Publications

RATIONALE

Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation.

OBJECTIVES

To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates.

METHODS

In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively.

MEASUREMENTS AND MAIN RESULTS

Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB.

CONCLUSIONS

Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.

OBJECTIVE

We examined whether nonadherence to hydroxychloroquine (HCQ) or immunosuppressive medications (ISMs) was associated with higher subsequent acute care utilization among Medicaid beneficiaries with systemic lupus erythematosus (SLE).

METHODS

We utilized US Medicaid data from 2000-2006 to identify adults ages 18-64 years with SLE who were new users of HCQ or ISMs. We defined the index date as receipt of HCQ or ISMs without use in the prior 6 months. We measured adherence using the medication possession ratio (MPR), the proportion of days covered by total days' supply dispensed, for the 1-year post-index date. Our outcomes were all-cause and SLE-related emergency department (ED) visits and hospitalizations in the subsequent year. We used multivariable Poisson regression models to examine the association between nonadherence (MPR <80%) and acute care utilization, adjusting for sociodemographics and comorbidities.

RESULTS

We identified 9,600 HCQ new users and 3,829 ISM new users with SLE. The mean ± SD MPR for HCQ was 47.8% ± 30.3% and for ISMs was 42.7% ± 30.7%. Seventy-nine percent of HCQ users and 83% of ISM users were nonadherent (MPR <80%). In multivariable models, among HCQ users, the incidence rate ratio (IRR) of ED visits was 1.55 (95% confidence interval [95% CI] 1.43-1.69) and the IRR of hospitalizations was 1.37 (95% CI 1.25-1.50), comparing nonadherers to adherers. For ISM users, the IRR of ED visits was 1.64 (95% CI 1.42-1.89) and of hospitalizations was 1.67 (95% CI 1.41-1.96) for nonadherers versus adherers.

CONCLUSION

In this cohort, nonadherence to HCQ and ISMs was common and was associated with significantly higher subsequent acute care utilization.

BACKGROUND

Antiretroviral therapy (ART) adherence interruptions have been associated with viral rebound; however, the true risk is unknown because HIV RNA has never been measured during ongoing interruptions.

METHODS

The Uganda AIDS Rural Treatment Outcomes Study is an observational longitudinal cohort of adults initiating ART. We monitored adherence with the device that wirelessly transmits records of device openings, and routinely assessed HIV RNA quarterly. When lapses of 48+ hours between device openings were detected, we made unannounced visits to participants to investigate the cause and assess HIV RNA. Generalized estimating equation logistic regressions were used to assess factors associated with viral rebound.

RESULTS

We followed 479 participants (median: 25 months per participant). Most were women (72%), median age was 36 years, median pre-ART CD4 count was 198 cells per microliter, median pre-ART HIV RNA level was 5.0 log10 copies per milliliter, and median duration of prior viral suppression was 13 months. A total of 587 adherence interruptions followed confirmed prior viral suppression, of which 13 (2%) had detectable viral rebound. Viral rebound was associated with duration of adherence interruption (odds ratio: 1.25 for each day beyond 48 hours; P = 0.007) and 30-day adherence before the interruption (odds ratio: 0.73; P = 0.02).

DISCUSSION

This article is the first demonstration of HIV RNA rebound during adherence interruptions objectively measured in real time. Odds of viral rebound increased by 25% with each day beyond 48 hours. Real-time adherence monitoring was feasible in a sub-Saharan African setting. Further research should assess the potential for real-time adherence interventions to sustain adherence to affordable first-line regimens.

INTRODUCTION

Numerous treatments are approved for metastatic castration-resistant prostate cancer (mCRPC), including sipuleucel-T, an FDA-approved immunotherapy.

MATERIALS AND METHODS

In this paper we review recent data providing insights into the mechanism of action of sipuleucel-T which suggests sipuleucel-T may be most effective when administered to mCRPC patients with a low burden of disease. Published and presented data from the sipuleucel-T clinical trials NeoACT (NCT00715104), IMPACT (NCT00065442), ProACT (NCT00715078), PROTECT (NCT00779402), OpenACT (NCT00901342), STAMP (NCT01487863) and STAND (NCT01431391), individually or across trials, were included in this review.

RESULTS

Overall, a growing body of evidence supports the concept that sipuleucel-T, like some other immunotherapies, has long term effects that result in an overall survival benefit. mCRPC patients with a low tumor burden may derive a greater therapeutic benefit, since the immune response may be more robust when the disease is less advanced and immunosuppressive effects from the tumor or traditional therapies may be less marked. In addition, treatment with sipuleucel-T in early mCRPC does not preclude subsequent treatment with other approved mCRPC therapies.

CONCLUSIONS

Collectively, clinical data to date suggest the optimal timing for sipuleucel-T treatment may be early in the mCRPC treatment paradigm.

BACKGROUND

Although social support is important for quality of life in patients undergoing surgery for ulcerative colitis, the impact of surgery on patient relationships is not known.

OBJECTIVE

We examined relationship parameters in patients with ulcerative colitis and their partners before and 6 months after surgery.

DESIGN

This was a prospective cohort in which we performed an exploratory analysis.

SETTINGS

Patients were enrolled from an academic medical center.

PATIENTS

Surgical patients with ulcerative colitis and their partners were invited to participate.

INTERVENTIONS

Patients underwent proctocolectomy in 1, 2, or 3 stages.

MAIN OUTCOME MEASURES

We measured quality of life and sexual function in patients, as well as relationship quality, empathy, and sexual satisfaction in patients and partners before and 6 months after surgery using validated questionnaires.

RESULTS

The study sample consisted of 74 participants, including 37 patients (25 men and 12 women) and their opposite-sex partners. Quality of life improved significantly in male and female patients after surgery. Sexual function scores also improved after surgery in male and female patients; however, the changes reached statistical significance in male patients only. Sexual satisfaction scores improved significantly after surgery in female patients and their partners. There was little change in relationship quality or empathy after surgery, with the exception of slightly improved relationship quality reported by male partners. In general, patients and partners reported levels of relationship quality and empathy similar to normative populations.

LIMITATIONS

This study included a small, highly selected sample.

CONCLUSIONS

Male and female patients with ulcerative colitis have high-quality relationships that are not negatively affected by surgical treatment. Changes in sexual function do not necessarily coincide with changes in sexual satisfaction in this patient population. Future studies should evaluate the effect of high-quality relationships on surgical outcomes.

Cancer and HIV are inextricably linked. Although the advent of antiretroviral therapy has led to a marked decline in the incidence of malignancies classically linked to immunosuppression (AIDS-defining malignancies, or ADMs), this decrease has been accompanied by a concomitant rise in the incidence of other malignancies (non-AIDS-defining malignancies, or NADMs). Population-based cancer registries provide key information about cancer epidemiology in people living with HIV (PLWH) within resource-rich countries. The risk for NADMs is elevated in PLWH compared with the general population, particularly for lung and anal cancers. Contributory factors include tobacco use, coinfection with oncogenic viruses such as human papillomavirus, and potentially direct effects of HIV itself. Data from resource-poor countries are limited and highlight the need for more studies in countries where the majority of PLWH reside. Strategies for early cancer detection and/or prevention are necessary in PLWH.