Development and implementation of a distributed data network between an academic institution and state health departments to investigate variation in time to HIV viral suppression in the Deep South.

BACKGROUND: Achieving early and sustained viral suppression (VS) following diagnosis of HIV infection is critical to improving outcomes for persons with HIV (PWH). The Deep South of the United States (US) is a region that is disproportionately impacted by the domestic HIV epidemic. Time to VS, defined as time from diagnosis to initial VS, is substantially longer in the South than other regions of the US. We describe the development and implementation of a distributed data network between an academic institution and state health departments to investigate variation in time to VS in the Deep South. METHODS: Representatives of state health departments, the Centers for Disease Control and Prevention (CDC), and the academic partner met to establish core objectives and procedures at the beginning of the project. Importantly, this project used the CDC-developed Enhanced HIV/AIDS Reporting System (eHARS) through a distributed data network model that maintained the confidentiality and integrity of the data. Software programs to build datasets and calculate time to VS were written by the academic partner and shared with each public health partner. To develop spatial elements of the eHARS data, health departments geocoded residential addresses of each newly diagnosed individual in eHARS between 2012-2019, supported by the academic partner. Health departments conducted all analyses within their own systems. Aggregate results were combined across states using meta-analysis techniques. Additionally, we created a synthetic eHARS data set for code development and testing. RESULTS: The collaborative structure and distributed data network have allowed us to refine the study questions and analytic plans to conduct investigations into variation in time to VS for both research and public health practice. Additionally, a synthetic eHARS data set has been created and is publicly available for researchers and public health practitioners. CONCLUSIONS: These efforts have leveraged the practice expertise and surveillance data within state health departments and the analytic and methodologic expertise of the academic partner. This study could serve as an illustrative example of effective collaboration between academic institutions and public health agencies and provides resources to facilitate future use of the US HIV surveillance system for research and public health practice.

Pain in older survivors of hematologic malignancies after blood or marrow transplantation: A BMTSS report.

BACKGROUND: Blood or marrow transplantation (BMT) is increasingly offered to older adults with hematologic malignancies; however, their risk for severe pain is poorly understood. Using the Bone Marrow Transplant Survivor Study, the current study investigated the prevalence and predictors of pain after BMT (allogeneic or autologous) as well as its association with physical performance impairments and frailty. METHODS: The cohort included 736 patients with hematologic malignancies who underwent BMT at an age ≥ 60 years at 1 of 3 transplant centers between 1974 and 2014 and survived ≥2 years after BMT; 183 unaffected siblings also participated. Study participants reported on 4 pain domains (nonminor everyday pain, moderate to severe bodily pain, prolonged pain, and moderate to extreme pain interference), and the presence of 1 or more domains was indicative of a severe and/or life-interfering pain composite variable. RESULTS: Overall, 39.4% of the BMT survivors reported severe pain with 2.6-fold greater odds of reporting pain in comparison with sibling controls. Among BMT recipients, those with less education, lower incomes, and active chronic graft-versus-host disease had higher odds of reporting pain. In multivariable analyses, BMT survivors with pain were more likely to have impaired physical performance and were more likely to meet the frailty criteria. BMT survivors reported higher use of pain medications (17.8% vs 9.3%) and opioid pain medications (6.5% vs 2.2%) in comparison with sibling controls. CONCLUSIONS: Nearly 40% of older BMT survivors who were followed for a median of 5 years after BMT reported pain, and BMT survivors had 2.6-fold higher odds of reporting severe, nonminor or life-interfering pain in comparison with siblings.

Late mortality after autologous blood or marrow transplantation in childhood: a Blood or Marrow Transplant Survivor Study-2 report.

