Bariatric surgery and all-cause mortality: A methodological review of studies using a non-surgical comparator.

AIM: Non-randomized studies on bariatric surgery have reported large reductions in mortality within 6-12 months after surgery compared with non-surgical patients. It is unclear whether these findings are the result of bias. STUDY DESIGN AND SETTING: We searched PubMed to identify all non-randomized studies investigating the effect of bariatric surgery on all-cause mortality compared with non-surgical patients. We assessed these studies for potential confounding and time-related biases. We conducted bias analyses to quantify the effect of these biases. RESULTS: We identified 21 cohort studies that met our inclusion criteria. Among those, 11 were affected by immortal time bias resulting from the misclassification or exclusion of relevant follow-up time. Five studies were subject to potential confounding bias because of a lack of adjustment for body mass index (BMI). All studies used an inadequate comparator group that lacked indications for bariatric surgery. Bias analyses to correct for potential confounding from BMI shifted the effect estimates towards the null [reported hazard ratio (HR): 0.78 vs. bias-adjusted HR: 0.92]. Bias analyses to correct for the presence of immortal time also shifted the effect estimates towards the null (adjustment for 2-year wait time: reported HR: 0.57 vs. bias-adjusted HR: 0.81). CONCLUSION: Several important sources of bias were identified in non-randomized studies of the effectiveness of bariatric surgery versus non-surgical comparators on mortality. Future studies should ensure that confounding by BMI is accounted for, considering the choice of the comparator group, and that the design or analysis avoids immortal time bias from the misclassification or exclusion.

Effectiveness and safety of empagliflozin: final results from the EMPRISE study.

AIMS/HYPOTHESIS: Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases. METHODS: We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we identified four a priori-defined effectiveness outcomes: (1) myocardial infarction (MI) or stroke; (2) hospitalisation for heart failure (HHF); (3) major adverse cardiovascular events (MACE); and (4) cardiovascular mortality or HHF. Safety outcomes included lower-limb amputations, non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), severe hypoglycaemia, retinopathy progression, and short-term kidney and bladder cancers. We estimated HRs and rate differences (RDs) per 1000 person-years, overall and stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD) and heart failure. RESULTS: We identified 115,116 matched pairs. Compared with DPP-4i, empagliflozin was associated with lower risks of MI/stroke (HR 0.88 [95% CI 0.81, 0.96]; RD -2.08 [95% CI (-3.26, -0.90]), HHF (HR 0.50 [0.44, 0.56]; RD -5.35 [-6.22, -4.49]), MACE (HR 0.73 [0.62, 0.86]; RD -6.37 [-8.98, -3.77]) and cardiovascular mortality/HHF (HR 0.57 [0.47, 0.69]; RD -10.36 [-12.63, -8.12]). Absolute benefits were larger in older individuals and in those with ASCVD/heart failure. Empagliflozin was associated with an increased risk of DKA (HR 1.78 [1.44, 2.19]; RD 1.59 [1.08, 2.09]); decreased risks of AKI (HR 0.62 [0.54, 0.72]; RD -2.39 [-3.08, -1.71]), hypoglycaemia (HR 0.75 [0.67, 0.84]; RD -2.46 [-3.32, -1.60]) and retinopathy progression (HR 0.78 [0.63, 0.96)]; RD -9.49 [-16.97, -2.10]); and similar risks of other safety events. CONCLUSIONS/INTERPRETATION: Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular mortality or HHF. Absolute risk reductions were larger in older individuals and in those who had history of ASCVD or heart failure. Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy, with no difference in the short-term risks of lower-extremity amputation, non-vertebral fractures, kidney and renal pelvis cancer, and bladder cancer.

Accuracy of GFR Estimating Equations in Patients with Discordances between Creatinine and Cystatin C-Based Estimations.

