Perceptions Among Backcountry Skiers During the COVID-19 Pandemic: Avalanche Safety and Backcountry Habits of New and Established Skiers.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic impacted the ski industry worldwide by closing or limiting access to ski resorts. Subsequently, anecdotal reports of increased backcountry use emerged in the press, with concerns of inexperienced skiers causing or having problems in the backcountry. This study attempted to quantify this and identify motivations for new backcountry skiers. METHODS: Self-identified backcountry skiers and snowboarders (aged ≥18 y) in the United States and Canada completed an anonymous 29-question online survey distributed by regional avalanche centers, education providers, and skiing organizations (n=4792). Respondents were stratified by backcountry experience, defining "newcomers" who began backcountry skiing from 2019 to 2021, coincident with the COVID-19 pandemic. Percentages of ski days spent in the backcountry were compared before and during the COVID-19 pandemic using paired t-tests and across cohorts using repeated-measures analysis of variance. Avalanche education was compared using unpaired χ2 tests. RESULTS: Of established skiers, 81% noticed more people in the backcountry and 27% reported increasing their own use. Participants reported spending 17% (95% CI, 15.8-17.9) more of their days in the backcountry during the COVID-19 pandemic, with newcomers increasing their time spent by 36% and established skiers increasing their time spent by 13% (P<0.0001). Of newcomers, 27% cited the COVID-19 pandemic as motivation to enter the backcountry and 24% lacked formal avalanche education, which is significantly higher than the 14% of established skiers (P<0.0001). CONCLUSIONS: Influenced by factors related to COVID-19, reported backcountry use increased during the pandemic. Newcomers had a lower level of avalanche education and less confidence in evaluating terrain. Because 80% of participants were recruited from avalanche safety or education websites, this likely underestimates skiers lacking avalanche awareness or education and is further limited by the nature of online surveys.

Changes in R-wave amplitude at implantation are associated with gender and orientation of insertable cardiac monitor: observations from the confirm Rx™ body posture and physical activity study.

BACKGROUND: Insertable cardiac monitors (ICMs) are small subcutaneously implanted devices that detect changes in R-wave amplitudes (RWAs), effective in arrhythmia-monitoring. Although ICMs have proven to be immensely successful, electrical artefacts are frequent and can lead to misdiagnosis. Thus, there is a growing need to sustain and increase efficacy in detection rates by gaining insight into various patient-specific factors such as body postures and activities. METHODS: RWAs were measured in 15 separate postures, including supine, lying on the right-side (RS) or left-side (LS) and sitting, and two separate ICM orientations, immediately after implantation of Confirm Rx™ ICM in 99 patients. RESULTS: The patients (53 females and 46 males, mean ages 66.62 ± 14.7 and 66.40 ± 12.25 years, respectively) had attenuated RWAs in RS, LS and sitting by ~ 26.4%, ~ 27.8% and ~ 21.2% respectively, compared to supine. Gender-based analysis indicated RWAs in RS (0.32 mV (0.09-1.03 mV), p < 0.0001) and LS (0.37 mV (0.11-1.03 mV), p = 0.004) to be significantly attenuated compared to supine (0.52 mV (0.20-1.03 mV) for female participants. Similar attenuation was not evident for male participants. Further, parasternally oriented ICMs (n = 44), attenuated RWAs in RS (0.37 mV(0.09-1.03 mV), p = 0.05) and LS (0.34 mV (0.11-1.03 mV), p = 0.02) compared to supine (0.48 mV (0.09-1.03 mV). Similar differences were not observed in participants with ICMs in the 45°-relative-to-sternum (n = 46) orientation. When assessing the combined effect of gender and ICM orientation, female participants demonstrated plausible attenuation in RWAs for RS and LS postures compared to supine, an effect not observed in male participants. CONCLUSION: This is the first known study depicting the effects on RWA due to body postures and activities immediately post-implantation with an overt impact by gender and orientation of ICM. Future work assessing the cause of gender-based differences in RWAs may be critical. TRIAL REGISTRATION: Clinical Trials, NCT03803969. Registered 15 January 2019 - Retrospectively registered, https://clinicaltrials.gov/NCT03803969.

