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Background: Persons with disabilities have often been overlooked in the context of HIV and AIDS risk prevention and service provision. This paper explores access to and use of HIV information and services among persons with disabilities. Methods: We conducted a multi-country qualitative research study at urban and rural sites in Uganda, Zambia, and Ghana: three countries selected to exemplify different stages of the HIV response to persons with disabilities. We conducted key informant interviews with government officials and service providers, and focus group discussions with persons with disabilities and caregivers. Research methods were designed to promote active, meaningful participation from persons with disabilities, under the guidance of local stakeholder advisors. Results: Persons with disabilities emphatically challenged the common assumption that persons with disabilities are not sexually active, pointing out that this assumption denies their rights and - by denying their circumstances - leaves them vulnerable to abuse. Among persons with disabilities, knowledge about HIV was limited and attitudes towards HIV services were frequently based upon misinformation and stigmatising cultural beliefs; associated with illiteracy especially in rural areas, and rendering people with intellectual and developmental disability especially vulnerable. Multiple overlapping layers of stigma towards persons with disabilities (including internalised self-stigma and stigma associated with gender and abuse) have compounded each other to contribute to social isolation and impediments to accessing HIV information and services. Participants suggested approaches to HIV education outreach that emphasise the importance of sharing responsibility, promoting peer leadership, and increasing the active, visible participation of persons with disabilities in intervention activities, in order to make sure that accurate information reflecting the vulnerabilities of persons with disabilities is accessible to people of all levels of education. Fundamental change to improve the skills and attitudes of healthcare providers and raise their sensitivity towards persons with disabilities (including recognising multiple layers of stigma) will be critical to the ability of HIV service organisations to implement programs that are accessible to and inclusive of persons with disabilities. Discussion: We suggest practical steps towards improving HIV service accessibility and utilisation for persons with disabilities, particularly emphasising the power of community responsibility and support; including acknowledging compounded stigma, addressing attitudinal barriers, promoting participatory responses, building political will and generating high-quality evidence to drive the continuing response. Conclusions: HIV service providers and rehabilitation professionals alike must recognise the two-way relationship between HIV and disability, and their multiple overlapping vulnerabilities and stigmas. Persons with disabilities demand recognition through practical steps to improve HIV service accessibility and utilisation in a manner that recognises their vulnerability and facilitates retention in care and adherence to treatment. In order to promote lasting change, interventions must look beyond the service delivery context and take into account the living circumstances of individuals and communities affected by HIV and disability. Implications for RehabilitationPersons with disabilities are vulnerable to HIV infection but have historically been excluded from HIV and AIDS services, including prevention education, testing, treatment, care and support. Fundamental change is needed to address practical and attitudinal barriers to access, including provider training.Rehabilitation professionals and HIV service providers alike must acknowledge the two-way relationship between HIV and disability: people with disability are vulnerable to HIV infection; people with HIV are increasingly becoming disabled.Peer participation by persons with disabilities in the design and implementation of HIV services is crucial to increasing accessibility.Addressing political will (through the National Strategic Plan for HIV) is crucial to ensuring long-term sustainable change in recognizing and responding to the heightened vulnerability of people with disability to HIV.

Importance: Patients with oligometastatic non-small cell lung cancer (NSCLC) may benefit from locally ablative therapy (LAT) such as surgery or stereotactic radiotherapy. Prior studies were conducted before the advent of immunotherapy, and a strong biological rationale for the use of immunotherapy exists in a minimal residual disease state., Objective: To evaluate whether the addition of pembrolizumab after LAT improves outcomes for patients with oligometastatic NSCLC., Design, Setting, and Participants: This single-arm phase 2 trial of pembrolizumab therapy was performed from February 1, 2015, through September 30, 2017, at an academic referral cancer center. The 51 eligible patients enrolled had oligometastatic NSCLC (≤4 metastatic sites) and had completed LAT to all known sites of disease. Data were analyzed from February 1, 2015, to August 23, 2018., Interventions: Within 4 to 12 weeks of completing LAT, patients began intravenous pembrolizumab therapy, 200 mg every 21 days, for 8 cycles, with provision to continue to 16 cycles in the absence of progressive disease or untoward toxic effects., Main Outcomes and Measures: The 2 primary efficacy end points were progression-free survival (PFS) from the start of LAT (PFS-L), which preceded enrollment in the trial, and PFS from the start of pembrolizumab therapy (PFS-P). The study was powered for comparison with historical data on the first efficacy end point. Secondary outcomes included overall survival, safety, and quality of life as measured by the Functional Assessment of Cancer Therapy-Lung instrument., Results: Of 51 patients enrolled, 45 (24 men [53%]; median age, 64 years [range, 46-82 years]) received pembrolizumab. At the time of analysis, 24 patients had progressive disease or had died. Median PFS-L was 19.1 months (95% CI, 9.4-28.7 months), significantly greater than the historical median of 6.6 months (P = .005). Median PFS-P was 18.7 months (95% CI, 10.1-27.1 months). Eleven patients died. Overall mean (SE) survival rate at 12 months was 90.9% (4.3%); at 24 months, 77.5% (6.7%). Neither programmed death ligand 1 expression nor CD8 T-cell tumor infiltration was associated with PFS-L. Pembrolizumab after LAT yielded no new safety signals and no reduction in quality of life., Conclusions and Relevance: Pembrolizumab after LAT for oligometastatic NSCLC appears to improve PFS with no reduction in quality of life., Trial Registration: ClinicalTrials.gov identifier: NCT02316002.

