Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related ...to these agents, which are renally cleared, but data regarding the risk thereof are lacking.
From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0-100, >100-200, >200-300, and >300 mg) and pregabalin (>0-100 and >100 mg).
In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%-41%) and fall (26%-30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively.
Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.
To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes ...in frailty over time and their association with death/delisting in patients too sick for liver transplantation.
Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk.
We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35–3.09).
Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.
Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.
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•In patients with cirrhosis, changes in frailty were significantly associated with death/delisting.•Patients with cirrhosis who experienced improvements in frailty over time had a lower risk of death/delisting.•Our data support the longitudinal measurement of frailty in patients with cirrhosis.•This study lays the foundation for interventional work aimed at reversing frailty.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Through this study, we aimed to assess the ability of routine neonatal screening at time of bronchopulmonary dysplasia (BPD) diagnosis to predict the development of late pulmonary hypertension ...(PHTN). This is a retrospective longitudinal cohort study of 37 premature infants with BPD assessing the utility of screening serum brain natriuretic peptide (BNP) and echocardiograms performed at the time of BPD diagnosis (‘early PHTN’) to predict ‘late PHTN’ at the last follow-up. Screening evaluation demonstrated early PHTN in 9/37 patients. At an average follow-up interval of 52.7 ± 38.7 weeks, 4/9 had late PHTN; one patient without early PHT had late PHT. At initial screening, infants with late PHTN were significantly more likely to have demonstrated elevated BNP values (
p
= 0.003), and echocardiographic evidence of right atrial dilatation (
p
= 0.01), right ventricular hypertrophy (
p
= 0.01), lower right ventricular area change percentage (
p
= 0.03), and larger main pulmonary artery Z-scores (
p
= 0.02). Serum BNP and echocardiographic evaluation performed at the time of BPD diagnosis can detect patients at increased risk of late PHTN. Large, prospective studies are necessary to further address this question.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Patients on hemodialysis frequently experience pain and may be particularly vulnerable to opioid-related complications. However, data evaluating the risks of opioid use in patients on hemodialysis ...are limited.
Using the US Renal Data System, we conducted a cohort study evaluating the association between opioid use (modeled as a time-varying exposure and expressed in standardized oral morphine equivalents) and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture among 140,899 Medicare-covered adults receiving hemodialysis in 2011. We evaluated risk according to average daily total opioid dose (>60 mg, ≤60 mg, and per 60-mg dose increment) and specific agents (per 60-mg dose increment).
The median age was 61 years old, 52% were men, and 50% were white. Sixty-four percent received opioids, and 17% had an episode of altered mental status (15,658 events), fall (7646 events), or fracture (4151 events) in 2011. Opioid use was associated with risk for all outcomes in a dose-dependent manner: altered mental status (lower dose: hazard ratio, 1.28; 95% confidence interval, 1.23 to 1.34; higher dose: hazard ratio, 1.67; 95% confidence interval, 1.56 to 1.78; hazard ratio, 1.29 per 60 mg; 95% confidence interval, 1.26 to 1.33), fall (lower dose: hazard ratio, 1.28; 95% confidence interval, 1.21 to 1.36; higher dose: hazard ratio, 1.45; 95% confidence interval, 1.31 to 1.61; hazard ratio, 1.04 per 60 mg; 95% confidence interval, 1.03 to 1.05), and fracture (lower dose: hazard ratio, 1.44; 95% confidence interval, 1.33 to 1.56; higher dose: hazard ratio, 1.65; 95% confidence interval, 1.44 to 1.89; hazard ratio, 1.04 per 60 mg; 95% confidence interval, 1.04 to 1.05). All agents were associated with a significantly higher hazard of altered mental status, and several agents were associated with a significantly higher hazard of fall and fracture.
Opioids were associated with adverse outcomes in patients on hemodialysis, and this risk was present even at lower dosing and for agents that guidelines have recommended for use.
Background and Aims
Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts ...waitlist mortality.
Approach and Results
Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo‐log‐likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease‐sodium (MELDNa) versus MELDNa alone in 3‐month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7‐5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval CI, 4.0‐4.8) for 3‐month mortality, 4.2 (95% CI, 4.1‐4.4) for 6‐month mortality, and 4.2 (95% CI, 4.1‐4.4) for 12‐month mortality. The AUC for prediction of 3‐month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79.
Conclusions
LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
IMPORTANCE: Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how ...frailty differs between women and men is unknown. OBJECTIVE: To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020. EXPOSURES: At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance). MAIN OUTCOMES AND MEASURES: The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men. RESULTS: Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 interquartile range (IQR), 50-63 years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 IQR, 14-23; men, 18 IQR, 15-22), but baseline LFI was higher in women (mean SD, 4.12 0.85 vs 4.00 0.82; P = .005). Women displayed worse balance of less than 30 seconds (145 25% vs 149 18%; P = .003), worse sex-adjusted grip (mean SD, −0.31 1.08 vs −0.16 1.08 kg; P = .01), and fewer chair stands per second (median, 0.35 IQR, 0.23-0.46 vs 0.37 IQR, 0.25-0.49; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty. CONCLUSIONS AND RELEVANCE: These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.
BACKGROUND
Guidelines recommend avoidance of several psychoactive medications such as hypnotics in older adults due to their adverse effects. Older patients on hemodialysis may be particularly ...vulnerable to complications related to use of these agents, but only limited data are available about the risks in this population.
OBJECTIVES
To evaluate the association between the use of psychoactive medications and time to first emergency department visit or hospitalization for altered mental status, fall, and fracture among older patients receiving hemodialysis.
DESIGN
Observational cohort study.
SETTING
National registry of patients receiving hemodialysis (US Renal Data System).
