Faculty Bibliography

Introduction Most persons on hemodialysis (HD) are older, and many have trouble with walking and self-care. Yet data are sparse on how mobility is shaped by personal factors such as motivation in this group. Our goal was to identify what personal factors impact the mobility of older adults on HD. Methods We included 1) older adults on HD (inclusion criteria: >=60 years; on outpatient HD) and 2) care partners (inclusion criteria: >=18 years; routinely helping an older adult on HD). Each had a single in-person assessment. We administered the Short Physical Performance Battery (SPPB, range 0-12 points) to assess mobility, and audio-recorded one-on-one semi-structured key informant interviews regarding personal factors for mobility. Unless requested, older adults and care partners were interviewed separately. Transcripts underwent descriptive and focused coding; the codebook was revised iteratively until consensus on all code definitions was reached. We identified codes that were personal factors using International Classification of Function criteria. A combined inductive and deductive approach extracted major themes. Results We enrolled 31 older adults on HD (42% female, 50% Black) with a mean age of 72.5+/-8.1(S.D.) years and a mean history on HD for 4.6+/-3.5 years. For the older adults on HD, mean SPPB was 3.6+/-2.8 points. Twelve care partners enrolled (75% female, 50% Black) with a mean age of 53.8+/-15.7 years. TheTable lists the themes that emerged. Conclusion Our diverse sample of older adults on HD had poor mobility, and had a mean SPPB score that is associated with 20% one-year mortality in other groups. They want mobility and independence, but mobility frequently flutuates, causing distress. They and their care partners have learned to be flexible in their expectations. Future studies should incorporate these insights in interventions to improve the mobility of older adults on HD

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of allogeneic hematopoietic cell transplantation (HCT) that often occurs following the development of acute graft-versus-host disease (aGVHD). In this study, we aimed to identify early TMA biomarkers among patients with aGVHD. We performed a nested-case-control study from a prospective cohort of allogeneic HCT recipients, matching on the timing and severity of antecedent aGVHD. We identified 13 TMA cases and 25 non-TMA controls from 208 patients in the cohort. Using multivariable conditional logistic regression, the odds ratio for TMA compared with non-TMA was 2.65 (95% confidence interval [CI], 1.00 to 7.04) for every 100 ng/mL increase in terminal complement complex sC5b9 and 2.62 (95% CI, 1.56 to 4.38) for every 1000 pg/mL increase in angiopoietin-2 (ANG2) at the onset of aGVHD. ADAMTS13 and von Willebrand factor (VWF) antigens were not appreciably associated with TMA. Using a Cox regression model incorporating sC5b9 >300 ng/mL and ANG2 >3000 pg/mL at the onset of aGVHD, the adjusted hazard ratio for mortality was 5.33 (95% CI, 1.57 to 18.03) for the high-risk group (both elevated) and 4.40 (95% CI, 1.60 to 12.07) for the intermediate-risk group (one elevated) compared with the low-risk group (neither elevated). In conclusion, we found that elevated sC5b9 and ANG2 levels at the onset of aGVHD were associated with the development of TMA and possibly mortality after accounting for the timing and severity of aGVHD. The results suggest important roles of complement activation and endothelial dysfunction in the pathogenesis of TMA. Measurement of these biomarkers at the onset of aGVHD may inform prognostic enrichment for preventive trials and improve clinical care.

