Importance of day 21 BM chimerism in sustained neutrophil engraftment following double-unit cord blood transplantation

Delayed or failed engraftment remains a concern after cord blood transplantation (CBT) even when using double-unit grafts. Therefore, we analyzed the association between BM assessment performed approximately 21 days after transplantation, and the speed and success of sustained donor-derived neutrophil engraftment in 56 myeloablative double-unit CBT (DCBT) recipients. Overall, the cumulative incidence of sustained neutrophil engraftment was 95% (95% confidence intervals (CI): 89-100). Of the percentage of myeloid precursors, the BM cellularity and the total donor chimerism the total donor chimerism percentage had the most critical association with the speed and success of engraftment. DCBT recipients who were 100% donor achieved a 98% engraftment rate at a median of 22 days. This compared with 100% engraftment in patients who were 90-99% donor, but at a delayed median of 29 days and only 68% engraftment in patients <90% donor at a median of 37 days (P=0.001). Multivariate analysis was performed in the subgroup of patients who had not engrafted at the time the BM analysis was performed, the subgroup of most clinical concern. This confirmed donor chimerism was predictive of subsequent neutrophil recovery (P=0.004). These findings demonstrate the importance of the day 21 BM chimerism determinations after DCBT.     

Rates and determinants of HIV-attributable mortality among rural female sex workers in Northern Karnataka, India

Female sex workers (FSWs) have among the highest rates of HIV infection in India. However, little is known about their HIV-specific mortality rates. In total, 1561 FSWs participated in a cohort study in Karnataka. Outcome data (mortality) were available on 1559 women after 15 months of follow-up. To gather details on deaths, verbal autopsy (VA) questionnaires were administered to key informants. Two physicians reviewed the VA reports and assigned underlying causes of death. Forty-seven deaths were reported during the follow-up (overall mortality rate was 2.44 per 100 person-years), with VA data available on 45 women. Thirty-five (75.6%) of these women were known to be HIV-positive, but only 42.5% were on antiretroviral therapy (ART). Forty deaths were assessed to be HIV-related, for an HIV-attributable mortality rate of 2.11 deaths per 100 person-years. Absence of a current regular partner (incidence rate ratio: 2.79; 95% confidence interval [CI]: 1.39-5.60) and older age (1.06; 1.01-1.11) were associated with increased HIV-attributable mortality. Reported duration in sex work was not related to HIV-attributable mortality. We found a high HIV-related mortality rate among this cohort of FSWs; nearly 10 times that of national mortality rates among women of a similar age group. Older age, but not reported duration in sex work, was associated with increased mortality, and suggests HIV acquisition prior to self-reported initiation into sex work. Despite significant efforts, there remain considerable gaps in HIV prevention near or before entry into sex work, as well as access and uptake of HIV treatment among FSWs.     

The development and validation of the hypertension evaluation of lifestyle and management knowledge scale

Hypertension knowledge is an integral component of the chronic care model. A valid scale to assess hypertension knowledge and self-management skills is needed. The hypertension evaluation of lifestyle and management (HELM) scale was developed as part of a community-based study designed to improve self-management of hypertension. Participants included 404 veterans with hypertension. Literature review and an expert panel were used to identify required skills. Items were generated and pilot tested in the target population. Validity was assessed through comparisons of performance with education, health numeracy, print numeracy, patient activation and self-efficacy, and hypertension control. The HELM knowledge scale had 14 items across 3 domains: general hypertension knowledge, lifestyle and medication management, and measurement and treatment goals. Scores were positively associated with education (0.28, P<.0001), print health literacy (0.21, P<.001), health numeracy (0.17, P<.001), and patient activation (0.12, P=.015) but no association was found with diastolic or systolic blood pressure. The HELM knowledge scores increased following the educational intervention from baseline (mean, 8.7; standard deviation, 2.2) to 12-month follow-up (mean, 9.2, standard deviation, 2.2; P<.001). We conclude that the HELM provides a valid measure of the knowledge required for patients to take an active role in the chronic disease management of hypertension.     

Adherence to evidence-based guidelines for heart failure in physicians and their patients: lessons from the Heart Failure Adherence Retention Trial (HART)

The Heart Failure Adherence and Retention Trial (HART) provided an opportunity to determine adherence to evidence-based guidelines (EBG) in patients with heart failure (HF). Ten hospitals were the source of 692 patients with HF (EF < 40%). Physicians of patients with HF were classified as adherent to EBG if the patient chart audit showed they were on a beta-blocker, ACE-inhibitor (ACE-I), or angiotensin receptor blocker (ARB). Patients were classified as adherent to EBG if MEMS pill caps were used appropriately more than 80% of the time. Sixty-three percent of physicians prescribed evidence-based medications that were adherent to clinical practice guidelines. New York Heart Association (NYHA) III patients were less likely to be adherent (P < 0.001), as were those with renal disease (P < 0.001) and asthmatics (P < 0.001). Nonadherent physicians were less likely to treat patients with beta-blockers (39% vs 98%, P < 0.001) and ACE-I or ARBs (71% vs 98% P < 0.001). Thirty-seven percent of patients prescribed evidence-based therapy failed to use the MEMS pill cap bottles appropriately and were more likely a minority or higher NYHA class. Adherence to evidence-based therapy is less than optimal in HF patients based on a combination of both physician and patient nonadherence.     

The impact of surveillance and rapid reduction in immunosuppression to control BK virus‐related graft injury in kidney transplantation

We prospectively screened 609 consecutive kidney (538) and kidney‐pancreas (71) transplant recipients for BK viremia over a 4‐year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30–50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus‐associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22–744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.     

Evolving Impact of COVID-19 on Transplant Center Practices and Policies in the United States

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19–positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.