PARTICIPANTS
A total of 60 007 adults 65 years or older receiving hemodialysis with Medicare Part D coverage in 2011.
MEASUREMENTS
The predictors were use of sedative‐hypnotics and anticholinergic antidepressants (modeled as separate time‐varying exposures). The outcomes were time to first emergency department visit or hospitalization for altered mental status, fall, and fracture (modeled separately).
RESULTS
Overall, 17% and 6% used sedative‐hypnotics and anticholinergic antidepressants, respectively, in 2011. In multivariable‐adjusted Cox regression, anticholinergic antidepressant use was associated with a 25%, 27%, and 39% higher hazard of altered mental status, fall, and fracture, respectively, compared with no use. Use of sedative‐hypnotics was not associated with adverse outcomes.
CONCLUSION
Anticholinergic antidepressants were associated with adverse outcomes in older hemodialysis patients, and alternative treatments should be considered. Sedative‐hypnotics were not associated with the risks evaluated in this study, but further investigation of the harms of this class of agents is warranted before their recommendation as a treatment option for insomnia in this population. J Am Geriatr Soc 67:449–454, 2019.
See related Editorial by Rasheeda Hall in this issue.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Adult experience evaluating left ventricular diastolic function (LVDFx) includes volume administration during catheterization while obtaining pulmonary capillary wedge pressures (PCWP) or ...left ventricular end diastolic pressures (LVEDP). Catheterization is inherently challenging in pediatric patients, making echocardiographic assessment ideal. Pediatric echocardiographic studies predicting LVDFx have variable hemodynamic and hydration conditions and have produced inconsistent results. We evaluated the association between simultaneous echocardiographic and catheterization assessment of LVDFx, using a fluid bolus for optimal loading conditions.
Methods
Prospective cohort study of pediatric heart transplant recipients receiving echocardiogram simultaneous with routine cardiac catheterization. Mitral valve inflow velocities, septal and lateral wall tissue Doppler indices, and PCWP and/or LVEDP were obtained and repeated following a 10 ml/kg bolus. Echocardiographic parameters were evaluated for an association with changes in PCWP or LVEDP following the bolus. Abnormal LVDFx was defined as PCWP or LVEDP ≥12 mm Hg.
Results
Twenty‐nine patients underwent catheterization. Median pre‐bolus PCWP and LVEDP were 11.0 mm Hg and 10.0 mm Hg, respectively. After bolus, median PCWP and LVEDP increased to 14.0 mm Hg (p < .001) and 13 mm Hg (p < .001), respectively. Of 21 patients with normal pre‐bolus catheterization hemodynamics, 14 (66.7%) increased to abnormal following fluid bolus. Using area under an ROC, no echocardiographic parameter of LVDFx, or their ratios, were associated with predetermined abnormal LVEDP and/or PCWP.
Conclusion
After bolus, our cohort demonstrated significant increases in LVEDP and/or PCWP, unmasking diastolic dysfunction. Fluid challenges should be considered in pediatric patients undergoing cardiac catheterization with suspected diastolic dysfunction. Echocardiographic measurements were unable to discriminate between normal and abnormal LVEDP and/or PCWP.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The use of ventricular assist devices (VADs) to bridge pediatric patients to transplant or recovery has been expanding. There are few current pediatric data assessing the impact of VAD support on ...post-transplant survival.
We performed a retrospective review of all pediatric (≤18 years old, n = 4,028) transplants performed between 1995 and 2011 and contained within the United Network for Organ Sharing data set. Transplants were divided into three eras: early (1995 to 2002, n = 1,450); intermediate (2003 to 2007, n = 1,138); and recent (2008 to 2011, n = 1,440). VADs were present at transplant in 398 patients (9.8%). Outcomes among patients with and without VADs were assessed and compared across eras.
The use of VADs for bridge to transplant has increased (early 1.1%, intermediate 10.5%, recent 17.9%; p < 0.0001). Mean weight among VAD-supported patients (early 63.5 kg, intermediate 42.3 kg, recent 28.8 kg; p < 0.0001) has decreased during this period. VAD patients <10 kg had an increased risk of stroke (odds ratio OR = 4.9, 95% confidence interval CI 2.1 to 10.8) compared with non-mechanical support patients. In multivariable analyses, extracorporeal VADs were the only type of VAD associated with higher post-transplant mortality (OR = 3.0, 95% CI 0.8 to 10.6). Other types of VAD had lower mortality (OR = 0.5, 95% CI 0.2 to 1.0). Long-term survival was unaffected by the use of a VAD pre-transplant.
Pediatric patients bridged to transplantation with VADs are increasingly younger and smaller. Complication rates remain high among patients <10 kg. Early post-transplant survival among intracorporeal and paracorporeal VAD patients is excellent and better when compared with unsupported patients. The use of short-term support devices is associated with higher post-transplant mortality. Long-term survival is unaffected by VAD use.
Abstract The recent private-public partnership to unlock and utilize all available health data has large-scale implications for public health and personalized medicine, especially within ...orthopaedics. Today, consumer-based technologies such as smartphones and “wearables” store tremendous amounts of personal health data (known as “mHealth”) that, when processed and contextualized, have the potential to open new windows of insight for the orthopaedic surgeon about their patients. However, a limitation of the current mHealth landscape is the fragmentation and lack of interconnectivity between the myriad of available apps. One solution is to transform patient small data to insightful big data by implementing an “open” architecture that affords universal data standards and a global interconnected network. In the present report, the landscape, role, and future technical considerations of mHealth are defined with particular examples in lower extremity arthroplasty. Furthermore, the importance behind the currently lacking open mHealth architecture is underscored by the offer of improved research, increased workflow efficiency, and value capture for the orthopaedic surgeon.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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