Azithromycin use increases the risk of sudden cardiac death in patients with hemodialysis-dependent kidney failure.

Azithromycin is an antibiotic with QT-prolonging potential commonly prescribed to individuals receiving hemodialysis. Hemodialysis patients have a high prevalence of clinical conditions, such as structural heart disease, that can enhance the pro-arrhythmic effects azithromycin, but were excluded from prior investigations evaluating the cardiac safety of azithromycin. Using data from the United States Renal Data System (2007-2017), we conducted two cohort studies to examine the cardiac safety of azithromycin relative to amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin (a fluoroquinolone antibiotic known to prolong the QT-interval) in the hemodialysis population. The primary outcome was five-day sudden cardiac death. Using inverse probability of treatment weighted survival models, we estimated hazard ratios, risk differences, and 95% confidence intervals. The azithromycin vs. amoxicillin-based antibiotic cohort included 282,899 patients and 725,431 treatment episodes (381,306 azithromycin and 344,125 amoxicillin-based episodes). Azithromycin vs. amoxicillin-based antibiotic treatment was associated with higher relative and absolute risks of sudden cardiac death, weighted hazard ratio of 1.70 (95% Confidence Interval, 1.36 to 2.11) and weighted risk difference per 100,000 treatment episodes of 25.0 (15.5 to 36.5). The azithromycin vs. levofloxacin cohort included 245,143 patients and 554,557 treatment episodes (387,382 azithromycin and 167,175 levofloxacin episodes). Azithromycin vs. levofloxacin treatment was associated with lower relative and absolute risks of sudden cardiac death, weighted hazard ratio of 0.79 (0.64 to 0.96) and weighted risk difference per 100,000 treatment episodes of -18.9 (-35.5 to -3.8). Thus, when selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks.

The modifying effect of the serum-to-dialysate potassium gradient on the cardiovascular safety of SSRIs in the hemodialysis population: a pharmacoepidemiologic study.

BACKGROUND: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs). METHODS: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus <4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study. RESULTS: The study included 25 099 patients: 11 107 (44.3%) higher QT-prolonging potential SSRI new users and 13 992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86-1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients <4 mEq/l [weighted HR 2.17 (95% CI 1.16-4.03) versus 0.95 (0.78-1.16)]. Nested case-control analyses yielded analogous results. CONCLUSIONS: The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted.

Proton pump inhibitors may enhance the risk of citalopram- and escitalopram-associated sudden cardiac death among patients receiving hemodialysis.

PURPOSE: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug-drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT-prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions. METHODS: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007-2017) and a new-user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1-year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11-1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06-1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85-1.26]). CONCLUSIONS: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients.

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

RATIONALE & OBJECTIVE: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 4,264 critically ill patients with COVID-19 (143 patients with pre-existing kidney failure receiving maintenance dialysis; 521 patients with pre-existing non-dialysis-dependent CKD; and 3,600 patients without pre-existing CKD) admitted to intensive care units (ICUs) at 68 hospitals across the United States. PREDICTOR(S): Presence (vs absence) of pre-existing kidney disease. OUTCOME(S): In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/cardiac arrest, thromboembolic events, major bleeds, and acute liver injury (secondary). ANALYTICAL APPROACH: We used standardized differences to compare patient characteristics (values>0.10 indicate a meaningful difference between groups) and multivariable-adjusted Fine and Gray survival models to examine outcome associations. RESULTS: Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median of 4 [IQR, 2-9] days for maintenance dialysis patients; 7 [IQR, 3-10] days for non-dialysis-dependent CKD patients; and 7 [IQR, 4-10] days for patients without pre-existing CKD). More dialysis patients (25%) reported altered mental status than those with non-dialysis-dependent CKD (20%; standardized difference=0.12) and those without pre-existing CKD (12%; standardized difference=0.36). Half of dialysis and non-dialysis-dependent CKD patients died within 28 days of ICU admission versus 35% of patients without pre-existing CKD. Compared to patients without pre-existing CKD, dialysis patients had higher risk for 28-day in-hospital death (adjusted HR, 1.41 [95% CI, 1.09-1.81]), while patients with non-dialysis-dependent CKD had an intermediate risk (adjusted HR, 1.25 [95% CI, 1.08-1.44]). LIMITATIONS: Potential residual confounding. CONCLUSIONS: Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies in this vulnerable population.

Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis.

BACKGROUND: Individuals receiving maintenance hemodialysis may be particularly susceptible to the lethal cardiac consequences of drug-induced QT prolongation because they have a substantial cardiovascular disease burden and high level of polypharmacy, as well as recurrent exposure to electrolyte shifts during dialysis. Electrophysiologic data indicate that among the selective serotonin reuptake inhibitors (SSRIs), citalopram and escitalopram prolong the QT interval to the greatest extent. However, the relative cardiac safety of SSRIs in the hemodialysis population is unknown. METHODS: In this retrospective cohort study, we used data from a cohort of Medicare beneficiaries receiving hemodialysis included in the US Renal Data System registry (2007-2014). We used a new-user design to compare the 1-year risk of sudden cardiac death among hemodialysis patients initiating SSRIs with a higher potential for prolonging the QT interval (citalopram, escitalopram) versus the risk among those initiating SSRIs with lower QT-prolonging potential (fluoxetine, fluvoxamine, paroxetine, sertraline). We estimated adjusted hazard ratios using inverse probability of treatment weighted survival models. Nonsudden cardiac death was treated as a competing event. RESULTS: The study included 30,932 (47.1%) hemodialysis patients who initiated SSRIs with higher QT-prolonging potential and 34,722 (52.9%) who initiated SSRIs with lower QT-prolonging potential. Initiation of an SSRI with higher versus lower QT-prolonging potential was associated with higher risk of sudden cardiac death (adjusted hazard ratio, 1.18; 95% confidence interval, 1.05 to 1.31). This association was more pronounced among elderly individuals, females, patients with conduction disorders, and those treated with other non-SSRI QT-prolonging medications. CONCLUSIONS: The heterogeneous QT-prolonging potential of SSRIs may differentially affect cardiac outcomes in the hemodialysis population.

Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance Hemodialysis.

Background Hospitalizations and 30-day readmissions are common in the hemodialysis population. Actionable clinical markers for near-term hospital encounters are needed to identify individuals who require swift intervention to avoid hospitalization. Aspects of volume management, such as failed target weight (i.e, estimated dry weight) achievement, are plausible modifiable indicators of impending adverse events. The short-term consequences of failed target weight achievement are not well established.Methods Statistically deidentified data were taken from a cohort of Medicare-enrolled, prevalent hemodialysis patients treated at a large dialysis organization from 2010 to 2012. We used a retrospective cohort design with repeated intervals, each consisting of 180-day baseline, 30-day exposure assessment, and 30-day follow-up period, to estimate the associations between failed target weight achievement and the risk of 30-day emergency department visits and hospitalizations. We estimated adjusted risk differences using inverse probability of exposure weighted Kaplan-Meier methods.Results A total of 113,561 patients on hemodialysis contributed 788,722 study intervals to analyses. Patients who had a postdialysis weight >1.0 kg above the prescribed target weight in ≥30% (versus <30%) of exposure period treatments had a higher absolute risk (risk difference) of 30-day: emergency department visits (2.13%; 95% confidence interval, 2.00% to 2.32%); and all-cause (1.47%; 95% confidence interval, 1.34% to 1.62%), cardiovascular (0.31%; 95% confidence interval, 0.24% to 0.40%), and volume-related (0.15%; 95% confidence interval, 0.11% to 0.21%) hospitalizations.Conclusions In the absence of objective measures of volume status, recurrent failure to achieve target weight is an easily identifiable clinical risk marker for impending hospital encounters among patients on hemodialysis.

A Comparative Study of Carvedilol Versus Metoprolol Initiation and 1-Year Mortality Among Individuals Receiving Maintenance Hemodialysis.

