Use of multiple pharmacodynamic measures to deconstruct the Nix-TB regimen in a short-course murine model of tuberculosis.

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen [bedaquiline-pretomanid-linezolid (BPaL)] during the first 3 weeks of treatment at human equivalent doses. The rRNA synthesis (RS) ratio, an exploratory pharmacodynamic (PD) marker of ongoing Mycobacterium tuberculosis rRNA synthesis, together with solid culture CFU counts and liquid culture time to positivity (TTP) were used as PD markers of treatment response in lung tissue; and their time-course profiles were mathematically modeled using rate equations with pharmacologically interpretable parameters. Antimicrobial interactions were quantified using Bliss independence and Isserlis formulas. Subadditive (or antagonistic) and additive effects on bacillary load, assessed by CFU and TTP, were found for bedaquiline-pretomanid and linezolid-containing pairs, respectively. In contrast, subadditive and additive effects on rRNA synthesis were found for pretomanid-linezolid and bedaquiline-containing pairs, respectively. Additionally, accurate predictions of the response to BPaL for all three PD markers were made using only the single-drug and pairwise effects together with an assumption of negligible three-way drug interactions. The results represent an experimental and PD modeling approach aimed at reducing combinatorial complexity and improving the cost-effectiveness of in vivo systems for preclinical TB regimen development.

Use of Multiple Pharmacodynamic Measures to Deconstruct the Nix-TB Regimen in a Short-Course Murine Model of Tuberculosis.

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen (bedaquiline-pretomanid-linezolid [BPaL]) during the first three weeks of treatment at human equivalent doses. RS ratio, an exploratory pharmacodynamic (PD) marker of ongoing Mycobacterium tuberculosis rRNA synthesis, to-gether with solid culture CFU and liquid culture time to positivity (TTP) were used as PD markers of treatment response in lung tissue; and their time course profiles were mathematically modeled using rate equations with pharmacologically interpretable parameters. Antimicrobial interactions were quantified using Bliss independence and Isserlis formulas. Subadditive (or antagonistic) and additive effects on bacillary load, assessed by CFU and TTP, were found for bedaquiline-pretomanid and linezolid-containing pairs, respectively. In contrast, subadditive and additive effects on rRNA synthesis were found for pretomanid-linezolid and bedaquiline-containing pairs, respectively. Additionally, accurate predictions of the response to BPaL for all three PD markers were made using only the single-drug and pairwise effects together with an assumption of negligible three-way drug interactions. The results represent an experimental and PD modeling approach aimed at reducing combinatorial complexity and improving the cost-effectiveness of in vivo systems for preclinical TB regimen development.

Bridging that gap: a qualitative study of perceptions of equality, diversity and inclusivity in colorectal surgery in the UK and Ireland.

BACKGROUND: There is a growing recognition on the importance of equality, diversity and inclusion (EDI) within surgery and the need to diversify the surgical community and its various organisations, in a bidto reflect the diverse populations they serve. To create, sustain and encourage a diverse surgical workforce requires an in-depth understanding of the current makeup of key surgical institutions, relevant issues pertaining to EDI and appropriate solutions and strategies to ensure tangible change. OBJECTIVES: Following on from the recent Kennedy Review into Diversity and Inclusion commissioned by the Royal College of Surgeons of England, the aim of this qualitative study was to understand the EDI issues which affected the membership of the Association of Coloproctology of Great Britain and Ireland, while seeking appropriate solutions to address them. DESIGN: Dedicated, online and qualitative focus groups. PARTICIPANTS: Colorectal surgeons, trainees and nurse specialists were recruited using a volunteer sampling strategy. METHODS: A series of online, dedicated, qualitative focus groups across the 20 chapter regions were held. Each focus group was run informed by a structured topic guide. All participants who were given the opportunity to remain anonymous were offered a debriefing at the end. This study has been reported in keeping with the Standards for Reporting Qualitative Research. RESULTS: Between April and May 2021, a total number of 20 focus groups were conducted, with a total of 260 participants across 19 chapter regions. Seven themes and one standalone code pertaining to EDI were identified: support, unconscious behaviours, psychological consequences, bystander behaviour, preconceptions, inclusivity and meritocracy and the one standalone code was institutional accountability. Five themes were identified pertaining to potential strategies and solutions: education, affirmative action, transparency, professional support and mentorship. CONCLUSION: The evidence presented here is of a range of EDI issues which affect the working lives of those within colorectal surgery in the UK and Ireland, and of potential strategies and solutions which can help build a more inclusive, equitable and diverse colorectal community.

