk factors, equaling 5.3 FC cases per 10,000 vaccinees (95%CI: -1.4; 12.2). DISCUSSION: Our findings demonstrate that MMRV-associated FC in 10-24 months old contributes very marginally to the overall rate of FC in this population. CONCLUSION: Given the low number of MMRV-specific FC cases, their transient nature and the benefit of vaccination, the overall benefit-risk of the vaccine can be considered favourable. Nonetheless, the option of separate immunization with MMR+V should be offered to parents, in order to maintain sufficient vaccine uptake in the population.

Sex differences in implantable cardioverter-defibrillator implantation indications and outcomes: lessons from the Nationwide Israeli-ICD Registry.

AIMS: Implantable cardioverter-defibrillators (ICDs) improve survival in certain high arrhythmic risk populations. However, there are sex differences regarding both the utilization and the benefit of these devices. Using a prospective national ICD registry, we aim to compare the indications for ICD implantation as well as outcomes in implanted women vs. men. METHODS AND RESULTS: All subjects implanted with an ICD or cardiac resynchronization therapy with a defibrillator (CRTD) in Israel between July 2010 and February 2013 were included. A total of 3544 subjects constructed the baseline cohort, of whom 615 (17%) were women. Women had the same age (64 years) and rate of secondary prevention indication (26%) as men. However, women were more likely than men to have significant heart failure symptoms (52 vs. 45%), QRS > 120 ms (41 vs. 36%), and a higher rate of non-ischaemic cardiomyopathy (54 vs. 21%, all P values <0.05). Using multivariate analysis, women were more likely to undergo CRTD implantation (odds ratio = 1.8, P < 0.01). Follow-up data were available for 1518 subjects with a mean follow-up of 12 months. During follow-up, there were no significant differences among genders in the rate of any single or the combined outcomes of appropriate device therapies, heart failure admissions, or death. First-year re-intervention rate was double among women (5.6 vs. 3.0%, P < 0.01). CONCLUSION: In real-world setting, women implanted with an ICD differ significantly from men in their baseline characteristics and in the use of CRTD devices. These, however, did not translate into outcome differences.

Aspiration thrombectomy in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the Acute Coronary Syndrome Israeli Survey 2010).

We assessed the impact of aspiration thrombectomy (AT) in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI) on major adverse cardiac events at 30 days and 1-year mortality in 517 consecutive patients who were included in the prospective, nationwide, multicenter, observational Acute Coronary Syndrome Israeli Survey in 2010. Two hundred seventeen patients (42%) underwent AT (AT-PPCI) and 300 patients conventional (C) PPCI. Both groups had similar infarct-related artery distribution and ostial or proximal culprit lesion. Patients in AT-PPCI versus C-PPCI had lower systolic blood pressure and worse Killip class on admission, more frequent Thrombolysis In Myocardial Infarction flow 0 or 1 before PPCI (80% vs 56%), less frequent restoration of flow after indwelling a guidewire in the infarct-related artery (32% vs 52%), and more use of IIb/IIIa glycoprotein inhibitors (69% vs 49%), respectively (p ≤0.05 for all comparisons). Thirty-day major adverse cardiac events was similar in the AT-PPCI and C-PPCI groups, 10.6% versus 9.7%, p = 0.73; adjusted odds ratio 0.97, 95% confidence interval 0.45 to 2.10, p = 0.95. One-year mortality was lower in the AT-PPCI versus C-PPCI group, 3.7% versus 6.7%, p = 0.13; adjusted hazard ratio 0.31, 95% confidence interval 0.10 to 0.96, p = 0.042. In conclusion, this study of consecutive patients with ST elevation myocardial infarction undergoing PPCI demonstrates that AT was an independent predictor of reduced 1-year mortality.

Clinical characteristics and outcomes of elderly patients treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy in a real-world setting: data from the Israeli ICD Registry.

BACKGROUND: Elderly patients are underrepresented in clinical trials of device therapy. OBJECTIVE: To provide real-world data regarding outcomes associated with device-based therapy in a large cohort of elderly patients enrolled in the Israeli ICD Registry. METHODS: Between July 2010 and June 2012, a total of 2807 consecutive patients undergoing implanted cardioverter-defibrillator/cardiac resynchronization therapy-defibrillator (ICD/CRT-D) implantation were prospectively enrolled in the Israeli ICD Registry. For the present analysis, patients were categorized into 3 age groups: ≤60 years (n = 1378 [49%]), 61-75 years (n = 863 [31%]), and >75 years (n = 566 [20%]). RESULTS: Elderly patients (>75 years of age) had more comorbid conditions and were more likely to undergo CRT-D implantation (all P < .01). However, the rate of device-related complications associated with surgical reinterventions at 1 year was <3% regardless of age (P = .70 for the comparison among the 3 age groups). Multivariate analysis showed that the risk of heart failure or death and of appropriate ICD therapy for ventricular arrhythmias was significantly increased with increasing age among patients who received an ICD. In contrast, the age-related increase in the risk of all end points was attenuated among patients who received CRT-D devices (all P values for age-by-device-type interactions are <.05). CONCLUSIONS: In a real-world scenario, elderly patients (>75 years of age) comprise approximately 20% of the ICD/CRT-D recipients and experience a device reintervention rate similar to that of their younger counterparts. Our data suggest that the association between advanced age and adverse clinical outcomes is attenuated in elderly patients implanted with CRT-D devices.