SIGNIFICANCE STATEMENT: Large discordances between eGFR on the basis of creatinine (eGFR cr ) or cystatin C (eGFR cys ) are common in clinical practice. However, which GFR estimating equation (eGFR cr , eGFR cys , or eGFR cr-cys ) is most accurate in these settings is not known. In this real-world study of 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance, all three equations performed similarly when eGFR cr and eGFR cys were similar (45% of cases). However, with large discordances (55% of cases), eGFR cr-cys was much more accurate than either alone. These findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer who have been underrepresented in research cohorts. Thus, when eGFR cr and eGFR cys are largely discordant in clinical practice, eGFR cr-cys is more accurate than eGFR cr or eGFR cys . BACKGROUND: Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin (eGFR cr-cys ) is the most accurate estimate in research studies, it is uncertain whether this is true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFR cr ) and that based on cystatin C (eGFR cys ). METHODS: We included 6185 adults referred for measured GFR (mGFR) using plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance. The performance of eGFR cr , eGFR cys , and eGFR cr-cys was assessed against mGFR with median bias, P30 , and correct classification of GFR categories. We stratified analyses within three categories: eGFR cys at least 20% lower than eGFR cr (eGFR cys eGFR cr ). RESULTS: eGFR cr and eGFR cys were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR cr-cys was much more accurate in cases of discordance. For example, when eGFR cys eGFR cr (8% of samples), the median biases were -4.5, 8.4, and 1.4 ml/min per 1.73m 2 . The findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer. CONCLUSIONS: When eGFR cr and eGFR cys are highly discordant in clinical practice, eGFR cr-cys is more accurate than either eGFR cr or eGFR cys .

Association of Sodium-Glucose Cotransporter-2 Inhibitors With Incident Atrial Fibrillation in Older Adults With Type 2 Diabetes.

Importance: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated many cardiovascular and kidney function benefits for patients with type 2 diabetes (T2D). However, the results of SGLT-2i use in primary prevention of atrial fibrillation (AF) were inconsistent in clinical trials, and incident AF was not a prespecified end point. Objective: To examine incident AF with initiation of an SGLT-2i compared with initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i) or a glucagonlike peptide-1 receptor agonist (GLP-1RA) among older adults (aged ≥66 years) with T2D in routine clinical practice. Design, Setting, and Participants: A population-based new-user cohort study included older adults with T2D who had no history of AF and were enrolled in Medicare fee-for-service from April 1, 2013, to December 31, 2018. Data analysis was performed from June 28 to December 1, 2021. Exposures: To control for potential confounding, new users of SGLT-2i were 1:1 propensity score (PS)-matched to new users of DPP-4is or GLP-1RAs in 2 pairwise comparisons based on 138 baseline covariates. Main Outcomes and Measures: The primary outcome was incident AF, defined as an inpatient diagnosis code for AF. Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years, with their 95% CIs, were estimated in the PS-matched groups. Results: New users of SGLT-2is were 1:1 PS-matched to new users of a DPP-4i (n = 74 868) or GLP-1RA (n = 80 475). Overall, the mean (SD) age of study participants was 72 (5) years, and 165 984 were women (53.4%). The risk of incident AF was lower in the SGLT-2i group than the matched DPP-4i group (HR, 0.82; 95% CI, 0.76 to 0.89; RD, -3.7; 95% CI, -5.2 to -2.2 per 1000 person-years) or the matched GLP-1RA group (HR, 0.90; 95% CI, 0.83 to 0.98; RD, -1.8; 95% CI, -3.2 to -0.3 per 1000 person-years). Results were consistent across several sensitivity and subgroup analyses. Conclusions and Relevance: The findings of this study suggest that the initiation of an SGLT-2i was associated with a reduced risk of incident AF compared with a DPP-4i or GLP-1RA. The results may be helpful when weighing the potential risks and benefits of various glucose level-lowering agents in older adults with T2D.

Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD). METHODS: We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia). RESULTS: A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m2). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion. CONCLUSIONS: Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.

Medication Burden and Prescribing Patterns in Patients on Hemodialysis in the USA, 2013-2017.

INTRODUCTION: The medication burden of patients with end-stage renal disease (ESRD) on hemodialysis, a patient population with a high comorbidity burden and complex care requirements, is among the highest of any of the chronic diseases. The goal of this study was to describe the medication burden and prescribing patterns in a contemporary cohort of patients with ESRD on hemodialysis in the USA. METHODS: We used the United States Renal Data System database from January 1, 2013, and December 31, 2017, to quantify the medication burden of patients with ESRD on hemodialysis aged ≥18 years. We calculated the average number of prescription medications per patient during each respective year (January-December), number of medications within classes, including potentially harmful medications, and trends in the number of medications and classes over the 5-year study period. RESULTS: We included a total of 163,228 to 176,133 patients from 2013 to 2017. The overall medication burden decreased slightly, from a mean of 7.4 (SD 3.8) medications in 2013 to 6.8 (SD 3.6) medications in 2017. Prescribing of potentially harmful medications decreased over time (74.0% with at least one harmful medication class in 2013-68.5% in 2017). In particular, the prescribing of non-benzodiazepine hypnotics, benzodiazepines, and opioids decreased from 2013 to 2017 (12.2%-6.3%, 23.4%-19.3%, and 60.0%-53.4%, respectively). This trend was consistent across subgroups of age, sex, race, and low-income subsidy status. CONCLUSIONS: Patients with ESRD on hemodialysis continued to have a high overall medication burden, with a slight reduction over time accompanied by a decrease in prescribing of several classes of harmful medications. Continued emphasis on assessment of appropriateness of high medication burden in patients with ESRD is needed to avoid exposure to potentially harmful or futile medications in this patient population.