Exploring Nurse Practitioner Students' Perceptions of a Sleep e-Learning Program.

AIM: The aim of this study was to explore nurse practitioner (NP) students' perceptions of a sleep e-learning program. BACKGROUND: Sleep assessment is uncommon as nursing curricula lack sleep education. By preparing NPs to conduct sleep assessment and screening and understand basic sleep diagnostics, sleep health is more likely to be part of the differential diagnosis. METHOD: The study is a qualitative descriptive study utilizing two focus groups. A directed content analysis, guided by the Kirkpatrick model, was used for analysis. RESULTS: Twenty-four students participated in focus groups. Two overarching themes emerged: perceptions of course design and content. Asynchronous, case-based scenarios and quizzes were favorable. Students spoke of content relevance to themselves and patients and intentions to adopt sleep assessment practices. CONCLUSION: NP students embraced sleep education and declared intention to apply learned skills in practice. This study highlights the feasibility of increasing curricular exposure to sleep education and ensuring NPs have skills to recognize implications of poor and disordered sleep in patients.

Society of Anesthesia and Sleep Medicine Position Paper on Patient Sleep During Hospitalization.

This article addresses the issue of patient sleep during hospitalization, which the Society of Anesthesia and Sleep Medicine believes merits wider consideration by health authorities than it has received to date. Adequate sleep is fundamental to health and well-being, and insufficiencies in its duration, quality, or timing have adverse effects that are acutely evident. These include cardiovascular dysfunction, impaired ventilatory function, cognitive impairment, increased pain perception, psychomotor disturbance (including increased fall risk), psychological disturbance (including anxiety and depression), metabolic dysfunction (including increased insulin resistance and catabolic propensity), and immune dysfunction and proinflammatory effects (increasing infection risk and pain generation). All these changes negatively impact health status and are counterproductive to recovery from illness and operation. Hospitalization challenges sleep in a variety of ways. These challenges include environmental factors such as noise, bright light, and overnight awakenings for observations, interventions, and transfers; physiological factors such as pain, dyspnea, bowel or urinary dysfunction, or discomfort from therapeutic devices; psychological factors such as stress and anxiety; care-related factors including medications or medication withdrawal; and preexisting sleep disorders that may not be recognized or adequately managed. Many of these challenges appear readily addressable. The key to doing so is to give sleep greater priority, with attention directed at ensuring that patients' sleep needs are recognized and met, both within the hospital and beyond. Requirements include staff education, creation of protocols to enhance the prospect of sleep needs being addressed, and improvement in hospital design to mitigate environmental disturbances. Hospitals and health care providers have a duty to provide, to the greatest extent possible, appropriate preconditions for healing. Accumulating evidence suggests that these preconditions include adequate patient sleep duration and quality. The Society of Anesthesia and Sleep Medicine calls for systematic changes in the approach of hospital leadership and staff to this issue. Measures required include incorporation of optimization of patient sleep into the objectives of perioperative and general patient care guidelines. These steps should be complemented by further research into the impact of hospitalization on sleep, the effects of poor sleep on health outcomes after hospitalization, and assessment of interventions to improve it.

Experiences of Mental Distress during COVID-19: Thematic Analysis of Discussion Forum Posts for Anxiety, Depression, and Obsessive-Compulsive Disorder.

The psychological impact of the COVID-19 pandemic on coronavirus patients, health care workers, and the general population is clear. Relatively few studies have, however, considered the impact of the pandemic on those with pre-existing mental health conditions. Therefore, the present study investigates the personal experiences of those with anxiety, depression, and obsessive-compulsive disorder during COVID-19. We conducted a qualitative study utilising Reddit discussion forum posts. We conducted three separate thematic analyses from 130 posts in subreddit forums aimed for people identifying with anxiety, depression, and obsessive-compulsive disorder. We identified a number of similar discussion forum themes (e.g., COVID-19 intensifying symptoms and a lack of social support), as well as themes that were unique to each forum type (e.g., hyperawareness and positive experiences during the pandemic). Findings should guide future practice and the support provided to those living with mental distress.

