Leg strength in peripheral arterial disease: associations with disease severity and lower-extremity performance

AbstractObjectiveThe purpose of this study was to determine relationships between lower-extremity arterial obstruction, leg strength, and lower-extremity functioning.DesignThe study design was cross-sectional. A total of 514 outpatients (269 with ankle-brachial index [ABI] <0.90), aged 55 and older, were identified from three Chicago-area hospitals. Individuals with history of lower-extremity revascularization were excluded.Main outcome measuresStrength in each leg, 6-minute walk, 4-meter walking velocity, accelerometer-measured physical activity, and a summary performance score were measured. The summary performance score is a composite measure of lower-extremity functioning, ranging from 0 to 12 (12 = best). The leg with the lower ABI was defined as the “index” leg, and the leg with higher ABI was defined as the “contralateral” leg.ResultsIndex leg ABI levels were associated linearly and significantly with strength for hip extension (P < .001), hip flexion (P < .001), knee extension (P = .066), and knee flexion (P = .003), adjusting for known and potential confounders. In adjusted analyses, the index ABI was also associated linearly and significantly with strength in the contralateral leg. Adjusting for confounders, including ABI, knee extension strength, was associated independently with functional measures.ConclusionAmong patients without prior leg revascularization, strength in each leg is highly correlated with the lower-leg ABI. Leg strength is associated independently with functional performance. Further study is needed to determine whether lower-extremity resistance training improves functioning in patients with peripheral arterial disease

Hybrid management of a spontaneous ilio-iliac arteriovenous fistula: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spontaneous iliac arteriovenous fistulae are a rare clinical entity. Such localized fistulation is usually a result of penetrating traumatic or iatrogenic injury. Clinical presentation can vary greatly but commonly includes back pain, high-output congestive cardiac failure and the presence of an abdominal bruit. Diagnosis, therefore, is often incidental or delayed.</p> <p>Case presentation</p> <p>We report a case of a spontaneous ilio-iliac arteriovenous fistula in a 68-year-old Caucasian man detected following presentation with unilateral claudication and congestive cardiac failure. Following computed tomography evaluation, the fistula was successfully treated with a combined endovascular (aorto-uni-iliac device) and open (femoro-femoral crossover) approach.</p> <p>Conclusion</p> <p>Endovascular surgery has revolutionized the management of such fistulae and we report an interesting case of a high-output iliac arteriovenous fistulae successfully treated with a hybrid vascular approach.</p

HLA-B*35-Px–mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses

A subset of HLA-B*35 alleles, B*35-Px, are strongly associated with accelerated HIV-1 disease progression for reasons that are not understood. Interestingly, the alternative set of B*35 subtypes, B*35-PY, have no detectable impact on HIV-1 disease outcomes, even though they can present identical HIV-1 epitopes as B*35-Px molecules. Thus, the differential impact of these alleles on HIV-1 disease progression may be unrelated to interactions with HIV-1–specific CD8+ T cells. Here, we show that the B*35-Px molecule B*3503 binds with greater affinity to immunoglobulin-like transcript 4 (ILT4), an inhibitory MHC class I receptor expressed on dendritic cells, than does the B*35-PY molecule B*3501, even though these two B*35 molecules differ by only one amino acid and present identical HIV-1 epitopes. The preferential recognition of B*3503 by ILT4 was associated with significantly stronger dendritic cell dysfunction in in vitro functional assays. Moreover, HIV-1–infected carriers of B*3503 had poor dendritic cell functional properties in ex vivo assessments when compared with carriers of the B*3501 allele. Differential interactions between HLA class I allele subtypes and immunoregulatory MHC class I receptors on dendritic cells thus provide a novel perspective for the understanding of MHC class I associations with HIV-1 disease progression and for the manipulation of host immunity against HIV-1

Defining the effect and mediators of two knowledge translation strategies designed to alter knowledge, intent and clinical utilization of rehabilitation outcome measures: a study protocol [NCT00298727]

BACKGROUND: A substantial number of valid outcome measures have been developed to measure health in adult musculoskeletal and childhood disability. Regrettably, national initiatives have merely resulted in changes in attitude, while utilization remains unacceptably low. This study will compare the effectiveness and mediators of two different knowledge transfer (KT) interventions in terms of their impact on changing knowledge and behavior (utilization and clinical reasoning) related to health outcome measures. METHOD/DESIGN: Physical and occupational therapists (n = 144) will be recruited in partnership with the national professional associations to evaluate two different KT interventions with the same curriculum: 1) Stakeholder-Hosted Interactive Problem-Based Seminar (SHIPS), and 2) Online Problem-Based course (e-PBL). SHIPS will consist of face-to-face problem-based learning (PBL) for 2 1/2 days with outcome measure developers as facilitators, using six problems generated in consultation with participants. The e-PBL will consist of a 6-week web-based course with six generic problems developed by content experts. SHIPS will be conducted in three urban centers in Canada. Participants will be block-allocated by a minimization procedure to either of the two interventions to minimize any prognostic differences. Trained evaluators at each site will conduct chart audits and chart-stimulated recall. Trained interviewers will conduct semi-structured interviews focused on identifying critical elements in KT and implementing practice changes. Interviews will be transcribed verbatim. Baseline predictors including demographics, knowledge, attitudes/barriers regarding outcome measures, and Readiness to Change will be assessed by self-report. Immediately post-intervention and 6 months later, these will be re-administered. Primary qualitative and quantitative evaluations will be conducted 6-months post-intervention to assess the relative effectiveness of KT interventions and to identify elements that contribute to changing clinical behavior. Chart audits will determine the utilization of outcome measures (counts). Incorporation of outcome measures into clinical reasoning will be assessed using an innovative technique: chart-stimulated recall. DISCUSSION: A strategy for optimal transfer of health outcome measures into practice will be developed and shared with multiple disciplines involved in primary and specialty management of musculoskeletal and childhood disability