BACKGROUND: Carvedilol and metoprolol are the ß-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of ß-blocker prescriptions. Despite well-established pharmacologic and pharmacokinetic differences between the 2 medications, little is known about their relative safety and efficacy in the hemodialysis population. STUDY DESIGN: A retrospective cohort study using a new-user design. SETTING & PARTICIPANTS: Medicare-enrolled hemodialysis patients treated at a large US dialysis organization who initiated carvedilol or metoprolol therapy from January 1, 2007, through December 30, 2012. PREDICTOR: Carvedilol versus metoprolol initiation. OUTCOMES: All-cause mortality, cardiovascular mortality, and intradialytic hypotension (systolic blood pressure decrease ≥ 20mmHg during hemodialysis plus intradialytic saline solution administration) during a 1-year follow-up period. MEASUREMENTS: Survival models were used to estimate HRs and 95% CIs in mortality analyses. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% CIs in intradialytic hypotension analyses. Inverse probability of treatment weighting was used to adjust for several demographic, clinical, laboratory, and dialysis treatment covariates in all analyses. RESULTS: 27,064 individuals receiving maintenance hemodialysis were included: 9,558 (35.3%) carvedilol initiators and 17,506 (64.7%) metoprolol initiators. Carvedilol (vs metoprolol) initiation was associated with greater all-cause (adjusted HR, 1.08; 95% CI, 1.02-1.16) and cardiovascular mortality (adjusted HR, 1.18; 95% CI, 1.08-1.29). In subgroup analyses, similar associations were observed among patients with hypertension, atrial fibrillation, heart failure, and a recent myocardial infarction, the main cardiovascular indications for ß-blocker therapy. During follow-up, carvedilol (vs metoprolol) initiators had a higher rate of intradialytic hypotension (adjusted IRR, 1.10; 95% CI, 1.09-1.11). LIMITATIONS: Residual confounding may exist. CONCLUSIONS: Relative to metoprolol initiation, carvedilol initiation was associated with higher 1-year all-cause and cardiovascular mortality. One potential mechanism for these findings may be the increased occurrence of intradialytic hypotension after carvedilol (vs metoprolol) initiation.

Definitions of intradialytic hypotension.

Intradialytic hypotension (IDH) is a common and often distressful complication of hemodialysis. However, despite its clinical significance, there is no consensus, evidence-based medical definition for the condition. Over the years, numerous definitions have been implemented in both the clinical and research settings. Definition inconsistencies have hindered data synthesis and the development of evidence-based guidelines for the prevention and treatment of IDH, as well as prevented accurate estimation of the population burden of IDH and patient risk assessment. Most existing IDH definitions are comprised of one or more of the following components: (1) intradialytic BP criteria (requisite BP declines or minimum BP thresholds), (2) the provision of interventions aimed at restoring effective arterial volume, and/or (3) patient-reported symptoms. Remarkably, there are insufficient data to inform IDH definition construction, and it remains unknown if a single, universal definition can adequately capture the condition across patient subgroups, and in clinical and research settings.

Target weight achievement and ultrafiltration rate thresholds: potential patient implications.

BACKGROUND: Higher ultrafiltration (UF) rates and extracellular hypo- and hypervolemia are associated with adverse outcomes among maintenance hemodialysis patients. The Centers for Medicare and Medicaid Services recently considered UF rate and target weight achievement measures for ESRD Quality Incentive Program inclusion. The dual measures were intended to promote balance between too aggressive and too conservative fluid removal. The National Quality Forum endorsed the UF rate measure but not the target weight measure. We examined the proposed target weight measure and quantified weight gains if UF rate thresholds were applied without treatment time (TT) extension or interdialytic weight gain (IDWG) reduction. METHODS: Data were taken from the 2012 database of a large dialysis organization. Analyses considered 152,196 United States hemodialysis patients. We described monthly patient and dialysis facility target weight achievement patterns and examined differences in patient characteristics across target weight achievement status and differences in facilities across target weight measure scores. We computed the cumulative, theoretical 1-month fluid-related weight gain that would occur if UF rates were capped at 13 mL/h/kg without concurrent TT extension or IDWG reduction. RESULTS: Target weight achievement patterns were stable over the year. Patients who did not achieve target weight (post-dialysis weight ≥ 1 kg above or below target weight) tended to be younger, black and dialyze via catheter, and had shorter dialysis vintage, greater body weight, higher UF rate and more missed treatments compared with patients who achieved target weight. Facilities had, on average, 27.1 ± 9.7% of patients with average post-dialysis weight ≥ 1 kg above or below the prescribed target weight. In adjusted analyses, facilities located in the midwest and south and facilities with higher proportions of black and Hispanic patients and higher proportions of patients with shorter TTs were more likely to have unfavorable facility target weight measure scores. Without TT extension or IDWG reduction, UF rate threshold (13 mL/h/kg) implementation led to an average theoretical 1-month, fluid-related weight gain of 1.4 ± 3.0 kg. CONCLUSIONS: Target weight achievement patterns vary across clinical subgroups. Implementation of a maximum UF rate threshold without adequate attention to extracellular volume status may lead to fluid-related weight gain.

