Publications by authors named "Dorry L Segev"

466 Publications

Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records.

J Heart Lung Transplant 2021 Feb 17. Epub 2021 Feb 17.

Saint Louis Transplant Center, St. Louis, Missouri, USA.

Background: Prescription opioid and benzodiazepine use have been associated with morbidity and mortality among some groups of solid organ transplant recipients, but implications for outcomes among lung transplant patients are not well described.

Methods: We conducted a retrospective cohort study using linked national transplant registry and pharmaceutical records to characterize the associations between benzodiazepine and opioid prescription fills in the years before and after lung transplant (2006-2017), with risk-adjusted posttransplant survival (adjusted hazard ratio, aHR).

Results: Among 11,568 recipients, 33.7% filled an opioid prescription, and 25.8% filled a benzodiazepine prescription before transplant. Compared to patients without prescriptions, those who filled both short- and long-acting benzodiazepine prescriptions before transplant had 2-fold higher mortality in the first year posttransplant (aHR, 2.12), after adjustment for baseline factors and opioid fills, while pretransplant opioid fills were not associated with posttransplant mortality after adjustment for benzodiazepine fills. Pretransplant opioid and benzodiazepine use strongly predicted more use after transplant. Fills of both short- and long-acting benzodiazepines in the first year posttransplant were associated with 77% increased mortality >1-to-2 years posttransplant (aHR, 1.77). Compared with no posttransplant opioid fills, there was a dose-dependent association between first-year opioid fills and subsequent adjusted mortality risk (level 2: aHR, 1.50 to level 4: aHR, 2.01). These effects were independent, and interactions were not detected.

Conclusions: Benzodiazepine prescription fills before and after lung transplant, and opioid fills after transplant, are independently associated with posttransplant mortality. Review of benzodiazepine and opioid use history is relevant to risk-stratifying patients before and after lung transplant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2021.02.004DOI Listing
February 2021

Panel Reactive Antibody and the Association of Early Steroid Withdrawal with Kidney Transplant Outcomes.

Transplantation 2021 Apr 5. Epub 2021 Apr 5.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD. Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, MD. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Early steroid withdrawal (ESW) is a viable maintenance immunosuppression strategy in low-risk kidney transplant recipients. A low panel reactive antibody (PRA) may indicate low-risk condition amenable to ESW. We aimed to identify the threshold value of PRA above which ESW may pose additional risk, and to compare the association of ESW with transplant outcomes across PRA strata.

Methods: We studied 121,699 deceased-donor kidney-only recipients in 2002-2017 from SRTR. Using natural splines and ESW-PRA interaction terms, we explored how the associations of ESW with transplant outcomes change with increasing PRA values, and identified a threshold value for PRA. Then, we assessed whether PRA exceeding the threshold modified the associations of ESW with 1-year acute rejection, death-censored graft failure, and death.

Results: The association of ESW with acute rejection exacerbated rapidly when PRA exceeded 60. Among PRA≤60 recipients, ESW was associated with a minor increase in rejection (aOR=1.001.051.10) and with a tendency of decreased graft failure (aHR=0.910.971.03). However, among PRA>60 recipients, ESW was associated with a substantial increase in rejection (aOR=1.191.271.36; interaction p<0.001) and with a tendency of increased graft failure (aHR=0.981.081.20; interaction p=0.028). The association of ESW with death was similar between PRA strata (PRA≤60, aHR=0.910.961.01; and PRA>60, aHR=0.900.991.09; interaction p=0.5).

Conclusions: Our findings show that the association of ESW with transplant outcomes is less favorable in recipients with higher PRA, especially those with PRA>60, suggesting a possible role of PRA in the risk assessment for ESW.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003777DOI Listing
April 2021

Ambient Air Pollution and Mortality among Older Patients Initiating Maintenance Dialysis.

Am J Nephrol 2021 Mar 31:1-11. Epub 2021 Mar 31.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Fine particulate matter (particulate matter with diameter <2.5 µm [PM2.5]) is associated with CKD progression and may impact the health of patients living with kidney failure. While older (aged ≥65 years) adults are most vulnerable to the impact of PM2.5, it is unclear whether older patients on dialysis are at elevated risk of mortality when exposed to fine particulate matter.

Methods: Older adults initiating dialysis (2010-2016) were identified from US Renal Data System (USRDS). PM2.5 concentrations were obtained from NASA's Socioeconomic Data and Application Center (SEDAC) Global Annual PM2.5 Grids. We investigated the association between PM2.5 and all-cause mortality using Cox proportional hazard models with linear splines [knot at the current Environmental Protection Agency (EPA) National Ambient Air Quality Standard for PM2.5 of 12 μg/m3] and robust variance.