Autologous blood or marrow transplantation (BMT) is a curative option for several types of childhood cancer. However, there is little information regarding the risk of late mortality. We examined all-cause mortality, relapse-related mortality (RRM), and nonrelapse-related mortality (NRM) in 2-year survivors of autologous BMT performed before age 22 between 1980 and 2010 at 1 of 2 US transplant centers. Vital status information was collected using medical records, National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. Cumulative incidence of mortality used competing risk methods. Standardized mortality ratio (SMR) was calculated using age-, sex-, and calendar-specific mortality rates from Centers for Disease Control and Prevention. Cox regression analysis was used to determine predictors of all-cause late mortality. Among the 345 2-year survivors, 103 deaths were observed, yielding an overall survival of 70.3% 15 years post-BMT. The leading causes of death included primary disease (50.0%), subsequent neoplasm (21.4%), and infection (18.2%). Overall, the cohort was at a 22-fold increased risk of late mortality (SMR, 21.8; 95% CI, 17.9-26.3), compared with the general population. Mortality rates remained elevated among the 10-year survivors (SMR, 20.6; 95% CI, 9.9-37.2) but approached those of the general population ≥15 years post-BMT. The 10-year cumulative incidence of RRM (14.3%) exceeded that of NRM (10.4%). The 10-year cumulative mortality rate declined over time (<1990, 35.1%; 1990-1999, 25.6%; 2000-2010, 21.8%; P = .05). In conclusion, childhood autologous BMT recipients have an increased risk of late mortality, compared with the general population. The late mortality rates have declined over the past 3 decades.

Venous Thromboembolism in Autologous Blood or Marrow Transplantation Survivors: A Report from the Blood or Marrow Transplant Survivor Study.

Hemostatic complications are commonly encountered in blood or marrow transplantation (BMT) recipients, increasing their morbidity and mortality and are well described in the immediate post-transplantation period. The risk of venous thromboembolism (VTE) in long-term survivors of autologous BMT has not been studied previously. Patients who underwent autologous BMT between January 1, 1974, and December 31, 2010 for a hematologic malignancy, lived 2 years or more after transplantation, and were age ≥18 years were surveyed for long-term outcomes. The median duration of follow-up was 9.8 years (interquartile range, 6.4 to 14.3 years). We analyzed the risk of VTE in 820 autologous BMT recipients who survived for ≥2 years, compared with 644 siblings. BMT survivors were at a 2.6-fold higher risk of VTE compared with siblings (95% confidence interval [CI], 1.6 to 4.4; P =.0004), after adjusting for sociodemographic characteristics. Conditional on surviving for ≥2 years after BMT, the mean cumulative incidence of VTE was 3.9 ± .8% at 5 years and 6.1 ± 1.1% at 10 years. A diagnosis of plasma cell disorder (hazard ratio [HR], 2.37; 95% CI, 1.3 to 4.2; P = .004) and annual household income ≤$50,000 (HR, 2.02; 95% CI, 1.2 to 3.6; P = .015) were associated with increased VTE risk. Our data indicate that autologous BMT survivors are at elevated risk for developing late-occurring VTE. The development of risk prediction models to identify autologous BMT survivors at greatest risk for VTE and thromboprophylaxis may help decrease the morbidity and mortality associated with VTE.

Late Mortality after Allogeneic Bone Marrow Transplantation in Childhood for Bone Marrow Failure Syndromes and Severe Aplastic Anemia.

Children with bone marrow failure syndromes and severe aplastic anemia (SAA) are treated with allogeneic blood or marrow transplantation (BMT). However, there is a paucity of studies examining late mortality risk after allogeneic BMT performed in childhood for bone marrow failure syndromes and SAA and evaluating how this risk differs between these diseases. We investigated cause-specific late mortality in 2-year survivors of allogeneic BMT for bone marrow failure syndromes and SAA performed before age 22years between 1974 and 2010 at 2 US transplantation centers. Vital status information was collected from medical records, the National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. The standardized mortality ratio (SMR) was calculated using age- sex-, and calendar-specific mortality rates from the Centers for Disease Control and Prevention. Among the 2-year survivors of bone marrow failure syndromes (n = 120) and SAA (n = 147), there were 15 and 19 deaths, respectively, yielding an overall survival of 86.4% for bone marrow failure syndromes and 93.1% for SAA at 15years post-BMT. Compared with the general population, patients with bone marrow failure syndromes were at a higher risk for premature death (SMR, 22.7; 95% CI, 13.1 to 36.2) compared with those with SAA (SMR, 4.5; 95% CI, 2.8 to 7.0) (P < .0001). The elevated relative risk persisted at ≥15years after BMT for both diseases. The hazard of all-cause late mortality was 2.9-fold (95% CI, 1.1 to 7.3) higher in patients with bone marrow failure syndromes compared with those with SAA. The high late mortality risk in recipients of allogeneic BMT in childhood for bone marrow failure syndromes calls for intensified life-long follow-up.

