Faculty Bibliography

Extraordinary Measures [Motion Picture] -- With potentially fatal illnesses, however, the prospect of one child getting better and one child languishing may be too grim for parents and doctors. [...] the use of a placebo would not be humane.\n

BACKGROUND: Currently used treatment response criteria in multiple myeloma (MM) are based in part on serum monoclonal protein (M-protein) measurements. A drawback of these criteria is that response is determined solely by the best level of M-protein reduction, without considering the serial trend. The authors hypothesized that metrics incorporating the serial trend of M-protein would be better predictors of progression-free survival (PFS). METHODS: Fifty-five patients with measurable disease at baseline (M-protein > or = 1 g/dL) who received > or = 4 cycles of treatment from 2 clinical trials in previously untreated MM were included. Three metrics based on the percentage of M-protein remaining relative to baseline (residual M-protein) were considered: metrics based on the number of times residual M-protein fell within prespecified thresholds, metrics based on area under the residual M-protein curve, and metrics based on the average residual M-protein reduction between Cycles 1 and 4. The predictive value of these metrics was assessed in Cox models using landmark analysis. RESULTS: The average residual M-protein reduction was found to be significantly predictive of PFS (P = .02; hazard ratio, 0.37), in which a patient with a 10% lower average residual M-protein reduction from Cycle 1 to 4 was estimated to be at least 2.7x more likely to develop disease progression or die early. None of the other metrics was predictive of PFS. The concordance index for the average residual M-protein reduction was 0.63, compared with 0.56 for best response. CONCLUSIONS: The average residual M-protein reduction metric is promising and needs further validation. This exploratory analysis is the first step in the search for treatment-based trend metrics predictive of outcomes in MM

OBJECTIVE: To determine whether alcohol consumption is associated with cardiovascular disease (CVD) among HIV-infected veterans. METHODS: Using established thresholds for alcohol consumption, we analyzed cross-sectional data from 4743 men (51% HIV infected) from the Veterans Aging Cohort Study, a prospective cohort of HIV-infected veterans and demographically similar HIV-uninfected veterans. Using logistic regression, we estimated the odds ratio (OR) for the association between alcohol consumption and prevalent CVD. RESULTS: Among HIV-infected and HIV-uninfected men, respectively, hazardous drinking (33.2% vs. 30.9%,), alcohol abuse and dependence (20.9% vs. 26.2%), and CVD (14.6% vs. 19.8%) were common. Among HIV-infected men, hazardous drinking [OR = 1.43, 95% confidence interval (CI) = 1.05 to 1.94] and alcohol abuse and dependence (OR = 1.55, 95% CI = 1.07 to 2.23) were associated with a higher prevalence of CVD compared with infrequent and moderate drinking. Among HIV-uninfected men, past drinkers had a higher prevalence of CVD (OR = 1.30, 95% CI = 1.01 to 1.67). For HIV-infected and HIV-uninfected men, traditional risk factors and kidney disease were associated with CVD. CONCLUSIONS: Among HIV-infected men, hazardous drinking and alcohol abuse and dependence were associated with a higher prevalence of CVD compared with infrequent and moderate drinking even after adjusting for traditional CVD risk factors, antiretroviral therapy, and CD4 count

The purpose of this study was to validate the use of Leigh's (1990) alcohol sex expectancies scale among HIV-infected individuals presenting for treatment as a way to facilitate research on sexual risk reduction among individuals in that population. The participants were 944 men who presented for treatment at infectious disease or general medicine clinics across 8 different VA Medical Center sites. A total of 534 of these men were HIV-positive and 410 were HIV-negative. The total sample was randomly divided in half within each HIV group to form exploratory (Sample 1) and confirmatory (Sample 2) subsamples. A principal components factor analysis with oblique rotation of the original 13-item Leigh scale within each HIV group in Sample 1 revealed a 2-factor (7 and 4 items, respectively) solution that was consistent across both HIV groups. These factors were named 'More Open to Sexual Pleasure' (Factor 1) and 'Reduced Inhibitions about Sex (Factor 2).' A confirmatory factor analysis of the 11-item, 2-factor solution on the full Sample 2 showed a modest fit to the data, excellent internal consistency reliability of both factors, a high correlation between the factors, and strong evidence for construct validity. These results were interpreted as supporting the use of the 11-item, 2-factor version of Leigh's scale in studies of clinical samples of HIV-positive adults, and directions for research on further scale refinement are discussed

There are several references in the hip and knee literature that mention converting fusions to a prosthetic total arthroplasty, but similar reports of total shoulder arthroplasty after glenohumeral fusion are lacking. The indication for conversion of a glenohumeral arthrodesis to a total shoulder arthroplasty is persistent periscapular pain refractory to conservative treatment. The purpose of the following article is to describe the preoperative plan and surgical technique in the conversion of a glenohumeral fusion to a total shoulder arthroplasty in single case of protracted scapulothoracic pain.

OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA.