Case-based, asynchronous sleep education outcomes among primary care nurse practitioner students.

STUDY OBJECTIVES: Primary care nurse practitioners (NPs) receive little sleep education in graduate programs but are often first-line providers for patients presenting with sleep-related symptoms. A pre-/postevaluation study was conducted using asynchronous, case-based sleep education modules in a cohort of primary care NP students enrolled in a single academic institution's nursing master's degree program. METHODS: Six virtual, case-based modules addressed adult sleep health and disorders, prioritized based on prevalence and primary care presentation. Kirkpatrick Training Evaluation Model guided outcome selection. Descriptive and paired comparative analyses were conducted. RESULTS: Participants were first-year NP students (n = 149; 88% female; 82% ≤ 35 years of age) in an adult primary care program that included psychiatric/mental health track. Participants reacted positively to course delivery methods and content. Insomnia was endorsed by 87% as most relevant to practice with healthy sleep (88%) and obstructive sleep apnea (50%) also frequently endorsed as practice relevant. Posttest knowledge scores significantly improved for all modules (P < .001). Self-rated confidence for future practice application was high. CONCLUSIONS: This novel asynchronous, virtual curriculum met Kirkpatrick levels 1 and 2 (positive reaction and knowledge transfer) in NP students who predicted an impact on their practice (Kirkpatrick level 3). Studies are needed to assess the benefits of increasing primary care NP knowledge in sleep medicine on quality of care and access to care (Kirkpatrick level 4). Future use of this novel sleep curriculum in other professional curricula, new-to-sleep clinical researchers, and practicing primary care providers may further potentiate care quality and sleep care access. CITATION: Sawyer AM, Saconi B, Lyons MM, et al. Case-based, asynchronous sleep education outcomes among primary care nurse practitioner students. J Clin Sleep Med. 2022;18(10):2367-2376.

Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors.

BACKGROUND AND PURPOSE: Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. MATERIALS AND METHODS: In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. RESULTS: Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. CONCLUSIONS: Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles.

Association between anxiety, depression, and emotional distress and hypoglossal nerve stimulator adherence.

PURPOSE: To evaluate relationships between hypoglossal nerve stimulator (HNS) adherence and the presence of anxiety, depression, and emotional distress. METHODS: This is a cross-sectional study of subjects with moderate to severe obstructive sleep apnea (OSA), who had HNS implanted and activated at The Ohio State University Medical Center (OSUMC). Patient usage data from the previous 6 months was obtained from 33 patients. Adherence was defined as ≥28 h of use per week. Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were administered, and the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) score was calculated for all subjects. RESULTS: Sixty-five percent were adherent with average usage of 46.5±11.7 h per week vs 7.7±7.5 h per week in the non-adherent group. The average GAD-7 were 3.90±3.98 in the adherent group vs. 8.27±6.69 in the non-adherent group (p=0.049). PHQ-9 score was 6.15±4.31 vs. 10.09±7.53 (p=0.118), and PHQ-ADS was 10.05±7.49 vs. 19.20±9.80 (p=0.035). There were no statistically significant differences in age, gender, pre-treatment AHI, and post-treatment AHI between the two groups, though there was a trend to higher age in the adherent group. CONCLUSIONS: This study demonstrated higher GAD-7 and PHQ-ADS scores in the non-adherent group compared to those who were adherent to HNS supporting that anxiety and emotional distress may contribute to HNS therapy adherence. To our knowledge, this is the first study evaluating the relationship between anxiety, depression, emotional distress, and HNS adherence. Screening patients with the GAD-7 and PHQ-9 prior to implantation may be helpful when evaluating patient adherence to therapy.

Diagnostic Performance of Machine Learning-Derived OSA Prediction Tools in Large Clinical and Community-Based Samples.