Late Mortality after Allogeneic Blood or Marrow Transplantation for Inborn Errors of Metabolism: A Report from the Blood or Marrow Transplant Survivor Study-2 (BMTSS-2).

Allogeneic blood or marrow transplantation (BMT) is currently considered the standard of care for patients with specific inborn errors of metabolism (IEM). However, there is a paucity of studies describing long-term survival and cause-specific late mortality after BMT in these patients with individual types of IEM. We studied 273 patients who had survived ≥2 years after allogeneic BMT for IEM performed between 1974 and 2014. The most prevalent IEM in our cohort were X-linked adrenoleukodystrophy (ALD; 37.3%), Hurler syndrome (35.1%), and metachromatic leukodystrophy (MLD; 10.2%). Conditional on surviving ≥2 years after BMT, the overall survival for the entire cohort was 85.5 ± 2.4% at 10 years and 73.5 ± 3.7% at 20 years. The cohort had a 29-fold increased risk of late death compared with an age- and sex-matched cohort from the general US population (95% CI, 22- to 38-fold). The increased relative mortality was highest in the 2- to 5-year period after BMT (standardized mortality ratio [SMR], 207; 95% confidence interval [CI], 130 to 308) and declined with increasing time from BMT, but remained elevated for ≥21 years after BMT (SMR, 9; 95% CI, 4 to 18). Sequelae from the progression of primary disease were the most common causes of late mortality in this cohort (76%). The use of T cell-depleted grafts in patients with ALD and Hurler syndrome was a risk factor for late mortality. Younger age at BMT and use of busulfan and cyclosporine were protective in patients with Hurler syndrome. Our findings demonstrate relatively favorable overall survival in ≥2-year survivors of allogeneic BMT for IEM, although primary disease progression continues to be responsible for the majority of late deaths.

Risk of venous thromboembolism in patients with non-Hodgkin lymphoma surviving blood or marrow transplantation.

BACKGROUND: Patients with non-Hodgkin lymphoma (NHL) have an increased risk of venous thromboembolism (VTE), particularly when they are receiving treatment. Blood or marrow transplantation (BMT) is recommended for relapsed/refractory NHL, and the risk of VTE after these patients undergo BMT is uncertain. METHODS: Patients with NHL who survived 2 years or longer after BMT were surveyed for long-term health outcomes, including VTE. The median follow-up was 8.1 years (interquartile range, 5.6-12.9 years). The risk of VTE in 734 patients with NHL versus 897 siblings without a history of cancer and the risk factors associated with VTE were analyzed. RESULTS: BMT survivors of NHL were at increased risk for VTE in comparison with siblings (odds ratio for allogeneic BMT survivors, 4.61; P < .0001; odds ratio for autologous BMT survivors, 1.75; P = .035). The cumulative incidence of VTE was 6.3% ± 0.9% at 5 years after BMT and 8.1% ± 1.1% at 10 years after BMT. In allogeneic BMT recipients, an increased body mass index (BMI; hazard ratio [HR] for BMI of 25-30 kg/m2 , 3.52; 95% confidence interval [CI], 1.43-8.64; P = .006; HR for BMI > 30 kg/m2 , 3.44; 95% CI, 1.15-10.23; P = .027) and a history of chronic graft-versus-host disease (HR, 3.33; 95% CI, 1.59-6.97; P = .001) were associated with an increased risk of VTE. Among autologous BMT recipients, a diagnosis of coronary artery disease (HR, 5.94; 95% CI, 1.7-20.71; P = .005) and prior treatment with carmustine (HR, 4.91; 95% CI, 1.66-14.51; P = .004) were associated with increased VTE risk. CONCLUSIONS: Patients with NHL who survive BMT are at risk for developing late occurring VTE, and ongoing vigilance for this complication is required. Future studies assessing the role of thromboprophylaxis in high-risk patients with NHL are needed.