RATIONALE/BACKGROUND:No direct comparisons of clinical features, laboratory values, and outcomes between critically ill patients with COVID-19 and influenza in the United States have been reported. OBJECTIVE:To evaluate the risk of mortality comparing critically ill patients with COVID-19 to seasonal influenza. METHODS:We retrospectively identified patients admitted to the intensive care units (ICUs) at two academic medical centers with laboratory confirmed SARS-CoV-2 or influenza A or B infections between January 1, 2019 and April 15, 2020. Clinical data were obtained by medical record review. All patients except one had follow-up to hospital discharge or death. We used relative risk regression adjusting for age, sex, number of comorbidities, and maximum sequential organ failure scores (SOFA) on ICU day 1 to determine the risk of hospital mortality and organ dysfunction in patients with COVID-19 compared to influenza. RESULTS:We identified 65 critically ill patients with COVID-19 and 74 with influenza. The mean (± standard deviation) age in each group was 60.4 +/- 15.7 and 56.8 +/- 17.6 years, respectively. Patients with COVID-19 were more likely to be male, have higher body mass index and higher rates of chronic kidney disease and diabetes. Thirty-seven percent of COVID-19 patients identified as Hispanic, compared to 10% of influenza patients. A similar proportion of patients had fever (~40%) and lymphopenia (~80%) on hospital presentation. Rates of acute kidney injury and shock requiring vasopressors were similar between the groups. While need for invasive mechanical ventilation was also similar in both groups, patients with COVID-19 had slower improvements in oxygenation, longer durations of mechanical ventilation, and lower rates of extubation compared to patients with influenza. Hospital mortality was 40% in COVID-19 patients and 19% in influenza patients (adjusted relative risk 2.13, 95% confidence interval 1.24 to 3.63; p = 0.006). CONCLUSIONS:Need for invasive mechanical ventilation was common in ICU patients with COVID-19 or influenza. Compared to those with influenza, ICU patients with COVID-19 had worse respiratory outcomes, including longer duration of mechanical ventilation. Additionally, patients with COVID-19 were at greater risk for in-hospital mortality, independent of age, sex, co-morbidities, and ICU severity of illness.

Background: Home blood pressure measurement (HBPM) has been a time-honored supplement to periodic in-office measurement to facilitate primary care physician (PCP) diagnosis of hypertension (HTN), its ongoing control and medication management. PCPs, in response to COVID-19, adopted telemedicine as the sole means of care, elevating HBPM as the essential HTN surveillance tool. We assessed the feasibility of this approach in a Veteran Affairs (VA) geriatric clinic.
Method(s): Study subjects included all the Veterans seen by New York Harbor VA geriatrics fellows' clinic between January 1, 2019 and March 1, 2020 and who have HTN listed as an electronic health record (EHR) diagnosis. Those with systolic blood pressure (SBP) > 140 mmHg were prioritized. We called these patients to assess adherence to BP self-care and reconcile medications, to identify reasons for poor adherence and to offer solutions. Patients were called again within two months to re-assess adherence, collect BP measures and adjust medications as needed.
Result(s): Among 102 patients diagnosed with HTN, 41 had not achieved the goal of SBP <140 mmHg prior to this intervention. We reached 78% (n=32) of these 41 patients (requiring 1-3 phone calls). All reported medical adherence, but none were found to consistently check BP at home with any frequency or proper technique. For the 14 patients having no BP monitor at home, we sent a monitor to 10 through prescription and enrolled 4 in a home telehealth (HT) program that uses daily remote measurement. We provided detailed instruction of proper HBPM during the initial interview. At follow-up, 47% (n=15) practiced HBPM and reported BP readings within goal, indicating no need for change in care. Of these 15, 11 had their own BP monitors; 2 achieved control through the HT program. However, only 2 of the 10 patients who received the prescribed BP monitor started HBPM and demonstrated good control.
Conclusion(s): Given our reliance on telemedicine, HBPM is feasible for outpatient HTN management. Close PCP follow-up to encourage consistent HBPM practice may improve and sustain the success of this strategy. The quality of self-reported data should be assessed during office visits

SOURCE CITATION:N Engl J Med. 2021;384:216-28. 33186492.

