Salimah Z. Shariff

Global trends in the rates of living kidney donation

As the worldwide prevalence of end-stage renal disease increases it is important to evaluate the rate of living kidney donation in various countries; however there is no comprehensive global assessment of these rates. To measure this, we compiled data from representatives, renal registries, transplant networks, published reports in the literature, and national health ministries from 69 countries and made estimates from regional weighted averages for an additional 25 countries where data could not be obtained. In 2006, about 27,000 related and unrelated legal living donor kidney transplants were performed worldwide, representing 39% of all kidney transplants. The number of living kidney donor transplants grew over the last decade, with 62% of countries reporting at least a 50% increase. The greatest numbers of living donor kidney transplants, on a yearly basis, were performed in the United States (6435), Brazil (1768), Iran (1615), Mexico (1459), and Japan (939). Saudi Arabia had the highest reported living kidney donor transplant rate at 32 procedures per million population (pmp), followed by Jordan (29), Iceland (26), Iran (23), and the United States (21). Our study shows that rates of living donor kidney transplant have steadily risen in most regions of the world, increasing its global significance as a treatment option for kidney failure.

The association between renal replacement therapy modality and long-term outcomes among critically ill adults with acute kidney injury: a retrospective cohort study*.

Objective:Among critically ill patients with acute kidney injury, the impact of renal replacement therapy modality on long-term kidney function is unknown. Compared with conventional intermittent hemodialysis, continuous renal replacement therapy may promote kidney recovery by conferring greater hemodynamic stability; yet continuous renal replacement therapy may not enhance patient survival and is resource intense. Our objective was to determine whether continuous renal replacement therapy was associated with a lower risk of chronic dialysis as compared with intermittent hemodialysis, among survivors of acute kidney injury. Design:Retrospective cohort study. Setting:Linked population-wide administrative databases in Ontario, Canada. Patients:Critically ill adults who initiated dialysis for acute kidney injury between July 1996 and December 2009. In the primary analysis, we considered those who survived to at least 90 days after renal replacement therapy initiation. Interventions:Initial receipt of continuous renal replacement therapy versus intermittent hemodialysis. Measurements and Main Results:Continuous renal replacement therapy recipients were matched 1:1 to intermittent hemodialysis recipients based on a history of chronic kidney disease, receipt of mechanical ventilation, and a propensity score for the likelihood of receiving continuous renal replacement therapy. Cox proportional hazards were used to evaluate the relationship between initial renal replacement therapy modality and the primary outcome of chronic dialysis, defined as the need for dialysis for a consecutive period of 90 days. We identified 2,315 continuous renal replacement therapy recipients of whom 2,004 (87%) were successfully matched to 2,004 intermittent hemodialysis recipients. Participants were followed over a median duration of 3 years. The risk of chronic dialysis was significantly lower among patients who initially received continuous renal replacement therapy versus intermittent hemodialysis (hazard ratio, 0.75; 95% CI, 0.65–0.87). This relation was more prominent among those with preexisting chronic kidney disease (p value for interaction term = 0.065) and heart failure (p value for interaction term = 0.035). Conclusions:Compared with intermittent hemodialysis, initiation of continuous renal replacement therapy in critically ill adults with acute kidney injury is associated with a lower likelihood of chronic dialysis.

The Secret of Immortal Time Bias in Epidemiologic Studies

In the March 2007 issue of JASN , Hemmelgarn et al. [1][1] reported a 50% reduction in the risk for all-cause mortality for patients who had chronic kidney disease (CKD) and attended multidisciplinary care (MDC) clinics compared with those who received usual care. Their survival curves showed a

Validity of the International Classification of Diseases, Tenth Revision code for acute kidney injury in elderly patients at presentation to the emergency department and at hospital admission