Association of Sodium-Glucose Cotransporter-2 Inhibitors With Fracture Risk in Older Adults With Type 2 Diabetes.

Importance: Whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are associated with an increased risk of fractures in older adults with type 2 diabetes (T2D) outside of clinical trials remains unknown. Objective: To examine the association of incident fracture among older adults with T2D with initiating an SGLT-2i compared with initiating a dipeptidyl peptidase 4 inhibitor (DPP-4i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA). Design, Setting, and Participants: This is a population-based, new-user cohort study including older adults (aged ≥65 years) with T2D enrolled in Medicare fee-for-service from April 2013 to December 2017. Data analysis was performed from October 2020 to April 2021. Exposures: New users of an SGLT-2i, DPP-4i, or GLP-1RA without a previous fracture were matched in a 1:1:1 ratio using 3-way propensity score matching. Main Outcomes and Measures: The primary outcome was a composite end point of nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention within 30 days. After 3-way 1:1:1 propensity score matching, multivariable Cox proportional hazards regression models were used to generate hazard ratios (HRs) for SGLT-2i compared with DPP-4i and GLP-1RA and Kaplan-Meier curves to visualize fracture risk over time across groups. Results: Of 466 933 new initiators of study drugs, 62 454 patients were new SGLT-2i users. After 3-way matching, 45 889 (73%) new SGLT-2i users were matched to new users of DPP-4i and GLP-1RA, yielding a cohort of 137 667 patients (mean [SD] age, 72 [5] years; 64 126 men [47%]) matched 1:1:1 for analyses. There was no difference in the risk of fracture in SGLT-2i users compared with DPP-4i users (HR, 0.90; 95% CI, 0.73-1.11) or GLP-1RA users (HR, 1.00; 95% CI, 0.80-1.25). Results were consistent across categories of sex, frailty (nonfrail, prefrail, and frail), age (<75 and ≥75 years), and insulin use (baseline users and nonusers). Conclusions and Relevance: In this nationwide Medicare cohort, initiating an SGLT-2i was not associated with an increased risk of fracture in older adults with T2D compared with initiating a DPP-4i or GLP-1RA, with consistent results across categories of frailty, age, and insulin use. These findings add to the evidence base evaluating the potential risks associated with SGLT-2i use for older adults outside of randomized clinical trials.

Differential Diagnoses and Clinical Implications of Medication Nonadherence in Older Patients with Chronic Kidney Disease: A Review.

Older adults with chronic kidney disease (CKD) often have many comorbidities, which requires them to take multiple medications. As the number of daily medications prescribed increases, the risk for polypharmacy increases. Understanding and improving medication adherence in this patient population is vital to avoiding the drug-related adverse events of polypharmacy. The primary objective of this review is to summarize the existing literature and to understand the factors leading to medication nonadherence in older patients with CKD. In this review, we discuss the prevalence of polypharmacy, the current lack of consensus on the incidence of medication nonadherence, the heterogeneity of assessing medication adherence, and the most common differential diagnoses for medication nonadherence in this population. Specifically, the most common differential diagnoses for medication nonadherence in older adults with CKD are (1) medication complexity; (2) cognitive impairment; (3) low health literacy; and (4) systems-based barriers. We provide tailored strategies to address these differential diagnoses and subsequently improve medication adherence. The clinical implications include deprescribing to decrease medication complexity and polypharmacy, utilizing a team-based approach to identify and support patients with cognitive impairment, enriching communication between health providers and patients with low health literacy, and improving health care access to address systems-based barriers. Further research is needed to determine the effects of addressing these differential diagnoses and medication adherence in older adults with CKD.