BACKGROUND: Prediction tools without patient-reported symptoms could facilitate widespread identification of OSA. RESEARCH QUESTION: What is the diagnostic performance of OSA prediction tools derived from machine learning using readily available data without patient responses to questionnaires? Also, how do they compare with STOP-BANG, an OSA prediction tool, in clinical and community-based samples? STUDY DESIGN AND METHODS: Logistic regression and machine learning techniques, including artificial neural network (ANN), random forests (RF), and kernel support vector machine, were used to determine the ability of age, sex, BMI, and race to predict OSA status. A retrospective cohort of 17,448 subjects from sleep clinics within the international Sleep Apnea Global Interdisciplinary Consortium (SAGIC) were randomly split into training (n = 10,469) and validation (n = 6,979) sets. Model comparisons were performed by using the area under the receiver-operating curve (AUC). Trained models were compared with the STOP-BANG questionnaire in two prospective testing datasets: an independent clinic-based sample from SAGIC (n = 1,613) and a community-based sample from the Sleep Heart Health Study (n = 5,599). RESULTS: The AUCs (95% CI) of the machine learning models were significantly higher than logistic regression (0.61 [0.60-0.62]) in both the training and validation datasets (ANN, 0.68 [0.66-0.69]; RF, 0.68 [0.67-0.70]; and kernel support vector machine, 0.66 [0.65-0.67]). In the SAGIC testing sample, the ANN (0.70 [0.68-0.72]) and RF (0.70 [0.68-0.73]) models had AUCs similar to those of the STOP-BANG (0.71 [0.68-0.72]). In the Sleep Heart Health Study testing sample, the ANN (0.72 [0.71-0.74]) had AUCs similar to those of STOP-BANG (0.72 [0.70-0.73]). INTERPRETATION: OSA prediction tools using machine learning without patient-reported symptoms provide better diagnostic performance than logistic regression. In clinical and community-based samples, the symptomless ANN tool has diagnostic performance similar to that of a widely used prediction tool that includes patient symptoms. Machine learning-derived algorithms may have utility for widespread identification of OSA.

[Roles of nurses in sleep medicine].

Sleep health becomes an important component of global public health. The incidence of sleep disorders is increasing rapidly worldwide, which seriously affects people's quality of life. In China, the lack of professional sleep physicians and technicians, the distribution of sleep centers and the unbalanced development of medical resources have seriously restricted the development of sleep medicine and the improvement of sleep health guarantee level. In Europe and America and other developed countries, sleep medicine has become a new interdisciplinary discipline. The development of nurses as sleep coordinator has become an irresistible trend. Nurses have been trained to become the main force of sleep technicians. These successful attempts in the field of sleep medicine provide reference for promoting the development of nursing care in China from the aspects of medical care, teaching and research.

Effects of a randomized controlled trial of a brief, student-nurse led, parent-based sexual health intervention on parental protective factors and HPV vaccination uptake.

BACKGROUND: Parents play a pivotal role in adolescent sexual health and Human Papillomavirus (HPV) vaccination. Nurses are on the frontlines of healthcare and play a critical role in promoting HPV vaccination and parent-child sexual health communication. We enhanced the Families Talking Together (FTT) parent-based sexual health curriculum to include adolescent vaccinations herein, FTT + HPV, and trained student nurses to provide a strong HPV vaccination and parent-child sexual health communication endorsement. METHODS: Using a randomized attention-controlled trial design, we examined the efficacy of FTT + HPV among 519 parents and their 11-14 year old youth recruited from medically underserved communities between 2015 and 2018. Participants were recruited from 22 after-school programs (e.g., Boys and Girls Clubs) and 19 charter schools. For parents, we examined protective factors including parent-child sexual health communication and parental involvement. For youth, we examined sexual health knowledge, parent-child sexual health communication, and parent-child connectedness. To assess HPV vaccination initiation and completion, we searched IMMTRAC immunization registry records for 85% of youth and used parental report for youth without registry records. Group differences were calculated using the estimated mean difference at one- and six months post-intervention with significance set at the p < 0.05 level. RESULTS: Baseline rates of HPV vaccination were low at 55.7%. No significant difference between the groups was seen in vaccination initiation or completion rates by one-month post-intervention. However, by six-months post intervention, there was a significant difference between the groups with 70.3% of the intervention group initiating the HPV vaccination series vs. 60.6% for the control group (p = 0.02). No difference between the groups was found for HPV series completion at six-months. There were significant differences in condom knowledge (p = 0.04), parent-child connectedness (p = 0.04), and communication frequency (p = 0.001) with greater improvement in the intervention vs. the control group. Rates of sexual activity remained low in both groups throughout the six-month follow-up period. CONCLUSION: A brief parent-based adolescent sexual health and HPV vaccination intervention delivered by student nurses can improve sexual health outcomes including protective parental factors, adolescent sexual health knowledge, and HPV vaccination initiation rates. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02600884 . Prospectively registered September 1, 2015.

