142 research outputs found
SMM881168 Supplemetal Material - Supplemental material for Imputing missing time-dependent covariate values for the discrete time Cox model
No full textSupplemental material, SMM881168 Supplemetal Material for Imputing missing time-dependent covariate values for the discrete time Cox model by Havi Murad, Rachel Dankner, Alla Berlin, Liraz Olmer and Laurence S Freedman in Statistical Methods in Medical Research</p
Diabetes, glucose control, glucose lowering medications, and cancer risk: A 10-year population-based historical cohort
No full textBackground: Both diabetes and glucose-lowering medications have been associated with an increased risk of cancer incidence. This study will compare cancer incidence rates in individuals with and without diabetes; and will investigate, in individuals with diabetes, an association between glucose control and cancer incidence; and between the use of specific glucose-lowering medications, as well as no drug exposure, and cancer incidence.Methods/design: This is a population based historical cohort study of all individuals aged 21 years or older (about 2,300,000) who were insured by Clalit Health Services, the largest health maintenance organization in Israel during a ten-year study period. Four study groups will be established according to the status of diabetes and cancer at study entry, Jan 1, 2002: cancer free, diabetes free; cancer free, diabetes prevalent; cancer prevalent, diabetes free; and cancer prevalent, diabetes prevalent. Individuals without diabetes at study entry will be followed for diabetes incidence, and all four groups will be followed for specific cancer incidence, including second primary neoplasms. Glucose control will be assessed by HbA1c and by fasting plasma glucose levels. Time dependent regression models for cancer incidence will account for glucose-lowering medications as they are added and changed over the follow-up period. A large number of demographic and clinical variables will be considered, including: age, gender, BMI, smoking status, concomitant medications, glucose control (assessed by HbA1c and by fasting plasma glucose) and cancer screening tests.Discussion: Strengths of this study include the large population; high quality comprehensive data; comparison to individuals without diabetes, and to those with diabetes but not treated with glucose-lowering medications; and the extensive range of variables available for analysis. The great increases in diabetes prevalence and in treatment options render this study particularly relevant and timely. The Israeli national healthcare system, characterized by high standard and uniform healthcare, offers an advantageous environment for its conduct. © 2012 Dankner et al.; licensee BioMed Central Ltd
The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study
No full textBackgroundAs 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.MethodsA 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).ResultsWe 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 (P-interaction 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.ConclusionIn 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
Time-dependent risk of cancer after a diabetes diagnosis in a cohort of 2.3 million adults
No full textUsing a time-dependent approach, we investigated all-site and site-specific cancer incidence in a large population stratified by diabetes status. The study analyzed a closed cohort comprised of Israelis aged 21-89 years, enrolled in a health fund, and followed from 2002 to 2012. Adjusting for age, ethnicity, and socioeconomic status, we calculated hazard ratios for cancer incidence using Cox regression separately for participants with prevalent and incident diabetes; the latter was further divided by time since diabetes diagnosis. Of the 2,186,196 individuals included in the analysis, 159,104 were classified as having prevalent diabetes, 408,243 as having incident diabetes, and 1,618,849 as free of diabetes. In both men and women, diabetes posed an increased risk of cancers of the liver, pancreas, gallbladder, endometrium, stomach, kidney, brain (benign), brain (malignant), colon/rectum, lung (all, adenocarcinoma, and squamous cell carcinoma), ovary, and bladder, as well as leukemia, multiple myeloma, non-Hodgkin lymphoma, and breast cancer in postmenopausal women. No excess risk was observed for breast cancer in premenopausal women or for thyroid cancer. Diabetes was associated with a reduced risk of prostate cancer. Hazard ratios for all-site and site-specific cancers were particularly elevated during the first year following diabetes diagnosis. The findings of this large study with a time-dependent approach are consistent with those of previous studies that have observed associations between diabetes and cancer incidence. © 2016 The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved
A historical cohort study on glycemic-control and cancer-risk among patients with diabetes