Ultrafiltration Rate and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Observational data have demonstrated an association between higher ultrafiltration rates and greater mortality among hemodialysis patients. Prior studies were small and did not consider potential differences in the association across body sizes and other related subgroups. No study has investigated ultrafiltration rates normalized to anthropometric measures beyond body weight. Also, potential methodological shortcomings in prior studies have led to questions about the veracity of the ultrafiltration rate-mortality association. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: 118,394 hemodialysis patients dialyzing in a large dialysis organization, 2008 to 2012. PREDICTORS: Mean 30-day ultrafiltration rates were dichotomized at 13 and 10mL/h/kg, separately and categorized using various cutoff points. Ultrafiltration rates normalized to body weight, body mass index, and body surface area were investigated. OUTCOMES: All-cause mortality. MEASUREMENTS: Multivariable survival models were used to estimate the association between ultrafiltration rate and all-cause mortality. RESULTS: At baseline, 21,735 (18.4%) individuals had ultrafiltration rates > 13mL/h/kg and 48,529 (41.0%) had ultrafiltration rates > 10mL/h/kg. Median follow-up was 2.3 years, and the mortality rate was 15.3 deaths/100 patient-years. Compared with ultrafiltration rates ≤ 13mL/h/kg, ultrafiltration rates > 13mL/h/kg were associated with greater mortality (adjusted HR, 1.31; 95% CI, 1.28-1.34). Compared with ultrafiltration rates ≤ 10mL/h/kg, ultrafiltration rates > 10mL/h/kg were associated with greater mortality (adjusted HR, 1.22; 95% CI, 1.20-1.24). Findings were consistent across subgroups of sex, race, dialysis vintage, session duration, and body size. Higher ultrafiltration rates were associated with greater mortality when normalized to body weight, body mass index, and body surface area. LIMITATIONS: Residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Regardless of the threshold implemented, higher ultrafiltration rate was associated with greater mortality in the overall study population and across key subgroups. Randomized controlled trials are needed to investigate whether ultrafiltration rate reduction improves clinical outcomes.

Identification of volume overload hospitalizations among hemodialysis patients using administrative claims: a validation study.

BACKGROUND: High rates of volume overload hospitalizations may indicate inadequate dialysis facility fluid management. Administrative claims databases are often used to study such outcomes, but these data are generated for billing purposes and may not capture clinical nuance. It is unknown if volume overload admissions can be correctly identified in administrative data and if a single claims-based definition for volume overload can be used across epidemiologic surveillance studies, observational studies of exposure-outcome associations and quality assessments. We conducted a validation study to assess the accuracy of claims-based definitions for volume overload hospitalizations among hemodialysis patients. METHODS: Data were taken from a random sample of 315 adult hemodialysis patients admitted to University of North Carolina Hospitals from January 2010 through June 2013. Standardized chart reviews were conducted to clinically adjudicate the presence or absence of volume overload at hospital admission. Claims-based definitions were constructed from varying combinations of fluid-related ICD-9 discharge diagnosis codes including fluid overload, pulmonary edema, pleural effusion, and heart failure. Using clinically adjudicated volume overload hospitalizations as the reference standard, validity metrics and their 95 % confidence intervals (CIs) were estimated for each definition. RESULTS: Of the 315 hospital admissions, 77 (24.4 %) were clinically adjudicated as volume overload hospitalizations. The prevalence of claims-identified volume overload admissions varied across definitions, ranging from 1.6 to 37.1 %. When definitions were constructed with discharge diagnosis codes present in any billing position, volume overload hospitalizations defined by fluid overload, pleural effusion or heart failure diagnosis codes had the highest sensitivity, 81.8 % (95 % CI: 71.4 %, 89.7 %). Volume overload hospitalizations defined by pulmonary edema diagnosis codes had the highest specificity, 98.3 % (95 % CI: 95.8 %, 99.5 %). Definitions constructed with discharge diagnosis codes present in any billing position (versus the primary position) captured more false positive events. CONCLUSIONS: Prevalence and validity estimates of volume overload hospitalizations vary across claims-based definitions. A universal claims-based definition for volume overload hospitalizations may not apply to all clinical and research scenarios. Investigators and regulators need to consider the implications of misclassifying events when evaluating and monitoring hemodialysis patient volume overload admissions with administrative data. Claims-based definitions should be selected accordingly.

