A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Methodology and challenges for harmonization of nutritional data from seven historical studies.

BACKGROUND: Collection of detailed dietary data is labor intensive and expensive, harmonization of existing data sets has been proposed as an effective tool for research questions in which individual studies are underpowered. METHODS: In this paper, we describe the methodology used to retrospectively harmonize nutritional data from multiple sources, based on the individual participant data of all available studies, which collected nutritional data in Israel between 1963 and 2014. This collaboration was established in order to study the association of red and processed meat with colorectal cancer. Two types of nutritional questionnaires, the Food Frequency Questionnaires (FFQ) and the 24-h dietary recall (24HR recall), and different food composition tables, were used by the participating studies. The main exposure of interest included type of meat (total meat, red meat, and poultry) and level of processing. RESULTS: A total of 29,560 Israeli men and women were enrolled. In studies using FFQ,the weighted mean intakes of total, red, processed meat, and poultry were 95, 27, 37 and 58 gr/day and 92, 25, 10, and 66 gr/day in studies using 24HR recall, respectively.. Despite several methodological challenges, we successfully harmonized nutritional data from the different studies. CONCLUSIONS: This paper emphasizes the significance and feasibility of harmonization of previously collected nutritional data, offering an opportunity to examine associations between a range of dietary exposures and the outcome of interest, while minimizing costs and time in epidemiological studies.

The Reliability and Validity of the OneStep Smartphone Application for Gait Analysis among Patients Undergoing Rehabilitation for Unilateral Lower Limb Disability.

An easy-to-use and reliable tool is essential for gait assessment of people with gait pathologies. This study aimed to assess the reliability and validity of the OneStep smartphone application compared to the C-Mill-VR+ treadmill (Motek, Nederlands), among patients undergoing rehabilitation for unilateral lower extremity disability. Spatiotemporal gait parameters were extracted from the treadmill and from two smartphones, one on each leg. Inter-device reliability was evaluated using Pearson correlation, intra-cluster correlation coefficient (ICC), and Cohen's d, comparing the application's readings from the two phones. Validity was assessed by comparing readings from each phone to the treadmill. Twenty-eight patients completed the study; the median age was 45.5 years, and 61% were males. The ICC between the phones showed a high correlation (r = 0.89-1) and good-to-excellent reliability (ICC range, 0.77-1) for all the gait parameters examined. The correlations between the phones and the treadmill were mostly above 0.8. The ICC between each phone and the treadmill demonstrated moderate-to-excellent validity for all the gait parameters (range, 0.58-1). Only 'step length of the impaired leg' showed poor-to-good validity (range, 0.37-0.84). Cohen's d effect size was small (d < 0.5) for all the parameters. The studied application demonstrated good reliability and validity for spatiotemporal gait assessment in patients with unilateral lower limb disability.

Metformin Treatment Among Men With Diabetes and the Risk of Prostate Cancer: A Population-Based Historical Cohort Study.

There is conflicting evidence regarding the association between metformin treatment and prostate cancer risk in diabetic men. We investigated this association in a population-based Israeli cohort of 145,617 men aged 21-89 years with incident diabetes who were followed over the period 2002-2012. We implemented a time-dependent covariate Cox model, using weighted cumulative exposure to relate metformin history to prostate cancer risk, adjusting for use of other glucose-lowering medications, age, ethnicity, and socioeconomic status. To adjust for time-varying glucose control variables, we used inverse probability weighting of a marginal structural model. With 666,553 person-years of follow-up, 1,592 men were diagnosed with prostate cancer. Metformin exposure in the previous year was positively associated with prostate cancer risk (per defined daily dose; without adjustment for glucose control, hazard ratio (HR) = 1.53 (95% confidence interval (CI): 1.19, 1.96); with adjustment, HR = 1.42 (95% CI: 1.04, 1.94)). However, exposure during the previous 2-7 years was negatively associated with risk (without adjustment for glucose control, HR = 0.58 (95% CI: 0.37, 0.93); with adjustment, HR = 0.60 (95% CI: 0.33, 1.09)). These positive and negative associations with previous-year and earlier metformin exposure, respectively, need to be confirmed and better understood.

Is health-related quality of life 1-year after coronary artery bypass graft surgery associated with living in a greener environment?