R-wave amplitude changes with posture and physical activity over time in an insertable cardiac monitor.

Background: Insertable cardiac monitors (ICMs) are accepted tools in cardiac arrhythmia management. Consistent R-wave amplitude (RWA) is essential for optimal detection. Objectives: Assess RWAs with posture/activities at insertion and at 30 days. Methods: Participants (n = 90) with Confirm Rx™ ICM had RWAs measured in different postures (supine, right-side [RS], left-side [LS], sitting, and standing) and defined physical activities (including isometric push [IPUSH] and pull) at 2 time points. ICMs were inserted in 45° to sternum and parasternal orientations. Results: There were significant reductions at insertion with RS, LS, sitting, or standing vs supine (reference position) (all P < .05). At 30 days, significant changes only occurred with LS and sitting (P < .05). Sex had an effect on RWAs, with females having significant variability at insertion (supine vs RS, LS, sitting, standing, and IPUSH; all P < .05). Males showed large RWA interpatient variabilities but minimal differences between positions vs supine. At 30 days, RS, LS, and sitting positions remained significant for females (P < .05), while in males RWAs were higher than at insertion for most postures and activities. The orientation 45° to sternum had consistently higher RWAs vs parasternal orientation at both time points (P < .0001). In females, ICM orientation had no significant effect on RWAs; however, in males the 45° to sternum produced higher RWAs. ICM movement from the insertion site showed no correlation with RWA changes. Conclusion: The mean RWAs were higher at 30 days with less interparticipant and interpostural variability; males had higher RWAs compared to females; 45° to sternum orientation had higher RWAs; and ICM migration from the insertion site did not affect RWAs.

Autologous Cultured Bone Marrow-Derived Mesenchymal Stem Cells in a Fibrin Spray to Treat Venous Ulcers: A Randomized Controlled Double-Blind Pilot Study.

We treated a small cohort of venous ulcers that were very unresponsive to standard and advanced therapies with autologous cultured bone marrow-derived mesenchymal stem cells (MSCs). This pilot clinical trial was randomized, controlled, and double-blinded. Subjects were treated with either normal saline (Group A), fibrin spray alone (Group B), or MSCs in fibrin (1 million cells/cm2 of wound bed surface) (Group C). The control and test materials were applied to the wound using a double-barreled syringe with thrombin and fibrinogen (with or without MSCs) in each barrel, or saline alone in both barrels. The MSCs were separated, cultured in vitro, and expanded in a dedicated Good Manufacturing Practice (GMP) facility from 30-50 ml of bone marrow aspirate obtained from the iliac crest in Group C subjects. To ensure that the study remained controlled and blinded, subjects who were randomized to one of the two control arms (saline or fibrin) underwent sham bone marrow aspiration performed by a hematologist who anesthetized the iliac crest area down to and pushing against the periosteum, but without penetrating the bone marrow. Therefore, both the clinician who evaluated wound progress and the study subjects had no knowledge of whether bone aspiration was actually performed and what treatment had been applied to the wound. The study was performed after full FDA investigational new drug (IND) approval. The primary endpoint was the rate of healing (wound closure as linear healing from the wound margins in cm/week), as measured by the Gilman equation. One-way ANOVA was used to calculate the statistical significance of differences between the mean healing rates of each of the 3 treatment groups every 4 weeks and over the 24 weeks of treatment. Overall, treatment with MSCs accelerated the healing rate by about 10-fold compared to those in the saline and fibrin control groups. Although the total number of patients in this pilot study was small (n=11), the statistical significance was surprisingly promising: p<0.01 and f-ratio of 15.9358. No serious adverse events were noted. This small but carefully performed prospective, controlled, randomized, and double-blinded pilot study in a rare population of totally unresponsive patients adds to previous reports showing the promise of MSCs in the treatment of chronic wounds and provides proof of principle for how to approach this type of very demanding clinical and translational research.