Late mortality after bone marrow transplant for chronic myelogenous leukemia in the context of prior tyrosine kinase inhibitor exposure: A Blood or Marrow Transplant Survivor Study (BMTSS) report.

BACKGROUND: Late mortality was investigated in patients with chronic myelogenous leukemia (CML) who underwent blood or bone marrow transplant (BMT) with or without prior tyrosine kinase inhibitor (TKI) therapy. METHODS: By using data from the Blood or Marrow Transplant Survivor Study, the authors examined late mortality in 447 patients with CML who underwent BMT between 1974 and 2010, conditional on surviving ≥2 years post-BMT. For vital status information, the medical records, the National Death Index, and the Accurint database were used. Standardized mortality ratios (SMRs) were calculated using general population age-specific, sex-specific, and calendar-specific mortality rates. Kaplan-Meier techniques and Cox regression were used for all-cause mortality analyses. Cumulative incidence and proportional subdistribution hazards models for competing risks were used for cause-specific mortality analyses. RESULTS: The 10-year overall survival rate was 65.7% and 73% for those who underwent transplant with and without pre-BMT exposure to TKI therapy, respectively. Patients who underwent transplant with and without pre-BMT TKI experienced SMRs of 6.4 and 6.4, respectively (P = .8); and the SMRs were 11.6 and 8.1, respectively, for those with high-risk disease (P = .2). Independent predictors of non-CML-related mortality included chronic graft-versus-host disease (hazard ratio [HR], 2.8; 95% CI, 1.8-4.4) and busulfan/cyclophosphamide conditioning (HR, 0.5; 95% CI, 0.3-0.9; reference, total body irradiation/cyclophosphamide conditioning). The 20-year cumulative incidence of CML-related and non-CML-related mortality was 6% and 36%, respectively, for the entire cohort. Both CML-related mortality (HR, 1.0; 95% CI, 0.1-12.6) and non-CML-related mortality (HR, 1.3; 95% CI, 0.6-3.1) were comparable for those with and without pre-BMT TKI therapy. CONCLUSIONS: The similar late mortality experienced by patients with CML who undergo transplantation with or without pre-BMT TKIs suggests that allogeneic BMT can be considered in the context of TKI intolerance or nonadherence. The prevention of post-BMT non-CML-related mortality could favorably affect long-term survival.

A Study Protocol to Increase Engagement in Evidence Based Hospital and Community Based Care Using a Serious Injection Related Infections (SIRI) Checklist and Enhanced Peer for Hospitalized PWID (ShaPe).

Background: With the opioid crisis, surging methamphetamine use, and healthcare disruptions due to SARS-CoV-2, serious injection related infections (SIRIs), like endocarditis, have increased significantly. Hospitalizations for SIRI provide a unique opportunity for persons who inject drugs (PWID) to engage in addiction treatment and infection prevention, yet many providers miss opportunities for evidence-based care due to busy inpatient services and lack of awareness. To improve hospital care, we developed a 5-item SIRI Checklist for providers as a standardized reminder to offer medication for opioid use disorder (MOUD), HIV and HCV screening, harm reduction counseling, and referral to community-based care. We also formalized an Intensive Peer Recovery Coach protocol to support PWID on discharge. We hypothesized that the SIRI Checklist and Intensive Peer Intervention would increase use of hospital-based services (HIV, HCV screening, MOUD) and linkage to community-based care: PrEP prescription, MOUD prescription, and related outpatient visit(s). Methods: This is a feasibility study and randomized control trial of a checklist and intensive peer intervention for hospitalized PWID with SIRI admitted to UAB Hospital. We will recruit 60 PWID who will be randomized to one of 4 groups (SIRI Checklist, SIRI Checklist + Enhanced Peer, Enhanced Peer, and Standard of Care). Results will be analyzed using a 2x2 factorial design. We will use surveys to collect data on drug use behaviors, stigma, HIV risk, and PrEP interest and awareness. Our primary outcome of feasibility will include the ability to recruit hospitalized PWID and retain them in the study to determine post-discharge clinical outcomes. Additionally, we will explore clinical outcomes using a combination of patient surveys and electronic medical record data (HIV, HCV testing, MOUD and PrEP prescriptions).This study is approved by UAB IRB #300009134. Discussion: This feasibility study is a necessary step in designing and testing patient-centered interventions to improve public health for rural and Southern PWID. By testing low barrier interventions that are accessible and reproducible in states without access to Medicaid expansion and robust public health infrastructure, we aim to identify models of care that promote linkage and engagement in community care. Trial Registration: NCT05480956.