Rapid ultrafiltration rates and outcomes among hemodialysis patients: re-examining the evidence base.

PURPOSE OF REVIEW: This review critically summarizes the evidence linking ultrafiltration rates to adverse outcomes among hemodialysis patients and provides research recommendations to address knowledge gaps. RECENT FINDINGS: Growing evidence suggests that fluid-related factors play important roles in hemodialysis patient outcomes. Ultrafiltration rate - the rate of fluid removal during hemodialysis - is one such factor. Existing observational data suggest a robust association between greater ultrafiltration rates and adverse cardiovascular outcomes, and such findings are supported by plausible physiologic rationale. Potential mechanistic pathways include ultrafiltration-related ischemia to the heart, brain, and gut, and volume overload-precipitated cardiac stress from reactive measures to ultrafiltration-induced hemodynamic instability. Inter-relationships among ultrafiltration rates and other fluid measures, such as interdialytic weight gain and chronic volume expansion, render the specific role of ultrafiltration rates in adverse outcomes difficult to study. Randomized trials must be conducted to confirm epidemiologic findings and examine the effect of ultrafiltration rate reduction on clinical and patient-centered outcomes. SUMMARY: Compelling observational data demonstrate an association between more rapid ultrafiltration rates and adverse clinical outcomes. Before translating these findings into clinical practice, randomized trials are needed to verify observational data results and to identify effective strategies to mitigate ultrafiltration-related risk.

Intradialytic Blood Pressure Abnormalities: The Highs, The Lows and All That Lies Between.

BACKGROUND: Frequent blood pressure (BP) measurements are necessary to ensure patient safety during hemodialysis treatments. Intradialytic BPs are not optimal tools for hypertension diagnosis and cardiovascular risk stratification, but they do have critical clinical and prognostic significance. We present evidence associating intradialytic BP phenomena including fall, rise and variability with adverse clinical outcomes and review related pathophysiologic mechanisms and potential management strategies. SUMMARY: Observational studies demonstrate associations between intradialytic hypotension, hypertension and BP variability and mortality. Lack of consensus regarding diagnostic criteria has hampered data synthesis, and prospective studies investigating optimal management strategies for BP phenomena are lacking. Mechanistic data suggest that cardiac, gut, kidney and brain ischemia may lie on the causal pathway between intradialytic hypotension and mortality, and endothelial cell dysfunction, among other factors, may be an important mediator of intradialytic hypertension and adverse outcomes. These plausible pathophysiologic links present potential therapeutic targets for future inquiry. The phenomenon of intradialytic BP variability has not been adequately studied, and practical clinical measures and treatment strategies are lacking. KEY MESSAGES: Intradialytic BP phenomena have important prognostic bearing. Clinical practice guidelines for both intradialytic hypotension and hypertension exist, but their underlying evidence is weak overall. Further research is needed to develop consensus diagnostic criteria for intradialytic hypotension, hypertension and BP variability and to elucidate optimal treatment and prevention strategies for each BP manifestation.

Incidence and Clinical Predictors of Nonresponse to Hepatitis B Vaccination among Patients Receiving Hemodialysis: Importance of Obesity.

OBJECTIVES: The objectives of this study were to quantify the incidence of hepatitis B virus (HBV) vaccine nonresponse and identify clinical characteristics associated with vaccine nonresponse. METHODS: A retrospective cohort study was conducted among patients undergoing hemodialysis (HD) receiving the HBV vaccine. Study inclusion criteria were age 18 years and older, receipt of HD treatment for ≥ 1 month, receipt of ≥ 1 dose of HBV vaccine, availability of anti-HB surface antibody (anti-HBs) laboratory values ≥ 2 weeks after last HBV vaccine, and prevaccine anti-HBs value <10 mIU/mL. Clinical data were abstracted from patients' medical records. The outcome of interest was vaccine nonresponse, defined as anti-HBs values <10 IU/mL. Multivariate regression was used to determine variables independently associated with vaccine nonresponse. Kaplan-Meier estimates were constructed for determining HBV vaccine response retention. RESULTS: Of the 119 patients evaluated, nonresponse was observed in 58%. Mean age at first vaccination for vaccine responders and nonresponders was 58.8 ± 16.5 and 65.9 ± 14.1 (P = 0.01), respectively. Variables independently associated with nonresponse were age 58 years and older (adjusted relative risk, 95% confidence interval 1.62, 1.06-2.46; P = 0.02) and body mass index ≥ 36.4 kg/m(2) (adjusted relative risk, 95% confidence interval 1.66, 1.34-2.07; P < 0.01). Among the 50 patients who achieved an initial vaccine response, 26% were not able to maintain vaccine response upon subsequent anti-HBs measurement. The probability of retaining vaccine response over time was significantly modified by body mass index ≥ 25 kg/m(2). CONCLUSIONS: The frequency of nonresponse to the HBV vaccine was high among patients undergoing HD. The clinical covariates most predictive of vaccine nonresponse were advanced age at the time of vaccination and excess body weight.

