Τρίτη 7 Ιουνίου 2022

Keeping up with the guidelines: design changes to the STREAM stage 2 randomised controlled non-inferiority trial for rifampicin-resistant tuberculosis

alexandrossfakianakis shared this article with you from Inoreader

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Results from the STREAM stage 1 trial showed that a 9-month regimen for patients with rifampicin-resistant tuberculosis was non-inferior to the 20-month regimen recommended by the 2011 WHO treatment guidelines...
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Intraoperative Redosing of Surgical Antibiotic Prophylaxis in Addition to Preoperative Prophylaxis Versus Single-dose Prophylaxis for the Prevention of Surgical Site Infection: A Meta-analysis and GRADE Recommendation

alexandrossfakianakis shared this article with you from Inoreader
imageObjective: The aim of this study was to determine the effect of preoperative surgical antibiotic prophylaxis (SAP) with additional intraoperative redosing compared to single-dose preoperative surgical antibiotic prophylaxis on the incidence of surgical site infections (SSI). Summary Background Data: Preoperative SAP is standard care for the prevention of SSI. During long surgical procedures, additional intraoperative redosing of SAP is advised, but there is great variability in redosing strategies and compliance rates. Methods: We performed a systematic search of MEDLINE (PubMed), Embase, CINAHL and CENTRAL on June 25th, 2021 according to PROSPERO registration CRD42021229035. We included studies that compared the effect of preoperative SAP with additional intraoperative redosing to single dose preoperative SAP (no redosing) on SSI incidence in patients undergoing any type of surgery. Two researchers performed data appraisal and extraction of summary data independently. Meta-analyses were stratified per study type. We used a generic inverse variance random-effects model to estimate a pooled odds ratio with corresponding 95% confidence intervals (CIs). Results: We included 2 randomized controlled trials (RCT) and 8 cohort studies comprising of 9470 patients. Pooled odds ratios for SSI in patients receiving intraoperative redosing compared to those without redosing were 0.47 (95% CI: 0.19–1.16. I2 = 36%) for RCTs and 0.55 (95% CI: 0.38–0.79, I2 = 56%) for observational cohorts. There was considerable clinical heterogeneity among antibiotics used and redosing protocols. GRADE-assessment showed overall low certainty of evidence. Conclusion: Intraoperative redosing of SAP may reduce incidence of SSI compared to a single dose preoperative SAP in any type of surgery, based on studies with considerable heterogeneity of antibiotic regimens and redosing protocols.
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Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: a contemporary single-institution experience

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity.
Methods
A single-center, retrospective study was conducted of patients age ≥18-years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18-months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses.
Results
Fifty-nine patients met criteria, with median age of 25-years (range 18-62y) and median follow-up of 6.5-years (range 0.7-23.1y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6Gy(relative biological effectiveness [RBE]), median total dose was 54.0Gy(RBE), 80 % received proton radiotherapy; 81% received chemotherapy. 5-year PFS and OS were 86.5% and 95.8%, respectively; 10-year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (p=0.04). Among eight recurrences, 25% presented after 5-years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (p = 0.05).
Conclusions
Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae.
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Cumulative erythemal ultraviolet radiation and risk of cancer in three large US prospective cohorts

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Abstract
Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and non-cutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined three U.S. prospective cohorts, the Health Professionals Follow-Up Study (HPFS) (1986) and Nurses' Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding non-melanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 males; 212,449 females) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as reference for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared to the lowest quintile, risk of any cancer was slightly increased across all o ther quintiles [highest quintile Hazard Ratio (HR),1.04; 95% Confidence Interval (CI),1.01,1.07; P-heterogeneity (P-het)=0.41]. All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR,1.17; 95% CI,1.04,1.31; P-het=0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and non-cutaneous cancers.
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