Sodium-glucose cotransporter 2 inhibitors for diabetic kidney disease: a primer for deprescribing.

Chronic kidney disease (CKD) is a critical global public health problem associated with high morbidity and mortality, poorer quality of life and increased health care expenditures. CKD and its associated comorbidities are one of the most complex clinical constellations to manage. Treatments for CKD and its comorbidities lead to polypharmacy, which exponentiates the morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown remarkable benefits in cardiovascular and renal protection in patients with type 2 diabetes mellitus (T2DM). The pleiotropic effects of SGLT2is beyond glycosuria suggest a promising role in reducing polypharmacy in diabetic CKD, but the potential adverse effects of SGLT2is should also be considered. In this review, we present a typical case of a patient with multiple comorbidities seen in a CKD clinic, highlighting the polypharmacy and complexity in the management of proteinuria, hyperkalemia, volume overload, hyperuricemia, hypoglycemia and obesity. We review the cardiovascular and renal protection effects of SGLT2is in the context of clinical trials and current guidelines. We then discuss the roles of SGLT2is in the management of associated comorbidities and review the adverse effects and controversies of SGLT2is. We conclude with a proposal for deprescribing principles when initiating SGLT2is in patients with diabetic CKD.

The missing piece: Clinical pharmacists enhancing the interprofessional nephrology clinic model.

OBJECTIVES: To embed pharmacy residents in an interprofessional nephrology clinic to conduct medication reconciliation in targeted high-risk patients with nondialysis kidney disease. SETTING: This pilot was a prospective quality improvement initiative conducted in an interprofessional outpatient nephrology clinic. PRACTICE DESCRIPTION: The nephrology clinic team includes nephrology providers, a social worker, and a geriatrician. The team is responsible for the management of conditions such as nondialysis kidney disease, resistant hypertension, acute kidney injury, proteinuria, and nephropathy. EVALUATION: Primary outcomes included the number and type of medication discrepancies and drug therapy problems identified. Secondary outcomes included the changes in care process directly resulting from the pharmacy residents' recommendations. The perceived value of the pharmacy residents to the interprofessional team was assessed through postintervention anonymous surveys and semistructured interviews. RESULTS: The pharmacy residents conducted 118 visits for 87 unique patients (mean age 73 years, 97% male) with nondialysis kidney disease (89% stages III-V), polypharmacy (87% of patients taking > 10 medications), and a heavy comorbidity burden (85% hypertension, 80% dyslipidemia, 59% diabetes mellitus type II) from January to October 2017. Pharmacists identified 344 medication discrepancies and 301 drug therapy problems, resulting in 398 changes in care process. The most frequently identified discrepancies and drug therapy problems were the omission of an active medication from the medication list (86 of 344 discrepancies, 25%) and potentially inappropriate medications (106 of 301 drug therapy problems, 35%). Pharmacists recommended 228 medication changes, provided 76 adherence devices, facilitated 24 consults or referrals, and communicated with the primary care team on 70 occasions. The interprofessional team members all strongly agreed that patients and the team benefited from the pharmacists' involvement. CONCLUSION: Pharmacy resident-led medication reconciliation resulted in the identification and resolution of medication discrepancies and drug therapy problems, leading to changes in the care process.

Cardiovascular Outcomes of Calcium-Free vs Calcium-Based Phosphate Binders in Patients 65 Years or Older With End-stage Renal Disease Requiring Hemodialysis.

