Kristin K. Clemens

Psychosocial health of living kidney donors: a systematic review

Knowledge of the psychosocial benefits and harms faced by living kidney donors is necessary for informed consent and follow‐up. We reviewed any English language study where psychosocial function was assessed using questionnaires in 10 or more donors after nephrectomy. We searched MEDLINE, EMBASE, Web of Science, Psych INFO, Sociological Abstracts and CINAHL databases and reviewed reference lists from 1969 through July 2006. Independently, two reviewers abstracted data on study, donor and control group characteristics, psychosocial measurements and their outcomes. Fifty‐one studies examined 5139 donors who were assessed an average of 4 years after nephrectomy. The majority experienced no depression (77–95%) or anxiety (86–94%), with questionnaire scores similar to controls. The majority reported no change or an improved relationship with their recipient (86–100%), spouse (82–98%), family members (83–100%) and nonrecipient children (95–100%). Some experienced an increase in self‐esteem. A majority (83–93%) expressed no change in their attractiveness. Although many scored high on quality of life measures, some prospective studies described a decrease after donation. A small proportion of donors had adverse psychosocial outcomes. Most kidney donors experience no change or an improvement in their psychosocial health after donation. Harms may be minimized through careful selection and follow‐up.

The Long-Term Quality of Life of Living Kidney Donors: A Multicenter Cohort Study

Previous studies that described the long‐term quality of life of living kidney donors were conducted in single centers, and lacked data on a healthy nondonor comparison group. We conducted a retrospective cohort study to compare the quality of life of 203 kidney donors with 104 healthy nondonor controls using validated scales (including the SF36, 15D and feeling thermometer) and author‐developed questions. Participants were recruited from nine transplant centers in Canada, Scotland and Australia. Outcomes were assessed a median of 5.5 years after the time of transplantation (lower and upper quartiles of 3.8 and 8.4 years, respectively). 15D scores (scale of 0 to 1) were high and similar between donors and nondonors (mean 0.93 (standard deviation (SD) 0.09) and 0.94 (SD 0.06), p = 0.55), and were not different when results were adjusted for several prognostic characteristics (p = 0.55). On other scales and author‐developed questions, groups performed similarly. Donors to recipients who had an adverse outcome (death, graft failure) had similar quality of life scores as those donors where the recipient did well. Our findings are reassuring for the practice of living transplantation. Those who donate a kidney in centers that use routine pretransplant donor evaluation have good long‐term quality of life.

Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study

Objective To determine whether the use of incretin based drugs compared with sulfonylureas is associated with an increased risk of incident pancreatic cancer in people with type 2 diabetes. Design Population based cohort. Setting Large, international, multicentre study combining the health records from six participating sites in Canada, the United States, and the United Kingdom. Participants A cohort of 972 384 patients initiating antidiabetic drugs between 1 January 2007 and 30 June 2013, with follow-up until 30 June 2014. Main outcome measures Within each cohort we conducted nested case-control analyses, where incident cases of pancreatic cancer were matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and duration of follow-up. Hazard ratios and 95% confidence intervals for incident pancreatic cancer were estimated, comparing use of incretin based drugs with use of sulfonylureas, with drug use lagged by one year for latency purposes. Secondary analyses assessed whether the risk varied by class (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) or by duration of use (cumulative duration of use and time since treatment initiation). Site specific hazard ratios were pooled using random effects models. Results During 2 024 441 person years of follow-up (median follow-up ranging from 1.3 to 2.8 years; maximum 8 years), 1221 patients were newly diagnosed as having pancreatic cancer (incidence rate 0.60 per 1000 person years). Compared with sulfonylureas, incretin based drugs were not associated with an increased risk of pancreatic cancer (pooled adjusted hazard ratio 1.02, 95% confidence interval 0.84 to 1.23). Similarly, the risk did not vary by class and evidence of a duration-response relation was lacking. Conclusions In this large, population based study the use of incretin based drugs was not associated with an increased risk of pancreatic cancer compared with sulfonylureas. Although this potential adverse drug reaction will need to be monitored long term owing to the latency of the cancer, these findings provide some reassurance on the safety of incretin based drugs.

Oral bisphosphonate use in the elderly is not associated with acute kidney injury

Intravenous bisphosphonates can cause acute kidney injury; however, this risk was not found with oral bisphosphonates in randomized clinical trials with restrictive eligibility criteria. In order to provide complementary safety data, we studied the risk of acute kidney injury in a population-based cohort of 122,727 patients aged 66 years and older discharged from hospital following a new fragility fracture and no history of bisphosphonate use in the prior year. Bisphosphonate treatment was identified within 120 days after discharge and event rates were measured from 90 days of therapy initiation. The primary outcome was hospitalization with acute kidney injury with secondary outcomes of new nephrology consultation and, in a subset of patients with laboratory values, acute kidney injury was defined as an increase in serum creatinine. We identified 18,286 bisphosphonate users and 104,441 non-users with a mean age of 81 years. Of 5772 patients with laboratory values, 40% had chronic kidney disease (eGFR <60 ml/min per 1.73 m(2)). Overall, there was no statistically significant difference in the risk of acute kidney injury among bisphosphonate users compared to non-users (adjusted odds ratio 1.03), and no significant differences in other outcomes or in subgroups of patients with baseline chronic kidney disease. Thus, in this older population-based cohort, oral bisphosphonate use was not associated with acute kidney injury.

