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.

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.

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.

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.

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.

Green spaces and adverse pregnancy outcomes.

OBJECTIVE: The objective of this study was to evaluate the associations between proximity to green spaces and surrounding greenness and pregnancy outcomes, such as birth weight, low birth weight (LBW), very LBW (VLBW), gestational age, preterm deliveries (PTD) and very PTD (VPTD). METHODS: This study was based on 39,132 singleton live births from a registry birth cohort in Tel Aviv, Israel, during 2000-2006. Surrounding greenness was defined as the average of satellite-based Normalised Difference Vegetation Index (NDVI) in 250 m buffers and proximity to major green spaces was defined as residence within a buffer of 300 m from boundaries of a major green space (5000 m(2)), based on data constructed from OpenStreetMap. Linear regression (for birth weight and gestational age) and logistic regressions models (for LBW, VLBW, PTD and VPTD) were used with adjustment for relevant covariates. RESULTS: An increase in 1 interquartile range greenness was associated with a statistically significant increase in birth weight (19.2 g 95% CI 13.3 to 25.1) and decreased risk of LBW (OR 0.84, 95% CI 0.78 to 0.90). Results for VLBW were in the same direction but were not statistically significant. In general, no associations were found for gestational age, PTD and VPTD. The findings were consistent with different buffer and green space sizes and stronger associations were observed among those of lower socioeconomic status. CONCLUSIONS: This study confirms the results of a few previous studies demonstrating an association between maternal proximity to green spaces and birth weight. Further investigation is needed into the associations with VLBW and VPTD, which has never been studied before.

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.

Increased incidence of Campylobacter spp. infection and high rates among children, Israel.

During 1999-2010, the annual incidence of Campylobacter spp. infection in Israel increased from 31.04 to 90.99 cases/100,000 population, a yearly increase of 10.24%. Children <2 years of age were disproportionally affected; incidence in this age group (356.12 cases/100,000 population) was >26-fold higher than for the 30-<50 age group.

Air pollution and congenital heart defects.

Environmental factors such as ambient air pollution have been associated with congenital heart defects. The aim of this study was to investigate the association between gestational exposure to air pollution and the risk of congenital heart defects. We conducted a registry-based cohort study with a total of 135,527 live- and still-births in the Tel-Aviv region during 2000-2006. We used a Geographic Information System-based spatiotemporal approach with weekly inverse distance weighting modeling to evaluate associations between gestational exposure to ambient air pollution during weeks 3-8 of pregnancy and the risk for congenital heart defects. The following pollutants were studied: carbon monoxide, nitrogen-dioxide, ozone, sulfur-dioxide and particulate matter with aerodynamic diameter smaller than 10 µm and 2.5 µm (PM10, PM2.5 respectively). Logistic models, adjusted for socio-demographic covariates were used to evaluate the associations. We found that maternal exposure to increased concentrations of PM10 was associated with multiple congenital heart defects (adjusted OR 1.05, 95% CI: 1.01 to 1.10 for 10 µg/m(3) increment). An inverse association was observed between concentrations of PM2.5 and isolated patent ductus arteriosus (adjusted OR 0.78, 95% CI: 0.68 to 0.91 for 5 µg/m(3) increment). Sensitivity analyses showed that results were consistent. Generally there were no evidence for an association between gaseous air pollutants and congenital heart defects.Our results for PM10 and congenital heart defects confirm results from previous studies. The results for PM2.5 need further investigations.

A time series study on the effects of heat on mortality and evaluation of heterogeneity into European and Eastern-Southern Mediterranean cities: results of EU CIRCE project.

