Self-reported physical activity properties and 20-year all-cause and cardiovascular mortality among community-dwelling older adults.

PURPOSE: Physical activity was previously associated with decreased mortality. Current guidelines recommend >150 min/week or >75 min/week of moderate or high-intensity exercise to maintain a healthy lifestyle; however, exercise properties most strongly associated with low mortality among the elderly may still be explored. METHODS: A total of 1210 community-dwelling older adults, from the third phase (1999-2004) of the Israel Study on Glucose Intolerance, Obesity, and Hypertension, were followed until 2016 and 2019 for cardiovascular and all-cause mortality, respectively. Physical activity properties were recorded and evaluated against all-cause and cardiovascular mortality. RESULTS: Mean age at baseline was 73 ± 7 years, with 638 (53%) females, and 585 (48%) reported habitual exercise. When compared to sedentary individuals, multivariable Cox regressions showed a significantly lower risk for all-cause mortality among currently active individuals [hazard ratio (HR) = 0.72, 95% confidence interval (CI): 0.59-0.88, P = .002], those engaging in light-moderate activity (HR = 0.72, 95% CI: 0.57-0.89, P = .003), those with diverse exercise types (HR = 0.59, 95% CI: 0.44-0.80, P = .001), more sessions/week (HR = 0.94, 95% CI: 0.92-0.97, P < .001), those meeting current exercise recommendations (HR = 0.79, 95% CI: 0.58-0.89, P = .03), those who engaged in walking (HR = 0.58, 95% CI: 0.45-0.76, P < .001), and swimming (HR = 0.66, 95% CI: 0.45-0.96, P = .03). Similar HRs were found for cardiovascular mortality, although a somewhat stronger protective association was observed for swimming (HR = 0.48, 95% CI: 0.24-0.95, P = .04) compared to a sedentary lifestyle. CONCLUSION: The study further supports current exercise guidelines among the elderly. It also underscores the importance of physical activity in older individuals while prioritizing a greater number of sessions/week in addition to the total duration, and highlights specific activity features associated with lower long-term mortality among older adults. Key message • What is already known on this topic - Physical activity was associated with a lower risk for mortality, although the specific properties and the preferred type of exercise among older adults are still debatable. • What this study adds - The study suggests the optimal activity characteristics in older adults while prioritizing activity sessions over time, light-moderate exercise over strenuous activity, diverse activity, and walking and swimming over other activities. • How this study might affect research, practice or policy - Future exercise guidelines should focus on increasing activity sessions throughout the week and not on the cumulative time to maximize the effect on mortality.

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.

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.

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.

The association between frailty biomarkers and 20-year all-cause and cardiovascular mortality among community-dwelling older adults.

OBJECTIVES: While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel biomarkers and frailty among community-dwelling older adults to enhance understanding of the pathophysiology of frailty. METHODS: Nine hundred and sixty-three older adults were screened during the third phase (1999-2008) of the Israel study on Glucose Intolerance, Obesity, and Hypertension (GOH). Frailty was defined as sedentary individuals, past 10 years hospitalizations, or at least one of the following: body mass index (BMI) <21 kg/m2; albumin <3.2 g/dl; ≥2 major baseline diseases. Biomarkers were evaluated for their association with frailty, all-cause, and cardiovascular mortality. RESULTS: Mean baseline age was 72 ± 7 years, 471 (49%) were women, and 195 (20%) were classified as frail. Median follow-up for cardiovascular and all-cause mortality was 11 and 13 years, with 179 (18.6%) and 466 (48.4%) deaths recorded, respectively. Multivariable logistic regression showed greater odds for frailty with lower quartile of alanine aminotransferase (ALT) (OR = 1.8, 95%CI: 1.2-2.8, p = 0.01), and for each 5 µmol/L increment in homocysteine levels (OR = 1.3, 95%CI: 1.1-1.5, p = 0.001). Multivariate Cox regression showed greater all-cause and cardiovascular mortality risk for individuals with low ALT (HR = 1.6, 95%CI: 1.3-2.0, p < 0.001 and HR = 1.5, 95% CI: 1.0-2.2, p = 0.03, respectively), and high homocysteine (HR = 1.1, 95%CI: 1.1-1.3, p = 0.003 and HR = 1.2, 95%CI: 1.0-1.3, p = 0.04, respectively). Homocysteine association with mortality was more pronounced in those with baseline ischemic heart disease (IHD) compared with subjects free of IHD (P for interaction = 0.01). CONCLUSIONS: Lower ALT and higher homocysteine were associated with frailty, all-cause and cardiovascular mortality. These available and low-cost biomarkers underscore the nutritional and metabolic aspects of frailty when screening high-risk older adults, especially those with IHD, and may be considered as preferable screening biomarkers to be tested among these individuals for frailty and mortality risk.