Objective To evaluate the validity of the International Classification of Diseases, Tenth Revision (ICD-10) code N17x for acute kidney injury (AKI) in elderly patients in two settings: at presentation to the emergency department and at hospital admission. Design A population-based retrospective validation study. Setting Southwestern Ontario, Canada, from 2003 to 2010. Participants Elderly patients with serum creatinine measurements at presentation to the emergency department (n=36 049) or hospital admission (n=38 566). The baseline serum creatinine measurement was a median of 102 and 39 days prior to presentation to the emergency department and hospital admission, respectively. Main outcome measures Sensitivity, specificity and positive and negative predictive values of ICD-10 diagnostic coding algorithms for AKI using a reference standard based on changes in serum creatinine from the baseline value. Median changes in serum creatinine of patients who were code positive and code negative for AKI. Results The sensitivity of the best-performing coding algorithm for AKI (defined as a ≥2-fold increase in serum creatinine concentration) was 37.4% (95% CI 32.1% to 43.1%) at presentation to the emergency department and 61.6% (95% CI 57.5% to 65.5%) at hospital admission. The specificity was greater than 95% in both settings. In patients who were code positive for AKI, the median (IQR) increase in serum creatinine from the baseline was 133 (62 to 288) µmol/l at presentation to the emergency department and 98 (43 to 200) µmol/l at hospital admission. In those who were code negative, the increase in serum creatinine was 2 (−8 to 14) and 6 (−4 to 20) µmol/l, respectively. Conclusions The presence or absence of ICD-10 code N17× differentiates two groups of patients with distinct changes in serum creatinine at the time of a hospital encounter. However, the code underestimates the true incidence of AKI due to a limited sensitivity.

Retrieving Clinical Evidence: A Comparison of PubMed and Google Scholar for Quick Clinical Searches

Background Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. Objective To compare the performance of searches in PubMed and Google Scholar. Methods We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Results Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). Conclusions For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles.

Detecting chronic kidney disease in population-based administrative databases using an algorithm of hospital encounter and physician claim codes

BackgroundLarge, population-based administrative healthcare databases can be used to identify patients with chronic kidney disease (CKD) when serum creatinine laboratory results are unavailable. We examined the validity of algorithms that used combined hospital encounter and physician claims database codes for the detection of CKD in Ontario, Canada.MethodsWe accrued 123,499 patients over the age of 65 from 2007 to 2010. All patients had a baseline serum creatinine value to estimate glomerular filtration rate (eGFR). We developed an algorithm of physician claims and hospital encounter codes to search administrative databases for the presence of CKD. We determined the sensitivity, specificity, positive and negative predictive values of this algorithm to detect our primary threshold of CKD, an eGFR <45 mL/min per 1.73 m2 (15.4% of patients). We also assessed serum creatinine and eGFR values in patients with and without CKD codes (algorithm positive and negative, respectively).ResultsOur algorithm required evidence of at least one of eleven CKD codes and 7.7% of patients were algorithm positive. The sensitivity was 32.7% [95% confidence interval: (95% CI): 32.0 to 33.3%]. Sensitivity was lower in women compared to men (25.7 vs. 43.7%; p <0.001) and in the oldest age category (over 80 vs. 66 to 80; 28.4 vs. 37.6 %; p < 0.001). All specificities were over 94%. The positive and negative predictive values were 65.4% (95% CI: 64.4 to 66.3%) and 88.8% (95% CI: 88.6 to 89.0%), respectively. In algorithm positive patients, the median [interquartile range (IQR)] baseline serum creatinine value was 135 μmol/L (106 to 179 μmol/L) compared to 82 μmol/L (69 to 98 μmol/L) for algorithm negative patients. Corresponding eGFR values were 38 mL/min per 1.73 m2 (26 to 51 mL/min per 1.73 m2) vs. 69 mL/min per 1.73 m2 (56 to 82 mL/min per 1.73 m2), respectively.ConclusionsPatients with CKD as identified by our database algorithm had distinctly higher baseline serum creatinine values and lower eGFR values than those without such codes. However, because of limited sensitivity, the prevalence of CKD was underestimated.

Atypical Antipsychotic Drugs and the Risk for Acute Kidney Injury and Other Adverse Outcomes in Older Adults: A Population-Based Cohort Study