Results: For older dialysis patients who resided in areas with high PM2.5, a 10 μg/m3 increase in PM2.5 was associated with 1.16-fold (95% CI: 1.08-1.25) increased risk of mortality; furthermore, those who were female (aHR = 1.26, 95% CI: 1.13-1.42), Black (aHR = 1.31, 95% CI: 1.09-1.59), or had diabetes as a primary cause of kidney failure (aHR = 1.25, 95% CI: 1.13-1.38) were most vulnerable to high PM2.5. While the mortality risk associated with PM2.5 was stronger at higher levels (aHR = 1.19, 95% CI: 1.08-1.32), at lower levels (≤12 μg/m3), PM2.5 was significantly associated with mortality risk (aHR = 1.04, 95% CI: 1.00-1.07) among patients aged ≥75 years (Pslope difference = 0.006).

Conclusions: Older adults initiating dialysis who resided in ZIP codes with PM2.5 levels >12 μg/m3 are at increased risk of mortality. Those aged >75 were at elevated risk even at levels below the EPA Standard for PM2.5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000514233DOI Listing
March 2021

Development of a Patient Reported Measure of Experimental Transplants with HIV and Ethics in the United States (PROMETHEUS).

J Patient Rep Outcomes 2021 Mar 18;5(1):28. Epub 2021 Mar 18.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Transplantation of HIV-positive (HIV+) donor organs for HIV+ recipients (HIV D+/R+) is now being performed as research in the United States, but raises ethical concerns. While patient-reported outcome measures are increasingly used to evaluate clinical interventions, there is no published measure to aptly capture patients' experiences in the unique context of experimental HIV D+/R+ transplantation. Therefore, we developed PROMETHEUS (patient-reported measure of experimental transplants with HIV and ethics in the United States). To do so, we created a conceptual framework, drafted a pilot battery using existing and new measures related to this context, and refined it based on cognitive and pilot testing. PROMETHEUS was administered 6-months post-transplant in a clinical trial evaluating these transplants. We analyzed data from the first 20 patient-participants for reliability and validity by calculating Cronbach's alpha and reviewing item performance characteristics.

Results: PROMETHEUS 1.0 consisted of 29 items with 5 putative subscales: Emotions; Trust; Decision Making; Transplant; and Decision Satisfaction. Overall, responses were positive. Cronbach's alpha was > 0.8 for all subscales except Transplant, which was 0.38. Two Transplant subscale items were removed due to poor reliability and construct validity.

Conclusions: We developed PROMETHEUS to systematically capture patient-reported experiences with this novel experimental transplantation program, nested it in an actual clinical trial, and obtained preliminary data regarding its performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s41687-021-00297-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973329PMC
March 2021

COVID-19 Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients.

Clin Infect Dis 2021 Mar 9. Epub 2021 Mar 9.

Departments of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: COVID-19 associated pulmonary aspergillosis (CAPA) occurs in critically ill COVID-19 patients. Risks and outcomes remain poorly understood.

Methods: A retrospective cohort study of adult mechanically ventilated COVID-19 patients admitted to five Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores.

Results: Amongst the cohort of 396 people, 39 met criteria for CAPA. Compared to those without, patients with CAPA were more likely to have underlying pulmonary vascular disease (41% vs 21.6%, p=0.01), liver disease (35.9% vs 18.2%, p=0.02), coagulopathy (51.3% vs 33.1%, p=0.03), solid tumors (25.6% vs 10.9%, p=0.017), multiple myeloma (5.1% vs 0.3%, p=0.027), corticosteroid exposure during index admission (66.7% vs 42.6%, p=0.005), and had a lower BMI (median 26.6 vs 29.9, p=0.04). People with CAPA had worse outcomes as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio 1.081.091.1, p<0.001), and advancing in severity almost twice as fast (subhazard ratio, sHR 1.31.82.5, p<0.001). People with CAPA were intubated twice as long as those without (sHR) 0.40.50.6, p<0.001) and had a longer hospital length of stay [median (IQR) 41.1 (20.5, 72.4) vs 18.5 (10.7, 31.8), p<0.001].

Conclusion: CAPA is associated with poor outcomes. Attention towards preventative measures (screening and/or prophylaxis) is warranted in people with high risk of developing CAPA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989534PMC
March 2021

Mortality and Access to Kidney Transplantation in Patients with Sickle Cell Disease-Associated Kidney Failure.

Clin J Am Soc Nephrol 2021 Mar 25;16(3):407-414. Epub 2021 Feb 25.