INTRODUCTION/BACKGROUND:Although weight gain has been reported with the use of integrase strand transfer inhibitors (InSTI), concurrent use of tenofovir alafenamide (TAF) has been implicated in recent studies. This study examined weight changes in people living with HIV (PLWH) who switched from tenofovir disoproxil fumarate (TDF) to TAF, to clarify the relative contribution to weight gain of core agents versus TDF to TAF switch. METHODS:Antiretroviral-experienced, virologically suppressed PLWH in the U.S. OPERA cohort were included if they switched from TDF to TAF (5NOV2015-28FEB2019) and either maintained all other antiretrovirals or switched from a non-InSTI to an InSTI. Linear mixed models were used to assess weight changes before/after the switch to TAF (restricted cubic splines on time) and rates of change over time (linear splines on time, based on the shape of the weight change curves). Changes in weight on TDF or TAF were assessed among those who maintained other antiretrovirals (overall, by core class), and those who maintained an InSTI or switched to an InSTI (by core agent). All models were adjusted for age, sex, race, (age-sex, race-sex interactions), BMI, CD4 cell count, endocrine disorders and concurrent medications that could affect weight. RESULTS:A total of 6908 PLWH were included, with 5479 maintaining all other antiretrovirals (boosted protease inhibitor: 746, non-nucleoside reverse transcriptase inhibitor: 1452, InSTI: 3281) and 1429 switching from a non-InSTI to an InSTI (elvitegravir/cobicistat: 1120, dolutegravir: 174, bictegravir: 129). In adjusted models, modest weight gain was observed over time on TDF for most (0.24 to 0.71 kg/year); raltegravir was the exception with weight loss. Switching to TAF was associated with early, pronounced weight gain for all (1.80 to 4.47 kg/year). This effect with TAF switch was observed both in PLWH maintaining other antiretrovirals and those switching to an InSTI, regardless of which InSTI agent was used. Weight gain tended to slow down or plateau approximately nine months after switch to TAF. CONCLUSIONS:In this large, diverse U.S. cohort of PLWH, switching from TDF to TAF was associated with pronounced weight gain immediately after switch, regardless of the core class or core agent, suggesting an independent effect of TAF on weight gain.

AIMS/OBJECTIVE:Sacubitril/valsartan combines renin-angiotensin-aldosterone system inhibition with amplification of natriuretic peptides. In addition to well-described effects, natriuretic peptides exert direct effects on pulmonary vasculature. The effect of sacubitril/valsartan on pulmonary artery pressure (PAP) has not been fully defined. METHODS AND RESULTS/RESULTS:This was a retrospective case-series of PAP changes following transition from angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) to sacubitril/valsartan in patients with heart failure reduced ejection fraction and a previously implanted CardioMEMS™ sensor. Pre-sacubitril/valsartan and post-sacubitril/valsartan PAPs were compared for each patient by examining averaged consecutive daily pressure readings from 1 to 5 days before and after sacubitril/valsartan exposure. PAP changes were also compared between patients based on elevated trans-pulmonary gradients (trans-pulmonary gradient ≥ 12 mmHg) at time of CardioMEMS™ sensor implantation. The cohort included 18 patients, 72% male, mean age 60.1 ± 13.6 years. There was a significant decrease in PAPs associated with transition from ACEI/ARB to sacubitril/valsartan. The median (interquartile range) pre-treatment and post-treatment change in mean, systolic and diastolic PAPs were -3.6 (-9.8, -0.7) mmHg (P < 0.001), -6.5 (-15.0, -2.0) mmHg (P = 0.001), and -2.5 (-5.7, -0.7) (P = 0.001), respectively. The decrease in PAPs was independent of trans-pulmonary gradient (F(1,16) = 0.49, P = 0.49). CONCLUSIONS:In this retrospective case series, transition from ACEI/ARB to sacubitril/valsartan was associated with an early and significant decrease in PAPs.

Introduction/UNASSIGNED:Reports from the United States suggest that acute kidney injury (AKI) frequently complicates COVID-19, but understanding of AKI risks and outcomes is incomplete. Additionally, whether kidney outcomes have evolved during the course of the pandemic is unknown. Methods/UNASSIGNED:We used electronic records to identify COVID-19 patients with and without AKI admitted to 3 New York Hospitals between March 2 and August 25, 2020. Outcomes included AKI overall and according to admission week, AKI stage, the requirement for new renal replacement therapy (RRT), mortality and recovery of kidney function. Logistic regression was utilized to assess associations of patient characteristics and outcomes. Results/UNASSIGNED:Out of 4732 admissions 1386 (29.3%) patients had AKI. Among those with AKI, 717 (51.7%) had Stage 1, 132 (9.5%) Stage 2, 537 (38.7%) stage 3, and 237 (17.1%) required RRT initiation. In March 536/1648 (32.5%) of patients developed AKI compared with 15/87 (17.2%) in August (P<0.001 for monthly trend) whereas RRT initiation was required in 6.9% and 0% of admission, in March and August respectively. Mortality was higher with than without AKI (51.6% vs 8.6%) and was 71.9% in individuals requiring RRT. However, most patients with AKI who survived hospitalization (77%) recovered to within 0.3 mg/dL of baseline creatinine. Among those surviving to discharge, 62% discontinued RRT. Conclusions/UNASSIGNED:AKI impacts a high proportion of admitted COVID-19 patients and is associated with high mortality, particularly when RRT is required. AKI incidence appears to be decreasing over time and kidney function frequently recovers in those who survive.