Context Acute kidney injury (AKI) is reportedly associated with atypical antipsychotic drugs, although the risk has not been quantified. Contribution This population-based cohort study found that persons who had received a prescription for any of 3 atypical antipsychotic drugs in the previous 90 days had an elevated risk for hospitalization with AKI. These drugs were also associated with increased risk for hypotension, acute urinary retention, and death. Caution Only older adults and 3 antipsychotic agents were studied. Implication An association with specific adverse events may explain the increased risk for AKI observed with certain atypical antipsychotic drugs. The Editors Each year, millions of older adults worldwide are prescribed atypical antipsychotic drugs (quetiapine, risperidone, and olanzapine). These drugs are frequently used to manage behavioral symptoms of dementia, which is not an approved indication, and such use has raised safety concerns (1, 2). These drugs antagonize -adrenergic, muscarinic, serotonin, and dopamine receptors (3). Acute kidney injury (AKI) (defined as a sudden loss of kidney function) from atypical antipsychotic drugs is described in several case reports (48). Adverse outcomes potentially attributable to these drugs, such as hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis, are known to cause AKI (411). Moreover, pneumonia, acute myocardial infarction, and ventricular arrhythmia have been associated with these drugs in previous population-based studies and AKI may also co-occur with these events (1214). However, no clinical or epidemiologic studies have quantified the risk for AKI from atypical antipsychotic drugs and information on outcomes of hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis is limited. Such information would contribute to growing knowledge of potential adverse events from this drug class. The U.S. Food and Drug Administration warns of an increased risk for death in older patients treated with these drugs based on analyses of randomized, placebo-controlled trials (averaging 10 weeks in duration) (1). For these reasons, we did this population-based study of older adults to investigate the 90-day risk for hospitalization with AKI and other adverse outcomes from new use of an oral atypical antipsychotic drug initiated in the nonhospital setting. Methods Design and Setting We conducted this study at the Institute for Clinical Evaluative Sciences according to a prespecified protocol that was approved by the research ethics board at Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Patient informed consent was not required. We did a population-based, retrospective cohort study of older adults using linked health care databases in Ontario, Canada. Ontario residents have universal access to hospital care and physician services, and those aged 65 years or older have universal prescription drug coverage. The reporting of this study followed guidelines for observational studies (Table 1 of the Supplement) (15). Supplement. Supplementary material Data Sources We ascertained patient characteristics, drug use, covariate information, and outcome data using records from 5 databases. We obtained vital statistics from the Registered Persons Database of Ontario, which contains demographic information on all Ontario residents who have ever been issued a health card. We used the Ontario Drug Benefit database to identify prescription drug use. This database contains highly accurate recordsthe error rate is less than 1%of all outpatient prescriptions dispensed to patients aged 65 years or older (16). We identified diagnostic and procedural information on all hospitalizations from the Canadian Institute for Health Information Discharge Abstract Database. We obtained covariate information from the Ontario Health Insurance Plan database, which includes health claims for inpatient and outpatient physician services. We identified diagnostic information on all admissions to adult mental health beds from the Ontario Mental Health Reporting System. We have used these databases to research adverse drug reactions and health outcomes (including AKI) (1722). The databases were complete for all variables used in this study, except for prescriber information (which was missing for 10.8% of patients in the cohort). Codes from the International Classification of Diseases, Ninth Revision (before 2002), and Tenth Revision (after 2002), were used to assess baseline comorbid conditions in the 5 years before cohort entry (Table 2 of the Supplement). Codes used to ascertain outcomes are detailed in Table 3 of the Supplement, which lists only codes from the Tenth Revision because all events would have occurred after implementation of that coding system. A subpopulation in southwestern Ontario had information on outpatient serum creatinine levels available before cohort entry; this group was in the catchment area of 12 hospitals in which linked laboratory values were also available (23). Patients We established a cohort of older adults with evidence of a new outpatient prescription for an oral atypical antipsychotic drug (quetiapine, risperidone, or olanzapine) between June 2003 and December 2011. The date of this prescription served as the index date (cohort entry date) for the drug recipients. We matched a group of drug nonrecipients similar in health status to the recipients. We randomly assigned an index date to the entire Ontario population according to the index date of the drug recipients. For example, if more recipients had an index date between 2003 and 2005, a greater proportion of the population would have been randomly assigned an index date between 2003 and 2005. From these adults, after applying our exclusions to both groups, we matched a drug nonrecipient to each recipient on the following 11 characteristics: age (within 2 years); sex; residential status (community-dwelling or long-term care); evidence of comorbid conditions (dementia, schizophrenia or other psychotic disorder, bipolar disorder, major depression or anxiety disorder, Parkinson disease, and chronic kidney disease); constituency in the subpopulation with available information on serum creatinine levels; and the logit of the propensity score for the predicted probability of newly receiving an atypical antipsychotic drug (within a caliper of 0.2 SDs). We derived this propensity score from a logistic regression model and selected 91 variables for inclusion in the score on the basis of their potential association with the study outcomes or atypical antipsychotic drug initiation (variables listed in Table 4 of the Supplement) (24). One of the variables was the Johns Hopkins Adjusted Clinical Group Aggregated Diagnosis Groups (a validated measure of the complexity of comorbid conditions based on groups of diagnoses) (25, 26). Before matching, we excluded the following patients from both groups: those with prescriptions for any antipsychotic drug in the 180 days before their index date to ensure that the drug was newly prescribed (or had the potential to be newly prescribed in the case of the nonrecipients); those who were discharged from a hospital in the 2 days before their index date to ensure that drug use was newly initiated in the nonhospitalized setting (as in Ontario, patients continuing atypical antipsychotic drug treatment initiated in a hospital would have their oral outpatient prescription dispensed the day of or the day after hospital discharge); and those with evidence of end-stage renal disease before their index date (because the development of AKI is no longer relevant). Among the drug recipients, those who received a prescription for more than 1 type of antipsychotic drug (for example, a prescription for quetiapine and olanzapine) on their index date were excluded to compare mutually exclusive groups in subgroup analyses. Among the nonrecipients, those who did not have at least 1 outpatient medication dispensed in the 90 days before their index date were excluded to ensure that such persons were able to receive a prescription. Each drug recipient and nonrecipient could be selected only once for cohort entry. Outcomes We followed patients for 90 days after the index date to assess the prespecified outcomes. We chose 90 days to focus on acute adverse events, avoid potential crossovers between the 2 groups that might occur with longer follow-up, and mimic the duration of follow-up described in clinical trials of atypical antipsychotic drugs in older patients (1, 2, 27). The primary outcome was hospitalization with AKI. The secondary adverse outcomes were known causes of AKI (hospitalization with hypotension, acute urinary retention, the neuroleptic malignant syndrome or rhabdomyolysis, pneumonia, acute myocardial infarction, and ventricular arrhythmia) and all-cause mortality. The diagnosis codes used to identify the outcomes and information on their accuracy are presented in Table 3 of the Supplement (2830). For hospitalization records, up to 25 diagnosis codes can be assigned per hospitalization (for example, codes for AKI or rhabdomyolysis). Therefore, patients with codes for multiple study outcomes were accounted for in the assessment of each outcome. We previously examined the validity of the database code for hospitalization with AKI used in the current study. In this previous validation study (30), the database code for AKI identified a median increase in serum creatinine level of 98 mol/L (1.11 mg/dL) (interquartile range [IQR], 43 to 200 mol/L [0.49 to 2.26 mg/dL]) at the time of hospital presentation from the most recent value before hospitalization. The absence of such a code represented no statistically significant change in serum creatinine level (6 mol/L [0.07 mg/dL]; IQR, 4 to 20 mol/L [0.05 to 0.23 mg/dL]) (30). Although specificity was greater than 95%, the sensitivity of the hospital diagnosis was