Objectives: Efficient use of nivolumab in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. In patients with metastatic melanoma treated with ipilimumab, a pretreatment neutrophil-to-lymphocyte ratio (NLR)<5 has been associated with improved survival. This retrospective cohort study aimed to determine whether the pretreatment NLR was associated with outcomes in NSCLC patients treated with nivolumab., Methods: We reviewed the medical records of all patients with previously treated advanced NSCLC who received nivolumab between March 2015 and March 2016 outside of a clinical trial at the University of Pennsylvania. Patients were dichotomized according to pretreatment NLR<5 vs. ≥5. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment NLR on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR)., Results: 175 patients were treated. Median age was 68 (range, 33-88); 54% were female. Twenty-five percent of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2; 46% had received ≥2 prior systemic therapies. In multivariate analyses, pretreatment neutrophil-to-lymphocyte ratio (NLR) ≥5 was independently associated with inferior OS (median 5.5 vs. 8.4 months; HR 2.07, 95% CI 1.3-3.3; p=0.002) and inferior PFS (median 1.9 vs. 2.8 months; HR 1.43, 95% CI 1.02-2.0; p=0.04)., Conclusions: In a cohort of patients with NSCLC treated with nivolumab in routine practice, pretreatment NLR≥5 was associated with inferior outcomes. It is unclear whether this marker is predictive or prognostic. Prospective studies are warranted to determine the utility of NLR in the context of other biomarkers of programmed death-1 (PD-1) therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Knowledge about experiences in accessing HIV services among persons with disabilities who are living with HIV in sub-Saharan Africa is limited. Although HIV transmission among persons with disabilities in Africa is increasingly acknowledged, there is a need to bring to life the experiences and voices from persons with disabilities living with HIV to raise awareness of programme implementers and policy makers about their barriers in accessing HIV services. This paper explores how the barriers faced by persons with disabilities living with HIV impede their ability to access HIV-related services and manage their disease., Methods: We conducted focus group discussions with 76 persons (41 females; 35 males) with physical, visual and/or hearing impairments who were living with HIV in Ghana, Uganda and Zambia (2012-2013). We explored challenges and facilitators at different levels (individual, psychosocial and structural) of access to HIV services. Transcripts were analyzed using a framework analysis approach., Results: Persons with disabilities living with HIV encountered a wide variety of challenges in accessing HIV services. Delays in testing for HIV were common, with most waiting until they were sick to be tested. Reasons for delayed testing included challenges in getting to the health facilities, lack of information about HIV and testing, and HIV- and disability-related stigma. Barriers to HIV-related services, including care and treatment, at health facilities included lack of disability-friendly educational materials and sign interpreters, stigmatizing treatment by providers and other patients, lack of skills to provide tailored services to persons with disabilities living with HIV and physically inaccessible infrastructure, all of which make it extremely difficult for persons with disabilities to initiate and adhere to HIV treatment. Accessibility challenges were greater for women than men due to gender-related roles. Challenges were similar across the three countries. Favourable experiences in accessing HIV services were reported in Uganda and Zambia, where disability-tailored services were offered by non-governmental organizations and government facilities (Uganda only)., Conclusions: Persons with disabilities living with HIV encounter many challenges in accessing HIV testing and continued care and treatment services. Changes are needed at every level to ensure accessibility of HIV services for persons with disabilities.