Association Between Incretin-Based Drugs and the Risk of Acute Pancreatitis

Importance The association between incretin-based drugs, such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, and acute pancreatitis is controversial. Objective To determine whether the use of incretin-based drugs, compared with the use of 2 or more other oral antidiabetic drugs, is associated with an increased risk of acute pancreatitis. Design, Setting, and Participants A large, international, multicenter, population-based cohort study was conducted using combined health records from 7 participating sites in Canada, the United States, and the United Kingdom. An overall cohort of 1 532 513 patients with type 2 diabetes initiating the use of antidiabetic drugs between January 1, 2007, and June 30, 2013, was included, with follow-up until June 30, 2014. Exposures Current use of incretin-based drugs compared with current use of at least 2 oral antidiabetic drugs. Main Outcomes and Measures Nested case-control analyses were conducted including hospitalized patients with acute pancreatitis matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and follow-up duration. Hazard ratios (HRs) and 95% CIs for hospitalized acute pancreatitis were estimated and compared current use of incretin-based drugs with current use of 2 or more oral antidiabetic drugs. Secondary analyses were performed to assess whether the risk varied by class of drug (DPP-4 inhibitors and GLP-1 agonists) or by duration of use. Site-specific HRs were pooled using random-effects models. Results Of 1 532 513 patients included in the analysis, 781 567 (51.0%) were male; mean age was 56.6 years. During 3 464 659 person-years of follow-up, 5165 patients were hospitalized for acute pancreatitis (incidence rate, 1.49 per 1000 person-years). Compared with current use of 2 or more oral antidiabetic drugs, current use of incretin-based drugs was not associated with an increased risk of acute pancreatitis (pooled adjusted HR, 1.03; 95% CI, 0.87-1.22). Similarly, the risk did not vary by drug class (DPP-4 inhibitors: pooled adjusted HR, 1.09; 95% CI, 0.86-1.22; GLP-1 agonists: pooled adjusted HR, 1.04; 95% CI, 0.81-1.35) and there was no evidence of a duration-response association. Conclusions and Relevance In this large population-based study, use of incretin-based drugs was not associated with an increased risk of acute pancreatitis compared with other oral antidiabetic drugs.

Trends in Antihyperglycemic Medication Prescriptions and Hypoglycemia in Older Adults: 2002-2013

Background Over the last decade, several new antihyperglycemic medications have been introduced including those associated with a lower hypoglycemia risk. We aimed to investigate how these medications are being prescribed to older adults in our region. Methods We conducted population-based cross-sectional analyses of older adults (mean age 75 years) with treated diabetes in Ontario, Canada from 2002 until 2013, to examine the percentage prescribed insulin, sulphonylureas, alpha-glucosidase inhibitors, metformin, thiazolidinediones, meglitinides, and dipeptidyl peptidase-4 inhibitors. Over the study period, we also examined their hospital encounters for hypoglycemia (emergency room or inpatient encounter). Results The mean age of treated patients increased slightly over the study quarters and the proportion that were women declined. With the exception of chronic kidney disease, cancer, dementia, and neuropathy, the percentage with a comorbidity appeared to decline. The percentage of treated patients prescribed metformin, gliclazide and dipeptidyl peptidase-4 inhibitors increased as did combination therapy. Glyburide and thiazolidinedione prescriptions declined, and insulin use remained stable. In those with newly treated diabetes, the majority were prescribed metformin, with smaller percentages prescribed insulin and other oral agents. Although the absolute number of treated patients with a hypoglycemia encounter increased until mid-2006 and then decreased, the overall percentage with an encounter declined over the study period (0.8% with an event in the first quarter, 0.4% with an event in the last quarter). Conclusions Antihyperglycemic medications with safer profiles are being increasingly prescribed to older adults. In this setting there has been a decrease in the percentage of treated patients with a hospital encounter for hypoglycemia.