Observation stays in administrative claims databases: underestimation of hospitalized cases.

PURPOSE: Recent policy changes in the USA have led to an increasing number of patients being placed into observation units rather than admitted directly to the hospital. Studies of administrative data that use inpatient diagnosis codes to identify cohorts, outcomes, or covariates may be affected by this change in practice. To understand the potential impact of observation stays on research using administrative healthcare data, we examine the trends of observation stays, short (≤2 days) inpatient admissions, and all inpatient admissions. METHODS: We examined a large administrative claims database of commercially insured individuals in the USA between 2002 and 2011. Observation stays were defined on the basis of the procedure codes reimbursable by Medicare or commercial insurers. We report monthly rates of observation stays and short inpatient admissions overall and by patient demographics. RESULTS: We identified 5 355 752 observation stays from 2002 to 2011. Over the course of study, the rate of observation stays increased, whereas the rate of short inpatient stays declined. The most common reason for observation stays was nonspecific chest pain, also the third most common reason for short inpatient stays. The increasing trend of observation stays related to circulatory diseases mirrors the decreasing trend of short inpatient stays. CONCLUSIONS: The use of observation stays has increased in patients with commercial insurance. Failure to account for observation stays may lead to an under-ascertainment of hospitalizations in contemporary administrative healthcare data from the USA.

Prescription and Dispensation of QT-Prolonging Medications in Individuals Receiving Hemodialysis.

Importance: Individuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population. Objective: To examine prescription and dispensation patterns of QT-prolonging medications with known TdP risk and selected interacting medications prescribed to individuals receiving hemodialysis. Design, Setting, and Participants: This cross-sectional study included patients 60 years or older who were enrolled in Medicare Parts A, B, and D receiving in-center hemodialysis from January 1 to December 31, 2019. Analyses were conducted from October 20, 2022, to June 16, 2023. Exposures: New-user prescriptions for the 7 most frequently filled QT-prolonging medications characterized by the timing of the new prescription relative to acute care encounters, the type of prescribing clinician and pharmacy that dispensed the medication, and concomitant use of selected medications known to interact with the 7 most frequently filled QT-prolonging medications with known TdP risk. Main Outcomes and Measures: The main outcomes were the frequencies of the most commonly filled and new-use episodes of QT-prolonging medications; the timing of medication fills relative to acute care events; prescribers and dispensing pharmacy characteristics for new use of medications; and the frequency and types of new-use episodes with concurrent use of potentially interacting medications. Results: Of 20 761 individuals receiving hemodialysis in 2019 (mean [SD] age, 74 [7] years; 51.1% male), 10 992 (52.9%) filled a study drug prescription. Approximately 80% (from 78.6% for odansetron to 93.9% for escitalopram) of study drug new-use prescriptions occurred outside of an acute care event. Between 36.8% and 61.0% of individual prescriptions originated from general medicine clinicians. Between 16.4% and 26.2% of these prescriptions occurred with the use of another QT-prolonging medication. Most potentially interacting drugs were prescribed by different clinicians (46.3%-65.5%). Conclusions and Relevance: In this cross-sectional study, QT-prolonging medications for individuals with dialysis-dependent kidney failure were commonly prescribed by nonnephrology clinicians and from nonacute settings. Prescriptions for potentially interacting medications often originated from different prescribers. Strategies aimed at minimizing high-risk medication-prescribing practices in the population undergoing dialysis are needed.