INTRODUCTION: Greenery in the residential environment and in the hospital has been associated with improved surgical outcomes and recovery. We investigated the association between the level of residential greenness of patients with coronary disease and their heart disease-related Quality of Life (HRQoL) 1-year after a coronary artery bypass grafting (CABG) surgery. METHODS: Participants in a prospective cohort study who underwent CABG surgery at seven cardiothoracic units throughout Israel during the years 2004-2007 filled in the MacNew HRQoL one day before and one year after surgery. Successful recovery was defined as ≥0.5 increase in the MacNew score between baseline and follow-up. Exposure to residential greenness in 90 m and 300 m buffers around the patient's home was assessed with Linear Spectral Unmixing analysis of Landsat 30 m imagery. RESULTS: The cohort comprised of 861 patients (22% female) with a mean age of 65.5 years, and 59.2% classified as low-income. In the total cohort, higher residential greenness was associated with an improvement in emotional HRQoL (OR = 1.33 (95%CI: 0.99-1.79)), adjusting for demographic and socio-economic factors, living in the periphery/center, presence of diabetes, attending cardiac rehabilitation following surgery, BMI, and change in physical fitness and depression over the 1-year follow-up. Although no association was found between greenness and change in the physical or social subscales, a positive association was specifically observed among the low-income patients for the global HRQoL score, OR = 1.42 (95%CI: 0.97-2.10), as compared to the higher-income patients, p for interaction = 0.03. CONCLUSIONS: Residential greenness is associated with improvement in HRQoL 1-year after CABG surgery, but not the physical and social scales, only in low-income patients. Ensuring greenery in the living environment may act as a social intervention that supports human health and disease recovery.

Metformin Treatment and Cancer Risk: Cox Regression Analysis, With Time-Dependent Covariates, of 320,000 Persons With Incident Diabetes Mellitus.

There is conflicting evidence regarding the association between metformin use and cancer risk in diabetic patients. During 2002-2012, we followed a cohort of 315,890 persons aged 21-87 years with incident diabetes who were insured by the largest health maintenance organization in Israel. We used a discrete form of weighted cumulative metformin exposure to evaluate the association of metformin with cancer incidence. This was implemented in a time-dependent covariate Cox model, adjusting for treatment with other glucose-lowering medications, as well as age, sex, ethnic background, socioeconomic status, smoking (for bladder and lung cancer), and parity (for breast cancer). We excluded from the analysis metformin exposure during the year before cancer diagnosis in order to minimize reverse causation of cancer on changes in medication use. Estimated hazard ratios associated with exposure to 1 defined daily dose of metformin over the previous 2-7 years were 0.98 (95% confidence interval (CI): 0.82, 1.18) for all-sites cancer (excluding prostate and pancreas), 1.05 (95% CI: 0.67, 1.63) for colon cancer, 0.98 (95% CI: 0.49, 1.97) for bladder cancer, 1.02 (95% CI: 0.59, 1.78) for lung cancer, and 0.88 (95% CI: 0.56, 1.39) for female breast cancer. Our results do not support an association between metformin treatment and the incidence of major cancers (excluding prostate and pancreas).

Methylphenidate enhances cognitive performance in adults with poor baseline capacities regardless of attention-deficit/hyperactivity disorder diagnosis.

We compare the view that the effect of methylphenidate (MPH) is selective to individuals with attention-deficit/hyperactivity disorder (ADHD) with an alternative approach suggesting that its effect is more prominent for individuals with weak baseline capacities in relevant cognitive tasks. To evaluate theses 2 approaches, we administered sustained attention, working memory, and decision-making tasks to 20 ADHD adults and 19 control subjects, using a within-subject placebo-controlled design. The results demonstrated no main effects of MPH in the decision-making tasks. In the sustained attention and working-memory tasks, MPH enhanced performance of both ADHD and non-ADHD adults to a similar extent compared with placebo. Hence, the effect of MPH was not selective to ADHD adults. In addition, those benefitting most from MPH in all 3 task domains tended to be individuals with poor task performance. However, in most tasks, individuals whose performance was impaired by MPH were not necessarily better (or worse) performers. The findings suggest that the administration of MPH to adults with ADHD should consider not only clinical diagnosis but also their functional (performance-based) profile.

Glucagon-Like Peptide-1 Receptor Agonists and Pancreatic Cancer Risk in Patients With Type 2 Diabetes.