Evaluation of Three Sampling Methods to Monitor Outcomes of Antiretroviral Treatment Programmes in Low- and Middle-Income Countries

BACKGROUND: Retention of patients on antiretroviral therapy (ART) over time is a proxy for quality of care and an outcome indicator to monitor ART programs. Using existing databases (Antiretroviral in Lower Income Countries of the International Databases to Evaluate AIDS and Médecins Sans Frontières), we evaluated three sampling approaches to simplify the generation of outcome indicators. METHODS AND FINDINGS: We used individual patient data from 27 ART sites and included 27,201 ART-naive adults (≥15 years) who initiated ART in 2005. For each site, we generated two outcome indicators at 12 months, retention on ART and proportion of patients lost to follow-up (LFU), first using all patient data and then within a smaller group of patients selected using three sampling methods (random, systematic and consecutive sampling). For each method and each site, 500 samples were generated, and the average result was compared with the unsampled value. The 95% sampling distribution (SD) was expressed as the 2.5(th) and 97.5(th) percentile values from the 500 samples. Overall, retention on ART was 76.5% (range 58.9-88.6) and the proportion of patients LFU, 13.5% (range 0.8-31.9). Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4-77.7) for random, 76.5% (75.3-77.5) for systematic and 76.0% (74.1-78.2) for the consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6-14.5), 13.5% (12.6-14.3) and 14.0% (12.5-15.5), respectively. With consecutive sampling, 50% of sites had SD within ±5% of the unsampled site value. CONCLUSIONS: Our results suggest that random, systematic or consecutive sampling methods are feasible for monitoring ART indicators at national level. However, sampling may not produce precise estimates in some sites

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial.

BACKGROUND: Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer. METHODS: The CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0-2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up. FINDINGS: Between April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35-58), median overall survival was 30 months (95% CI 24-34) in the twice-daily group versus 25 months (21-31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95-1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50-62) in the twice-daily group and 51% (45-57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI -3·2% to 13·7%]). The most common grade 3-4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3-4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3-4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group). INTERPRETATION: Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting. FUNDING: Cancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups)

Adherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Antiretroviral therapy (ART) dramatically improves outcomes for children in Africa; however excellent adherence is required for treatment success. This study describes the utility of different measures of adherence in detecting lapses in infants and young children in Cape Town, South Africa.</p> <p>Methods</p> <p>In a prospective cohort of 122 HIV-infected children commenced on ART, adherence was measured monthly during the first year of treatment by medication return (MR) for both syrups and tablets/capsules. A questionnaire was administered to caregivers after 3 months of treatment to assess experience with giving medication and self-reported adherence. Viral and immune response to treatment were assessed at the end of one year and associations with measured adherence determined.</p> <p>Results</p> <p>Medication was returned for 115/122 (94%) children with median age (IQR) of 37 (16 – 61) months. Ninety-one (79%) children achieved annual average MR adherence ≥ 90%. This was an important covariate associated with viral suppression after adjustment for disease severity (OR = 5.5 [95%CI: 0.8–35.6], p = 0.075), however was not associated with immunological response to ART. By 3 months on ART, 13 (10%) children had deceased and 11 (10%) were lost to follow-up. Questionnaires were completed by 87/98 (90%) of caregivers of those who remained in care. Sensitivity of poor reported adherence (missing ≥ 1 dose in the previous 3 days) for MR adherence <90% was only 31.8% (95% CI: 10.7% – 53.0%). Caregivers of 33/87 (38.4%) children reported difficulties with giving medication, most commonly poor palatability (21.8%). Independent socio-demographic predictors of MR adherence ≥ 90% were secondary education of caregivers (OR = 4.49; 95%CI: 1.10 – 18.24) and access to water and electricity (OR = 2.65; 95%CI: 0.93 – 7.55). Taking ritonavir was negatively associated with MR adherence ≥ 90% (OR = 0.37; 95%CI: 0.13 – 1.02).</p> <p>Conclusion</p> <p>Excellent adherence to ART is possible in African infants and young children and the relatively simple low technology measure of adherence by MR strongly predicts viral response. Better socio-economic status and more palatable regimens are associated with better adherence.</p

Impact of a Randomized Campus/Community Trial to Prevent High-Risk Drinking Among College Students

High-risk drinking by college students continues to pose a significant threat to public health. Despite increasing evidence of the contribution of community-level and campus-level environmental factors to high risk drinking, there have been few rigorous tests of interventions that focus on changing these interlinked environments. The Study to Prevent Alcohol Related Consequences (SPARC) assessed the efficacy of a comprehensive intervention using a community organizing approach to implement environmental strategies in and around college campuses. The goal of SPARC was to reduce high-risk drinking and alcohol-related consequences among college students