No full textAims: This population-based historical cohort study examined whether poor glycemic-control (i.e., high glucose and HbA1c blood levels) in patients with diabetes is associated with cancer-risk. Methods: From a large healthcare database, patients aged 21–89 years, diagnosed with diabetes before January 2002 (prevalent) or during 2002–2010 (incident), were followed for cancer during 2004–2012 (excluding cancers diagnosed within the first 2 years since diabetes diagnosis). Risks of selected cancers (all-sites, colon, breast, lung, prostate, pancreas and liver) were estimated according to glycemic-control in a Cox regression model with time-dependent covariates, adjusted for age, sex, ethnic origin, socioeconomic status, smoking and parity. Missing glucose or HbA1c values were imputed. Results: Among 440,000 patients included in our analysis, cancer was detected more than 2 years after diabetes diagnosis in 26,887 patients (6%) during the follow-up period. Associations of poor glycemic-control with all-sites cancer and most specific cancers were either null or only weak (hazard ratios (HRs) for a 1% HbA1c or a 30 mg/dl glucose increase between 0.94 and 1.09). Exceptions were pancreatic cancer, for which there was a strong positive association (HRs: 1.26–1.51), and prostate cancer, for which there was a moderate negative association (HRs: 0.85–0.96). Conclusion: Overall, poor glycemic-control appears to be only weakly associated with cancer-risk, if at all. A substantial part of the positive association with pancreatic cancer is attributable to reverse causation, with the cancer causing poorer glycemic-control prior to its diagnosis. The negative association with prostate cancer may be related to lower PSA levels in those with poor control. © 2018 The Author
Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11 year historical population follow-up study of more than 1 million men
No full textAims/hypothesis: An inverse association has consistently been shown between diabetes and prostate cancer incidence. We investigated whether lower prostate cancer incidence among men with diabetes is attributable to lower detection due to prostate cancer screening patterns. Methods: We studied a population-based historical cohort of 1,034,074 Israeli men aged 21–90 years, without a previous history of cancer. The cohort was followed-up from 2002 to 2012, according to diabetes morbidity, for frequency of prostate-specific antigen (PSA) testing, mean PSA values and detection of prostate cancer, after adjustment for age, ethnic origin, socioeconomic status and PSA testing. Results: In January 2002, 74,756 men had prevalent diabetes. During the 11 year follow-up, 765,483 (74%) remained diabetes-free and 193,835 developed diabetes. Approximately 10% more PSA screening was performed in men with than without diabetes, but the rate of PSA positivity (>4 μg/l) was 20% lower in men with diabetes. PSA values were already significantly lower in men who developed diabetes than in those who did not, 3 years before diabetes diagnosis. Reduced prostate cancer risk was observed among men with incident diabetes only for low–moderate grade tumours (Gleason score 2–6: adjusted HR 0.83; 95% CI 0.77, 0.89). No association was observed for high-grade tumours (Gleason score 7–10: HR 0.99; 95% CI 0.88, 1.11). Conclusions/interpretation: Our findings suggest that diabetes comorbidity is a factor to be considered in prostate cancer screening strategies, and specifically in the interpretation of PSA levels. Furthermore, our demonstration of reduced incidence of low–moderate grade but not high-grade prostate cancer tumours among men with diabetes supports the possibility that low PSA levels, rather than lower tumour risk, explains the observed reduced incidence of prostate cancer in men with diabetes. Trial registration:: ClinicalTrials.gov NCT02072902 © 2016, The Author(s)
Symptoms of depression and anxiety and 11-year all-cause mortality in men and women undergoing coronary artery bypass graft (CABG) surgery
No full textObjectives
To investigate the overall and the sex-specific association of preoperative and one-year post coronary artery bypass (CABG) surgery symptoms of depression and anxiety with 11-year all-cause mortality.
Methods
A multicenter prospective study including 1125 patients who completed the Hospital Anxiety and Depression Scale (HADS) before an elective CABG surgery, of whom 850 completed the HADS again at one-year follow-up. Information on all-cause mortality was obtained through the Israeli Ministry of Internal Affairs Register. Multivariable adjusted Cox regression models quantified the association of symptoms of depression and anxiety with all-cause mortality.
Results
Females comprised 22.7% of the cohort and were 5.5 years older than males (70.0 ± 9.3 and 64.4 ± 10.3 years, respectively). Controlling for sociodemographic and lifestyle factors, illness severity and post-surgery participation in cardiac rehabilitation, there was little evidence of an association between preoperative symptoms of depression and mortality in males [adjusted hazard ratio (aHRmales)=1.03, 95% CI 0.99–1.07, p =0.21] or females (aHRfemales=1.01, 95% CI 0.95–1.08, p=0.7). One-year postoperative symptoms of depression were associated with mortality in both males (aHRmales =1.05, 95% CI 1.01–1.10, p =0.03) and females (aHRfemales=1.07, 95% CI 1.02–1.13, p=0.013). Preoperative symptoms of anxiety were unrelated to mortality overall, but among females postoperative symptoms of anxiety predicted 11-year mortality (aHRfemales =1.07, 95% CI 1.00–1.14, p=0.049). There was no HADS by sex interaction (p for interaction =0.12–0.99).
Conclusions
Symptoms of depression one-year after surgery were positively related to mortality with little evidence for sex differences. These findings underscore the need for identification and treatment of psychiatric symptoms in patients undergoing CABG surgery.</p
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