Although controversy exists in the management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), clinicians often use induction chemotherapy for treatment of the most advanced cases. One promising regimen combines weekly cetuximab (400 mg/m 2 loading dose followed by 250 mg/m 2 ) with carboplatin (AUC of 2) and paclitaxel (90 mg/m 2 ). We retrospectively evaluated patients treated with this regimen prior to definitive chemoradiation or surgery between May 2008 and December 2011. The primary endpoint used for this retrospective analysis was feasibility. Thirty consecutive, unselected patients were included. Median follow-up was 13.7 months (range, 5.0-38.7 months). All but one patient had stage IV SCCHN. Dose intensity was high for carboplatin (92%), paclitaxel (93%) and cetuximab (85%). Grade 3-4 toxicities occurred in <7% of the study population and were limited to rash, neutropenia and infusion reactions. Response rate (RR) to induction chemotherapy was 97% (30% complete response, 67% partial response). All patients completed subsequent chemoradiotherapy or surgery. Nineteen patients (63%) demonstrated a complete response and 11 patients (37%) demonstrated a partial response. Median overall survival and progression-free survival data are not yet mature. The RR to therapy in our off-protocol experience is at least comparable to that observed in the two phase II studies of this regimen and appears superior to that observed with docetaxel, cisplatin and fluorouracil (TPF).

Rationale and Objectives: Phosphorous magnetic resonance spectroscopy ((31)P MRS) has been used to evaluate and predict treatment response in squamous cell carcinoma of the head and neck (HNSCC). Several studies have also shown the potential of proton MRS ((1)H MRS) in assessing response in HNSCC. In view of the inherent limitations associated with performing (31)P MRS in clinical settings, the current study was performed to explore whether (1)H MRS could provide similar or complementary metabolic information in HNSCC., Materials and Methods: Fifteen patients with HNSCC underwent pretreatment magnetic resonance imaging. Both (1)H MRS and (31)P MRS were performed on viable solid parts of the metastatic lymph nodes of these patients. Peak areas of total choline (tCho) and unsuppressed water as observed on (1)H MRS and phosphomonoester (PME) and beta-nucleotide triphosphate (beta-NTP) on (31)P MRS were computed. Pearson's correlation coefficient was used to correlate the tCho/water and PME/beta-NTP ratios., Results: In all patients, the metastatic nodes appeared hyperintense on T2-weighted images and hypointense on T1-weighted images with variable signal intensity. A prominent resonance of tCho on (1)H MRS and a resonance of PME on (31)P MRS from the metastatic nodes of all patients were observed. A moderate correlation of 0.31 was observed between tCho/water and PME/beta-NTP (P > .05)., Conclusions: The biochemical pathways involved in (1)H MRS of tCho may be different from the phospholipid metabolites seen on (31)P MRS of head and neck cancers, and thus the two MRS techniques may be complementary to each other.

Purpose/objectives: To test a model of family caregiving derived from the interactionist approach to role theory that hypothesized that three caregiving role implementation variables (caregiving demand, mutuality between caregivers and patients, and preparedness for caregiving) would predict multiple caregiving-specific and generic outcomes with different patterns of association across outcomes., Design: Descriptive, correlational., Setting: Surgical, radiation, and medical oncology settings., Sample: 87 family caregivers of adults receiving treatment for solid tumors or lymphoma., Methods: Caregivers completed the Demand and Difficulty subscales of the Caregiving Burden Scale; the Mutuality, Preparedness, and Global Strain scales of the Family Care Inventory; and the 30-item short form of the Profile of Mood States. Data were analyzed with simultaneous multiple regression., Main Research Variables: Caregiving demand, mutuality, preparedness, caregiving difficulty, global caregiver strain, tension, depression, anger, fatigue, vigor, confusion, and total mood disturbance., Findings: The model explained statistically significant proportions of variance in each outcome, with different patterns of association across outcomes. Demand was associated most strongly with caregiving difficulty and global strain. Mutuality was associated most strongly with caregiver anger. Unexpectedly, preparedness was associated more strongly with mood disturbance outcomes than with the caregiving-specific variables of difficulty and strain., Conclusions: Further research should explore models that address implementation of the caregiving role to better elucidate how family caregivers learn and carry out the important role., Implications for Nursing: Clinical assessment should include caregiving demand, the quality of the relationship between caregiver and patient, and preparedness for caregiving. Interventions could be tailored to meet caregiver needs in each area.