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.

Emulated Trial for Discharge Prescription of Guideline-Directed Medical Therapy and 15-Year Survival After Coronary Artery Bypass Graft Surgery.

OBJECTIVES: To explore admission and discharge prescription rates of guideline-directed medical therapy (GDMT), defined as aggregate antiplatelet agents, statins, and ß-blockers, after coronary artery bypass graft (CABG) surgery and to reveal its association with long-term survival. PATIENTS AND METHODS: This is a prospective cohort study-based emulated trial of patients undergoing elective or semi-elective isolated CABG surgery in 7 cardiothoracic units in Israel from January 1, 2004, to December 31, 2007, and followed up until December 31, 2020, for all-cause mortality. RESULTS: Only 59.2% of 968 patients (n=573) were discharged on GDMT after CABG surgery. Admission GDMT use conferred a 7 times greater likelihood of discharge GDMT prescription (odds ratio, 7.07; 95% CI, 5.04 to 9.91; P<.001), with no sex differences observed. After applying inverse probability of treatment weighting, baseline characteristics were well balanced between groups. During a median follow-up of 13.7 years, a Cox regression model with propensity score-adjusted inverse probability of treatment weighting revealed lower mortality in patients with discharge GDMT prescription who underwent CABG surgery than in their counterparts (hazard ratio, 0.75; 95% CI, 0.60 to 0.93; P=.008). CONCLUSION: The use of aggregate GDMT before surgery conferred a greater likelihood of GDMT prescription upon discharge, which, in turn, is associated with better long-term survival. Educational efforts of pertinent medical professionals are needed to minimize preventive treatment gaps. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00356863.

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.

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.

Sex specific serum uric acid levels are associated with ischemic changes on ECG and with 20-year all-cause mortality among older adults.

BACKGROUND: Uric acid is an emerging biomarker for cardiovascular morbidity and mortality, but its association with all-cause mortality and ECG findings remains unestablished, specifically among older adults. We aimed to evaluate the association between serum uric acid (SUA) with incidental findings of ECG abnormalities and with long-term all-cause mortality. METHODS: We conducted a prospective cohort study of 851 community dwelling men and women, who were examined between 1999 and 2008, and followed over 20 years until December 2019 for all-cause mortality. Subjects free of Gout or diuretics treatment at baseline were included. SUA was categorized according to sex-specific tertiles and evaluated against baseline ECG findings and all-cause mortality. RESULTS: Mean baseline age was 72±7 years and 416 (49%) were females. Ischemic changes on ECG were observed in 85 (10.0%) participants, of them 36 (13.5%) belonged to the upper SUA tertile and 49 (8.4%) to the lower ones (p = 0.02). Multivariable logistic regression showed 80% higher odds for ischemic changes on ECG among participants in the high SUA tertile (adjusted-OR = 1.8, 95%CI 1.1-2.9, p = 0.03) compared with the lower SUA two-tertiles. During a median follow-up of 14 years, 380 (44.7%) participants died. SUA ≥5.3 mg/dl for women and ≥ 6.2 mg/dl for men, was associated with a 30% greater risk for all-cause mortality in a multivariable Cox regression model (HR = 1.3, 95%CI: 1.0-1.6, p = 0.03). CONCLUSIONS: High SUA level was associated with ischemic changes on ECG and with an increased risk for all-cause mortality over 20 years of follow-up among community dwelling older adults free of Gout. Even lower sex-specific thresholds of SUA were associated with all-cause mortality than previously proposed. SUA should be considered as a biomarker for cardiovascular risk and all-cause mortality.