Importance: Guidelines restricting use of calcium-based phosphate binders in all patients with end-stage renal disease owing to their potential contribution to increased cardiovascular risk shifted prescribing from calcium acetate toward the costlier sevelamer carbonate products. Objective: To compare cardiovascular events and mortality between patients with end-stage renal disease (ESRD) undergoing hemodialysis receiving sevelamer vs calcium acetate in real-world practice. Design, Setting, and Participants: An observational cohort study was conducted using the United States Renal Data System linked to Medicare claims data (May 1, 2012, to December 31, 2013). Data analysis was performed from October 2017 to September 2018. Participants included patients 65 years or older with ESRD within 180 days after starting hemodialysis (sevelamer, 2647; calcium acetate, 2074). Exposures: New use of sevelamer (calcium-free phosphate binder) vs calcium acetate (calcium-based phosphate binder). Main Outcomes and Measures: Hazard ratios (HRs) with 95% CIs were estimated for fatal or nonfatal cardiovascular events (myocardial infarction or ischemic stroke: primary outcome) and all-cause mortality (secondary outcome) using Cox proportional hazards regression with fine stratification on the propensity score to control for potential confounders, including phosphorus and calcium levels. Results: After propensity score weighting, 2639 patients initiating sevelamer treatment (1184 men [44.9%]; mean [SD] age, 75.6 [6.9] years) and 2065 patients initiating calcium acetate treatment (930 men [45.0%]; mean [SD] age, 75.5 [7.1] years) were included in the analysis. Crude incidence rates (IRs) for cardiovascular events of 458 per 1000 person-years for sevelamer and 464 per 1000 person-years for calcium acetate were observed. After propensity score fine-stratification weighting, HRs of 0.96 (95% CI, 0.84-1.10) for cardiovascular events were observed. Results were consistent within subgroups of age (<75 y: primary outcome, HR, 1.02; 95% CI, 0.85-1.24; vs ≥75 years: primary outcome, HR, 0.83; 95% CI, 0.69-1.01) and sex (primary outcome in men: HR, 1.02; 95% CI, 0.83-1.26). Conclusions and Relevance: The results of the study do not suggest increased cardiovascular safety of sevelamer in the routine clinical practice of patients with ESRD compared with calcium acetate; this study's findings suggest that well-designed, long-term, randomized clinical trials are needed.

The Burden of Frailty Among U.S. Veterans and Its Association With Mortality, 2002-2012.

BACKGROUND: Frailty is a key determinant of clinical outcomes. We sought to describe frailty among U.S. Veterans and its association with mortality. METHODS: Nationwide retrospective cohort study of regular Veterans Affairs (VA) users, aged at least 65 years in 2002-2012, followed through 2014, using national VA administrative and Medicare and Medicaid data. A frailty index (FI) for VA (VA-FI) was calculated using the cumulative deficit method. Thirty-one age-related deficits in health from diagnostic and procedure codes were included and were updated biennially. Survival analysis assessed associations between VA-FI and mortality. RESULTS: A VA-FI was calculated for 2,837,152 Veterans over 10 years. In 2002, 35.5% were non-frail (FI = 0-0.10), 32.6% were pre-frail (FI = 0.11-0.20), 18.9% were mildly frail (FI = 0.21-0.30), 8.7% were moderately frail (FI = 0.31-0.40), and 4.3% were severely frail (FI > 0.40). From 2002 to 2012, the prevalence of moderate frailty increased to 12.7%and severe frailty to 14.1%. Frailty was strongly associated with survival and was independent of age, sex, race, and smoking; the VA-FI better predicted mortality than age alone. Although prevalence of frailty rose over time, compared to non-frail Veterans, 2 years' hazard ratios (95% confidence intervals) for mortality declined from a peak in 2004 of 2.01 (1.97-2.04), 3.49 (3.44-3.55), 5.88 (5.79-5.97), and 10.39 (10.23-10.56) for pre-frail, mildly, moderately, and severely frail, respectively, to 1.51 (1.49-1.53), 2.36 (2.33-2.39), 3.68 (3.63-3.73), 6.62 (6.53-6.71) in 2012. At every frailty level, risk of mortality was lower for women versus men and higher for blacks versus whites. CONCLUSIONS: Frailty affects at least 3 of every 10 U.S. Veterans aged 65 years and older, and is strongly associated with mortality. The VA-FI could be used to more accurately estimate life expectancy and individualize care for Veterans.

The Role of Deprescribing in Older Adults with Chronic Kidney Disease.

Older adults with chronic kidney disease (CKD) often experience polypharmacy, a recognized predictor of prescribing problems including inappropriately dosed medications, drug-drug and drug-disease interactions, morbidity and mortality. Polypharmacy is also associated with nonadherence, which leads to recurrent hospitalizations and poorer hemodialysis outcomes in CKD patients. Further complicating medication management in this vulnerable population are the physiologic changes that occur with both age and CKD. This guide for pharmacists and prescribers offers considerations in medication evaluation and management among older adults with CKD. Careful prescribing with the aid of tools such as the American Geriatrics Society Beers Criteria can support safe medication use and appropriate prescribing. Polypharmacy may be systematically addressed through 'deprescribing,' an evidence-based process that enables identification and elimination of unnecessary or inappropriate medications. Detailed guidance for deprescribing in older adults with CKD has not been published previously. We highlight three specific targets for medication optimization and deprescribing in older adults with CKD: (1) proton pump inhibitors, (2) oral hypoglycemic agents, including newer classes of agents, and (3) statins. These medication classes have been chosen as they represent three of the most commonly prescribed classes of medications in the United States. For each area, we review considerations for medication use in older adults with CKD and provide strategies to avoid, modify, or discontinue these medications when clinically indicated. By utilizing deprescribing techniques, pharmacists are well positioned to help decrease the medication burden in older adults with CKD, thereby potentially reducing the risk of morbidity and mortality associated with polypharmacy.

