Association between physician characteristics and payments from industry in 2015-2017: observational study.

OBJECTIVE:To investigate the association between physician characteristics and the value of industry payments. DESIGN:Observational study. SETTING AND PARTICIPANTS:Using the 2015-2017 Open Payments reports of industry payments linked to the Physician Compare database, we examined the association between physician characteristics (physician sex, years in practice, medical school attended and specialty) and the industry payment value, adjusting for other physician characteristic and institution fixed effects (effectively comparing physicians practicing at the same institution). MAIN OUTCOME MEASURES:Our primary outcome was the value of total industry payments to physicians including (1) general payments (all forms of payments other than those classified for research purpose, eg, consulting fees, food, beverage), (2) research payments (payments for research endeavours under a written contract or protocol) and (3) ownership interests (eg, stock or stock options, bonds). We also investigated each category of payment separately. RESULTS:Of 544 264 physicians treating Medicare beneficiaries, a total of $5.8 billion in industry payments were made to 365 801 physicians during 2015-2017. The top 5% of physicians, by cumulative payments, accounted for 91% of industry payments. Within the same institution, male physicians, physicians with 21-30 years in practice and physicians who attended top 50 US medical schools (based on the research ranking) received higher industry payments. Across specialties, orthopaedic surgeons, neurosurgeons and endocrinologists received the highest payments. When we investigated individual types of payment, we found that orthopaedic surgeons received the highest general payments; haematologists/oncologists were the most likely to receive research payments and surgeons were the most likely to receive ownership interests compared with other types of physicians. CONCLUSIONS:Industry payments to physicians were highly concentrated among a small number of physicians. Male sex, longer length of time in clinical practice, graduated from a top-ranked US medical school and practicing certain specialties, were independently associated with higher industry payments

Efficacy of needle-placement technique in radiofrequency ablation for treatment of lumbar facet arthropathy.

BACKGROUND:Many studies have assessed the efficacy of radiofrequency ablation to denervate the facet joint as an interventional means of treating axial low-back pain. In these studies, varying procedural techniques were utilized to ablate the nerves that innervate the facet joints. To date, no comparison studies have been performed to suggest superiority of one technique or even compare the prevalence of side effects and complications. MATERIALS AND METHODS:A retrospective chart review was performed on patients who underwent a lumbar facet denervation procedure. Each patient's chart was analyzed for treatment technique (early versus advanced Australian), preprocedural visual numeric scale (VNS) score, postprocedural VNS score, duration of pain relief, and complications. RESULTS:Pre- and postprocedural VNS scores and change in VNS score between the two groups showed no significant differences. Patient-reported benefit and duration of relief was greater in the advanced Australian technique group (P=0.012 and 0.022, respectively). The advanced Australian technique group demonstrated a significantly greater median duration of relief (4 months versus 1.5 months, P=0.022). Male sex and no pain-medication use at baseline were associated with decreased postablation VNS scores, while increasing age and higher preablation VNS scores were associated with increased postablation VNS scores. Despite increasing age being associated with increased postablation VNS scores, age and the advanced Australian technique were found to confer greater patient self-reported treatment benefit. CONCLUSION:The advanced Australian technique provides a significant benefit over the early Australian technique for the treatment of lumbar facet pain, both in magnitude and duration of pain relief

Transcriptional profiling of single fiber cells in a transgenic paradigm of an inherited childhood cataract reveals absence of molecular heterogeneity.

Our recent single-cell transcriptomic analysis has demonstrated that heterogeneous transcriptional activity attends molecular transition from the nascent to terminally differentiated fiber cells in the developing mouse lens. To understand the role of transcriptional heterogeneity in terminal differentiation and the functional phenotype (transparency) of this tissue, here we present a single-cell analysis of the developing lens, in a transgenic paradigm of an inherited pathology, known as the lamellar cataract. Cataracts hinder transmission of light into the eye. Lamellar cataract is the most prevalent bilateral childhood cataract. In this disease of early infancy, initially, the opacities remain confined to a few fiber cells, thus presenting an opportunity to investigate early molecular events that lead to cataractogenesis. We used a previously established paradigm that faithfully recapitulates this disease in transgenic mice. About 500 single fiber cells, manually isolated from a 2-day-old transgenic lens were interrogated individually for the expression of all known 17 crystallins and 78 other relevant genes using a Biomark HD (Fluidigm). We find that fiber cells from spatially and developmentally discrete regions of the transgenic (cataract) lens show remarkable absence of the heterogeneity of gene expression. Importantly, the molecular variability of cortical fiber cells, the hallmark of the WT lens, is absent in the transgenic cataract, suggesting absence of specific cell-type(s). Interestingly, we find a repetitive pattern of gene activity in progressive states of differentiation in the transgenic lens. This molecular dysfunction portends pathology much before the physical manifestations of the disease

Factors associated with retention in Option B+ in Malawi: a case control study.