Use of Clinical Decision Support Systems for Kidney-Related Drug Prescribing: A Systematic Review

BACKGROUND Clinical decision support systems (CDSSs) have the potential to improve kidney-related drug prescribing by supporting the appropriate initiation, modification, monitoring, or discontinuation of drug therapy. STUDY DESIGN Systematic review. We identified studies by searching multiple bibliographic databases (eg, MEDLINE and EMBASE), conference proceedings, and reference lists of all included studies. SETTING & POPULATION CDSSs used in hospital or outpatient settings for acute kidney injury and chronic kidney disease, including end-stage renal disease (chronic dialysis patients or transplant recipients). SELECTION CRITERIA FOR STUDIES Studies prospectively using CDSSs to aid in kidney-related drug prescribing. INTERVENTION Computerized or manual CDSSs. OUTCOMES Clinician prescribing and patient-important outcomes as reported by primary study investigators. CDSS characteristics, such as whether the system was computerized, and system setting. RESULTS We identified 32 studies. In 17 studies, CDSSs were computerized, and in 15 studies, they were manual pharmacist-based systems. Systems intervened by prompting for drug dosing adjustments in relation to the level of decreased kidney function (25 studies) or in response to serum drug concentrations or a clinical parameter (7 studies). They were used most in academic hospital settings. For computerized CDSSs, clinician prescribing outcomes (eg, frequency of appropriate dosing) were considered in 11 studies, with all 11 reporting statistically significant improvements. Similarly, manual CDSSs that incorporated clinician prescribing outcomes showed statistically significant improvements in 6 of 8 studies. Patient-important outcomes (eg, adverse drug events) were considered in 7 studies of computerized CDSSs, with statistically significant improvements in 2 studies. For manual CDSSs, 6 studies measured patient-important outcomes and 5 reported statistically significant improvements. Cost-savings also were reported, mostly for manual CDSSs. LIMITATIONS Studies were heterogeneous in design and often limited by the evaluation method used. Benefits of CDSSs may be reported selectively in this literature. CONCLUSION CDSSs are available for many dimensions of kidney-related drug prescribing, and results are promising. Additional high-quality evaluations will guide their optimal use.