HIV and Addiction Services for People Who Inject Drugs: Healthcare Provider Perceptions on Integrated Care in the U.S. South.

This qualitative study evaluates physician training and experience with treatment and prevention services for people who inject drugs (PWID) including medications for opioid use disorder (MOUD) and HIV pre-exposure prophylaxis (PrEP). The Behavioral Model of Healthcare Utilization for Vulnerable Populations was applied as a framework for data analysis and interpretation. Two focus groups were conducted, one with early career physicians (n = 6) and one with mid- to late career physicians (n = 3). Focus group transcripts were coded and analyzed using thematic analysis to identify factors affecting implementation of treatment and prevention services for PWID. Respondents identified that increasing the availability of providers prescribing MOUD was a critical enabling factor for PWID seeking and receiving care. Integrated, interdisciplinary services were identified as an additional resource although these remain fragmented in the current healthcare system. Barriers to care included provider awareness, stigma associated with substance use, and access limitations. Providers identified the interwoven risk factors associated with injection drug use that must be addressed, including the risk of HIV acquisition, notably more at the forefront in the minds of early career physicians. Additional research is needed addressing the medical education curriculum, health system, and healthcare policy to address the addiction and HIV crises in the U.S. South.

Using Principles of an Adaptation Framework to Adapt a Transdiagnostic Psychotherapy for People With HIV to Improve Mental Health and HIV Treatment Engagement: Focus Groups and Formative Research Study.

BACKGROUND: HIV treatment engagement is critical for people with HIV; however, behavioral health comorbidities and HIV-related stigma are key barriers to engagement. Treatments that address these barriers and can be readily implemented in HIV care settings are needed. OBJECTIVE: We presented the process for adapting transdiagnostic cognitive behavioral psychotherapy, the Common Elements Treatment Approach (CETA), for people with HIV receiving HIV treatment at a Southern US HIV clinic. Behavioral health targets included posttraumatic stress, depression, anxiety, substance use, and safety concerns (eg, suicidality). The adaptation also included ways to address HIV-related stigma and a component based on Life-Steps, a brief cognitive behavioral intervention to support patient HIV treatment engagement. METHODS: We applied principles of the Assessment, Decision, Administration, Production, Topical Experts, Integration, Training, Testing model, a framework for adapting evidence-based HIV interventions, and described our adaptation process, which included adapting the CETA manual based on expert input; conducting 3 focus groups, one with clinic social workers (n=3) and 2 with male (n=3) and female (n=4) patients to obtain stakeholder input for the adapted therapy; revising the manual according to this input; and training 2 counselors on the adapted protocol, including a workshop held over the internet followed by implementing the therapy with 3 clinic patients and receiving case-based consultation for them. For the focus groups, all clinic social workers were invited to participate, and patients were referred by clinic social workers if they were adults receiving services at the clinic and willing to provide written informed consent. Social worker focus group questions elicited reactions to the adapted therapy manual and content. Patient focus group questions elicited experiences with behavioral health conditions and HIV-related stigma and their impacts on HIV treatment engagement. Transcripts were reviewed by 3 team members to catalog participant commentary according to themes relevant to adapting CETA for people with HIV. Coauthors independently identified themes and met to discuss and reach a consensus on them. RESULTS: We successfully used principles of the Assessment, Decision, Administration, Production, Topical Experts, Integration, Training, Testing framework to adapt CETA for people with HIV. The focus group with social workers indicated that the adapted therapy made conceptual sense and addressed common behavioral health concerns and practical and cognitive behavioral barriers to HIV treatment engagement. Key considerations for CETA for people with HIV obtained from social worker and patient focus groups were related to stigma, socioeconomic stress, and instability experienced by the clinic population and some patients' substance use, which can thwart the stability needed to engage in care. CONCLUSIONS: The resulting brief, manualized therapy is designed to help patients build skills that promote HIV treatment engagement and reduce symptoms of common behavioral health conditions that are known to thwart HIV treatment engagement.