BACKGROUND: Rotator cuff injury in the setting of type II superior labrum anterior posterior lesions is a common finding. Although predictable surgical outcomes can be expected after type II superior labrum anterior posterior repair, the effect of rotator cuff tears on surgical outcome is unknown. HYPOTHESIS: Rotator cuff tears will not negatively affect surgical outcome of type II superior labrum anterior posterior repairs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The study group included 93 patients younger than 50 years who underwent arthroscopic type II superior labrum anterior posterior repair and were available for review at a minimum of 2 years after surgery. Group 1 patients were identified as having normal rotator cuffs at the time of repair. Group 2 patients were identified as having rotator cuff injury at the time of repair (either partial-thickness or full-thickness tears). Statistical analysis was performed comparing the postoperative University of California, Los Angeles shoulder scores and overall improvement in University of California, Los Angeles score using the Student t test for significance. RESULTS: Mean follow-up was 2.54 years; 52.7% of patients had evidence of rotator cuff tears at the time of surgery. The mean postoperative University of California, Los Angeles score for group 1 was 32.9 (improvement of 11.0), and the mean postoperative University of California, Los Angeles score for group 2 was 33.3 (improvement of 12.2). There was not a significant difference in any of the outcome measures between groups. CONCLUSION: Predictable short-term surgical results and return to activity can be expected after repair of type II superior labrum anterior posterior lesions in patients younger than 50 years who have coexistent rotator cuff tear. Although cuff lesions did not have a negative effect on the short-term outcome in patients with type II superior labrum anterior posterior lesions, longer-term follow-up is needed to determine natural history of this pathologic condition.

AIMS/OBJECTIVE:To assess pharmacy claims and self-report data as measures of medication adherence and to describe baseline characteristics of subjects in the Improving Diabetes Outcomes Study. METHODS:Multi-ethnic, lower-income, insured adults (n = 526) in New York City with Type 2 diabetes were enrolled in a randomized, controlled, behavioural intervention study delivered by telephone. Baseline data were examined, including glycated haemoglobin (HbA(1c)), objective measures of diabetes medication adherence [claims data medication possession ratio (MPR)], and two self-report measures [Morisky Medication-taking Scale and the medication-taking item of the Summary of Diabetes Self-Care Activities (SDSCA)]. Associations of highest tertile HbA(1c) (>or= 9.3%) with lowest tertile MPR (< 42%) were assessed with logistic regression models adjusting for potential confounders. Subset analyses were performed based on assessment of potential interaction. RESULTS:Participants (mean +/- sd age 56 +/- 7 years) had median (interquartile range) HbA(1c) 8.6% (8.0-10.0). Correlations of baseline MPR with Morisky score and SDSCA medication-taking item were strongly significant (both rho = 0.21, P < 0.001). Lowest MPR was significantly (P = 0.008) associated with highest HbA(1c) in the group as a whole and among the subset taking two or more oral glucose-lowering agents (OGLA) (P = 0.002), but not among the subset taking only one (P = 0.83). Self-report adherence measures were not significantly associated with HbA(1c) in either the whole group or either subset. CONCLUSIONS:These results support the validity of MPR as an adherence measure for OGLA among insured diabetes patients with poorly controlled HbA(1c), especially those taking two or more OGLA.

Vaccine manufacturers are blamed for using outdated technologies, delay in shipments and contaminated batches. The reason they are so targeted is because the American public is nervous about disease, and nervous about anything they put into their bodies to protect against it. And while they are nervous, they may forget to stop criticizing long enough to sing the praises of a manufacturer when a groundbreaking new vaccine comes along. It is time for the world to applaud a drug company's effort. If a manufacturer could win a Nobel, this might be the time

OBJECTIVE:In patients with active Cushing's syndrome (CS), cardiac structural and functional changes have been described in a limited number of patients. It is unknown whether these changes reverse after successful treatment. We therefore evaluated the changes in cardiac structure and dysfunction after successful treatment of CS, using more sensitive echocardiographic parameters (based on two-dimensional strain imaging) to detect subtle changes in cardiac structure and function. METHODS:In a prospective study design, we studied 15 consecutive CS patients and 30 controls (matched for age, sex, body surface area, hypertension, and left ventricular (LV) systolic function). Multidirectional LV strain was evaluated by two-dimensional speckle tracking strain imaging. Systolic (radial thickening, and circumferential and longitudinal shortening) and diastolic (longitudinal strain rate at the isovolumetric relaxation time (SR(IVRT))) parameters were measured. RESULTS:At baseline, CS patients had similar LV diameters but had significantly more LV hypertrophy and impaired LV diastolic function, compared to controls. In addition, CS patients showed impaired LV shortening in the circumferential (-16.5+/-3.5 vs -19.7+/-3.4%, P=0.013) and longitudinal (-15.9+/-1.9 vs -20.1+/-2.3%, P<0.001) directions and decreased SR(IVRT) (0.3+/-0.15 vs 0.4+/-0.2/ s, P=0.012) compared to controls. After normalization of corticosteroid excess, LV structural abnormalities reversed, LV circumferential and longitudinal shortening occurred, and SR(IVRT) normalized. CONCLUSION/CONCLUSIONS:CS induces not only LV hypertrophy and diastolic dysfunction but also subclinical LV systolic dysfunction, which reverses upon normalization of corticosteroid excess.