Treatment with Oral Ondansetron for Ultramarathon-Associated Nausea: The TOO FUN Study.

Nausea and vomiting are common for runners during ultramarathons and often contribute to non-finishes. We aimed to determine the efficacy of ondansetron, a commonly used antiemetic, to treat nausea and vomiting in runners during an ultramarathon. Runners who had a previous history of frequent nausea or vomiting during races and entered in 160, 80, and 55 km ultramarathons in 2018 and 2019 were randomized in a double-blind fashion to 4 mg ondansetron or placebo capsules to use if they developed nausea or vomiting during the race with the ability to take three additional doses. Study participants completed a post-race online survey to assess medication use and efficacy. Of 62 study participants, 31 took either ondansetron (20) or placebo (11). In this small study, there were no group differences in those reporting any improvement in nausea and vomiting (p = 0.26) or in the amount of improvement (p = 0.15). We found no evidence that ondansetron capsules improve nausea and vomiting during ultramarathons.

Clinical and coronary haemodynamic determinants of recurrent chest pain in patients without obstructive coronary artery disease - A pilot study.

BACKGROUND: Coronary haemodynamic testing frequently identifies abnormal pathophysiological parameters in patients with angina and non-obstructed coronaries on angiography (NoCAD) but the clinical utility of these measures has received limited attention. OBJECTIVE: This study aims to identify the clinical and coronary haemodynamic determinants of recurrent chest pain at one month in patients with NoCAD. METHODS: Patients with angina, NoCAD (<50% stenosis) and normal LV systolic function underwent invasive coronary haemodynamic testing involving: (1) angiographic TIMI frame and opacification rate, (2) microvascular functional measures including coronary flow reserve (CFR) and hyperaemic microvascular resistance (HMR), (3) coronary endothelial function assessment with low dose intracoronary acetylcholine (IC-ACh) infusions (0.18 µg/min & 1.8 µg/min over 2 min), and (4) Provocative spasm testing with high dose IC-ACh boluses (25, 50 and 100 µg). Clinical and health status were assessed at baseline and one month. RESULTS: In the 49 NoCAD patients (78% female, mean age of 54 ±â€¯11) undergoing comprehensive coronary haemodynamic testing, 33 (67%) continued to experience chest pain at one month. Determinants of recurrent chest pain on univariate analysis included baseline chest pain status or a HMR > 1.9. Multivariate logistic regression analysis identified frequent angina at baseline (OR: 68.9 [4.1, 1165.0], p = 0.003), previous unstable angina admission (OR: 43.9 [3.5, 547.9], p = 0.003) and a HMR > 1.9 (OR: 15.6 [2.1, 114.0], p = 0.007) as independent predictors of recurrent chest pain. CONCLUSION: In this small pilot study, an abnormal HMR was the only coronary haemodynamic parameter that was a determinant of ongoing angina at short-term follow-up.

Antibiotic overprescribing: Still a major concern.

Despite universal agreement that antibiotic overprescribing is a problem, the practice continues to vex us. Antibiotic use--whether appropriate or not--has been linked to rising rates of antimicrobial resistance, disruption of the gut microbiome leading to Clostridium difficile infections, allergic reactions, and increased health care costs. And yet, physicians continue to overprescribe this class of medication. A 2016 Centers for Disease Control and Prevention report estimates that at least 30% of antibiotics prescribed in US outpatient settings are unnecessary. Another report cites a slightly higher figure across a variety of health care settings. Pair these findings with the fact that there are currently few new drugs in development to target resistant bacteria, and you have the potential for a post-antibiotic era in which common infections could become lethal. Family practitioners are on the front lines of this battle. Here's what we can do now.

An in vitro priming step increases the expression of numerous epidermal growth and migration mediators in a tissue-engineering construct.