Division of Transplantation, Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland

Background And Objectives: Patients with sickle cell disease-associated kidney failure have high mortality, which might be lowered by kidney transplantation. However, because they show higher post-transplant mortality compared with patients with other kidney failure etiologies, kidney transplantation remains controversial in this population, potentially limiting their chance of receiving transplantation. We aimed to quantify the decrease in mortality associated with transplantation in this population and determine the chance of receiving transplantation with sickle cell disease as the cause of kidney failure as compared with other etiologies of kidney failure.

Design, Setting, Participants, & Measurements: Using a national registry, we studied all adults with kidney failure who began maintenance dialysis or were added to the kidney transplant waiting list in 1998-2017. To quantify the decrease in mortality associated with transplantation, we measured the absolute risk difference and hazard ratio for mortality in matched pairs of transplant recipients versus waitlisted candidates in the sickle cell and control groups. To compare the chance of receiving transplantation, we estimated hazard ratios for receiving transplantation in the sickle cell and control groups, treating death as a competing risk.

Results: Compared with their matched waitlisted candidates, 189 transplant recipients with sickle cell disease and 220,251 control recipients showed significantly lower mortality. The absolute risk difference at 10 years post-transplant was 20.3 (98.75% confidence interval, 0.9 to 39.8) and 19.8 (98.75% confidence interval, 19.2 to 20.4) percentage points in the sickle cell and control groups, respectively. The hazard ratio was also similar in the sickle cell (0.57; 95% confidence interval, 0.36 to 0.91) and control (0.54; 95% confidence interval, 0.53 to 0.55) groups (interaction =0.8). Nonetheless, the sickle cell group was less likely to receive transplantation than the controls (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.61 to 0.87). Similar disparities were found among waitlisted candidates (subdistribution hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72).

Conclusions: Patients with sickle cell disease-associated kidney failure exhibited similar decreases in mortality associated with kidney transplantation as compared with those with other kidney failure etiologies. Nonetheless, the sickle cell population was less likely to receive transplantation, even after waitlist registration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.02720320DOI Listing
March 2021

High-dose opioid utilization and mortality among individuals initiating hemodialysis.

BMC Nephrol 2021 Feb 23;22(1):65. Epub 2021 Feb 23.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street W6033, Baltimore, MD, 21205, USA.

Background: Individuals undergoing hemodialysis in the United States frequently report pain and receive three-fold more opioid prescriptions than the general population. While opioid use is appropriate for select patients, high-dose utilization may contribute to an increased risk of death due to possible accumulation of opioid metabolites.

Methods: We studied high-dose opioid utilization (≥120 morphine milligram equivalents [MME] per day) among adults initiating hemodialysis in the United States between 2007 and 2014 using national registry data. We calculated the cumulative incidence (%) of high-dose utilization and depicted trends in the average percentage of days individuals were exposed to opioids. We used adjusted Cox proportional hazards models to identify which opioid doses were associated with mortality.

Results: Among 327,344 adults undergoing hemodialysis, the cumulative incidence of high-dose utilization was 14.9% at 2 years after initiating hemodialysis. Among patients with ≥1 opioid prescription during follow-up, the average percentage of days exposed to high-dose utilization increased from 13.9% in 2007 to 26.1% in 2014. Compared to 0MME per day, doses < 60MME were not associated with an increased risk of mortality, but high-dose utilization was associated with a 1.63-fold (95% CI, 1.57, 1.69) increased risk of mortality. The risk of mortality associated with opioid dose was highest in the first year after hemodialysis initiation.

Conclusions: The risk of mortality associated with opioid utilization among individuals on hemodialysis increases as doses exceed 60MME per day and is greatest during periods of high-dose utilization. Patients and clinicians should carefully weigh the risks and benefits of opioid doses exceeding 60MME per day.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-021-02266-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901089PMC
February 2021

Early Development and Durability of SARS-CoV-2 Antibodies Among Solid Organ Transplant Recipients: A Pilot Study.

Transplantation 2021 Jan 19. Epub 2021 Jan 19.

1 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. 2 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 3 Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003637DOI Listing
January 2021

Examination of Racial and Ethnic Differences in Deceased Organ Donation Ratio Over Time in the US.

JAMA Surg 2021 Feb 10:e207083. Epub 2021 Feb 10.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: Historically, deceased organ donation was lower among Black compared with White populations, motivating efforts to reduce racial disparities. The overarching effect of these efforts in Black and other racial/ethnic groups remains unclear.

Objective: To examine changes in deceased organ donation over time.

Design, Setting, And Participants: This population-based cohort study used data from January 1, 1999, through December 31, 2017, from the Scientific Registry of Transplant Recipients to quantify the number of actual deceased organ donors, and from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Detailed Mortality File to quantify the number of potential donors (individuals who died under conditions consistent with organ donation). Data were analyzed from December 2, 2019, to May 14, 2020.