Importance: Concerns have been raised that glucagon-like peptide-1 receptor agonists (GLP-1RA) may increase the risk of pancreatic cancer. Objective: To investigate the association of GLP-1RA treatment with pancreatic cancer incidence over 9 years of follow-up. Design, Setting, and Participants: In this population-based historical cohort study, adult patients (aged 21 to 89 years) with type 2 diabetes insured by Clalit Healthcare Services, the largest state-mandated health organization in Israel, were followed up from 2009, when GLP-1RA became available in Israel, until pancreatic cancer diagnosis, death, reaching age 90 years, or end of follow-up (December 2017). Data were analyzed from June 2022 to November 2023. Exposures: Treatment with GLP-1RA was compared with basal insulin. Main Outcome and Measures: Pancreatic cancer incidence was compared according to weighted cumulative exposures to GLP-1RA and to basal insulin in a Cox model implemented in discrete time, with time origin at 2 years after diabetes diagnosis, adjusting for confounding. In sensitivity analyses, propensity score-matched pair new-user design and prevalent new-user design were used for the comparison. Because of risk for reverse-causation bias, results in the fifth to seventh year after medication were emphasized. Results: During a cumulative follow-up of 3 290 439 person-years of 543 595 adults with a mean (SD) age of 59.9 (12.8) years (277 502 women [51%]) with incident diabetes, 1665 patients received pancreatic cancer diagnoses. In total, 33 377 patients (6.1%) used GLP-1RA and 106 849 (19.7%) used basal insulin. The estimated hazard ratio (HR) for pancreatic cancer associated with incremental use of 1 defined daily dose per day of GLP-1RA compared with basal insulin in the fifth to seventh year previously (all other characteristics, including age, sex, ethnic background, sociodemographic status, baseline body mass index, smoking history, history of pancreatitis, other glucose-lowering medications treatment history, and length of diabetes, being equal) was 0.50 (95% CI, 0.15-1.71). The new-user and prevalent new-user designs showed HRs from the fifth year onwards following initiation of GLP-1RA vs basal insulin of 0.52 (95 % CI, 0.19-1.41) and 0.75 (95 % CI, 0.37-1.53), respectively. Conclusions and Relevance: In this historical cohort study of adults with type 2 diabetes, no support for an increased pancreatic cancer incidence over 7 years following start of GLP-1RA treatment was found. However, monitoring for pancreatic cancer risk beyond 7 years following initiation of therapy is still required. Trial Registration: ClinicalTrials.gov Identifier: NCT02072902.

A historical cohort study on predictors for successful weaning from prolonged mechanical ventilation and up to 3-year survival follow-up in a rehabilitation center.

BACKGROUND: We followed prolonged mechanically ventilated (PMV) patients for weaning attempts and explored factors associated with successful weaning and long-term survival. METHODS: This historical cohort study included all adult PMV patients admitted to a single rehabilitation hospital during 2015-2018 and followed for survival according to weaning success up to 3 years or the end of 2021. RESULTS: The study included 223 PMV patients. Of them, 124 (55.6 %) underwent weaning attempts, with 69 (55.6 %) successfully weaned, 55 (44.4 %) unsuccessfully weaned, and 99 patients with no weaning attempts. The mean age was 67 ± 20 years, with 39 % female patients. Age, sex distributions and albumin levels at admission were not significantly different among the groups. The successful weaning group had a 6 % higher proportion of conscious patients than the failed weaning group (55 % vs. 49 %, respectively, p = 0.45). Patients successfully weaned were less frequently treated with antibiotics for 5 days or more than those unsuccessfully weaned (74 % vs 80 %, respectively, p = 0.07). They also had a lower proportion of time from intubation to tracheostomy greater than 14 days (45 % vs 66 %, p = 0.02). The age, sex, antibiotic treatment, time to tracheostomy exceeding 14 days and time from admission to first weaning attempt adjusted one-year mortality risk of successful vs. failed weaning was somewhat lower, HR = 0.75, 95%CI: 0.33-1.60, p = 0.45, with the same trend by the end of 3 years, HR = 0.77, 95%CI: 0.42-1.39, p = 0.38. CONCLUSION: Successful weaning from PMV may be associated with better survival and allows chronically ventilated patients to become independent on a ventilator. A larger study is needed to further validate our findings.