Temporal Trends in Surgical Resection Rates and Biologic Prescribing in Crohn's Disease: A Population-based Cohort Study.

BACKGROUND: The use of biologic therapy for Crohn's disease [CD] continues to evolve, however, the effect of this on the requirement for surgery remains unclear. We assessed changes in biologic prescription and surgery over time in a population-based cohort. METHODS: We performed a retrospective cohort study of all 1753 patients diagnosed with CD in Lothian, Scotland, between January 1, 2000 and December 31, 2017, reviewing the electronic health record of each patient to identify all CD-related surgery and biologic prescription. Cumulative probability and hazard ratios for surgery and biologic prescription from diagnosis were calculated and compared using the log-rank test and Cox regression analysis stratified by year of diagnosis into cohorts. RESULTS: The 5-year cumulative risk of surgery was 20.4% in cohort 1 [2000-2004],18.3% in cohort 2 [2005-2008], 14.7% in cohort 3 [2009-2013], and 13.0% in cohort 4 [2014-2017] p <0.001. The 5-year cumulative risk of biologic prescription was 5.7% in cohort 1, 12.2% in cohort 2, 22.0% in cohort 3, and 44.9% in cohort 4 p <0.001. CONCLUSIONS: The increased and earlier use of biologic therapy in CD patients corresponded with a decreasing requirement for surgery over time within our cohort. This could mean that adopting a top-down or accelerated step-up treatment strategy may be effective at reducing the requirement for surgery in newly diagnosed CD.

Global burden of sleep-disordered breathing and its implications.

One-seventh of the world's adult population, or approximately one billion people, are estimated to have OSA. Over the past four decades, obesity, the main risk factor for OSA, has risen in striking proportion worldwide. In the past 5 years, the WHO estimates global obesity to affect almost two billion adults. A second major risk factor for OSA is advanced age. As the prevalence of the ageing population and obesity increases, the vulnerability towards having OSA increases. In addition to these traditional OSA risk factors, studies of the global population reveal select contributing features and phenotypes, including extreme phenotypes and symptom clusters that deserve further examination. Untreated OSA is associated with significant comorbidities and mortality. These represent a tremendous threat to the individual and global health. Beyond the personal toll, the economic costs of OSA are far-reaching, affecting the individual, family and society directly and indirectly, in terms of productivity and public safety. A better understanding of the pathophysiology, individual and ethnic similarities and differences is needed to better facilitate management of this chronic disease. In some countries, measures of the OSA disease burden are sparse. As the global burden of OSA and its associated comorbidities are projected to further increase, the infrastructure to diagnose and manage OSA will need to adapt. The use of novel approaches (electronic health records and artificial intelligence) to stratify risk, diagnose and affect treatment are necessary. Together, a unified multi-disciplinary, multi-organizational, global approach will be needed to manage this disease.

A personalized behavioral intervention implementing mHealth technologies for older adults: A pilot feasibility study.

Sedentary behavior has been associated with adverse health outcomes such as disturbed sleep in older adults. We conducted a single-group pretest and posttest study to evaluate the feasibility of a personalized behavioral intervention program using mobile health technology in improving physical activity and sleep in older adults. The four-week intervention included: personalized physical activity training, real-time physical activity self-monitoring, interactive prompts and feedback with a smartwatch, phone consultation with an exercise trainer and research team members, and weekly financial incentives for achieving weekly physical activity goals. Eight cognitively intact older adults were recruited and completed the study. Findings suggested that the intervention was feasible in this sample of older adults and provided favorable changes in levels of physical activity during the intervention and at post-intervention. Future studies will include a fully powered trial to evaluate the efficacy of this intervention in sedentary older adults.