An FDA-approved, prototypic, living, bilayered skin construct (BSC) has been used for non-healing wounds. Using this particular construct as proof of principle, we hypothesized that an in vitro 'priming' step may enhance its repertoire of expression of key mediators and genes. The priming step used here was incubation in Dulbecco's modified Eagle's medium (DMEM) for 24 h at 37°C and 5% CO2 , with or without construct meshing. Microarray and ingenuity pathway analysis (IPA) showed that >1000 genes were overexpressed by the priming step, including interleukin 6 (IL-6), which plays important roles in wound healing. Genes highly overexpressed by priming were those involved in epidermal proliferation and migration. Quantitative real-time PCR (qRT-PCR), immunostaining and western blots verified the results. An epiboly assay (epidermal migration over dermis) showed that BSC epiboly was inhibited by IL-6 neutralizing antibody. Back wounds of nude mice were treated with primed or control BSCs for 3 days prior to harvesting; primed BSCs showed a significantly (p = 0.006) greater level of epidermal migration vs unprimed. Our study demonstrates that an in vitro priming step induces wound healing-related genes in the BSC, leading to a construct that could prove more effective in stimulating wound healing. Copyright © 2014 John Wiley & Sons, Ltd.

Urology and nephrology update: proteinuria and hematuria.

Proteinuria and hematuria can be benign or can be signs of more serious underlying pathology. The diagnostic evaluation should take into account the age of the patient as well as medical history, family history, concurrent symptoms, initial physical examination findings, and basic office laboratory test results. There are many tests to consider for proteinuria and hematuria. Routine screening for proteinuria is not recommended in the general population, but it is recommended for high-risk patients, such as those with diabetes and hypertension. Asymptomatic patients should not be screened for hematuria. Patients should be referred to a nephrology subspecialist if proteinuria is drug-resistant, if there is persistent hematuria with concomitant proteinuria, or if a renal biopsy is being considered. Patients should be referred to a urology subspecialist for abnormal genitourinary anatomy, trauma, stones, tumors, nonglomerular gross hematuria, or persistent microscopic hematuria.

Urology and nephrology update: anemia of chronic kidney disease.

Anemia is associated with chronic kidney disease (CKD) at all stages, and it is nearly universal among patients with stage 5 CKD. Nonetheless, anemia of CKD is a diagnosis of exclusion. When anemia is detected in a patient with CKD, etiologies other than CKD must be considered and ruled out. Iron deficiency also is common among patients with CKD, and iron replenishment improves the anemia and the response to erythropoiesis-stimulating agents. Current guidelines for managing anemia of CKD recommend a hemoglobin goal of 11 to 12 g/dL, but lower hemoglobin may be acceptable for asymptomatic patients. Some patients do not benefit from erythropoiesis-stimulating agents, or they lose their responsiveness to treatment and transfusions must be considered. Other agents are being investigated as management for anemia of CKD, with vitamin C (ascorbic acid) showing some promise.

Urology and nephrology update: bladder and kidney cancer.

It has been estimated that bladder and kidney cancers would be diagnosed in approximately 140,000 Americans in 2013, with approximately 30,000 dying from these cancers. Urinary tract cancers affect men more commonly than they do women, and the median age at diagnosis is 65 years. Major risk factors for these cancers include tobacco smoking, certain chemical exposures, family history, age, and obesity. Unexplained hematuria in adults should be evaluated to exclude bladder and kidney cancer. Staging of bladder and kidney cancer should be based on the TNM staging system, which, along with tumor grade, provides important treatment and prognostic information. Urothelial cell carcinoma is the most common type of bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma is the most common type of kidney cancer. Treatment options for bladder cancer vary widely, depending on the grade of the cancer. Early non-muscle-invasive bladder cancer may be removed cystoscopically and/or treated with intravesical immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder tumors typically require surgery. Management of kidney cancer is almost always surgical, unless the patient is too ill to undergo surgery or chooses palliative care.

Urology and nephrology update: recurrent urinary tract infection.