The efficacy of calorimetry-based nutritional support versus recommended dietary intake-based nutritional support in the successful weaning of chronically ventilated patients: A study protocol for a double blind randomized controlled trial.

BACKGROUND & AIMS: Mechanically ventilated patients are weaned during acute care hospitalization when it is determined that they are ready for withdrawal. If weaning fails, patients are admitted to a rehabilitation medical center for continued supportive care and additional weaning attempts. This study's objective is to increase the success rate of weaning from prolonged mechanical ventilation (PMV), and to shorten the overall weaning period by tailoring the patient's caloric intake according to their individually measured energy needs. METHODS: We designed a randomized, controlled, double-blinded trial to be conducted among PMV patients undergoing routine ventilation-weaning attempts. Patients in the intervention arm will be fed according to energy needs determined by calorimetry. Patients in the control arm will be fed according to the standard of care, namely the Recommended Dietary Allowance (RDA) guidelines. Each patient will undergo up to five weaning attempts. Study outcomes will include successful weaning rate, time to successful weaning, and 3-12 months survival rate. DISCUSSION: This trial aims to examine the safety and efficacy of a nutritional diet based on an individual's measured caloric needs in terms of weaning rates and weaning time. We hypothesize that calorimetry-based nutrition plan will prove to be superior in both success rate and time to successful weaning compared to the standard nutrition plan based on the resting energy expenditure (REE) formula during the weaning process. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04825717.

Polypharmacy is differentially associated with 20-year mortality among community-dwelling elderly women and men: The Israel Glucose Intolerance, Obesity and Hypertension cohort study.

BACKGROUND: Elderly individuals are characterized by multimorbidity and high medication intake, entailing risks for adverse events. We examined the overall and sex-specific association of polypharmacy (≥5 drugs concurrently) with 20-year mortality among community-dwelling older adults. METHODS: Survivors of the longitudinal Israel Study of Glucose Intolerance, Obesity, and Hypertension underwent extensive evaluation during 1999-2004, and were followed-up for all-cause mortality until 2019. Cox regression examined association of polypharmacy with all-cause mortality. RESULTS: Data included 1210 participants (mean baseline age 72.9 ± 7.4 years, 53% females), 50.7% of them died over a median follow-up of 12.8 years. Women received a higher mean number of drugs (4.3 vs 3.5; p < 0.0001), were twice more likely to take vitamins, and had higher comorbidity. Polypharmacy prevalence was 38.3%, and more frequent with age, female sex, European-American origin, sedentary lifestyle and poor self-rated health. Polypharmacy was independently associated with mortality in women only (HR=1.41, 95%CI:1.05-1.89). An interaction was found with sex (p = 0.045). CONCLUSIONS: Polypharmacy was more prevalent in older women than men and associated with increased 20-year mortality in women only. Sex-specific adaptation of guidelines for appropriate drug use among community-dwelling older adults is warranted.

The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study.

BACKGROUND: As indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults. METHODS: A retrospective, pharmacovigilance study of the FDA's global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (≥ 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR). RESULTS: We identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51-68] years, 2,339 [9.6%] aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 - 487.3] vs adj.ROR = 250.2 [79.3 - 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 - 58.8] vs adj.ROR = 88.0 [27.0 - 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 - 34.8] vs adj.ROR = 23.3 [19.2 - 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 - 11.2] vs adj.ROR = 8.6 [7.2 - 10.3]), nocturia (adj.ROR = 5.5 [3.7 - 8.2] vs adj.ROR = 6.7 [2.8 - 15.7]), dehydration (adj.ROR = 2.5 [2.3 - 2.8] vs adj.ROR = 2.6 [2.1 - 3.3]), and fractures (adj.ROR = 1.7 [1.4 - 2.1] vs adj.ROR = 1.5 [1.02 - 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (Pinteraction threshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 - 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 - 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults. CONCLUSION: In this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.

High variation between healthcare professionals in nutrition therapy plans of patients with feeding tubes admitted to a long-term rehabilitation center from an acute-care hospital.