Exposures: Race and ethnicity of deceased and potential donors.

Main Outcomes And Measures: For each racial/ethnic group and year, a donation ratio was calculated as the number of actual deceased donors divided by the number of potential donors. Direct age and sex standardization was used to allow for group comparisons, and Poisson regression was used to quantify changes in donation ratio over time.

Results: A total of 141 534 deceased donors and 5 268 200 potential donors were included in the analysis. Among Black individuals, the donation ratio increased 2.58-fold from 1999 to 2017 (yearly change in adjusted incidence rate ratio [aIRR], 1.05; 95% CI, 1.05-1.05; P < .001). This increase was significantly greater than the 1.60-fold increase seen in White individuals. Nevertheless, substantial racial differences remained, with Black individuals still donating at only 69% the rate of White individuals in 2017 (P < .001). Among other racial minority populations, changes were less drastic. Deceased organ donation increased 1.80-fold among American Indian/Alaska Native and 1.40-fold among Asian or Pacific Islander populations, with substantial racial differences remaining in 2017 (American Indian/Alaska Native population donation at 28% and Asian/Pacific Islander population donation at 85% the rate of the White population). Deceased organ donation differences between Hispanic/Latino and non-Hispanic/Latino populations increased over time (4% lower in 2017).

Conclusions And Relevance: The findings of this cohort study suggest that differences in deceased organ donation between White and some racial minority populations have attenuated over time. The greatest gains were observed among Black individuals, who have been the primary targets of study and intervention. Despite improvements, substantial differences remain, suggesting that novel approaches are needed to understand and address relatively lower rates of deceased organ donation among all racial minorities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamasurg.2020.7083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876622PMC
February 2021

Safety of the First Dose of SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients.

Transplantation 2021 Feb 4. Epub 2021 Feb 4.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003654DOI Listing
February 2021

Response to "COVID-19 in SOT versus non-SOT".

Am J Transplant 2021 Feb 9. Epub 2021 Feb 9.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013353PMC
February 2021

Response to "The real number of organs from uncontrolled donation after circulatory determination of death donors".

Am J Transplant 2021 Feb 8. Epub 2021 Feb 8.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16526DOI Listing
February 2021

Association Between Treatment of Secondary Hyperparathyroidism and Posttransplant Outcomes.

Transplantation 2021 Jan 27. Epub 2021 Jan 27.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Surgical Oncology Program, National Cancer Institute, National Institute of Health, Bethesda, MD.

Background: Secondary hyperparathyroidism (SHPT) affects nearly all patients on maintenance dialysis therapy. SHPT treatment options have considerably evolved over the past 2 decades, but vary in degree of improvement in SHPT. Therefore, we hypothesize that the risks of adverse outcomes after kidney transplantation (KT) may differ by SHPT treatment.

Methods: Using the SRTR and Medicare claims data, we identified 5,094 adults (age≥18) treated with cinacalcet or parathyroidectomy for SHPT prior to receiving KT between 2007-2016. We quantified the association between SHPT treatment and delayed graft function and acute rejection using adjusted logistic models and tertiary hyperparathyroidism (THPT), graft failure, and death using adjusted Cox proportional hazards; we tested whether these associations differed by patient characteristics.

Results: Of 5094 KT recipients who were treated for SHPT while on dialysis, 228 (4.5%) underwent parathyroidectomy and 4866 (95.5%) received cinacalcet. There was no association between treatment of SHPT and posttransplant delayed graft function, graft failure or death. However, compared to patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (aHR=0.56, 95%CI: 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (pinteraction=0.039). Among patients on maintenance dialysis therapy for ≥3 years prior to KT (n=3,477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (aHR=0.43, 95%CI: 0.24-0.79).

Conclusions: Parathyroidectomy should be considered as treatment for SHPT, especially in KT candidates on maintenance dialysis for ≥3 years. Additionally, patients treated with cinacalcet for SHPT should undergo close surveillance for development of tertiary hyperparathyroidism post-KT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003653DOI Listing
January 2021

Better Understanding the Disparity Associated With Black Race in Heart Transplant Outcomes: A National Registry Analysis.

Circ Heart Fail 2021 Feb 2;14(2):e006107. Epub 2021 Feb 2.

Department of Surgery (H.M., M.G.B., A.B.M., S.B., A.K., S.O., R.S.D.H., D.L.S., E.L.B.), Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality.

Methods: We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics.