Urinary tract infections (UTIs) are common among children and adults, with the greatest prevalence in women. One-half of all women will develop a UTI at some point. Approximately one-third of children with UTIs develop recurrent infections, and because recurrent UTIs have been thought to lead to renal scarring, practice has focused on identifying patients at risk of UTIs and limiting recurrence. It is difficult to determine which children are at risk of renal damage, and the benefits of antibiotics or surgery in preventing recurrent UTIs in children are unclear. Therefore, recent guidelines have taken a less aggressive approach to the prevention of recurrent UTIs in children. Recurrent UTIs also may be an issue for women. Sexual intercourse is a major risk factor, and postcoital prophylactic antibiotic treatment has been shown to be effective. Immediate antibiotic treatment of UTI symptoms also has shown efficacy. Although cranberry supplements or juice may be effective, the benefit of other commonly recommended treatments, such as frequent or postcoital voiding, increased fluid consumption, and avoiding bubble baths, has not been shown.

Bone marrow cell mobilization by the systemic use of granulocyte colony-stimulating factor (GCSF) improves wound bed preparation.

Innovative approaches are needed to accelerate the healing of human chronic wounds not responding to conventional therapies. An evolving and promising treatment is the use of stem cells. Our group has previously described the use of expanded (in vitro) autologous stem cells aspirated from human bone marrow and applied topically in a fibrin spray to human acute and chronic wounds. More recently, we have sought ways to mobilize stem cells directly from the bone marrow, without in vitro expansion. In this report, we show that systemic injections of granulocyte colony-stimulating factor (GCSF) can mobilize stem cells from bone marrow into the peripheral blood and then to the wound site. Our objectives were to optimize parameters for this method by using mouse models and proof of principle in a human chronic wound situation. Mice were injected for 5 days with 2 different formulations of GCSF and compared to control saline. To monitor stem cell mobilization, flow cytometric measurements of Sca-1 and c-Kit and colony-forming cell assays were performed. Full-thickness tail wounds in mice were created and monitored for healing, and polyvinyl alcohol sponges were implanted dorsally to assess collagen accumulation. To determine bone marrow stem cell homing to the wound site, chimeric mice transplanted with Green Fluorescent Protein bone marrow cells were scanned by live imaging. Additionally, as proof of principle, we tested the systemic GCSF approach in a patient with a nonhealing venous ulcer. Our findings lay the ground work and indicate that the systemic administration of GCSF is effective in mobilizing bone marrow stem cells into the peripheral blood and to the wound site. These findings are associated with an increased accumulation of collagen and promising results in terms of wound bed preparation and healing.

Cardiac hemodynamics in men versus women during acute ST-segment elevation myocardial infarction.

Several biologic and clinical factors contribute to the increased 30-day mortality and re-infarction rate in women with ST-segment elevation myocardial infarction (STEMI). Sex differences in cardiac hemodynamic parameters such as pulmonary capillary wedge pressure (PCWP) have not been examined and might play an important role. The objectives of the present study were to examine whether female sex is an independent determinant of PCWP during acute STEMI and whether an elevated PCWP contributes to all-cause 30-day mortality and re-infarction in women. The clinical, angiographic, and hemodynamic features of 470 consecutive patients with STEMI (n = 135 women) undergoing emergency coronary angiography with right-side heart catheterization were evaluated with respect to sex. Women had an elevated PCWP (20 ± 8 vs 16 ± 7 mm Hg, p <0.001) and reduced mixed venous oxygen saturation (67 ± 11% vs 71 ± 9%, p = 0.004). On multivariate analysis, female sex (ß = 4.04, 95% confidence interval [CI] 2.04 to 6.04, p <0.001), hypertension (ß = 2.07, 95% CI 0.31 to 3.83, p = 0.021), and creatine kinase-estimated infarct size (ß = 0.001, 95% CI 0.001 to 0.002, p ≤0.001) were independent predictors of an elevated PCWP. Female sex exerted a minor independent effect on 30-day mortality and re-infarction (odds ratio 2.36, 95% CI 1.25 to 4.46, p = 0.008). However, once PCWP was entered into the mediation model, sex was no longer significant, suggesting that the effect of sex on the post-STEMI outcomes is potentially mediated through PCWP (odds ratio 1.07, 95% CI 1.02 to 1.12, p = 0.011). In conclusion, during acute STEMI, women have greater left ventricular filling pressures compared with men, independent of age, hypertension, and infarct size. The biologic explanation for this difference requires additional investigation, although it does not appear to contribute to the increased 30-day mortality and re-infarction rate observed in women.

