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1.
Journal of Neuro-Oncology - Survivors of pediatric embryonal brain tumors (BT) are at high risk for sensorineural hearing loss (SNHL) associated with neurocognitive decline. However, previous...  相似文献   
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ABSTRACT

HIV-positive men who have sex with men (HIV+MSM) in India need culturally-relevant interventions to promote safer sex. We tested a multi-level intervention among HIV+MSM that targeted individual, interpersonal, and community factors, based on the Social-Personal and Social Ecological Models. We conducted a 2?×?2 factorial RCT with 119 HIV+MSM randomised to receive either an individual-level intervention (ILI) using motivational interviewing to promote safer sex, a community-level intervention (CLI) to strengthen community norms toward safer sex and reduce stigma among MSM communities, a multi-level intervention combining the individual- and community-level interventions (ILI?+?CLI), or standard-of-care control. Participants completed pre- and post-intervention assessments of a composite sexual risk score and a process evaluation to assess fidelity and satisfaction. Out of the 119 HIV+MSM, 106 (89.0%) completed pre- and post-intervention assessments. Generalised Estimating Equation models showed that both CLI (Incidence Rate Ratio [IRR]?=?.67, 95% CI .47 to .96) and ILI?+?CLI (IRR?=?.66, 95% CI .48 to .91) groups had a statistically significant decrease in sexual risk compared to the standard-of-care. The interventions had high levels of fidelity and satisfaction. This pilot RCT demonstrated feasibility and potential effectiveness of a multi-level intervention that addresses individual, interpersonal and community-level contributors of sexual risk among HIV+MSM.  相似文献   
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Background: The clinical benefits of biologic therapies for moderate-to-severe psoriasis are well established, but wide variations exist in patient response.

Objectives: To determine the number needed to treat (NNT) to achieve a 75% and 90% reduction in the Psoriasis Area and Severity Index (PASI-75/90) with FDA-approved agents and evaluate the incremental cost per PASI-75 or PASI-90 responder.

Methods: The relative probabilities of achieving PASI-75 and PASI-90, as well as NNTs, were estimated using a network meta-analysis. Costs (2017 USD) included drug acquisition and administration. The incremental cost per PASI-75 or PASI-90 responder for each treatment was estimated for the clinical trial period, and annually.

Results: Compared with supportive care, the NNT to achieve PASI-75 was 1.18 for ixekizumab, 1.29 for secukinumab 300?mg, 1.37 for infliximab, 1.48 for adalimumab, 1.53 for secukinumab 150?mg, 1.58 for ustekinumab, 2.25 for etanercept, and 3.71 for apremilast. The one-year incremental cost per PASI-75 responder relative to supportive care was $59,830 for infliximab, $88,775 for secukinumab 300?mg, $91,837 for adalimumab, $95,898 for ixekizumab, $97,363 for ustekinumab, $105,131 for secukinumab 150?mg, $129,665 for apremilast, and $159,328 for etanercept. Results were similar for PASI-90.

Conclusion: The NNT and incremental cost per responder are meaningful ways to assess comparative effectiveness and cost effectiveness among psoriasis treatments.  相似文献   
7.

Background

Cranioplasty is a surgical procedure used to treat a bone defect or deformity in the skull. To date, there is little consensus on the standard-of-care for graft materials used in such a procedure. Graft materials must have sufficient mechanical strength to protect the underlying brain as well as the ability to integrate and support new bone growth. Also, the ideal graft material should be individually customized to the contours of the defect to ensure a suitable aesthetic outcome for the patient.

Purpose

Customized 3D-printed scaffolds comprising of polycaprolactone-β-tricalcium phosphate (PCL-TCP) have been developed with mechanical properties suitable for cranioplasty. Osteostimulation of PCL-TCP was enhanced through the addition of a bone matrix-mimicking heparan sulphate glycosaminoglycan (HS3) with increased affinity for bone morphogenetic protein-2 (BMP-2). Efficacy of this PCL-TCP/HS3 combination device was assessed in a rat critical-sized calvarial defect model.

Method

Critical-sized defects (5 mm) were created in both parietal bones of 19 Sprague Dawley rats (Male, 450–550 g). Each cranial defect was randomly assigned to 1 of 4 treatment groups: (1) A control group consisting of PCL-TCP/Fibrin alone (n = 5); (2) PCL-TCP/Fibrin-HSft (30 μg) (n = 6) (HSft is the flow-through during HS3 isolation that has reduced affinity for BMP-2); (3) PCL-TCP/Fibrin-HS3 (5 μg) (n = 6); (4) PCL-TCP/Fibrin-HS3 (30 μg) (n = 6). Scaffold integration and bone formation was evaluated 12-weeks post implantation by μCT and histology.

Results

Treatment with PCL-TCP/Fibrin alone (control) resulted in 23.7% ± 1.55% (BV/TV) of the calvarial defect being filled with new bone, a result similar to treatment with PCL-TCP/Fibrin scaffolds containing either HSft or HS3 (5 μg). At increased amounts of HS3 (30 μg), enhanced bone formation was evident (BV/TV = 38.6% ± 9.38%), a result 1.6-fold higher than control. Further assessment by 2D μCT and histology confirmed the presence of enhanced bone formation and scaffold integration with surrounding host bone only when scaffolds contained sufficient bone matrix-mimicking HS3.

Conclusion

Enhancing the biomimicry of devices using a heparan sulphate with increased affinity to BMP-2 can serve to improve the performance of PCL-TCP scaffolds and provides a suitable treatment for cranioplasty.  相似文献   
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Thoracic epidural anesthesia is an adjunct to general anesthesia in cardiac surgery. Decrease in heart rate and blood pressure are frequently seen beneficial effects. There are several other hemodynamic effects of thoracic epidural anesthesia such as decrease in systemic vascular resistance, cardiac index, left ventricular stroke work index among others. However, the effect of thoracic epidural anesthesia on pulmonary artery pressure (PAP) has not been studied extensively in humans. Thoracic epidural anes-thesia decreased pulmonary artery pressure in experimen-tally induced pulmonary hypertension in animals. The mechanisms involved in such reduction are ill understood. We describe in this report, a significant reduction in PAP in a patient with Marfan’s syndrome scheduled to under-go aortic valve replacement. The possible mechanisms of decrease in pulmonary artery pressure in the described case are, decrease in the venous return to the heart, decrease in the systemic vascular resistance, decrease in the right ventric-ular function and finally, improvement in myocardial contraction secondary to all the above. The possibility of Marfan’s syndrome contributing to the decrease in PAP appears remote. The authors present this case to generate discussion about the possible mechanisms involved in thoracic epidural anesthesia producing beneficial effects in patients with secondary pulmonary hypertension. Thoracic epidural anesthesia appears to decrease pulmonary artery pressure by a combination of several mechanisms, some unknown to us. This occurrence, if studied and understood well could be put to clinical use in pulmonary hypertensives.  相似文献   
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