Results: Among recipients aged 18 to 30 years, Black recipients had 2.05-fold (95% CI, 1.67-2.51) higher risk of mortality compared with non-Black recipients (<0.001, interaction <0.001); however, the risk was significant only in the first year post-transplant (first year: adjusted hazard ratio, 2.30 [95% CI, 1.60-3.31], <0.001; after first year: adjusted hazard ratio, 0.84 [95% CI, 0.54-1.29]; =0.4). This association was attenuated among recipients aged 31 to 40 and 41 to 60 years, in whom Black recipients had 1.53-fold ([95% CI, 1.25-1.89] <0.001) and 1.20-fold ([95% CI, 1.09-1.33] <0.001) higher risk of mortality. Among recipients aged 61 to 80 years, no significant association was seen with Black race (adjusted hazard ratio, 1.12 [95% CI, 0.97-1.29]; =0.1).

Conclusions: Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887117PMC
February 2021

Increasing the Donor Pool: Organ Transplantation from Donors with HIV to Recipients with HIV.

Annu Rev Med 2021 01;72:107-118

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

Implementation of the HIV Organ Policy Equity (HOPE) Act marks a new era in transplantation, allowing organ transplantation from HIV+ donors to HIV+ recipients (HIV D+/R+ transplantation). In this review, we discuss major milestones in HIV and transplantation which paved the way for this landmark policy change, including excellent outcomes in HIV D-/R+ recipient transplantation and success in the South African experience of HIV D+/R+ deceased donor kidney transplantation. Under the HOPE Act, from March 2016 to December 2018, there were 56 deceased donors, and 102 organs were transplanted (71 kidneys and 31 livers). In 2019, the first HIV D+/R+ living donor kidney transplants occurred. Reaching the full estimated potential of HIV+ donors will require overcoming challenges at the community, organ procurement organization, and transplant center levels. Multiple clinical trials are ongoing, which will provide clinical and scientific data to further extend the frontiers of knowledge in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-060419-122327DOI Listing
January 2021

Transplanting Organs from Donors with HIV or Hepatitis C: The Viral Frontier.

World J Surg 2021 Jan 20. Epub 2021 Jan 20.

Department of Surgery, Epidemiology Research Group in Organ Transplantation, Johns Hopkins University School of Medicine, 2000 E Monument St, Baltimore, MD, 21205, USA.

A wide gap between the increasing demand for organs and the limited supply leads to immeasurable loss of life each year. The organ shortage could be attenuated by donors with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). The transplantation of organs from HIV+ deceased donors into HIV+ individuals (HIV D+ /R+) was initiated in South Africa in 2010; however, this practice was forbidden in the USA until the HIV Organ Policy Equity (HOPE) Act in 2013. HIV D+/R+ transplantation is now practiced in the USA as part of ongoing research studies, helping to reduce waiting times for all patients on the waitlist. The introduction of direct acting antivirals for HCV has revolutionized the utilization of donors with HCV for HCV-uninfected (HCV-) recipients. This is particularly relevant as the HCV donor pool has increased substantially in the context of the rise in deaths related to drug overdose from injection drug use. This article serves to review the current literature on using organs from donors with HIV or HCV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-020-05924-1DOI Listing
January 2021

Changes in Functional Status Among Kidney Transplant Recipients: Data From the Scientific Registry of Transplant Recipients.

Transplantation 2021 Jan 12. Epub 2021 Jan 12.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Background: With stressors of dialysis pre-KT and restoration of kidney function post-KT, it is likely that KT recipients experience a decline in functional status while on the waitlist and improvements post-KT.

Methods: We leveraged 224,832 KT recipients from the national registry (SRTR, 2/1990-5/2019) with measured Karnofsky Performance Status (KPS, 0-100%) at listing, KT admission, and post-KT. We quantified the change in KPS from listing to KT using generalized linear models. We described post-KT KPS trajectories using adjusted mixed effects models and tested whether those trajectories differed by age, sex, race, and diabetes status using a Wald test among all KT recipients. We then quantified risk adverse post-KT outcomes (mortality and all-cause graft loss (ACGL)) by preoperative KPS and time-varying KPS.

Results: Mean KPS declined from listing (83.7%) to admission (78.9%) (mean=4.76%, 95%CI:-4.82,-4.70). After adjustment, mean KPS improved post-KT (slope=0.89%/year, 95%CI:0.87,0.91); younger, female, non-Black, and diabetic recipients experienced greater post-KT improvements (pinteractions<0.001). Lower KPS (per 10% decrease) at admission was associated with greater mortality (aHR=1.11, 95%CI:1.10,1.11) and ACGL (aHR=1.08, 95%CI:1.08,1.09) risk. Lower post-KT KPS (per 10% decrease; time-varying) were more strongly associated with mortality (aHR=1.93, 95%CI:1.92,1.94) and ACGL (aHR=1.84, v95%CI:1.83,1.85).

