Anti-diabetic drug use and reduced risk of Parkinson's disease: A community-based cohort study.

BACKGROUND: Emerging evidence suggests a potential association between certain anti-diabetic drugs and a reduced risk of Parkinson's disease (PD). Limited population-based studies have investigated users of newer anti-diabetic drugs such as GLP-1 agonists or SGLT2 inhibitors. OBJECTIVE: The aim of this study was to assess the risk of PD among individuals with type 2 diabetes mellitus (T2DM) who were treated with various types of anti-diabetic drugs over time. METHODS: A population-based cohort comprising T2DM patients aged over 30 who used metformin, GLP-1 agonists, thiazolidinediones, sulfonylureas, DPP4 inhibitors, SGLT2 inhibitors, or meglitinides between January 1, 1999 and December 31, 2018. Data were obtained between the diabetes registration and drug purchase databases of Maccabi Healthcare Services. Time-dependent Cox regression models, adjusted for sex, age, and comorbidities were employed to calculate the adjusted hazard ratios (HRs) for the PD risk associated with different anti-diabetic drugs over time. RESULTS: The study population comprised 86,229 T2DM patients, with 53.9 % males. The mean age at the first anti-diabetic drug purchase was 59.0 ± 11.0 and 62.0 ± 11.0 years for men and women respectively. Compared to metformin, several drug types were associated with a significantly lower PD risk: thiazolidinediones (HR = 0.91, 95 % CI:0.074-1.14); DPP4 inhibitors (HR = 0.60, 95 % CI:0.53-0.67); meglitinides (HR = 0.63, 95 % CI:0.53-0.74); GLP-1 agonists (HR = 0.54, 95 % CI:0.39-0.73); and SGLT2 inhibitors (HR = 0.15, 95 % CI:0.10-0.21). CONCLUSIONS: Our results suggest a reduced risk of PD with certain anti-diabetic drugs, particularly SGLT2 inhibitors and GLP-1 agonists. Validation through extensive big-data studies is essential to confirm these results and to optimize PD prevention and management.

Incidence of cardiovascular morbidity among Parkinson's disease patients; a large-scale cohort study in a 16-year time window around disease onset.

OBJECTIVES: To examine the risk of any or specific types of cardiovascular diseases (CVDs) in patients with Parkinson's disease (PD), in the 16 years around disease onset, and to compare it to that in the general population. METHODS: This is a large-scale population-based retrospective cohort study of newly diagnosed PD patients, members of Maccabi Health Services (MHS), who started taking anti-parkinsonian drugs (APD) between 1/1/2000-31/12/2019 (study period). We collected information about CVD incidence (Congestive heart failure-CHF, Myocardial infarction-MI, Stroke) from MHS-CVD registry. We applied Cox regression to estimate adjusted-HR and 95%CI of CVD risks. We calculated Standardized-Incidence-Ratio (SIR) comparing CVD risks in the PD cohort to that of MHS population. RESULTS: The PD cohort comprised 10,840 patients. During a mean follow up of 16.3 ± 4.3y around disease onset, 20.7% (n = 2241) were diagnosed with any CVD: 7.9% with CHF; 6.7% with MI, and 10.5% with stroke. Risks were higher for men: HR = 1.95 (95%CI 1.58-2.40), and for above age 75y at first APD treatment, HR = 2.00 (95% CI 1.65-2.43). Compared to the MHS population, the PD cohort exhibited a significantly lower risk for CVDs, especially for men: SIRmen = 0.21 (95%CI 0.20-0.22), SIRwomen = 0.29 (95% CI 0.27-0.31). These trends were similar for the specific CVDs. CONCLUSIONS: The findings suggest that the risks that PD patients and particularly men, will develop any type of CVD are lower than those of the general population. Further studies are needed to confirm this finding and examine the underlying mechanisms.