Effectiveness of a smoking cessation algorithm integrated into HIV primary care: Study protocol for a randomized controlled trial.

BACKGROUND: While addressing smoking cessation in the context of HIV primary care may increase the acceptability of smoking cessation treatment for patients, HIV care providers have not been trained in offering these treatments. Tools that aid providers in treatment selection, such as computer-generated algorithms, may address barriers to providing effective and efficient treatment options to their patients. OBJECTIVE: To test the effectiveness of a computer-generated smoking cessation pharmacotherapy recommendation algorithm fully integrated into HIV primary care against an enhanced usual care condition. METHODS: Six hundred adult smokers living with HIV will be recruited from 3 medical clinics that provide HIV care in Birmingham, AL, Seattle, WA, and Boston, MA. Participants will be asked to complete a baseline visit and 4 follow-up visits, which will include self-report assessments and carbon monoxide monitoring. Additionally, participants have the option to respond to weekly text-message based surveys sent over an 11-week period between baseline and end of treatment. Participants randomized to the AT condition will have a tailored, algorithm-generated smoking cessation pharmacotherapy recommendation delivered to their HIV care provider via EHR, with the potential to receive up to 12 weeks of smoking cessation pharmacotherapy. CONCLUSIONS: A smoking cessation pharmacotherapy recommendation algorithm integrated into HIV primary care may increase treatment utilization and smoking abstinence among smokers living with HIV. If successful, the intervention would be ready for use across the entire CFAR Network of Integrated Clinical Systems network and, more broadly, in HIV clinics that utilize an EHR system.

Integrating geriatric assessment into routine gastrointestinal (GI) consultation: The Cancer and Aging Resilience Evaluation (CARE).

BACKGROUND: Integrating Geriatric Assessment (GA) in the management of older adults with cancer is recommended, yet rarely practiced in routine oncologic care. Our objective was to assess the feasibility of integrating routine GA in the management of older adults with gastrointestinal (GI) malignancies and characterize impairments in this population. METHODS: Patients ≥60yo referred for consultation to the GI Oncology clinic were asked to complete the Cancer and Aging Resilience Evaluation (CARE) on their first visit. CARE was adapted from the Cancer and Aging Research Group GA with modifications to create a completely patient-reported version of the GA. Feasibility was defined as completion of CARE by ≥80% of eligible patients during the initial consultation. RESULTS: Of the eligible 354 new patients seen in the GI Oncology Clinic, 323 (91.2%) completed the CARE survey. Most patients (83.1%) felt the length of time to complete was appropriate (median time of 10 min [IQR 10-15.7 min]). GA impairments were prevalent: 54.7% reported dependence in Instrumental Activities of Daily Living, 15.5% reported dependence in Activities of Daily Living, 20.9% reported ≥1 fall, 35.9% reported a performance status ≥2, 55.7% were limited in walking one block, 74.0% reported polypharmacy (≥4 medications), and 36.4% had ≥3 comorbidities. CONCLUSIONS: Performing a GA in the routine care of older adults with GI malignancies is feasible, and GA impairments are common among this population. A fully patient-reported GA such as the CARE may facilitate broader incorporation of GA in the routine clinic work flow.

Randomization to randomization probability: Estimating treatment effects under actual conditions of use.