Conclusions: Functional status declines pre-KT and improves post-KT in the national registry. Despite post-KT improvements, poorer functional status at KT and post-KT are associated with greater mortality and ACGL risk. Due to its dynamic nature, clinicians should repeatedly screen for lower functional status pre-KT to refer vulnerable patients to prehabilitation in hopes of reducing risk of adverse post-KT outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003608DOI Listing
January 2021

A Multicenter Pilot Randomized Clinical Trial of a Home-Based Exercise Program for Patients With Cirrhosis: The Strength Training Intervention (STRIVE).

Am J Gastroenterol 2020 Dec 23;Publish Ahead of Print. Epub 2020 Dec 23.

Department of Medicine, University of California-San Francisco, San Francisco, California, USA; Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA; Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Introduction: We developed the strength training intervention (STRIVE), a home-based exercise program targeting physical function in patients with cirrhosis. In this pilot study, we aimed to evaluate the safety and efficacy of STRIVE.

Methods: Eligible were adult patients with cirrhosis at 3 sites. Patients were randomized 2:1-12 weeks of STRIVE, a 30-minute strength training video plus a health coach or standard of care (SOC). Physical function and quality of life were assessed using the Liver Frailty Index (LFI) and Chronic Liver Disease Questionnaire (CLDQ), respectively.

Results: Fifty-eight and 25 were randomized to STRIVE and SOC arms, respectively: 43% women, median age was 61 years, MELDNa, Model for End-Stage Liver Disease Sodium was 14, and 54% were Child-Pugh B/C. Baseline characteristics were similar in the STRIVE vs SOC arms except for rates of hepatic encephalopathy (19 vs 36%). LFI @ 12 weeks was available in 43 STRIVE and 20 SOC participants. After 12 weeks, the median LFI improved from 3.8 to 3.6 (ΔLFI -0.1) in the STRIVE arm and 3.7 to 3.6 (ΔLFI -0.1) in the SOC arm (P = 0.65 for ΔLFI difference). CLDQ scores improved from 4.6 to 5.2 in STRIVE participants (ΔCLDQ 0.38) and did not change in SOC participants (4.2-4.2; ΔCLDQ -0.03) (P = 0.09 for ΔCLDQ difference). One patient died (SOC arm) of bleeding. Only 14% of STRIVE participants adhered to the strength training video for 10-12 weeks. No adverse events were reported by STRIVE participants.

Discussion: STRIVE, a home-based structured exercise program for patients with cirrhosis, was safely administered at 3 sites, but adherence was low. Although all participants showed minimal improvement in the LFI, STRIVE was associated with a substantial improvement in quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ajg.0000000000001113DOI Listing
December 2020

Association of Frailty and Sex With Wait List Mortality in Liver Transplant Candidates in the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

JAMA Surg 2021 Mar;156(3):256-262

Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, New York.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamasurg.2020.5674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774043PMC
March 2021

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Am J Transplant 2021 04 27;21(4):1612-1621. Epub 2021 Feb 27.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR =  1.68 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF =  2.09 ; PFNC =  2.40 ; PCC =  2.24 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR =  1.62 ) than CLDKT (aHR =  2.29 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016719PMC
April 2021

Rising Cost of Thyroid Surgery in Adult Patients.

J Surg Res 2021 Apr 11;260:28-37. Epub 2020 Dec 11.

Endocrine Surgery, Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: The aim of this study is to describe the economic trends in adults who underwent elective thyroidectomy.

Methods: We performed a population-based study utilizing the Premier Healthcare Database to examine adult patients who underwent elective thyroidectomy between January 2006 and December 2014. Time was divided into three equal time periods (2006-2008, 2009-2011, and 2012-2014). To examine trend in patient charges, we modeled patient charges using generalized linear regressions adjusting for key covariates with standard errors clustered at the hospital level.

Results: Our study cohort consisted of 52,012 adult patients who underwent a thyroid operation. During the study period, the most common procedure changed from a thyroid lobectomy to bilateral thyroidectomy. Over the study period, there was an increase in the proportion of completion thyroidectomies from 1.1% to 1.6% (P < 0.001), malignant diagnoses from 21.7% to 26.8% (P < 0.001), procedures performed at teaching hospitals from 27.7% to 32.9% (P < 0.001), and procedures performed on an outpatient basis from 93.85% to 97.55% (P < 0.001). The annual increase in median patient charge adjusted for inflation was $895 or 4.3% resulting in an increase of 38.8% over 9 y. Higher thyroidectomy charges were associated with male patients, malignant surgical pathology, patients undergoing limited or radical neck dissection, experiencing complications, those with managed health care insurance, and a prolonged length of stay.