The Association Between High Ambient Temperature and Mortality in the Mediterranean Basin: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: The Mediterranean basin is highly vulnerable to climate change. This study is aimed at quantifying the risk of mortality associated with exposure to high ambient temperature in the Mediterranean basin in the general population and in vulnerable sub-populations. RECENT FINDINGS: We retrieved effect estimates from studies linking temperature and mortality in the Mediterranean basin, between 2000 and 2021. In a meta-analysis of 16 studies, we found an increased risk of all-cause mortality due to ambient heat/high temperature exposure in the Mediterranean basin, with a pooled RR of 1.035 (95%CI 1.028-1.041) per 1 °C increase in temperature above local thresholds (I2 = 79%). Risk was highest for respiratory mortality (RR = 1.063, 95% CI 1.052-1.074) and cardiovascular mortality (RR = 1.046, 95% CI 1.036-1.057). Hot ambient temperatures increase the mortality risk across the Mediterranean basin. Further studies, especially in North African, Asian Mediterranean, and eastern European countries, are needed to bolster regional preparedness against future heat-related health burdens.

Excess mortality in Israel associated with COVID-19 in 2020-2021 by age group and with estimates based on daily mortality patterns in 2000-2019.

BACKGROUND: We aimed to build a basic daily mortality curve in Israel based on 20-year data accounting for long-term and annual trends, influenza-like illness (ILI) and climate factors among others, and to use the basic curve to estimate excess mortality during 65 weeks of the COVID-19 pandemic in 2020-2021 stratified by age groups. METHODS: Using daily mortality counts for the period 1 January 2000 to 31 December 2019, weekly ILI counts, daily climate and yearly population sizes, we fitted a quasi-Poisson model that included other temporal covariates (a smooth yearly trend, season, day of week) to define a basic mortality curve. Excess mortality was calculated as the difference between the observed and expected deaths on a weekly and periodic level. Analyses were stratified by age group. RESULTS: Between 23 March 2020 and 28 March 2021, a total of 51 361 deaths were reported in Israel, which was 12% higher than the expected number for the same period (expected 45 756 deaths; 95% prediction interval, 45 325-46 188; excess deaths, 5605). In the same period, the number of COVID-19 deaths was 6135 (12% of all observed deaths), 9.5% larger than the estimated excess mortality. Stratification by age group yielded a heterogeneous age-dependent pattern. Whereas in ages 90+ years (11% excess), 100% of excess mortality was attributed to COVID-19, in ages 70-79 years there was a greater excess (21%) with only 82% attributed to COVID-19. In ages 60-69 and 20-59 years, excess mortality was 14% and 10%, respectively, and the number of COVID-19 deaths was higher than the excess mortality. In ages 0-19 years, we found 19% fewer deaths than expected. CONCLUSION: The findings of an age-dependent pattern of excess mortality may be related to indirect pathways in mortality risk, specifically in ages <80 years, and to the implementation of the lockdown policies, specifically in ages 0-19 years with lower deaths than expected.

Real World Pharmacological First Treatment Patterns of Patients With Parkinson Disease and Disease Duration: A Large-Scale Cohort Study Using an Health Maintenance Organization Database.

OBJECTIVES: Real-world data were used to describe first antiparkinsonian drug (FAPD) prescription patterns among Parkinson disease (PD) patients and to evaluate disease duration until levodopa (l-DOPA) treatment and until death, as related to FAPD, by age group. METHODS: The community-based cohort (2000-2012) included 6243 patients, members of an Israeli Health Maintenance Organizations. Time from FAPD purchase to 2 end points (l-DOPA purchase and death) was calculated. Cox regressions were used to estimate adjusted heart rate (HR) to either end point as related to FAPD type, by age group. RESULTS: During a mean follow-up of 4.8 ± 3.2 years, one third of the cohort died. The percent of l-DOPA use as a start drug increased with age, whereas the percent of dopamine agonists (DAs) and monoamine oxidase inhibitor B inhibitor (MAO-BI) decreased with age. Younger women were treated more often with DA as a start drug compared with younger men. In ages of younger than 50 years, time to l-DOPA start in the initial DA-group was 4 times longer than in the initial MAO-BI group (HR, 0.23; 95% confidence interval, 0.08-0.43; 1/0.23, 4.35). All age groups exhibited a similar survival time trend associated with initial drug type. An age-pooled HR with initial l-DOPA-group as a reference group yielded that survival time was 2.4 times longer for the initial DA group (HR, 0.41; 95% confidence interval, 0.31-0.55; 1/0.41, 2.44), 1.9 times and 1.4 times for initial MAO-BI or amantadine, respectively. CONCLUSIONS: First antiparkinsonian drug choice might be associated with time until l-DOPA initiation but may represent disease severity at the time of prescription, thus also affecting survival time as well. Real-world data illustrated that this choice is also age and sex dependent.