Use of administrative medical databases in population-based research.

Administrative medical databases are massive repositories of data collected in healthcare for various purposes. Such databases are maintained in hospitals, health maintenance organisations and health insurance organisations. Administrative databases may contain medical claims for reimbursement, records of health services, medical procedures, prescriptions, and diagnoses information. It is clear that such systems may provide a valuable variety of clinical and demographic information as well as an on-going process of data collection. In general, information gathering in these databases does not initially presume and is not planned for research purposes. Nonetheless, administrative databases may be used as a robust research tool. In this article, we address the subject of public health research that employs administrative data. We discuss the biases and the limitations of such research, as well as other important epidemiological and biostatistical key points specific to administrative database studies.

Predictors of high-risk angiographic findings in patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Current risk assessment of patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) may fail to identify some patients with severe coronary artery disease (CAD). We aimed to identify predictors of the angiographic extent and severity of CAD in patients with NSTE-ACS undergoing early angiography and to evaluate its impact on prognosis. METHODS: We evaluated 923 patients with NSTE-ACS who underwent coronary angiography. High-risk coronary anatomy (HRCA) was defined as left main disease > 50%, proximal LAD lesion > 70%, or 2- to 3-vessel disease involving the LAD. Clinical characteristics, in-hospital, and 30-day outcome and 1-year mortality were compared between the high-risk (N = 370) and the low-risk groups (N = 553). RESULTS: Proportion of patients with elevated cardiac biomarkers was similar in both groups. The presence of peripheral vascular disease (OR = 1.88, 95% confidence interval [CI] = 1.62-5.80, P < 0.001) and a GRACE score of >140 (OR = 1.88, 95% CI = 1.29-2.75, P < 0.001) were the strongest predictors of HRCA. Patients with HRCA were prone to more complications during hospitalization and at 30 days (11.9% vs. 6%, P < 0.01) and increased 1-year mortality (6.7% vs. 0.9%, P < 0.001). HRCA was the strongest predictor for 30-day MACCE (OR = 2.32, 95% CI = 1.42-3.79, P < 0.001). HRCA (OR = 8.36, 95% CI = 1.01-69.4, P = 0.049; OR = 3.64, 95% CI = 1.2-11.07, P = 0.02) and GRACE score of >140 (OR = 6.86, 95% CI = 1.68-27.9, P = 0.007; OR = 4.84, 95% CI = 1.74-13.5, P = 0.002) were significant predictors of 30-day and 1-year mortality, respectively. CONCLUSIONS: HRCA is predicted by clinical parameters and was not associated with elevated cardiac biomarkers. These patients fared worse when compared with those with low-risk anatomy. We suggest that HRCA predictors should be included in the risk stratification of patients with NSTE-ACS.

Birth order and private voluntary immunization--a study of 110,902 children.

BACKGROUND: Introduction of new private, voluntary immunizations often results in low vaccine uptake among certain sub-groups within the population. Revealing factors associated with underimmunization is crucial in vaccine endorsement and distribution. OBJECTIVE: Our goal was to investigate the effect of child's birth order on private voluntary varicella vaccination. METHODS: A nested case-control study was conducted on a cohort of 110,902 Israeli children under the age of 5 years. We compared social and demographic factors of immunized and unimmunized participants. Logistic regression models were built to examine the association between birth order and vaccination, controlling for child's age, gender, country of birth, ethnicity, parents' country of birth, area of residence, and socioeconomic status (SES). RESULTS: Ethnicity had the highest association with varicella immunization status. The odds of vaccination in the general Jewish and Ultra-Orthodox Jewish populations were 25.55- (95%CI:20.13;32.42) and 15.04- (95%CI:10.18;22.22) times the odds in Arab population, respectively. Child's birth order was inversely related to vaccination status and presented a nonlinear exposure-response relationship. This relationship was maintained in different ethnicity and SES groups. Child's birth order was associated with vaccination differently in large (> 3 siblings) and small to average-sized sibships (≤ 3 siblings). Other parameters associated with vaccination were child's and parents' country of origin, area of residence and SES. CONCLUSIONS: Birth order is an independent risk factor for underimmunization, associated with child's vaccination status beyond economic, social, and demographic parental characteristics.