Conclusions: Despite recent changes in thyroid surgery practices to decrease the economic burden of hospitals, costs continue to rise 4.3% annually. Additional prospective studies are needed to identify factors associated with this increasing cost.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2020.11.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946711PMC
April 2021

Decreased incidence of acute rejection without increased incidence of cytomegalovirus (CMV) infection in kidney transplant recipients receiving rabbit anti-thymocyte globulin without CMV prophylaxis - a cohort single-center study.

Transpl Int 2021 Feb 31;34(2):339-352. Epub 2020 Dec 31.

Department of Nephrology, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil.

Induction therapy with rabbit anti-thymocyte globulin (rATG) in low-risk kidney transplant recipients (KTR) remains controversial, given the associated increased risk of cytomegalovirus (CMV) infection. This natural experiment compared 12-month clinical outcomes in low-risk KTR without CMV prophylaxis (January/3/13-September/16/15) receiving no induction or a single 3 mg/kg dose of rATG. We used logistic regression to characterize delayed graft function (DGF), negative binomial to characterize length of hospital stay (LOS), and Cox regression to characterize acute rejection (AR), CMV infection, graft loss, death, and hospital readmissions. Recipients receiving 3 mg/kg rATG had an 81% lower risk of AR (aHR 0.19 , P < 0.001) but no increased rate of hospital readmissions because of infections ( 0.91 , P = 0.5). There was no association between 3 mg/kg rATG and CMV infection/disease (aHR 1.10 , P = 0.5), even when the analysis was stratified according to recipient CMV serostatus positive (aHR 1.25 , P = 0.1) and negative (aHR 0.57 , P = 0.1). There was no association between 3 mg/kg rATG and mortality (aHR 1.25 , P = 0.6), and graft loss (aHR 0.73 , P = 0.4). Among low-risk KTR receiving no CMV pharmacological prophylaxis, 3 mg/kg rATG induction was associated with a significant reduction in the incidence of AR without an increased risk of CMV infection, regardless of recipient pretransplant CMV serostatus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.13800DOI Listing
February 2021

Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort.

Am J Transplant 2020 Dec 7. Epub 2020 Dec 7.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p < .001), hypertension (69% vs. 44%, p = .001), HIV (7% vs. 1.4%, p = .024), and peripheral vascular disorders (19% vs. 8%, p = .018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p = .13), length-of-stay (sHR: 1.1 , p = .5), or mortality (sHR: 0.4 , p = .19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3-4]) (p = .042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.81 , p < .001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16431DOI Listing
December 2020

Inconsistencies in the association of clinical factors with the choice of early steroid withdrawal across kidney transplant centers: A national registry study.

Clin Transplant 2021 Feb 12;35(2):e14176. Epub 2020 Dec 12.

Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Background: Approximately 30% of kidney transplant recipients undergo early steroid withdrawal (ESW) for maintenance immunosuppression. However, there is no consensus on which patients are suitable for ESW, and transplant centers may disagree on how various clinical factors characterize individual recipients' suitability for ESW.

Methods: To examine center-level variation in the association of clinical factors with the choice of ESW, we studied 206 544 kidney transplant recipients from 278 centers in 2002-2017 using SRTR data. We conducted multi-level logistic regressions to characterize the association of clinical factors with the choice of ESW at each transplant center.

Results: The association of clinical factors with the choice of ESW varied substantially across centers. We found particularly greater inconsistency in recipient age, PRA, re-transplantation, living/deceased donor, post-transplant length of stay, and delayed graft function. For example, across the entire population, re-transplantation was associated with lower odds of ESW (population odds ratio =  0.40 ). When estimated at each center, this odds ratio was significantly lower than the population odds ratio at 48 (17.3%) centers and significantly higher at 28 (10.1%) centers.

Conclusions: We have observed apparent inconsistencies across transplant centers in the practice of tailoring ESW to the recipient's risk profile. Standardized guidelines for ESW tailoring are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ctr.14176DOI Listing
February 2021

Heterogeneous circles for liver allocation.

Hepatology 2020 Nov 20. Epub 2020 Nov 20.

Department of Mathematics, United States Naval Academy, Annapolis, MD, United States.

In February 2020, the Organ Procurement and Transplantation Network replaced donor service area-based allocation of livers with acuity circles, a system based on three homogeneous circles around each donor hospital. This system has been criticized for neglecting to consider varying population density and proximity to coast and national borders. Using Scientific Registry of Transplant Recipients data from 07/2013-06/2017, we designed novel, heterogeneous circles to reduce both circle size and variation in liver supply/demand ratios across transplant centers. We weighted liver demand by MELD/PELD because higher MELD/PELD candidates are more likely to be transplanted. Transplant centers in the West had the largest circles; transplant centers in the Midwest and South had the smallest circles. Supply/demand ratios ranged from 0.471 to 0.655 livers per MELD-weighted incident candidate. Our heterogeneous circles had lower variation in supply/demand ratios than homogeneous circles of any radius between 150-1,000 nm. Homogeneous circles of 500 nm, the largest circle used in the acuity circles allocation system, had a variance in supply/demand ratios 16 times higher than our heterogeneous circles (0.0156 vs 0.0009) and a range of supply/demand ratios 2.3 times higher than our heterogeneous circles (0.421 vs 0.184). Our heterogeneous circles had a median (IQR) radius of only 326 (275-470) nautical miles, but reduced disparities in supply/demand ratios significantly by accounting for population density, national borders, and the geographic variation of supply and demand. In conclusion, large homogeneous circles create logistical burdens on transplant centers that do not need them, while small homogeneous circles increase geographic disparity. Using carefully designed heterogeneous circles can reduce geographic disparity in liver supply/demand ratios, compared to homogeneous circles of radius ranging from 150-1,000 nm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31648DOI Listing
November 2020

Immunosuppression Regimen Use and Outcomes in Older and Younger Adult Kidney Transplant Recipients: A National Registry Analysis.

Transplantation 2020 Nov 18. Epub 2020 Nov 18.

University of Iowa, Iowa City, IA, USA.

Background: Although the population of older transplant recipients has increased dramatically, there are limited data describing the impact of immunosuppression regimen choice on outcomes in this recipient group.

Methods: National data for U.S. Medicare-insured adult kidney recipients (N=67,362; 2005-2016) were examined to determine early immunosuppression regimen and associations with acute rejection, death-censored graft failure and mortality using multivariable regression analysis in younger (18-64 years) and older (>65 years) adults.

Results: The use of anti-thymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (reference) was less common in older compared with younger (36.9% vs 47.0%) recipients, as was TMG/ALEM + steroid avoidance (19.2% vs 20.1%) and mTORi-based (6.7% vs 7.7%) treatments. Conversely, older patients were more likely to receive IL2-receptor antibody (IL2rAb) + triple maintenance (21.1% vs 14.7%), IL2rAb + steroid avoidance (4.1% vs 1.8%), and cyclosporine-based (8.3% vs 6.6%) immunosuppression. Compared to older recipients treated with TMG/ALEM + triple maintenance (reference regimen), those managed with TMG/ALEM + steroid avoidance (adjusted odds ratio (aOR), 0.440.520.61) and IL2rAb + steroid-avoidance (aOR, 0.390.550.79) had lower risk of acute rejection. Older patients experienced more death censored graft failure when managed with Tac+ antimetabolite avoidance (adjusted hazard (aHR), 1.411.782.25), mTORi-based (aHR, 1.702.142.71), and cyclosporine-based (aHR, 1.411.782.25) regimens, versus the reference regimen. mTORi-based and cyclosporine-based regimens were associated with increased mortality in both older and younger patients.

Conclusions: Lower-intensity immunosuppression regimens (e.g. steroid-sparing) appear beneficial for older kidney transplant recipients, while mTORi and cyclosporine-based maintenance immunosuppression are associated with higher risk of adverse outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003547DOI Listing
November 2020

The Tangible Benefits of Living Donation: Results of a Qualitative Study of Living Kidney Donors.

Transplant Direct 2020 Dec 10;6(12):e626. Epub 2020 Nov 10.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

The framework currently used for living kidney donor selection is based on estimation of acceptable donor risk, under the premise that benefits are only experienced by the recipient. However, some interdependent donors might experience tangible benefits from donation that cannot be considered in the current framework (ie, benefits experienced directly by the donor that improve their daily life, well-being, or livelihood).

Methods: We conducted semistructured interviews with 56 living kidney donors regarding benefits experienced from donation. Using a qualitative descriptive and constant comparative approach, themes were derived inductively from interview transcripts by 2 independent coders; differences in coding were reconciled by consensus.

Results: Of 56 participants, 30 were in interdependent relationships with their recipients (shared household and/or significant caregiving responsibilities). Tangible benefits identified by participants fell into 3 major categories: health and wellness benefits, time and financial benefits, and interpersonal benefits. Participants described motivations to donate a kidney based on a more nuanced understanding of the benefits of donation than accounted for by the current "acceptable risk" paradigm.

Discussion: Tangible benefits for interdependent donors may shift the "acceptable risk" paradigm (where no benefit is assumed) of kidney donor evaluation to a risk/benefit paradigm more consistent with other surgical decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TXD.0000000000001068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665258PMC
December 2020