Interrelationships between Survival, Sex, and Blood Pressure in Patients with Multiple System Atrophy.

OBJECTIVE: The aim of this study is to estimate survival among patients with multiple system atrophy-parkinsonian type (MSA-P) or cerebellar type MSA (MSA-C) in relation to blood pressure (BP) measurements, by sex. METHODS: A cohort of 99 MSA patients was studied retrospectively. Their BP measurements were obtained during prolonged (40 min, vertical position) drug-free tilt testing. We used K-M survival curves and Cox regression to calculate adjusted (to age of onset) hazard ratios (HRs) of BP measurements on time to death by MSA subtype and sex. RESULTS: Fifty-two MSA patients were males and 47 were females. Sixty-three of them had MSA-P and 36 had MSA-C. The mean age at motor symptom onset was 61.1 ± 10.4 years, and mean disease duration at the time of BP assessment was 8.0 ± 4.7 years. The 2 study groups (MSA-P and MSA-C) did not differ significantly in age at MSA onset, sex ratio, or disease duration. Survival time did not differ between the groups {medians: 12 years (95% confidence interval [CI]: 8-28) and 10 years (95% CI: 8-13), respectively}. The MSA-P group showed a trend towards better survival for males (log-rank p = 0.0925). The maximal diastolic orthostatic BP decline during tilt testing had a borderline positive association with death risk among MSA-C males (adjusted HR = 1.18, p = 0.0665), and systolic BP after 10 min in a supine position had a significant positive association with death risk among MSA-P males (adjusted HR = 1.06, p = 0.0354). CONCLUSIONS: The findings of a sex-based difference in the effect of BP on death risk may be important for adjusting the therapeutic approach to MSA patients.

Validation of the Hebrew Version of the Unified Dyskinesia Rating Scale.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS. METHODS: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations. RESULTS: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS. CONCLUSION: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings.

The Modifying Effect of Age on Survival in Parkinson's Disease: A Population-Based Cohort Study.

BACKGROUND: To estimate the survival of a population-based cohort of Parkinson's disease (PD) patients stratified by age and sex over a 13-year period. METHODS: The dynamic PD cohort included 6,622 incident PD patients who initiated anti-parkinsonian medications at age >40 years. The reference population (n = 401,498) consisted of members of a large health maintenance organization. We estimated the PD patients' death risk and sex- and age-specific standardized mortality ratio (SMR). RESULTS: During a follow-up of 5.2 ± 3.3 years, 36% of the cohort died. Older age at first PD treatment was associated with a 55% increase in mortality (for 5-year increase, p < 0.01). More PD patients died when compared to the same age and sex reference population in all age groups, with significant results at age groups >60 years at first treatment. The age-pooled SMR was twofold (SMR for the males = 2.05, 95% CI 1.73-2.42; SMR females = 2.13, 95% CI 1.74-2.62). The highest excess death for males was 2.5-fold for those aged 60-69 years, decreasing to twofold for those in the age range 70-79 years and to 1.5-fold for those aged 80+ years. A similar trend was found among females. CONCLUSION: Our large-scale cohort enabled us to find an age-differential standardized death risk among PD patients, with the largest increased risk at ages 60-69 years. Comorbidities and other contributory factors warrant further investigation.

Anemia in men and increased Parkinson's disease risk: A population-based large scale cohort study.

OBJECTIVE: To evaluate the association between anemia and Parkinson's disease risk (PD) in men and women. METHODS: A population-based cohort of 474,129 individuals (aged 40-79 years at date of first Hb test, 47.4% men) with repeated Hb levels was derived from a large Healthcare Maintenance Organization that serves 2 million citizens in Israel (study-period 1.1.1999-31.12.2012). An annual anemia indicator [Hb levels (g/dL) for men <13; for women <12.0] was assessed for each individual and they were followed from first Hb test until the date of PD incidence, death or end of the study. Cox-proportional hazards models, stratified by sex and age, with time-dependent anemia covariate were used to estimate adjusted Hazard Ratio with 95% of confidence intervals (HR, 95%CI) for PD. RESULTS: During a mean follow up of 8.8 ±â€¯3.9 years (7.0 ±â€¯3.6 for men and 7.9 ±â€¯4.1 for women), 2427 incident PD cases were detected. Cumulative PD incidence at ages over 65 years was 3.3%. The mean levels of Hb at baseline was 14.8 ±â€¯1.1 g/dL among men; 12.8 ±â€¯1.1 g/dL among women. Anemia was associated with significant PD risk among men, age-pooled HR = 1.19 (95%CI: 1.04-1.37), with the highest risk between ages 60-64 years [HR = 1.41 (95%CI: 1.03-1.93)]. Anemia was not associated with PD risk among women across all age-groups. The age-pooled HR for women was 1.02 (95%CI 0.95-1.09). CONCLUSIONS: The finding that anemia was associated with PD risk in men, especially in middle age, warrants further investigations on common pathophysiologic processes between Hb abnormalities and brain dysfunction.

Higher serum cholesterol and decreased Parkinson's disease risk: A statin-free cohort study.

BACKGROUND: Higher levels of serum cholesterol are well-established risk factors for coronary artery disease and stroke. The role of serum cholesterol in neurodegeneration is not clear. OBJECTIVE: We evaluated the association between serum cholesterol levels over time and the risk of Parkinson's disease (PD) among statin-free individuals. METHODS: A population-based cohort study of 261,638 statin-free individuals (aged 40-79 years at their first serum cholesterol test, 42.7% men), with repeated measures of total, low, and high-density lipoprotein cholesterol was performed from 1999 to 2012. Individuals were followed from their first cholesterol test until PD incidence, death, or end of study. The PD incidence was assessed using a validated antiparkinsonian-drug tracing approach. Cox models stratified by sex and age with time-dependent cholesterol variables were applied to estimate PD hazard ratios. RESULTS: A total of 764 (3.3% patients aged 65 + years) incident PD cases were detected during a mean follow-up of 7.9 (±3.6) years. Among men, the middle and upper tertiles of total and low-density lipoprotein cholesterol compared to the lowest were significantly associated with a lower PD risk. Age-pooled hazard ratios (95% confidence interval) for middle and upper tertiles were 0.82 (0.66-1.01) and 0.71 (0.55-0.93), respectively, for total cholesterol, and 0.80 (0.65-0.98) and 0.72 (0.54-0.95) respectively, for low-density lipoprotein cholesterol. Among women, the association between total and low-density lipoprotein cholesterol levels with PD risk was not significant. Null results were found for both sexes for high-density lipoprotein cholesterol. CONCLUSIONS: Higher levels of total and low-density lipoprotein cholesterol among men over time indicated a decreased PD risk. The potential role of cholesterol in disease protection warrants further investigation. © 2018 International Parkinson and Movement Disorder Society.

Ambient temperature and age-related notified Campylobacter infection in Israel: A 12-year time series study.

BACKGROUND: Campylobacter spp. are the leading cause of foodborne infection worldwide, with a seasonal disease peak that might be affected by temperature increase. We studied the relationship between ambient temperature and weekly notified Campylobacter spp.infections. METHODS: Data on 29,762 laboratory-confirmed cases of Campylobacter infection for the period, January, 1999 to December, 2010 were retrieved from the Ministry of Health registry. To estimate the association between the number of weekly cases of Campylobacter infection and the national average temperature at lags 0-3 weeks, firstly, we used GAM models, and secondly two-segment piecewise linear Poisson regressions. The effect of temperature was adjusted for seasonality, long-term trends and holidays. RESULTS: We found a J-shaped relationship between ambient temperature and notified Campylobacter spp. CASES: For C. jejuni in all ages, the curve below the threshold was constant and the percent increase in cases for 1 °C above a threshold of 27 °C was 15.4% (95%CI: 6.7-24.1%). For ages 3-10 yr and > =26 yr the curve was constant below the threshold and positive above it; the percent increase in cases for 1 °C was 17.7%(95%CI: 6.0-29.4%) and 23.7%(95%CI: 11.6-35.8%), respectively. For ages 0-2 yr the curve was linear with no threshold and the percent increase for 1 °C was 5.1%(95%CI: 2.1-8.1%). For ages 11-25 yr the curve was always constant. Results for C. coli were similar. CONCLUSION: Our findings indicate that higher temperatures throughout the year affect Campylobacter spp. morbidity, especially in younger children. This should be taken into consideration in public education and health system preparedness for temperature increases as a result of climate change.

Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

BACKGROUND: The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. METHODS: The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version. RESULTS: The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors. CONCLUSIONS: The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS.

Two Ethnic Clusters with Huntington Disease in Israel: The Case of Mountain Jews and Karaites.

BACKGROUND: Worldwide prevalence estimates of Huntington disease (HD) vary widely, with no reliable information regarding the Jewish population in Israel. METHODS: This specialized tertiary single-center cross-sectional study assessed clinical, cognitive, and demographic characteristics of 84 HD patients who were treated at the Movement Disorder Unit of the Tel Aviv Medical Center, Israel. RESULTS: Our cohort was composed of one-third Ashkenazi Jews, 27% Mountain Jews (Caucasus Jews), 18% Sephardi Jews, and 21% Karaites, with both Mountain Jews and Karaites over-represented compared to their relevant proportion in the population of the state of Israel, which is less than 1%. No between-group differences were detected regarding the number of CAG (cytosine-adenine-guanine) repeats, age at onset, disease duration, years from symptom onset to diagnosis, gender, years of education, Unified Huntington Disease Rating Scale scores, or the Montreal Cognitive Assessment scores. CONCLUSION: We detected clustering of HD among the population treated at our Medical Center, which has the only specialized HD clinic in the country, with a high percentage of HD among 2 relatively small subpopulations of Jews: Mountain Jews and Karaites.

Statin adherence and the risk of Parkinson's disease: A population-based cohort study.

BACKGROUND: While experimental data provided some compelling evidence on the benefits of statins on dopaminergic neurons, observational studies reported conflicting results regarding the potential of statins to effect the risk of Parkinson's disease (PD). OBJECTIVES: To evaluate the association between changes in statin adherence over time and PD risk. METHODS: A population-based cohort of new statin users (ages 40-79, years 1999-2012) was derived from a large Israeli healthcare services organization. Data included history of statin purchases and low density lipoprotein cholesterol (LDL-C) levels. Personal statin adherence was measured annually by the proportion of days covered (PDC). PD was detected employing a drug-tracer approach. Stratified (by sex, LDL-C levels at baseline and age) Cox proportional hazards models with time-dependent covariates were used to compute adjusted Hazard Ratio (HR) with 95%CI. RESULTS: The cohort included 232,877 individuals, 49.3% men. Mean age at first statin purchase was 56.5 (±9.8) years for men and 58.7 (±9.2) years for women. PDC distribution for the whole follow up period differed between men and women: medians 58.3% and 54.1% respectively. During a mean follow up of 7.6 (±3.4) years, 2,550 (1.1%) PD cases were identified. In a 1-year lagged analysis, we found no association between annual statin adherence and PD risk in all age-groups regardless of statin type and potency. Age-pooled HR (95%CI) for men and women with LDL-C levels at baseline ≤160mg/dL were: 0.99 (0.99-1.01), 1.01 (1.00-1.02); and for men and women with LDL-C >160mg/dL levels: 0.99 (0.98-1.01), 0.97 (0.98-1.01). CONCLUSIONS: Our findings suggest that statin adherence over time does not affect PD risk. Future studies should use large-scale cohorts and refining assessments of long-term profiles in statin adherence.

Comparison of Selegiline and Rasagiline Therapies in Parkinson Disease: A Real-life Study.

BACKGROUND: We aimed to compare indicators of Parkinson disease (PD) progression between patients first prescribed either selegiline or rasagiline as their antiparkinsonian drugs (APDs) on the basis of real-life data. METHODS: Pharmacy data on members of a large Israeli health maintenance organization, treated as patients with PD during 2001-2012 and prescribed selegiline or rasagiline as their first APD, were analyzed. The first APD was selegiline for 349 patients (2001-2006) and rasagiline for 485 patients (2007-2012). Time from monoamine oxidase type B inhibitor prescription until initiating treatment with dopamine agonists (DAs) or levodopa was compared between the groups using Cox regression adjusted to sex and age at initiation of APD. RESULTS: The selegiline group was significantly older at first monoamine oxidase type B inhibitor purchase. In a similar follow-up time (3.0 [1.7] year for selegiline group, 3.1 y [1.4] for rasagiline group), the time to initiation of levodopa treatment did not differ between the 2 groups (adjusted hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.86-1.31). The time to initiation of DA treatment was longer in the selegiline group (adjusted HR, 1.93; 95% CI, 1.49-2.53). For those who were treated with DA before levodopa (n = 276), the time to initiation of levodopa treatment was longer in the rasagiline group (adjusted HR, 0.77; 95% CI, 0.56-1.07). CONCLUSIONS: The similarity in time to levodopa in both groups suggests no differences between selegiline and rasagiline in their effect on the natural history of PD. A possible interaction effect between rasagiline and DA might exist. A better symptomatic profile of selegiline more than that of rasagiline in the earlier stages of PD may explain the difference between the 2 groups in time to DA initiation.

Cancer incidence among Parkinson's disease patients in a 10-yrs time-window around disease onset: A large-scale cohort study.

OBJECTIVE: To compare the incidences of any cancer and specific types among patients with Parkinson's disease (PD) in a 10-yrs time window around diagnosis, to that of the general population. METHODS: We conducted a population-based, retrospective large-scale cohort study on 7125 newly diagnosed PD patients who had just initiated anti-parkinsonian medications between 1.1.2000 and 12.31.2012; all members of Maccabi Health Services (MHS), a large Israeli HMO. Cancer incidence during the same period was collected from MHS cancer-registry. Standardized-Incidence-Ratio (SIR) accounting for age, chronological-year and sex were calculated to compare cancer risks of PD patients to that of MHS population. RESULTS: The PD cohort (54% males) had a mean age at initiation of anti-parkinsonian medications of 71.2 ± 10.3years. In a time-window of 6.6 ± 3.4years before and 4.0 ± 3.9years after PD was first treated, 21% of the men and 15% of the women were diagnosed with incident-cancer. We found no-difference in any cancer risk for the PD cohort compared to the reference population: SIR = 0.99 (95%CI: 0.92-1.06) for males and 0.98 (95%CI: 0.89-1.07) for females. Risks for lung and colon cancers in the PD cohort were significantly lower for both sexes compared to the reference population. Risks for breast, central nervous system, kidney, leukemia, lymphoma, melanoma, ovarian, pancreatic, prostatic, rectal and thyroid were similar for the two populations. The SIRs did not differ between the sexes. CONCLUSIONS: We found no difference in the risk of any-type of cancer among PD patients compared to the general population, focusing on 10yrs time-window around the initiation of anti-parkinsonian medications.

Complex clinical and microbiological effects on Legionnaires' disease outcone; A retrospective cohort study.

BACKGROUND: Legionnaires' disease (LD) is associated with high mortality rates and poses a diagnostic and therapeutic challenge. Use of the rapid urinary antigen test (UAT) has been linked to improved outcome. We examined the association between the method of diagnosis (UAT or culture) and various clinical and microbiological characteristics and outcome of LD. METHODS: Consecutive patients with pneumonia and confirmation of Legionella infection by a positive UAT and/or a positive culture admitted between the years 2006-2012 to a university hospital were retrospectively studied. Isolated L. pneumophila strains were subject to serogrouping, immunological subtyping and sequence-based typing. Variables associated with 30-day all-cause mortality were analyzed using logistic regression as well as cox regression. RESULTS: Seventy-two patients were eligible for mortality analyses (LD study group), of whom 15.5 % have died. Diagnosis based on positive L. pneumophila UAT as compared to positive culture (OR = 0.18, 95 % CI 0.03-0.98, p = 0.05) and administration of appropriate antibiotic therapy within 2 hospitalization days as compared to delayed therapy (OR = 0.16, 95 % CI 0.03-0.90, p = 0.04) were independently associated with reduced mortality. When controlling for intensive care unit (ICU) admissions, the method of diagnosis became non-significant. Survival analyses showed a significantly increased death risk for patients admitted to ICU compared to others (HR 12.90, 95 % CI 2.78-59.86, p = 0.001) and reduced risk for patients receiving appropriate antibiotic therapy within the first two admissions days compared to delayed therapy (HR 0.13, 95 % CI 0.04-0.05, p = 0.001). Legionella cultures were positive in 35 patients (including 29 patients from the LD study group), of whom 65.7 % were intubated and 37.1 % have died. Sequence type (ST) ST1 accounted for 50.0 % of the typed cases and ST1, OLDA/Oxford was the leading phenon (53.8 %). Mortality rate among patients in the LD study group infected with ST1 was 18.2 % compared to 42.9 % for non-ST1 genotypes (OR = 0.30, 95 % CI 0.05-1.91, p = 0.23). CONCLUSIONS: The study confirms the importance of early administration of appropriate antibiotic therapy and at the same time highlights the complex associations of different diagnostic approaches with LD outcome. Infection with ST1 was not associated with increased mortality. Genotype effects on outcome mandate examination in larger cohorts.