IntroductionThere are limited data on factors associated with retention in Option B+. We sought to explore the characteristics of women retained in Option B+ in Malawi, with a focus on the role of HIV disclosure, awareness of partner HIV status, and knowledge around the importance of Option B+ for maternal-child health. Methods We performed a case-control study of HIV-infected women in Malawi initiated on antiretroviral therapy (ART) under Option B+. Cases were enrolled if they met criteria for default from Option B+ (out of ART for >60 days), and controls were enrolled in approximately 3:1 ratio if they were retained in care for at least 12 months. We surveyed socio-demographic characteristics, HIV disclosure and awareness of partner HIV status, self-report about receiving pre-ART education, and knowledge of Option B+. Univariate logistic regression was performed to determine factors associated with retention. Multivariate logistic regression model was used to evaluate the relationship between HIV disclosure, Option B+ knowledge, and retention after adjusting for age, schooling, and travel time to clinic.ResultsWe enrolled 50 cases and 153 controls. Median age was 30 years (interquartile range (IQR) 25-34), and the majority (82%) initiated ART during pregnancy at a median gestational age of 24 weeks (IQR 16-28). Ninety-one per cent of the cases (39/43) who started ART during pregnancy defaulted by three months postpartum. HIV disclosure to the primary sex partner was more common among women retained in care (100% versus 78%, p < 0.001). Odds of retention were significantly higher among women with: age >25 years (odds ratio (OR) 2.44), completion of primary school (OR 3.06), awareness of partner HIV status (OR 5.20), pre-ART education (OR 6.17), higher number of correct answers to Option B+ knowledge questions (OR 1.82), and support while taking ART (OR 3.65). Pre-ART education and knowledge were significantly correlated (r = 0.43, p < 0.001). In multivariate analysis, awareness of partner HIV status (OR 4.07, 95% confidence interval (CI) 1.51-10.94, p = 0.02) and Option B+ knowledge (OR 1.60, 95% CI 1.15-2.23, p = 0.004) remained associated with retention.ConclusionsInterventions that address partner disclosure and strengthen pre-ART education around the benefits of ART for maternal and child health should be evaluated to improve retention in Malawi's Option B+ programme

Smoking Enhances Risk for New External Genital Warts in Men

Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs

Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D.

Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes has a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of T helper 17 (Th17) and Th1, but not Th2 responses in human peripheral blood mononuclear cells (PBMCs). P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA, and IL-17RC, and triggered IL-17 secretion from CD4(+), but not from CD8(+) T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naive CD4(+)CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6, and transforming growth factor-β-neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and D could be effective tools to modulate Th17-mediated diseases such as acne

Effects of calorie restriction and IGF-1 receptor blockade on the progression of 22Rv1 prostate cancer xenografts.

Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile

Myeloid suppressor cell depletion augments antitumor activity in lung cancer.

BackgroundMyeloid derived suppressor cells (MDSC) are important regulators of immune responses. We evaluated the mechanistic role of MDSC depletion on antigen presenting cell (APC), NK, T cell activities and therapeutic vaccination responses in murine models of lung cancer.Principal findingsIndividual antibody mediated depletion of MDSC (anti-Gr1 or anti-Ly6G) enhanced the antitumor activity against lung cancer. In comparison to controls, MDSC depletion enhanced the APC activity and increased the frequency and activity of the NK and T cell effectors in the tumor. Compared to controls, the anti-Gr1 or anti-Ly6G treatment led to increased: (i) CD8 T cells, (ii) NK cells, (iii) CD8 T or NK intracytoplasmic expression of IFNγ, perforin and granzyme (iv) CD3 T cells expressing the activation marker CD107a and CXCR3, (v) reduced CD8 T cell IL-10 production in the tumors (vi) reduced tumor angiogenic (VEGF, CXCL2, CXCL5, and Angiopoietin1&2) but enhanced anti-angiogenic (CXCL9 and CXCL10) expression and (vii) reduced tumor staining of endothelial marker Meca 32. Immunocytochemistry of tumor sections showed reduced Gr1 expressing cells with increased CD3 T cell infiltrates in the anti-Gr1 or anti-Ly6G groups. MDSC depletion led to a marked inhibition in tumor growth, enhanced tumor cell apoptosis and reduced migration of the tumors from the primary site to the lung compared to controls. Therapeutic vaccination responses were enhanced in vivo following MDSC depletion with 50% of treated mice completely eradicating established tumors. Treated mice that rejected their primary tumors acquired immunological memory against a secondary tumor challenge. The remaining 50% of mice in this group had 20 fold reductions in tumor burden compared to controls.SignificanceOur data demonstrate that targeting MDSC can improve antitumor immune responses suggesting a broad applicability of combined immune based approaches against cancer. This multifaceted approach may prove useful against tumors where MDSC play a role in tumor immune evasion