BACKGROUND: The Mediterranean region is particularly vulnerable to the effect of summer temperature.Within the CIRCE project this time-series study aims to quantify for the first time the effect of summer temperature in Eastern-Southern Mediterranean cities and compared it with European cities around the Mediterranean basin, evaluating city characteristics that explain between-city heterogeneity. METHODS: The city-specific effect of maximum apparent temperature (Tappmax) was assessed by Generalized Estimation Equations, assuming a linear threshold model. Then, city-specific estimates were included in a random effect meta-regression analysis to investigate the effect modification by several city characteristics. RESULTS: Heterogeneity in the temperature-mortality relationship was observed among cities. Thresholds recorded higher values in the warmest cities of Tunis (35.5°C) and Tel-Aviv (32.8°C) while the effect of Tappmax above threshold was greater in the European cities. In Eastern-Southern Mediterranean cities a higher effect was observed among younger age groups (0-14 in Tunis and 15-64 in Tel-Aviv and Istanbul) in contrast with the European cities where the elderly population was more vulnerable. Climate conditions explained most of the observed heterogeneity and among socio-demographic and economic characteristics only health expenditure and unemployment rate were identified as effect modifiers. CONCLUSIONS: The high vulnerability observed in the young populations in Eastern-Southern Mediterranean cities represent a major public health problem. Considering the large political and economic changes occurring in this region as well future temperature increase due to climate change, it is important to strengthen research and public health efforts in these Mediterranean countries.

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.

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.

Periodicity and time trends in the prevalence of total births and conceptions with congenital malformations among Jews and Muslims in Israel, 1999-2006: a time series study of 823,966 births.

BACKGROUND Congenital malformations (CMs) are a leading cause of infant disability. Geophysical patterns such as 2-year, yearly, half-year, 3-month, and lunar cycles regulate much of the temporal biology of all life on Earth and may affect birth and birth outcomes in humans. Therefore, the aim of this study was to evaluate and compare trends and periodicity in total births and CM conceptions in two Israeli populations. METHODS Poisson nonlinear models (polynomial) were applied to study and compare trends and geophysical periodicity cycles of weekly births and weekly prevalence rate of CM (CMPR), in a time-series design of conception date within and between Jews and Muslims. The population included all live births and stillbirths (n = 823,966) and CM (three anatomic systems, eight CM groups [n = 2193]) in Israel during 2000 to 2006. Data were obtained from the Ministry of Health. RESULTS We describe the trend and periodicity cycles for total birth conceptions. Of eight groups of CM, periodicity cycles were statistically significant in four CM groups for either Jews or Muslims. Lunar month and biennial periodicity cycles not previously investigated in the literature were found to be statistically significant. Biennial cycle was significant in total births (Jews and Muslims) and syndactyly (Muslims), whereas lunar month cycle was significant in total births (Muslims) and atresia of small intestine (Jews). CONCLUSION We encourage others to use the method we describe as an important tool to investigate the effects of different geophysical cycles on human health and pregnancy outcomes, especially CM, and to compare between populations.

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.

Computer-based, personalized cognitive training versus classical computer games: a randomized double-blind prospective trial of cognitive stimulation.

BACKGROUND: Many studies have suggested that cognitive training can result in cognitive gains in healthy older adults. We investigated whether personalized computerized cognitive training provides greater benefits than those obtained by playing conventional computer games. METHODS: This was a randomized double-blind interventional study. Self-referred healthy older adults (n = 155, 68 ± 7 years old) were assigned to either a personalized, computerized cognitive training or to a computer games group. Cognitive performance was assessed at baseline and after 3 months by a neuropsychological assessment battery. Differences in cognitive performance scores between and within groups were evaluated using mixed effects models in 2 approaches: adherence only (AO; n = 121) and intention to treat (ITT; n = 155). RESULTS: Both groups improved in cognitive performance. The improvement in the personalized cognitive training group was significant (p < 0.03, AO and ITT approaches) in all 8 cognitive domains. However, in the computer games group it was significant (p < 0.05) in only 4 (AO) or 6 domains (ITT). In the AO analysis, personalized cognitive training was significantly more effective than playing games in improving visuospatial working memory (p = 0.0001), visuospatial learning (p = 0.0012) and focused attention (p = 0.0019). CONCLUSIONS: Personalized, computerized cognitive training appears to be more effective than computer games in improving cognitive performance in healthy older adults. Further studies are needed to evaluate the ecological validity of these findings.

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.

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.