Parkinson's Disease Prevalence and Proximity to Agricultural Cultivated Fields.

The risk for developing Parkinson's disease (PD) is a combination of multiple environmental and genetic factors. The Negev (Southern Israel) contains approximately 252.5 km(2) of agricultural cultivated fields (ACF). We aimed to estimate the prevalence and incidence of PD and to examine possible geographical clustering and associations with agricultural exposures. We screened all "Clalit" Health Services members in the Negev (70% of the population) between the years 2000 and 2012. Individual demographic, clinical, and medication prescription data were available. We used a refined medication tracer algorithm to identify PD patients. We used mixed Poisson models to calculate the smoothed standardized incidence rates (SIRs) for each locality. We identified ACF and calculate the size and distance of the fields from each locality. We identified 3,792 cases of PD. SIRs were higher than expected in Jewish rural localities (median SIR [95% CI]: 1.41 [1.28; 1.53] in 2001-2004, 1.62 [1.48; 1.76] in 2005-2008, and 1.57 [1.44; 1.80] in 2009-2012). Highest SIR was observed in localities located in proximity to large ACF (SIR 1.54, 95% CI 1.32; 1.79). In conclusion, in this population based study we found that PD SIRs were higher than expected in rural localities. Furthermore, it appears that proximity to ACF and the field size contribute to PD risk.

The Relationship Between Foot and Pelvic Alignment While Standing.

A normal motion and segmental interrelationship has been determined as a significant factor in normal function. Yet, the relationship between distal segments and pelvic alignment needs further investigation. The aim of this study was to investigate the interrelationship between distal and proximal lower extremity segments while standing and during induced feet hyperpronation. Changes in alignment of the pelvis and lower extremities were measured at a gait laboratory using the VICON 612 computerized motion analysis system. Thirty-five healthy volunteer subjects were recruited. Four randomized repeated-measure standing modes were used: standing directly on the floor and then on three wedges angled at 10°, 15° and 20° to induce bilateral hyperpronation for 20 seconds. A significant (p<0.05) bi-variate relationship was found between the anterior pelvic tilt and thigh internal rotation, in all four standing positions (.41≤r≤.46, in all p<0.014). A combined effect of rotational alignment between segments and the cumulative effect of foot hyperpronation on pelvic tilt revealed that only the shank significantly affected pelvic alignment, acting as a mediator between a foot and a thigh with the thigh having a crude significant effect on the pelvis. When internal rotation of the shank occurs, calcaneal eversion couples with thigh internal rotation and anterior pelvic tilt. It can be concluded that in response to induced hyperpronation, the shank is a pivotal segment in postural adjustment.

Head-up tilt testing for detecting orthostatic hypotension: how long do we need to wait?

BACKGROUND: Orthostatic hypotension (OH) is a common underdiagnosed condition characterized by a fall in systolic or diastolic blood pressure (BP). There is some uncertainty about the minimum duration needed to detect OH beyond 3 min (delayed OH). We aimed to define a minimum time range for measurement of delayed OH in subjects referred to as tilt testing. METHODS: A repeated measurements study Tel-Aviv Medical Center, on 692 subjects who underwent prolonged (40 min, vertical position) drug-free tilt testing. Survival curves were used to study time to an OH event; logistic regression to study factors associated with delayed OH and mixed models to study the pattern of repeated BP measures. RESULTS: In our sample, 17% had OH within 3 min, 35% within 30 min, and 40% within 40 min. Among the 270 OH patients, 43 and 91% were identified within 3 and 30 min, respectively. Delayed OH was associated with female gender (OR = 1.95, 1.16-3.27) and age <65 years (OR = 2.17, 1.24-3.80). Older patients differed significantly from younger patients in BP pattern changes and had a higher rate of a fall in systolic BP. CONCLUSION: Tilt testing for 30 min identifies most cases of delayed OH in older patients, while those younger than 65 years need 10 min longer.