Impact of Thrombotic Microangiopathy on Renal Outcomes and Survival after Hematopoietic Stem Cell Transplantation.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication of hematopoietic stem cell transplantation (HSCT). We characterized the incidence, risk factors, and long-term outcomes associated with TA-TMA by performing a comprehensive review of all adult patients (n = 1990) undergoing allogeneic HSCT at the Dana Farber Cancer Institute/Brigham and Women's Hospital between 2005 and 2013. Using the City of Hope criteria, we identified 258 patients (13%) with "definite" TMA and 508 patients (26%) with "probable" TMA. Mismatched donor transplantation (subdistribution hazard ratio [sHR], 1.79; 95% confidence interval [CI], 1.17 to 2.75; P = .007), sirolimus-containing graft-versus-host disease prophylaxis (sHR, 1.73; 95% CI, 1.29 to 2.34; P < .001), myeloablative conditioning (sHR, 1.93, 95% CI, 1.38 to 2.68; P < .001), and high baseline lactate dehydrogenase (LDH) level (sHR, 1.64; 95% CI, 1.26 to 2.13; P < .001) were associated with definite TMA. Moreover, positive cytomegalovirus serostatus (sHR, 1.41; 95% CI, 1.16 to 1.71; P < .001), high and very high disease risk index (sHR, 1.48; 95% CI, 1.12 to 1.96, P = .007), and high baseline LDH level (sHR, 1.25; 95% CI, 1.05 to 1.49; P = .011) were associated with probable TMA. In multivariable analyses, definite and probable TMA were each independently associated with higher mortality (HR, 5.24; 95% CI, 4.43 to 6.20 and HR, 2.12; 95% CI, 1.84 to 2.44, respectively), and long-term kidney dysfunction (HR, 5.43; 95% CI, 4.61 to 6.40 and HR, 2.20; 95% CI, 1.92 to 2.51, respectively). Definite and probable TMA were also independently associated with an increased risk of nonrelapse mortality and shorter progression-free survival. Our findings indicate that TA-TMA is common following HSCT and is independently associated with increased risk of death and kidney dysfunction.

Determinants of plasma parathyroid hormone levels in young women.

While the effects of calcium, phosphorus intake, and vitamin D on parathyroid hormone (PTH) have been well studied, less is known about other factors that impact PTH. Our goal was to delineate associations between demographic, dietary, and plasma factors and PTH. We conducted a cross-sectional study of intact PTH among 1,288 nonblack women in the Nurses Health Study II aged 33-53 with BMI <30 kg/m2 and eGFR > or = 60 ml/min/1.73 m2. Median PTH was 30.7 pg/ml. After adjusting for 25-hydroxyvitamin D and other factors, PTH was 4.1 pg/ml lower (95% CI -7.7 to -0.5) in women who smoked 1-14 cigarettes/day and 6.4 pg/ml lower (95% CI -11.2 to -1.7) in women who smoked >15 cigarettes/day compared to nonsmokers. After multivariate adjustment, women whose BMI was 27-29 kg/m2 had PTH levels 2.0 pg/ml higher (95% CI 0.2-3.9) compared to BMI of 21-22 kg/m2 and women in the highest quartile of plasma phosphorus had PTH levels 4.1 pg/ml lower (95% CI -5.8 to -2.4) than women in the lowest quartile. Higher vitamin A intake was independently associated with lower PTH, whereas lower calcium intake, lower plasma calcium, lower plasma 25-hydroxyvitamin D, and winter blood draw were associated with higher PTH. Intakes of phosphorus, animal protein, magnesium, alcohol, and caffeine were not associated with PTH. Factors not classically associated with calcium-phosphorus metabolism impact PTH. Additional research is needed to elucidate the mechanisms whereby smoking, vitamin A, and phosphorus affect PTH and to examine how body size and season may affect PTH independent of 25(OH)D.