Purpose-Physical activity (PA) has been shown to enhance quality of life (QOL) in older adults. Findings from these studies indicate that the relationship between PA and QOL is indirect and likely mediated by variables such as physical self-esteem, exercise self-efficacy, and affect. As PA varies greatly by age, the purpose of the current study is to extend this area of research to young adults and explore the complex relationship between PA and QOL in this target population.Methods-Data were collected via anonymous questionnaire from N = 590 undergraduate students. PA was assessed with the Godin Leisure Time Exercise Questionnaire, and QOL was assessed by the Satisfaction with Life Scale. Path analysis was used to test the relationship between PA and QOL, with mediators of exercise self-efficacy, physical self-esteem, and affect.Results-The PA model (RMSEA = .03, CFI = .99) accounted for 25 % of the variance in QOL. PA had positive direct effects on exercise self-efficacy (β = .28, P < .001), physical self-esteem (β = .10, P < .001), positive affect (β = .10, P < .05), and negative affect (β = .08, P < .05). Physical self-esteem was found to be the most powerful mediating variable on QOL (β = .30, P < .001), followed by positive affect (β = .27, P < .001) and negative affect (β = .14, P < .001).Conclusion-Physical self-esteem and, to a lesser extent, positive affect emerged as integral components in the link between PA and QOL. Findings suggest that health education programs designed to promote regular PA and increase physical self-esteem may be effective in improving QOL in young adults.

Diagnostic error research has largely focused on individual clinicians' decision making and system design, while overlooking information from patients. We analyzed a unique new data source of patient-and family-reported error narratives to explore factors that contribute to diagnostic errors. From reports of adverse medical events submitted in the period January 2010-February 2016, we identified 184 unique patient narratives of diagnostic error. Problems related to patient-physician interactions emerged as major contributors. Our analysis identified 224 instances of behavioral and interpersonal factors that reflected unprofessional clinician behavior, including ignoring patients' knowledge, disrespecting patients, failing to communicate, and manipulation or deception. Patients' perspectives can lead to a more comprehensive understanding of why diagnostic errors occur and help develop strategies for mitigation. Health systems should develop and implement formal programs to collect patients' experiences with the diagnostic process and use these data to promote an organizational culture that strives to reduce harm from diagnostic error. D iagnostic errors pose a significant risk to patient safety, affecting an estimated twelve million US adult outpatients annually 1 and leading to an estimated 6-17 percent of all adverse events in hospitalized patients. 2,3 The 2015 National Academies of Science, Engineering, and Medicine report titled Improving Diagnosis in Health Care defined diagnostic error as "the failure to (a) establish an accurate and timely explanation of the patient's health problem(s) or (b) communicate that explanation to the patient." 2(p xiii) This definition signals a shift in focus that includes the patient's perspective in diagnostic error literature and highlights the fact that communication of a health issue to the patient is a fundamental part of the diagnostic process, as patients bear the most risk for harm. 2 Within the diagnostic process, patient-centered care requires strong communication; a willingness to engage patients as participants; and the ability to be responsive to patients' preferences, needs, and values. 2 Continued movement away from disease-or physician-centered care toward more patient-centric care models can foster a trusting and healing relationship between clinicians and patients. 4

ObjectiveGeographic and racial disparities may contribute to variation in the incidence and outcomes of HIV-associated cancers in the United States.MethodUsing the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed Kaposi sarcoma (KS) incidence and survival by race and geographic region during the combined antiretroviral therapy era. Reported cases of KS in men from 2000 to 2013 were obtained from 17 SEER cancer registries. Overall and age-standardized KS incidence rates were calculated and stratified by race and geographic region. We evaluated incidence trends using joinpoint analyses and calculated adjusted hazard ratios (aHR) for overall and KS-specific mortality using multivariable Cox proportional hazards models.ResultsOf 4,455 KS cases identified in men younger than 55 years (median age 40 years), the annual percent change (APC) for KS incidence significantly decreased for white men between 2001 and 2013 (APC -4.52, p = 0.02). The APC for AA men demonstrated a non-significant decrease from 2000–2013 (APC -1.84, p = 0.09). Among AA men in the South, however, APC has significantly increased between 2000 and 2013 (+3.0, p = 0.03). In addition, compared with white men diagnosed with KS during the same time period, AA men were also more likely to die from all causes and KS cancer-specific causes (aHR 1.52, 95% CI 1.34–1.72, aHR 1.49, 95% CI 1.30–1.72 respectively).ConclusionAlthough overall KS incidence has decreased in the U.S., geographic and racial disparities in KS incidence and survival exist.