Magnetic resonance imaging for vestibular schwannoma: cost-effective protocol for referrals.

OBJECTIVE: Vestibular schwannoma is the most common neoplasm in the cerebellopontine angle, and fast spin-echo T2-weighted magnetic resonance imaging is the most sensitive test for diagnosing it. This study evaluated the financial and time costs of unnecessary magnetic resonance imaging referrals before and after the application of a magnetic resonance imaging protocol. METHOD: A full audit cycle was used for the assessment. The first cycle in January 2012 was retrospective and evaluated the financial impact of current selection criteria for magnetic resonance imaging referral against standard guidelines. The second cycle in January 2014 was prospective after implementation of the protocol. RESULTS: There were 46 and 112 patients who had magnetic resonance imaging during first and second cycle, respectively. Of the referrals for magnetic resonance imaging, 65 per cent versus 81 per cent of the referrals were appropriate in the first and second cycles, respectively. The relative risk was reduced from 0.5 to 0.2. The waiting times for magnetic resonance imaging scans improved. CONCLUSION: Selection criteria for magnetic resonance imaging referral are important in reducing waiting times for scans, patient anxiety and conserving trust resources.

Severe Rhinitis Medicamentosa Successfully Treated with Rhinolight® Endonasal UV Phototherapy

Aim Report successful application of UV endonasal phototherapy as a treatment for severe rhinitis medicamentosa and allergic rhinitis. Methods Allergic rhinitis confirmed by history and skin prick testing; rhinitis medicamentosa based on history. Both confirmed at nasendoscopy. Symptom score before & after treatment. Introduction of Rhinolight endonasal u/v phototherapy for allergic rhinitis. Single patient report. Results Successful remission of Rhinitis Medicamentosa confirmed with patient after eight sessions Rhinolight endonasal phototherapy. Use of nasal decongestant dropped from 2 bottles/daily x 4 years to zero. Symptoms reduced from 25 pre-treatment to 6 post-treatment. Rhinitis medicamentosa is clinically characterized by nasal congestion without rhinorrhea, postnasal drip, or sneezing that begins after using a nasal decongestant for more than 3 days. Treatment involves discontinuation of the offending drug. Discussion Rhinolight endonasal phototherapy is a new treatment for allergic rhinitis and offered as last resort for a patient with untreated allergic rhinitis and overuse of topical decongestants. Patient reports a significant improvement in symptoms with cessation of topical decongestant. Report a successful application of UV endonasal phototherapy as a treatment for severe rhinitis medicamentosa against a background of long standing allergic rhinitis.

Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort.

BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

Screening for Obstructive Sleep Apnea in Commercial Drivers Using EKG-Derived Respiratory Power Index.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in commercial motor vehicle operators (CMVOs); however, polysomnography (PSG), the gold-standard diagnostic test, is expensive and inconvenient for screening. OSA is associated with changes in heart rate and voltage on electrocardiography (EKG). We evaluated the utility of EKG parameters in identifying CMVOs at greater risk for sleepiness-related crashes (apnea-hypopnea index [AHI] ≥ 30 events/h). METHODS: In this prospective study of CMVOs, we performed EKGs with concurrent PSG, and calculated the respiratory power index (RPI) on EKG, a surrogate for AHI calculated from PSG. We evaluated the utility of two-stage predictive models using simple clinical measures (age, body mass index [BMI], neck circumference, Epworth Sleepiness Scale score, and the Multi-Variable Apnea Prediction [MVAP] score) in the first stage, followed by RPI in a subset as the second-stage. We assessed area under the receiver operating characteristic curve (AUC), sensitivity, and negative posttest probability (NPTP) for this two-stage approach and for RPI alone. RESULTS: The best-performing model used the MVAP, which combines BMI, age, and sex with three OSA symptoms, in the first stage, followed by RPI in the second. The model yielded an estimated (95% confidence interval) AUC of 0.883 (0.767-0.924), sensitivity of 0.917 (0.706-0.962), and NPTP of 0.034 (0.015-0.133). Predictive characteristics were similar using a model with only BMI as the first-stage screen. CONCLUSIONS: A two-stage model that combines BMI or the MVAP score in the first stage, with EKG in the second, had robust discriminatory power to identify severe OSA in CMVOs.