The impact of seasonal operating room closures on wait times for oral cancer surgery

Background Operating room slowdowns occur at specific intervals in the year as a cost-saving measure. We aim to investigate the impact of these slowdowns on the care of oral cavity cancer patients at a Canadian tertiary care centre. Methods A total of 585 oral cavity cancer patients seen between 1999 and 2015 at the London Health Science Centre (lhsc) Head and Neck Multidisciplinary Clinic were included in this study. Operating room hours and patient load from 2006 to 2014 were calculated. Our primary endpoint was the wait time from consultation to definitive surgery. Exposure variables were defined according to wait time intervals occurring during time periods with reduced operating room hours. Results Overall case volume rose significantly from 2006 to 2014 (p \u3c 0.001), while operating room hours remained stable (p = 0.555). Patient wait times for surgery increased from 16.3 days prior to 2003 to 25.5 days in 2015 (p = 0.008). Significant variability in operating room hours was observed by month, with lowest reported for July and August (p = 0.002). The greater the exposure to these months, the more likely patients were to wait longer than 28 days for surgery (odds ratio per day [or]: 1.07, 95% confidence interval [ci]: 1.05 to 1.10, p \u3c 0.001). Individuals seen in consultation preceding a month with below average operating room hours had a higher risk of disease recurrence and/or death (hazard ratio [hr]: 1.59, 95% ci: 1.10 to 2.30, p = 0.014). Conclusions Scheduled reductions in available operating room hours contribute to prolonged wait times and higher disease recurrence. Further work is needed to identify strategies maximizing efficient use of health care resources without negatively affecting patient outcomes

Insecticidal Evaluation of Some Botanical Leaf Powders On Cowpea Beetle Callosobruchus maculatus (F.) On Stored Bambara Groundnut (Vigna subterranea

Abstract Two Laboratory trials were conducted at the Department of Crop Protection, Faculty o

Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (\u3e20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive tumors. By contrast, in HPV-negative tumors, NSD1 and COL1A11 were found to be more frequently mutated in heavy smokers, while CASP8 was more frequently altered in never smokers. HPV-negative patients with NSD1 mutations experienced significantly improved overall survival compared with NSD1 WT patients. This improved prognosis was validated in an independent cohort of 77 oral cavity cancer patients and a meta-analysis that included 2 additional data sets (688 total patients, hazard ratio for death 0.44, 95% CI, 0.30-0.65). NSD1 mutations are more common in HPV-negative heavy smokers, define a cohort with favorable prognosis, and may represent a clinically useful biomarker to guide treatment deintensification for HPV-negative patients

Surgical preferences of patients at risk of hip fractures: hemiarthroplasty versus total hip arthroplasty

BACKGROUND: The optimal treatment of displaced femoral neck fractures in patients over 60 years is controversial. While much research has focused on the impact of total hip arthroplasty (THA) and hemiarthroplasty (HA) on surgical outcomes, little is known about patient preferences for either alternative. The purpose of this study was to elicit surgical preferences of patients at risk of sustaining hip fracture using a novel decision board. METHODS: We developed a decision board for the surgical management of displaced femoral neck fractures presenting risks and outcomes of HA and THA. The decision board was presented to 81 elderly patients at risk for developing femoral neck fractures identified from an osteoporosis clinic. The participants were faced with the scenario of sustaining a displaced femoral neck fracture and were asked to state their treatment option preference and rationale for operative procedure. RESULTS: Eighty-five percent (85%) of participants were between the age of 60 and 80 years; 89% were female; 88% were Caucasian; and 49% had some post-secondary education. Ninety-three percent (93%; 95% confidence interval [CI], 87-99%) of participants chose THA as their preferred operative choice. Participants identified several factors important to their decision, including the perception of greater walking distance (63%), less residual pain (29%), less reoperative risk (28%) and lower mortality risk (20%) with THA. Participants who preferred HA (7%; 95% CI, 1-13%) did so for perceived less invasiveness (50%), lower dislocation risk (33%), lower infection risk (33%), and shorter operative time (17%). CONCLUSION: The overwhelming majority of patients preferred THA to HA for the treatment of a displaced femoral neck fracture when confronted with risks and outcomes of both procedures on a decision board

Inhibition of the NLRP3 inflammasome prevents ovarian aging

Inflammation is a hallmark of aging and is negatively affecting female fertility. In this study, we evaluate the role of the NLRP3 inflammasome in ovarian aging and female fertility. Age-dependent increased expression of NLRP3 in the ovary was observed in WT mice during reproductive aging. High expression of NLRP3, caspase-1, and IL-1β was also observed in granulosa cells from patients with ovarian insufficiency. Ablation of NLRP3 improved the survival and pregnancy rates and increased anti-Müllerian hormone levels and autophagy rates in ovaries. Deficiency of NLRP3 also reduced serum FSH and estradiol levels. Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3−/− mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility

Displaced midshaft fractures of the clavicle: non-operative treatment versus plate fixation (Sleutel-TRIAL). A multicentre randomised controlled trial

Contains fulltext : 96826.pdf (publisher's version ) (Open Access)BACKGROUND: The traditional view that the vast majority of midshaft clavicular fractures heal with good functional outcomes following non-operative treatment may be no longer valid for all midshaft clavicular fractures. Recent studies have presented a relatively high incidence of non-union and identified speciic limitations of the shoulder function in subgroups of patients with these injuries. AIM: A prospective, multicentre randomised controlled trial (RCT) will be conducted in 21 hospitals in the Netherlands, comparing fracture consolidation and shoulder function after either non-operative treatment with a sling or a plate fixation. METHODS/DESIGN: A total of 350 patients will be included, between 18 and 60 years of age, with a dislocated midshaft clavicular fracture. The primary outcome is the incidence of non-union, which will be determined with standardised X-rays (Antero-Posterior and 30 degrees caudocephalad view). Secondary outcome will be the functional outcome, measured using the Constant Score. Strength of the shoulder muscles will be measured with a handheld dynamometer (MicroFET2). Furthermore, the health-related Quality of Life score (ShortForm-36) and the Disabilities of Arm, Shoulder and Hand (DASH) Outcome Measure will be monitored as subjective parameters. Data on complications, bone union, cosmetic aspects and use of painkillers will be collected with follow-up questionnaires. The follow-up time will be two years. All patients will be monitored at regular intervals over the subsequent twelve months (two and six weeks, three months and one year). After two years an interview by telephone and a written survey will be performed to evaluate the two-year functional and mechanical outcomes. All data will be analysed on an intention-to-treat basis, using univariate and multivariate analyses. DISCUSSION: This trial will provide level-1 evidence for the comparison of consolidation and functional outcome between two standardised treatment options for dislocated midshaft clavicular fractures. The gathered data may support the development of a clinical guideline for treatment of clavicular fractures. TRIAL REGISTRATION: Netherlands National Trial Register NTR2399

Mutations in TOP3A Cause a Bloom Syndrome-like Disorder

Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjects’ cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis

Comparing the costs and outcomes of an integrated twin compression screw (ITCS) nail with standard of care using a single lag screw or a single helical blade cephalomedullary nail in patients with intertrochanteric hip fractures

© 2018 The Author(s). Background: Surgical treatment is the optimal strategy for managing intertrochanteric fractures as it allows for early rehabilitation and functional recovery. The purpose of the study was to assess the cost-effectiveness of commonly used cephalomedullary nails for the treatment of unstable intertrochanteric hip fractures. Methods: A decision analytic model was developed from a US payer's perspective using clinical data from a pairwise meta-analysis of randomised controlled trials (RCTs) and comparative observational studies comparing the integrated twin compression screw (ITCS) nail versus two single-screw or blade cephalomedullary nails [single lag screw (SLS) nail and single helical blade (SHB) nail]. The model considered a cohort of 1000 patients with a mean age of 76, as reported in the clinical studies over a 1-year time period. Cost data was obtained from the Center for Medicare and Medicaid Services website and published literature and adjusted for inflation. One-way and probabilistic sensitivity analyses were conducted to assess the effect of uncertainty in model parameters on model conclusions. Results: The model estimated 0.546 quality-adjusted life years (QALYs) and 0.78 complications avoided by using the ITCS nail and 0.455 QALYs and 0.67 complications avoided for the standard of care, using SLS or SHB nails. The cost per patient was $34,336 for patients treated with an ITCS nail and$37,036 for patients treated with the standard of care respectively, resulting in a cost saving of $2700 in favour of the ITCS nail. More savings were observed when the ITCS nail was compared to the SHB ($3280 per patient) and SLS ($1652 per patient). The findings were robust to a range of both one-way and the probabilistic sensitivity analyses. Conclusion: In conclusion, the ITCS nail can be considered a cost saving intervention in patients undergoing intertrochanteric fracture fixation with an intramedullary device. Clinicians and policy makers should be encouraged to adopt healthcare technologies such as ITCS that will help them to provide quality healthcare despite falling budgets

Research trends in combinatorial optimization

Acknowledgments This work has been partially funded by the Spanish Ministry of Science, Innovation, and Universities through the project COGDRIVE (DPI2017-86915-C3-3-R). In this context, we would also like to thank the Karlsruhe Institute of Technology. Open access funding enabled and organized by Projekt DEAL.Peer reviewedPublisher PD

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons