Impact of Specialized Versus Non-Specialized Acute Hospital Care on Survival Among Patients With Acute Incomplete Traumatic Spinal Cord Injuries: A Population-Based Observational Study from British Columbia, Canada.

Given the complexity of care necessitated after an acute traumatic spinal cord injury (SCI), it seems intuitively beneficial for such care to be delivered at hospitals with specialized SCI expertise. Demonstrating these benefits is not straightforward, however. We sought to determine whether specialized acute hospital care influenced the most fundamental outcomes after SCI: mortality within the first year of injury. We compared survival among patients with incomplete tSCI admitted to a single quaternary-level trauma hospital with a specialized acute SCI program versus those admitted to trauma hospitals without specialized acute SCI care. We performed a population-based retrospective observational cohort study using administrative and clinical data linked from multiple sources in British Columbia (BC) from 2001 to 2017. Among a cohort of 1920 patients, there were 193 deaths within one year. We failed to identify a significant overall benefit for survival after adjusting for potential confounders, and the confidence intervals (CIs) were compatible with both benefit and harm (odds ratio [OR] 1.01, 95% CI 0.17 to 6.11, p = 0.99). Significant associations were observed with age greater than 65 (OR 4.92, 95% CI 1.66 to 14.57, p < 0.01), Charlson Comorbidity Index (OR 1.61, 95% CI 1.42 to 1.83, p < 0.01), Injury Severity Score (OR 1.08, 95% CI 1.06 to 1.11, p < 0.01), and traumatic brain injury (OR 2.12, 95% CI 1.32 to 3.41, p < 0.01). Among patients with acute tSCI, admission to a hospital with specialized acute SCI care was not associated with improved overall one-year survival. Subgroup analyses, however, suggested heterogeneity of effects, with little benefit for older patients with less polytrauma and substantial benefit for younger patients with greater polytrauma.

The effect of rurality and distance from care on health outcomes, environmental barriers, and healthcare utilization patterns in persons with traumatic spinal cord injury.

STUDY DESIGN: Cohort study. OBJECTIVES: To evaluate the association between residential living location and health outcomes, environmental barriers, quality of life, and healthcare utilization patterns after traumatic spinal cord injury (tSCI). SETTING: Community setting, Atlantic Canada. METHODS: An ambispective study of data collected on a subset of individuals enrolled in the Rick Hansen Spinal Cord Injury Registry (RHSCIR) from 2012 to 2018. Outcomes were analyzed using two measures of rurality: postal codes at community follow-up (rural versus urban) and residential travel distance to the nearest RHSCIR facility (>100 km versus ≤100 km). Outcomes studied included the Craig Hospital Inventory of Environmental Factors-Short Form (CHIEF-SF), Short Form-36 Version 2 (SF36v2), Life Satisfaction Questionnaire (LISAT-11), Spinal Cord Independence Measure (SCIM), secondary health complications and healthcare utilization patterns. Outcomes were assessed 9 to 24 months post-discharge from initial hospitalization. RESULTS: 104 participants were studied, 21 rural and 83 urban based on postal codes at community follow-up. 59 participants lived more than 100 km away from the nearest RHSCIR facility, while 45 participants lived within 100 km. Individuals from urban area codes reported a greater magnitude of perceived barriers on the policies and work/school subscales of the CHIEF-SF. No differences in function, quality of life, and healthcare utilization patterns according to the measures of rurality were observed. Individuals living >100 km from the nearest RHSCIR facility reported greater rates of sexual dysfunction. CONCLUSIONS: Despite differences in environmental barriers, individuals from urban and rural locations in Eastern Canada reported similar health outcomes and quality of life after tSCI.

Lack of Effect of Oral Melatonin on Platelet Parameters in Normal Healthy Dogs.

A randomized, prospective, blinded, placebo-controlled study on the effect of oral melatonin on platelet parameters was performed on 40 healthy dogs with normal physical examinations and no clinically significant findings on serum chemistry evaluation. Dogs were randomly assigned to the study group or the placebo-control group and administered oral melatonin or an oral inert tablet, respectively, for 28 days. Dogs in the study group were administered melatonin at 3 mg per os q 12 hr for dogs weighing <15 kg and 6 mg per os q 12 hr for dogs weighing 15 kg or more. Complete blood counts were obtained at 0, 7, 14, and 28 days of medication administration. No adverse effects or sedation were noted in any dog. The placebo group had a statistically significant transient increase in both plateletcrit and mean platelet volume on day 7 relative to baseline, which was not observed in the melatonin group. Oral melatonin did not appear to have a direct thrombopoietic effect in normal healthy dogs. Future studies are required to investigate the pharmacokinetics of melatonin in dogs and the potential benefits of melatonin in both thrombocytopenia and immune-mediated diseases.

Use of Advanced Practice Providers to Improve Patient Access in Urology.

INTRODUCTION: Increasing the use of advanced practice providers in urological practices is a potential strategy to decrease the effect of national urologist shortages. Advanced practice providers may fill various roles in urological practices including the evaluation of new and established patients, thereby improving patient access to specialty care. The metric "next third available appointment" has been established as a reliable benchmark for patient access. We hypothesized that the addition of advanced practice providers to a urological practice would improve patient access and we sought to determine if patient access benchmarks could be included in an evaluation of overall advanced practice provider productivity. METHODS: We examined patient access and productivity data for physicians and advanced practice providers in a single academic urology department from 2013 to 2017. We evaluated various access markers including new patient appointment wait time and third available appointment, and productivity data including appointment booking ratios to determine if hiring advanced practice providers helped improve patient access while maintaining adequate booking ratios. RESULTS: We identified 2 advanced practice providers hired in 2014 to 2015 who worked in the outpatient setting. The addition of these advanced practice providers helped decrease the median new patient appointment wait time by 15 days and improved the department's time to third available appointment by approximately 5 days. Our department's advanced practice providers have an average booking ratio of 80.2% compared to 82.0% for our physicians. CONCLUSIONS: Advanced practice providers can help improve patient access to urological care by decreasing the lag time for patients to see a provider in a subspecialty clinic while maintaining adequate booking ratios for our providers.

Amitriptyline and Sexual Function: A Systematic Review Updated for Sexual Health Practice.

Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with amitriptyline comes from only one clinical trial and several case reports from three decades ago. In the current study, a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) related to amitriptyline and sexual dysfunction (SD) was performed. The frequency, gender-difference, types, disease-specificity and time course of SD, and the relationship between SD and nonsexual adversity were studied. A total of 14 publications, including 8 qualified randomized clinical trials, were eligible. The frequency of SD in overall, male and female patients was 5.7, 11.9 and 1.7%, respectively. SD was six-fold higher in men than women. The frequency of SD was 6.9% in depressive patients compared with 0.8% in non-depressive patients ( p = .008), and gradually decreased at 8 weeks after treatment ( p = .02). Amitriptyline impacted arousal and libido more than orgasm and ejaculation in male patients but mainly libido in female patients. SD was significantly correlated with insomnia linearly whereas somnolence and nausea dually. Therefore, amitriptyline-associated SD mainly occurs in depressive and male patients, disturbs each phase of the sexual response cycle in men but mainly libido in women, gradually decreases under long-term treatment, and can be predicted by the co-existence of insomnia, somnolence or nausea during treatment. Clinicians should caution and tailor the gender and disease vulnerability of amitriptyline in their practice.

Topiramate-associated sexual dysfunction: A systematic review.

INTRODUCTION: Sexual pharmacotoxicity renders patients with epilepsy at a risk for sexual dysfunction (SD). This study is aimed to analyze the relationship between sexual function and topiramate to avoid topiramate-associated SD. METHODS: A systematic review following the PRISMA guidelines was performed to elucidate any SD occurrence in patients receiving topiramate. RESULTS: A total of 17 publications were reviewed. Based on limited polytherapy observational studies, the frequency of self-reported topiramate-associated SD, libido disorder, and orgasmic disorder in patients with polytherapy was 9.0%, 9.0%, and 2.6%, respectively (grade C evidence). Female patients mainly had anorgasmia, whereas male patients principally had erectile dysfunction. The daily dose of topiramate in patients with SD was within the recommended dose. Sexual adversity usually occurred from 4weeks after topiramate use but favorably subsided without eventful complications after topiramate substitution or dose reduction in all patients. CONCLUSIONS: Topiramate can elicit different patterns of SD, especially anorgasmia in women and erectile dysfunction in men, even with a therapeutic dose. Detailed drug education and careful monitoring are necessary to maximize sexual health, especially in persons undergoing polytherapy and with other risks for SD. Moreover, a rapid response, such as substitution or reduction of the dose, is suggested when SD occurs during its use.

Trinucleotide repeat containing 6a (Tnrc6a)-mediated microRNA function is required for development of yolk sac endoderm.

Tnrc6 family members (Tnrc6a/b/c) are key components of the RNA-induced silencing complex in microRNA (miRNA)-mediated gene suppression. Here, we show that Tnrc6a, also known as GW182, is selectively expressed in the yolk sac endoderm and that gene trap disruption of GW182 leads to growth arrest and apoptosis. We found that targets of miRNAs highly expressed in the yolk sac are significantly derepressed in GW182(gt/gt) mutant mice, although levels of miRNAs are not altered. Specifically, growth arrest and apoptosis phenotype are associated with significant derepression of Cdkn1a (p21), Cdkn1c (P27), Lats1, Lats2, Rb1, Rbl, Bim, and Pten, known targets of miRNAs from miR-17/20/93/106 clusters highly expressed in yolk sac endoderm. Together, these data strongly suggest that GW182 is an essential functional component in the RNA-induced silencing complex for miRNA-mediated gene silencing in vivo, and selectively regulation of miRNA activity plays an important role in the proper development of yolk sac.

Guided tissue regeneration in periapical surgery.

Tissue regeneration by using membrane barriers and bone grafting materials in periapical surgery is an example of tissue engineering technology. Membrane barriers and/or bone grafts are often used to enhance periapical new bone formation. However, the periapical tissues also consist of the periodontal ligament (PDL) and cementum. For regeneration of the periapical tissues after periapical surgery, one of the important requirements is recruitment and differentiation of progenitor/stem cells into committed pre-osteoblasts, pre-PDL cells, and pre-cementoblasts. Homing of progenitor/stem cells into the wounded periapical tissues is regulated by factors such as stromal cell-derived factor 1, growth factors/cytokines, and by microenvironmental cues such as adhesion molecules and extracellular matrix and associated noncollagenous molecules. Tissue regeneration after injury appears to recapitulate the pathway of normal embryonic tissue development. Multiple tissue regeneration involves a complex interaction between different cells, extracellular matrix, growth/differentiation factors, and microenvironmental cues. Little is known concerning the biologic mechanisms that regulate temporal and spatial relationship between alveolar bone, PDL, and cementum regeneration during periapical wound healing. Simply applying a membrane barrier and/or bone graft during periapical surgery might not result in complete regeneration of the periapical tissues. It has not been clearly demonstrated that these biomaterials are capable of recruiting progenitor/stem cells and inducing these undifferentiated mesenchymal cells to differentiate into PDL cells and cementoblasts after periapical surgery.

Amended final report of the safety assessment of t-Butyl Alcohol as used in cosmetics.

t-Butyl Alcohol (t-BuOH) is a tertiary aliphatic alcohol that is used as a solvent or an alcohol denaturant and as a perfume carrier in cosmetics. t-BuOH was reported as an ingredient in 32 formulations of eye makeup, fragrance, and shaving preparations, at concentrations ranging from 0.00001% and 0.3%. There is little acute oral toxicity in animals; e.g., the acute oral LD(50) in rats was 3.0 to 3.7 g/kg. In short-term oral studies in rats, t-BuOH at 2% (w/v) or less in drinking water did not cause gross organ or tissue damage in mice, although weight loss was reported and microscopic damage to livers and kidney and alterations such as centrilobular necrosis, vacuolation in hepatocytes, and loss of hepatic architecture were noted. Subchronic oral dosing with t-BuOH increased the mineralization of the kidney, nephropathy, and urinary bladder transitional cell epithelial hyperplasia in rats; and liver damage, chronic inflammation, hyperplasia of transitional cell epithelium urinary, and proliferative changes including hyperplasia and neoplasia in the thyroid in mice. Male rats exposed to t-BuOH were susceptible to alpha 2mu-globulin nephropathy. t-BuOH (99.9%) was a moderate to severe ocular irritant to rabbits and caused mild to moderate dermal irritation to rabbits. It was not considered to be a primary dermal irritant to rabbits. In animal studies, fetotoxicity generally increased with concentration, and fetal weights were slightly depressed at concentrations of 0.5% to 1% t-BuOH. t-BuOH produced a significant increase in the number of resorptions per litter. There was also a significant decrease in the number of live fetuses per litter. t-BuOH reduced maternal weight gain, litter sizes, birth weights, and weights at weaning, and increased perinatal and postnatal mortality. t-BuOH was not mutagenic in several bacterial and mammalian test systems. The principal effects from 2 years of exposure to t-BuOH in drinking water (up to 10 mg/ml for rats and 20 mg/ml for mice) were proliferative lesions (hyperplasia, adenoma, and carcinoma) in the kidneys of exposed male rats, and nephropathy in all exposed groups of female rats. There was some evidence of carcinogenic activity, but it was not consistent between species, sexes, or doses. A repeat-insult patch test (RIPT) test showed no potential for eliciting either dermal irritation or sensitization by 100% t-BuOH. Dermatitis can result from dermal exposure of humans to t-BuOH. In consideration of these data, it was concluded that t-BuOH was (at most) a weak carcinogen and unlikely to have significant carcinogenic potential as currently used in cosmetic formulations. In addition, the renal tubule effects found in male rats were likely an effect of alpha 2mu-globulin. In consideration of the reproductive and developmental toxicity data, the increased incidence of still births occurred at high exposure levels and was likely secondary to maternal toxicity. Based on the available animal and clinical data in this report, it was concluded that t-BuOH is safe as used in cosmetic products.

Wombs for rent: an examination of prohibitory and regulatory approaches to governing preconception arrangements.

On October 9, 2002, Bill C-13 had its first reading in the Canadian House of Commons. Bill C-13 was in the same form as Bill C-56 of the First Session of the Thirty-seventh Parliament, which had its first reading on May 9, 2002. Bill C-13, an Act respecting assisted human reproduction, prohibits the practice of commercial surrogacy or preconception agreements in Canada, under threat of criminal sanction. In the first half of the article, the author discusses the deficiencies of the Bill's prohibitory approach to governing surrogacy agreements. These problems include the difficulty of implementing a criminal regime, the weak constitutional basis on which the federal government claims jurisdiction to enact a criminal prohibition of commercial surrogacy and the legislation's inability to prevent exploitation and coercion of vulnerable parties in surrogacy arrangements. In the second half of the article, the author examines an alternative regulatory scheme proposed by the Ontario Law Reform Commission and compares it to the prohibitory approach. The author concludes that the regulatory approach is much more effective than the prohibitory approach in governing the practice of commercial and non-commercial surrogacy arrangements. Regulation minimises the potentially exploitative aspects of surrogacy and provides legal protection to both parties in the agreement. The regulatory scheme proposed by the Ontario Law Reform Commission is also more effective in protecting the best interests of the child born as a result of a preconception agreement.