Blinded randomized controlled trials (RCT) require participants to be uncertain if they are receiving a treatment or placebo. Although uncertainty is ideal for isolating the treatment effect from all other potential effects, it is poorly suited for estimating the treatment effect under actual conditions of intended use-when individuals are certain that they are receiving a treatment. We propose an experimental design, randomization to randomization probabilities (R2R), which significantly improves estimates of treatment effects under actual conditions of use by manipulating participant expectations about receiving treatment. In the R2R design, participants are first randomized to a value, π, denoting their probability of receiving treatment (vs. placebo). Subjects are then told their value of π and randomized to either treatment or placebo with probabilities π and 1-π, respectively. Analysis of the treatment effect includes statistical controls for π (necessary for causal inference) and typically a π-by-treatment interaction. Random assignment of subjects to π and disclosure of its value to subjects manipulates subject expectations about receiving the treatment without deception. This method offers a better treatment effect estimate under actual conditions of use than does a conventional RCT. Design properties, guidelines for power analyses, and limitations of the approach are discussed. We illustrate the design by implementing an RCT of caffeine effects on mood and vigilance and show that some of the actual effects of caffeine differ by the expectation that one is receiving the active drug. (PsycINFO Database Record

Assessment of Late Mortality Risk After Allogeneic Blood or Marrow Transplantation Performed in Childhood.

Importance: Allogeneic blood or marrow transplantation (BMT) is a curative option for malignant and nonmalignant diseases of childhood. However, little is known about trends in cause-specific late mortality in this population during the past 3 decades. Objectives: To examine cause-specific late mortality among individuals who have lived 2 years or more after allogeneic BMT performed in childhood and whether rates of late mortality have changed over time. Design, Setting, and Participants: A retrospective cohort study was conducted of individuals who lived 2 years or more after undergoing allogeneic BMT performed in childhood between January 1, 1974, and December 31, 2010. The end of follow-up was December 31, 2016. Exposure: Allogeneic BMT performed in childhood. Main Outcomes and Measures: All-cause mortality, relapse-related mortality, and non-relapse-related mortality. Data on vital status and causes of death were collected using medical records, the National Death Index Plus Program, and Accurint databases. Results: Among 1388 individuals (559 females and 829 males) who lived 2 years or more after allogeneic BMT performed in childhood, the median age at transplantation was 14.6 years (range, 0-21 years). In this cohort, there was a total of 295 deaths, yielding an overall survival rate of 79.3% at 20 years after BMT. The leading causes of death were infection and/or chronic graft-vs-host disease (121 of 244 [49.6%]), primary disease (60 of 244 [24.6%]), and subsequent malignant neoplasms (45 of 244 [18.4%]). Overall, the cohort had a 14.4-fold increased risk for death (95% CI, 12.8-16.1) compared with the general population (292 deaths observed; 20.3 deaths expected). Relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9; 95% CI, 2.0-4.1). The absolute excess risk for death from any cause was 12.0 per 1000 person-years (95% CI, 10.5-13.5). The cumulative incidence of non-relapse-related mortality exceeded that of relapse-related mortality throughout follow-up. The 10-year cumulative incidence of late mortality decreased over time (before 1990, 18.9%; 1990-1999, 12.8%; 2000-2010, 10.9%; P = .002); this decrease remained statistically significant after adjusting for demographic and clinical factors (referent group: <1990; 1990-1999: hazard ratio, 0.64; 95% CI, 0.47-0.89; P = .007; 2000-2010: hazard ratio, 0.49; 95% CI, 0.31-0.76; P = .002; P < .001 for trend). Conclusions and Relevance: Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.

Comparisons of Fatty Acid Taste Detection Thresholds in People Who Are Lean vs. Overweight or Obese: A Systematic Review and Meta-Analysis.

Given the increasing evidence that supports the ability of humans to taste non-esterified fatty acids (NEFA), recent studies have sought to determine if relationships exist between oral sensitivity to NEFA (measured as thresholds), food intake and obesity. Published findings suggest there is either no association or an inverse association. A systematic review and meta-analysis was conducted to determine if differences in fatty acid taste sensitivity or intensity ratings exist between individuals who are lean or obese. A total of 7 studies that reported measurement of taste sensations to non-esterified fatty acids by psychophysical methods (e.g.,studies using model systems rather than foods, detection thresholds as measured by a 3-alternative forced choice ascending methodology were included in the meta-analysis. Two other studies that measured intensity ratings to graded suprathreshold NEFA concentrations were evaluated qualitatively. No significant differences in fatty acid taste thresholds or intensity were observed. Thus, differences in fatty acid taste sensitivity do not appear to precede or result from obesity.