Nivolumab is a standard treatment option in several advanced malignancies, but safety and efficacy are still unknown in patients with human immunodeficiency virus (HIV) infection. We describe a case series of people living with HIV (PLWH) receiving nivolumab in the Veterans Health Administration (VA) and report responses and toxicities. We identified all PLWH who received nivolumab at any VA facility since 2000 in the Corporate Data Warehouse (CDW), which provides nationwide research access to VA electronic medical records. We identified 16 HIV-infected nivolumab recipients. The median number of nivolumab doses received was 6 (range, 1-32). Changes in CD4 count during therapy were variable, with 70% (7/10) of patients experiencing increases. Half of PLWH were treated for non-small-cell lung cancer; 2 for Hodgkin lymphoma (HL), 2 for renal cell carcinoma, and 4 for off-label cancers. For non-small-cell lung cancer, 7 patients had evaluable responses. Although 5 of 7 patients immediately progressed, 1 had a partial response and 1 had stable disease, which were both durable. Two of 16 (14%) PLWH had complete responses; both with HL (2/2 HL, 100%). The prevalence of immune-related adverse effects was 40% overall (6/15); 27% (4/15) had pneumonitis. To our knowledge, this is the largest case series reporting outcomes with nivolumab in PLWH. Outcomes were comparable with those seen in studies of HIV-uninfected patients, and particularly interesting for HL. The reason for the high proportions of immune-related adverse effects is unclear, but needs to be confirmed in larger studies.

Bacterial vaginosis (BV) is a common vaginal disorder in women of reproductive age, especially among women with HIV-1 infection. Several bacterial products including lipopolysaccharides (LPS), lipoteichoic acids (LTA), and peptidoglycans (PGN) are stimulatory ligands for Toll-like receptors (TLRs), and recent evidence indicates the important role of variation in TLR genes for permitting overgrowth of gram negative and BV-type flora. We assessed whether genetic polymorphisms in five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR9) could be determinants of differential host immune responses to BV in 159 HIV-1-positive African American adolescents enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) study. BV was assessed biannually and diagnosed either by a Nugent Score of at least 7 of 10, or using the Amsel Criteria. Cox-proportional hazards regression models, adjusted for concurrent Chlamydia and Gonorrhea infections, douching, and absolute CD4 cell count, were used to identify host genetic factors associated with BV. Two SNPs were associated with BV as diagnosed by the Nugent Score and the combined criteria: a minor allele G of rs4986790 (frequency=0.07), which encodes a His to Tyr substitution in TLR4 (HR=1.47, 95% CI 1.15–1.87) and rs187084 (frequency=0.24) on TLR9. The minor allele of rs1898830 (frequency=0.13) was associated with an increased hazard of BV defined by the Amsel criteria (HR=1.86, 95%CI 1.17–2.95). Further studies are warranted to confirm the associations of TLR gene variants and also to understand the underlying pathways and immunogenetic correlates in the context of HIV-1 infection.

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Genetic changes occurring in different stages of pre-cancer lesions reflect causal events initiating and promoting the progression to cancer. Co-existing pre-cancerous lesions including low- and high-grade squamous intraepithelial lesion (LGSIL and HGSIL), and adjacent “normal” cervical epithelium from six formalin-fixed paraffin-embedded samples were selected. Tissues from these 18 samples were isolated using laser-capture microdissection, RNA was extracted and sequenced. RNA-sequencing generated 2.4 billion raw reads in 18 samples, of which ~50.1% mapped to known and annotated genes in the human genome. There were 40 genes up-regulated and 3 down-regulated (normal to LGSIL) in at least one-third of the sample pairs (same direction and FDR p < 0.05) including S100A7 and KLK6. Previous studies have shown that S110A7 and KLK7 are up-regulated in several other cancers, whereas CCL18, CFTR, and SLC6A14, also differentially expressed in two samples, are up-regulated specifically in cervical cancer. These differentially expressed genes in normal to LGSIL progression were enriched in pathways related to epithelial cell differentiation, keratinocyte differentiation, peptidase, and extracellular activities. In progression from LGSIL to HGSIL, two genes were up-regulated and five down-regulated in at least two samples. Further investigations using co-existing samples, which account for all internal confounders, will provide insights to better understand progression of cervical pre-cancer.

Background: Although declining rates of incident AIDS-related Kaposi sarcoma (KS) have been reported, KS incidence rates have noted race/ethnic, age, and geographic diversity. We performed a comprehensive assessment of recent secular trends in AIDS-related KS incidence in the United States. Methods: We identified incident KS diagnosed in men aged 20–54 years (who comprise most AIDS-related KS in the United States) using the US Cancer Statistics registry data. Joinpoint analysis assessed for trends in age-adjusted incidence rates between 2000 and 2014 calculating average annual percentage changes (AAPCs) with 95% confidence intervals. Heat maps were generated to compare age-adjusted HIV incidence rates with KS incidence rates. Results: Age-adjusted KS incidence rates nationwide decreased from 1.44/100,000 to 0.95/100,000 between 2000 and 2014. Observed rate changes varied across subgroups; eg, there were significant decreases in 30–44 years (AAPC = −5.4%), particularly in Whites and Blacks, significant increases among 20–29 years (AAPC = 2.7), primarily in Blacks, and stable rates among 45–54 years (AAPC = −0.03). In Southern United States, the incidence rates among Blacks did not significantly change. The states with highest average age-adjusted rates over the study period were Georgia (2.71/100,000), New York (2.16/100,000), California (2.02/100,000), Florida (1.90/100,000), and Texas (1.39/100,000), with significantly decreasing trends over time, except Georgia where rates increased (AAPC = 1.8). Conclusions: Although KS incidence rates have decreased nationally, age, racial, and geographic disparities persist, including increasing risk among younger Black men and particularly elevated rates in some southern states and urban areas. Further research is needed to address racial and geographic AIDS-related KS disparities.