Evaluation of gender differences in Door-to-Balloon time in ST-elevation myocardial infarction.

BACKGROUND: A delayed Door-to-Balloon (DTB) time in women with ST-elevation myocardial infarction (STEMI) has been associated with an increased mortality. The objectives of this study were to (a) quantify the components of the delayed DTB time in women and (b) assess the independent effect of gender on DTB time in patients undergoing percutaneous coronary intervention (PCI) for STEMI. METHODS: Clinical parameters were prospectively collected for 735 STEMI patients undergoing primary PCI from 2006 to 2010, with particular attention to the components of DTB time, including the onset of chest pain and the 'code' notification of the STEMI team by the Emergency Department. RESULTS: Women were significantly older with more co-morbidity. Upon hospital arrival they also experienced delays in Door-to-Code (23 vs. 17 min, P=.012), Code-to-Balloon (63 vs. 57 min, P=.001) and thus DTB time (88 vs. 72 min, P=.001). After multivariate adjustment, independent determinants of DTB time included female gender (ratio of geometric means [RGM]=1.13; 95% CI 1.02-1.26; P=.022), hypertension (RGM=1.12, 95% CI 1.02-1.23, P=.014), maximum ST-elevation (RGM=0.97, 95% CI 0.94-0.98, P<.001), office hours (RGM=0.84, 95% CI 0.78-0.92, P<.001) and triage category (RGM=1.23, 95% CI 1.09-1.40, P=.001). CONCLUSIONS: Women experience delays in identification of the STEMI diagnosis and also in the PCI process. Thus a multifaceted approach addressing both the diagnosis and management of STEMI in women is required.

Chest pain in patients with 'normal angiography': could it be cardiac?

Approximately 20% of patients undergoing diagnostic angiography for the evaluation of chest pain are found to have a normal coronary angiogram. Although this finding is generally associated with a low risk of cardiac events, approximately half will continue to experience chest pain over the next 12 months. Therefore, the finding of normal angiography warrants further evaluation of the potential causes for the presenting chest pain if we are to improve the disability suffered by these patients. In this review, the potential non-cardiac and cardiac causes for the chest pain in patients with normal angiography are briefly discussed with an in-depth focus on coronary vasomotor disorders including coronary artery spasm (variant angina) and microvascular disorders such as syndrome X, microvascular angina, the coronary slow flow phenomenon and microvascular spasm.

Diagnostic utility of cytokeratin 17 immunostaining in morpheaform basal cell carcinoma and for facilitating the detection of tumor cells at the surgical margins.

BACKGROUND: The morpheaform subtype of basal cell carcinoma (BCC) often presents a diagnostic histological challenge, and its true margin may be difficult to determine with accuracy. This tumor may also be difficult to distinguish from other adnexal neoplasms having a benign clinical course. Previous work has shown that cytokeratin 17 (CK17 or K17) expression is high in BCC. OBJECTIVE: To confirm the expression of K17 across the subtypes of superficial, nodular and morpheaform BCC variants and to compare K17 expression in each of these subtypes of BCC with that in two other adnexal neoplasms. METHODS: Tissue specimens from each tumor category were randomly collected, immunolabeled, and scored for K17 expression according to intensity and extent of immunostaining. RESULTS: Our results indicate that K17 is a useful marker in the identification and outlining of BCC. Moreover, in morpheaform BCC, K17 immunostaining clearly detected individual tumor cells well away from the dermal tumor strands that otherwise seemed nonmalignant according to hematoxylin and eosin staining alone. In addition, the expression of K17 in morpheaform BCC is capable (100% of specimens; p < .001) of distinguishing this tumor from desmoplastic trichoepithelioma. CONCLUSION: We propose that K17 immunostaining could improve the diagnostic and surgical management of these tumors.