Reverse causation biases weighted cumulative exposure model estimates, but can be investigated in sensitivity analyses.

OBJECTIVES: To examine the effects of reverse causation on estimates from the weighted cumulative exposure (WCE) model that is used in pharmacoepidemiology to explore drug-health outcome associations, and to identify sensitivity analyses for revealing such effects. STUDY DESIGN AND SETTING: 314,099 patients with diabetes under Clalit Health Services, Israel, were followed over 2002-2012. The association between metformin and pancreatic cancer (PC) was explored using a WCE model within the framework of discrete-time Cox regression. We used computer simulations to explore the effects of reverse causation on estimates of a WCE model and to examine sensitivity analyses for revealing and adjusting for reverse causation. We then applied those sensitivity analyses to our data. RESULTS: Simulation demonstrated bias in the weighted cumulative exposure model and showed that sensitivity analysis could reveal and adjust for these biases. In our data, a positive association was observed (hazard ratio (HR) = 3.24, 95% confidence interval (CI): 2.24-4.73) with metformin exposure in the previous 2 years. After applying sensitivity analysis, assuming reverse causation operated up to 4 years before cancer diagnosis, the association between metformin and PC was no longer apparent. CONCLUSION: Reverse causation can cause substantial bias in the WCE model. When suspected, sensitivity analyses based on causal analysis are advocated.

Ultimatum bargaining behavior of people affected by schizophrenia.

Forty-nine people suffering from schizophrenia performed an interactive bargaining task involving small monetary rewards, known in classical game theory as the Ultimatum Game. In this task, the subject, in the role of the Proposer, has to offer his or her (anonymous) counterpart, the Responder, a share of a given sum of money. If the Responder accepts the offer, then the sum is split accordingly between the two. Otherwise, if he or she decides to reject the offer, both receive nothing. The patients' strategic behavior in both roles was compared with that of healthy and clinical controls. It was hypothesized that cognitive deficits characterizing schizophrenia, together with difficulties in social judgment, would impair the patients' bargaining ability. We found that in general schizophrenic patients did not fully exploit their strategic power as Proposers. In contrast, as Responders, schizophrenic patients acted not significantly different from controls. Further investigation is needed to establish the links between cognitive and symptomatic mediators and strategic decision-making ability.

Cancer prevalence in Israeli men and women with schizophrenia.

The aim of this cross-sectional study was to compare cancer prevalence rates among patients with schizophrenia to those of the non-schizophrenia population. The study population included members of Clalit Health Services aged 25 to 74 years and all data was taken from patients' electronic health records. Of the 2,060,314 members who were included in the study, 32,748 had a diagnosis of schizophrenia. Cancer prevalence rates in women with and without schizophrenia were 491 per 10,000 and 439 per 10,000, respectively; in men, cancer prevalence rates were 226 per 10,000 and 296 per 10,000, respectively. The age-adjusted prevalence rate of all-type cancer was significantly lower among men with schizophrenia, compared to men without schizophrenia; specifically, men with schizophrenia had a lower rate of prostate cancer, and of cancers in the "other" category, compared to men without schizophrenia. Reduced cancer rates in men with schizophrenia may reflect under-diagnosis of some cancer types, likely due to insufficient medical attention. An effort to improve screening regimes should be made.

Non-specific effects of methylphenidate (Ritalin) on cognitive ability and decision-making of ADHD and healthy adults.

INTRODUCTION: The effect of a single dose of methylphenidate (MPH) on cognitive measures and decision-making processes was assessed in a sample of adults with ADHD and in a control sample. METHODS: Thirty-two adults satisfying DSM-IV criteria for ADHD and 26 healthy controls performed several cognitive tasks. Half of the participants received MPH prior to performing the tasks, and the other half received placebo in a randomized, double-blind manner. RESULTS: The average digit-span test score was higher in the groups receiving MPH compared to the groups receiving placebo, while diagnosis did not have an effect upon scores. In decision-making tasks, however, MPH did not have an effect upon performance, whereas in one of the tasks the average proportion of risky choices was higher in ADHD adults compared to controls. CONCLUSION: Our data therefore demonstrates that (a) MPH is capable of enhancing specific aspects of cognitive performance and (b) this enhancement is not specific to ADHD.