Beta-blockers and cardiovascular outcomes in dialysis patients: a cohort study in Ontario, Canada

BACKGROUND Beta-blockers may be cardioprotective in patients receiving chronic dialysis. We examined cardiovascular outcomes among incident dialysis patients receiving beta-blocker therapy. METHODS We conducted a retrospective cohort study employing linked healthcare databases in Ontario, Canada. We studied all consecutive chronic dialysis patients aged≥66 years who initiated dialysis between 1 July 1991 and 31 July 2007. Patients were divided into three groups according to new medication use after the initiation of chronic dialysis. The three groups were patients initiated on beta-blockers, calcium channel blockers and statins only. Patients in the beta-blocker and calcium channel blocker groups could also be concurrently receiving a statin. The primary outcome was time to a composite endpoint of death, myocardial infarction, stroke or coronary revascularization. RESULTS There were a total of 1836 patients (504 beta-blocker, 570 calcium channel blocker and 762 statin-only users). Compared to statin-only use, beta-blocker use was not associated with improved cardiovascular outcomes [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.92-1.23]. As expected, calcium channel blocker use was also not associated with improved cardiovascular outcomes (aHR 0.91, 95% CI 0.79-1.06). Among all subgroup analyses by beta-blocker attributes, only high-dose beta-blocker therapy was associated with better cardiovascular outcomes as compared to low-dose beta-blockers (aHR 0.50, 95% CI 0.29-0.88). CONCLUSIONS We observed no beneficial effect of beta-blocker use among patients receiving chronic dialysis relative to our comparator groups. Given current uncertainty around the cardioprotective benefits of beta-blockers in patients receiving dialysis, a large randomized clinical trial is warranted.

Secular trends in antihyperglycaemic medication prescriptions in older adults with diabetes and chronic kidney disease: 2004-2013.

To examine how antihyperglycaemic medications were prescribed to older adults with diabetes and chronic kidney disease over the last decade.

The Hypoglycemic Risk of Glyburide (Glibenclamide) Compared with Modified-Release Gliclazide

OBJECTIVES The risk for hypoglycemia when taking glyburide compared with modified-release gliclazide remains to be established in older adults in routine care. We investigated the risk of a hospital encounter with hypoglycemia following a new prescription for glyburide compared with modified-release gliclazide. METHODS In 2 population-based matched retrospective cohort studies in Ontario, Canada, between 2002 and 2011, we examined older adults who were newly prescribed glyburide or gliclazide as monotherapy or in the presence of metformin. Our primary outcome was a hospital encounter with hypoglycemia assessed within 90 days. RESULTS The baseline characteristics between matched groups were similar. Initiating glyburide vs. gliclazide as monotherapy was associated with a higher risk for a hospital encounter with hypoglycemia (69 patients of 4374 taking glyburide [1.58%] vs. 8 patients of 4374 taking gliclazide [0.18%], absolute risk increase 1.40% [95% CI 1.01% to 1.79%], number needed to harm 71 [55 to 99], odds ratio 8.63 [95% CI 4.15 to 17.93], p<0.0001). Similar findings were noted when glyburide vs. gliclazide was initiated in the presence of metformin (110 patients of 8038 taking glyburide [1.37%] vs. 19 patients of 8038 taking gliclazide [0.24%], absolute risk increase 1.13% [95% CI 0.86% to 1.40%], number needed to harm 77 [71 to 116], odds ratio 6.06 [95% CI 3.68 to 9.97], p<0.0001). CONCLUSIONS Glyburide was associated with a higher risk for hypoglycemia than modified-release gliclazide. The results of our studies may help to convince healthcare professionals who use glyburide to consider modified-release gliclazide as a safer alternative.

Validation of an International Statistical Classification of Diseases and Related Health Problems 10th Revision coding algorithm for hospital encounters with hypoglycemia

OBJECTIVES To determine the positive predictive value and sensitivity of an International Statistical Classification of Diseases and Related Health Problems, 10th Revision, coding algorithm for hospital encounters concerning hypoglycemia. METHODS We carried out 2 retrospective studies in Ontario, Canada. We examined medical records from 2002 through 2014, in which older adults (mean age, 76) were assigned at least 1 code for hypoglycemia (E15, E160, E161, E162, E1063, E1163, E1363, E1463). The positive predictive value of the algorithm was calculated using a gold-standard definition (blood glucose value <4 mmol/L or physician diagnosis of hypoglycemia). To determine the algorithms sensitivity, we used linked healthcare databases to identify older adults (mean age, 77) with laboratory plasma glucose values <4 mmol/L during a hospital encounter that took place between 2003 and 2011. We assessed how frequently a code for hypoglycemia was present. We also examined the algorithms performance in differing clinical settings (e.g. inpatient vs. emergency department, by hypoglycemia severity). RESULTS The positive predictive value of the algorithm was 94.0% (95% confidence interval 89.3% to 97.0%), and its sensitivity was 12.7% (95% confidence interval 11.9% to 13.5%). It performed better in the emergency department and in cases of more severe hypoglycemia (plasma glucose values <3.5 mmol/L compared with ≥3.5 mmol/L). CONCLUSIONS Our hypoglycemia algorithm has a high positive predictive value but is limited in sensitivity. Although we can be confident that older adults who are assigned 1 of these codes truly had a hypoglycemia event, many episodes will not be captured by studies using administrative databases.