BACKGROUND: Nutrition therapy plans (NTPs) in discharge summaries of tube-fed patients transferred from acute-care hospitals to rehabilitation centers are fundamental for continuity of care. This study examined the presence and quality of NTPs in discharge summaries of tube-fed patients. METHODS: This cross-sectional study was based on data retrieved from electronic medical records. The outcome measures were the presence of NTPs in discharge summaries, the presence of key elements of the NTPs, and the level of compatibility between multiple NTPs per discharge summary prepared by different health professionals. Descriptive statistics were used to assess the number of NTPs, the presence of key elements, and the degree of compatibility between NTPs for the same patient. RESULTS: A total of 100 discharge summaries of tube-fed patients admitted to a rehabilitation hospital during 2015-2017 were identified. The majority (91%) of discharge summaries included at least one NTP; 57 included more than one. Variance in the presence of key elements was observed in 165 NTPs prepared by physicians, nurses, and dietitians. Water amount and nutrition route were least reported by dietitians (6.3% and 9.4%, respectively), compared with physicians (77.6% and 81%) and nurses (77.3% and 62.7%). However, nutrition details were reported more frequently by dietitians (65.6%) than physicians (20.7%) and nurses (32%). Low compatibility was observed between dietitians and both nurses and physicians, in the range of 0%-26%. CONCLUSION: Large discrepancies were found between NTPs for the same patient prepared by dietitians, physicians, and/or nurses, and a portion of patients arrived without any NTP.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

The insulin sensitivity Mcauley index (MCAi) is associated with 40-year cancer mortality in a cohort of men and women free of diabetes at baseline.

BACKGROUND: The association between insulin resistance and cancer-mortality is not fully explored. We investigated the association between several insulin sensitivity indices (ISIs) and cancer-mortality over 3.5 decades in a cohort of adult men and women. We hypothesized that higher insulin resistance will be associated with greater cancer-mortality risk. METHODS: A cohort of 1,612 men and women free of diabetes during baseline were followed since 1979 through 2016 according to level of insulin resistance (IR) for cause specific mortality, as part of the Israel study on Glucose Intolerance, Obesity and Hypertension (GOH). IR was defined according to the Mcauley index (MCAi), calculated by fasting insulin and triglycerides, the Homeostatic Model Assessment (HOMA), the Matsuda Insulin Sensitivity Index (MISI), and the Quantitative Insulin Sensitivity Check Index (QUICKI), calculated by plasma glucose and insulin. RESULTS: Mean age at baseline was 51.5 ± 8.0 years, 804 (49.9%) were males and 871 (54.0%) had prediabetes. Mean follow-up was 36.7±0.2 years and 47,191 person years were accrued. Cox proportional hazard model and competing risks analysis adjusted for age, sex, country of origin, BMI, blood pressure, total cholesterol, smoking and glycemic status, revealed an increased risk for cancer-mortality, HR = 1.5 (95% CI: 1.1-2.0, p = 0.005) for the MCAi Q1 compared with Q2-4. No statistically significant associations were observed between the other ISIs and cancer-mortality. CONCLUSION: The MCAi was independently associated with an increased risk for cancer-mortality in adult men and women free of diabetes and should be further studied as an early biomarker for cancer risk.

[PREDICTION MODEL FOR ASSESSING PHYSICAL FITNESS IN CARDIAC PATIENTS].

AIMS: To develop and validate a readily-available tool for the evaluation of the fitness of cardiac patients. BACKGROUND: Physical fitness is an important factor in the tertiary prevention for cardiac patients. METHODS: In this cross-sectional study, 154 cardiac patients: 119 men and 35 women, mean age 63.1±11.2 years, entering the cardiac-rehabilitation program at the Sheba Medical Center, gave informed consent and completed a 24-hour recall physical activity questionnaire. Information on BMI, medication use and on their performance on a symptom-free limited treadmill test, i.e. measured estimated VO2 (ml/kg/min) and resting heart rate (bpm), were obtained from the medical chart. RESULTS: A linear-regression equation for predicting the measured estimated VO2 includes the overall physical activity index calculated from the physical activity questionnaire, sex, age, BMI, type of coronary heart disease (acute myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention), duration of illness, resting heart rate, use of beta-blockers and level of education. The correlation coefficient between measured VO2 values and calculated values is r=0.6. Upon categorizing patients to high and low physical fitness according to the VO2 median value, the validity of the equation was found to be good: sensitivity=61.2%, specificity=65.2%, positive predictive value=68.4%, negative predictive value=57.7%. CONCLUSIONS: The prediction equation for assessing VO2 in cardiac patients is a simple, inexpensive tool, which may be used for monitoring changes in the patients' physical fitness. It may assist the physician in following a cardiac patient's response to physical activity recommendations and improving fitness when the ergometric stress-test availability is low.