BACKGROUND:There is limited understanding about why sarcopenia is happening in bladder cancer, and which modifiable and nonmodifiable patient-level factors affect its occurrence. OBJECTIVE:The objective is to determine the extent to which nonmodifiable risk factors, modifiable lifestyle risk factors, or cancer-related factors are determining body composition changes and sarcopenia in bladder cancer survivors. DESIGN, SETTING, AND PARTICIPANTS:Patients above 18 yr of age with a histologically confirmed diagnosis of bladder cancer and a history of receiving care at Duke University Medical Center between January 1, 1996 and June 30, 2017 were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Bladder cancer survivors from our institution were assessed for their dietary intake patterns utilizing the Diet History Questionnaire II (DHQ-II) and physical activity utilizing the International Physical Activity Questionnaire long form (IPAQ-L) tools. Healthy Eating Index 2010 (HEI2010) scores were calculated from DHQ-II results. Body composition was evaluated using Slice-O-Matic computed tomography scan image analysis at L3 level and the skeletal muscle index (SMI) calculated by three independent raters. RESULTS AND LIMITATIONS:A total of 285 patients were evaluated in the study, and the intraclass correlation for smooth muscle area was 0.97 (95% confidence interval: 0.94-0.98) between raters. The proportions of patients who met the definition of sarcopenia were 72% for men and 55% of women. Univariate linear regression analysis demonstrated that older age, male gender, and black race were highly significant predictors of SMI, whereas tumor stage and grade, chemotherapy, and surgical procedures were not predictors of SMI. Multivariate linear regression analysis demonstrated that modifiable lifestyle factors, including total physical activity (p=0.830), strenuousness (high, moderate, and low) of physical activity (p=0.874), individual nutritional components (daily calories, p=0.739; fat, p=0.259; carbohydrates, p=0.983; and protein, p=0.341), and HEI2010 diet quality (p=0.822) were not associated with SMI. CONCLUSIONS:Lifestyle factors including diet quality and physical activity are not associated with SMI and therefore appear to have limited impact on sarcopenia. Sarcopenia may largely be affected by nonmodifiable risk factors. PATIENT SUMMARY:In this report, we aim to determine whether lifestyle factors such as diet and physical activity were the primary drivers of body composition changes and sarcopenia in bladder cancer survivors. We found that lifestyle factors including dietary habits, individual nutritional components, and physical activity do not demonstrate an association with skeletal muscle mass, and therefore may have limited impact on sarcopenia.

PURPOSE/OBJECTIVE:The National Death Index (NDI) is an important resource for mortality ascertainment. Methods selected to process NDI search results are rarely described in studies using linked data and can have an impact on resources and mortality ascertainment. We evaluate methods to process NDI search results among a 9/11-exposed cohort-the World Trade Center Health Registry (Registry). METHODS:We describe three approaches to process search results (NDI-recommended cutoff points [NDIc]; National Program of Cancer Registries [NPCR] algorithm, and modified National Institute of Occupational Safety and Health algorithm [mNIOSH]). We calculate percent agreement, positive predictive value, sensitivity, specificity, and quantify the burden of manual review to compare the approaches. RESULTS:Of 51,158 Registry enrollees submitted for linkage, 9449 enrollee-level and 17,909 record-level matches were identified. NPCR and mNIOSH were highly concordant (97.1%); more record pairs required manual review for mNIOSH (mNIOSH: 2.7% and NPCR: 1.8%). NDIc sensitivity was 82.9%, with differences observed by race and ethnicity (Asian: 74.4% and White: 86.1%). CONCLUSIONS:NPCR algorithm minimized false matches and reduced the manual review burden. NDIc had nonrandom distribution of missed matches and low sensitivity. NDI search processing methods have important implications for resulting linked data; measures of linkage quality should be available to data users.