Trends in Psychotropic Dispensing Among Older Adults with Dementia Living in Long-Term Care Facilities: 2004-2013.

OBJECTIVE Guidelines worldwide have cautioned against the use of antipsychotics as first-line agents to treat neuropsychiatric symptoms of dementia. We aimed to investigate the changes over time in the dispensing of antipsychotics and other psychotropics among older adults with dementia living in long-term care facilities. METHODS We used drug claims data from Ontario, Canada, to calculate quarterly rates of prescription dispensing of six psychotropic drug classes among all elderly (≥65 years of age) long-term care residents with dementia from January 1, 2004, to March 31, 2013. Psychotropic drugs were classified into the following categories: atypical and conventional antipsychotics, non-sedative and sedative antidepressants, anti-epileptics, and benzodiazepines. We used time-series analysis to assess trends over time. RESULTS The study sample increased by 21% over the 10-year study period, from 49,251 patients to 59,785 patients. The majority of patients (within the range of 75%-79%) were dispensed at least one psychotropic medication. At the beginning of the study period atypical antipsychotics (38%) were the most frequently dispensed psychotropic, followed by benzodiazepines (28%), non-sedative antidepressants (27%), sedative antidepressants (17%), anti-epileptics (7%), and conventional antipsychotics (3%). Dispensing of anti-epileptics (2% increase) and conventional antipsychotics (1% decrease) displayed modest changes over time, but we observed more pronounced changes in dispensing of benzodiazepines (11% decrease) and atypical antipsychotics (4% decrease). Concurrently, we observed a substantial growth in the dispensing of both sedative (15% increase) and non-sedative (9% increase) antidepressants. The proportion of patients dispensed two or more psychotropic drug classes increased from 42% in 2004 to 50% in 2013. CONCLUSIONS Utilization patterns of psychotropic drugs in institutionalized patients with dementia have changed over the past decade. Although their use declined slightly over the study period, atypical antipsychotics continue to be used at a high rate. A decline in the use of benzodiazepines along with an increased use of sedative and non-sedative antidepressants suggests that the latter class of drugs is being substituted for the former in the management of neuropsychiatric symptoms. Psychotropic polypharmacy continues to be highly prevalent in these patient samples.

Filtering Medline for a clinical discipline: diagnostic test assessment framework

Objective To develop and test a Medline filter that allows clinicians to search for articles within a clinical discipline, rather than searching the entire Medline database. Design Diagnostic test assessment framework with development and validation phases. Setting Sample of 4657 articles published in 2006 from 40 journals. Reviews Each article was manually reviewed, and 19.8% contained information relevant to the discipline of nephrology. The performance of 1 155 087 unique renal filters was compared with the manual review. Main outcome measures Sensitivity, specificity, precision, and accuracy of each filter. Results The best renal filters combined two to 14 terms or phrases and included the terms “kidney” with multiple endings (that is, truncation), “renal replacement therapy”, “renal dialysis”, “kidney function tests”, “renal”, “nephr” truncated, “glomerul” truncated, and “proteinuria”. These filters achieved peak sensitivities of 97.8% and specificities of 98.5%. Performance of filters remained excellent in the validation phase. Conclusions Medline can be filtered for the discipline of nephrology in a reliable manner. Storing these high performance renal filters in PubMed could help clinicians with their everyday searching. Filters can also be developed for other clinical disciplines by using similar methods.