Association between Self-Classification of COVID-19 Risk Levels and Adverse Lifestyle Changes among Physically Active Older Adults Following the Coronavirus Outbreak.

The COVID-19 pandemic has imposed barriers to a healthy lifestyle, especially for older adults who are considered to be at a high-risk of infection. This study examined the associations between negative changes and the self-classification to COVID-19 risk level among physically active older adults who are members of a nationwide health club chain. A cross-sectional digital survey was sent to 19,160 older adults (age ≥ 65). The data collected included information on the subjects' self-classification to the COVID-19 high-risk group (HRG) and changes in physical activity (PA), body weight, and smoking habits since the outbreak. Logistic regression models were used to investigate the associations between the dependent variables of 'experienced a negative change' and the independent variables. Of the 1670 survey respondents, 78.3% classified themselves as COVID-19 HRG. Over half of the respondents reported a reduction in PA hours, 26.6% reported weight gain, and 17.7% of smokers increased their amount of smoking. A self-classification to the HRG was associated with 1.46 (95%CI 1.10−1.93, p < 0.009) and 1.67 (95%CI 1.21−2.31, p < 0.002) greater odds for reduced hours of exercise and weight gain compared to the not high-risk group, respectively. Decision makers should consider how policies may cause barriers to a healthy lifestyle and develop risk communication strategies to encourage positive health-related behaviors, even during a pandemic.

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.

Hyperglycaemic disorders associated with PCSK9 inhibitors: a real-world, pharmacovigilance study.

AIMS: While genetic and biological studies indicated a potential association between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and hyperglycaemia, real-world data are limited. Therefore, we sought to investigate this association using the FDA adverse event reporting system (FAERS). METHODS AND RESULTS: The FAERS database (2015-2020) was retrospectively queried to characterize reporting of hyperglycaemic adverse events (AEs) with PCSK9i. Disproportionality analyses were performed using the adjusted reporting odds ratio (adj.ROR), and the lower bound of the information component (IC) 95% credibility interval (IC025 > 0 is deemed significant). Among 7 295 624 eligible patients, 71 748 reports of evolocumab and 15 976 of alirocumab were identified. Compared to the full database, PCSK9i treatment was associated with increased reporting of hyperglycaemic AEs [n = 1841, adj.ROR = 1.14 (1.07-1.22), IC025 = 0.13]. Hyperglycaemic AEs were primarily mild hyperglycaemia [n = 1469, adj. ROR = 1.48 (1.36-1.62), IC025 = 0.51] rather than diabetes [n = 372, adj. ROR = 0.67 (0.60-0.74), IC025 = -0.90]. Among PCSK9i agents, evolocumab, but not alirocumab, was associated with hyperglycaemic AEs [n = 1587, adj. ROR = 1.24 (1.15-1.32), IC025 = 0.20; n = 254, adj. ROR = 0.73 (0.60-0.88), IC025 = -0.38, respectively]. Hyperglycaemic AEs were reported more often with PCSK9i compared to ezetimibe [adj.ROR = 1.99 (1.35-2.94)], and less often compared to statins [adj.ROR = 0.26 (0.25-0.28)]. Notably, hyperglycaemic AEs were reported more frequently by diabetic than by non-diabetic patients (P < 0.001), mostly occurred within 6 months of treatment and were reversible upon drug discontinuation. CONCLUSION: In a real-world setting, PCSK9i treatment was associated with increased reporting of mild hyperglycaemia, but not diabetes. While initial monitoring is warranted, the favourable glycaemic safety profile compared to statins supports their essential role in the management of lipid disorders.