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Context: Arthrogenic muscle inhibition (AMI) is a common neurophysiological response to joint injury. While athletic trainers (ATs) are constantly treating patients with AMI, it is unclear how clinicians are using the available evidence to treat the condition. Objective: To investigate ATs’ general knowledge, clinical practice, and barriers for treating AMI. Methods: A cross-sectional web-based survey was utilized. The survey was distributed to a random sample of 3000 ATs from the National Athletic Trainers’ Association and through social media. 143 board certified ATs (age: 34.6 [10.3] y; experience: 11.7 [9.8] y) from various clinical settings and educational backgrounds were included in the analysis. Results: One hundred one respondents were able to correctly identify the definition of AMI. The majority of these respondents correctly reported that joint effusion (n = 95, 94.1%) and abnormal activity from joint receptors (n = 91, 90.1%) resulted in AMI. Of the 101 respondents, only 58 (57.4%) reported using disinhibitory interventions to treat AMI. The most frequently used evidence supported interventions were transcutaneous electrical nerve stimulation (n = 38, 65.5%), neuromuscular electrical stimulation (n = 33, 56.9%), and focal joint cooling (n = 25, 43.1%). The interventions used correctly most often based on current evidence were neuromuscular electrical stimulation (n = 29/33, 87.9%) and transcutaneous electrical nerve stimulation (n = 26/38, 68.4%). Overall, difficulty quantifying AMI (n = 62, 61.24%) and lack of education (n = 71, 76.2%) were most frequently perceived as barriers. Respondents that did not use disinhibitory interventions perceived lack of experience treating AMI, understanding the terminology, and access to therapeutic modalities more often than the respondents that reported using disinhibitory interventions. Conclusion: Further education about concepts and treatment about AMI is warranted for ATs. Continued understanding of ATs’ clinical practice in regard to AMI may help identify gaps in athletic training clinical education.

Knowledge about systemic lupus erythematosus (SLE) outcomes among US Asian patients is lacking. The present study was undertaken to examine SLE disease activity, severity, and damage among Asian patients of primarily Chinese and Filipino descent in a multiethnic cohort.California Lupus Epidemiology Study (n = 328) data were analyzed. Data were collected in English, Cantonese, Mandarin, or Spanish using validated instruments for disease activity (Systemic Lupus Erythematosus Disease Activity Index), disease severity (Lupus Severity Index [LSI]), and disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). We assessed differences in SLE outcomes among racial/ethnic groups using multivariable linear regression including interaction terms for age at diagnosis and race/ethnicity.Asian was the largest racial/ethnic group (38% [Chinese = 22%; Filipino = 9%; Other = 7%]). Average age at diagnosis was younger among Asian patients (27.9 years), particularly Filipino patients (22.2 years), compared with White (29.4 years) and Black patients (34.0 years). After adjustment, disease activity and damage were not significantly different across groups. Disease severity among Asian patients was significantly higher than among White patients (LSI score 7.1 versus 6.5; P 0.05) but similar among Black and Hispanic patients. Early age at diagnosis was associated with greater organ damage among Asian, Black, and Hispanic patients, but not White patients.SLE was more severe among US Asian patients compared to White patients. Filipinos were affected at strikingly young ages. Asian patients and non-White groups with younger age at diagnosis had greater organ damage than White patients. Such racial/ethnic distinctions suggest the need for heightened clinical awareness to improve health outcomes among Asian patients with SLE. Further study of SLE outcomes across a range of US Asian subgroups is important.

PURPOSE Docetaxel and abiraterone acetate plus prednisone or prednisolone (AAP) both improve survival when commenced alongside standard of care (SOC) androgen deprivation therapy in locally advanced or metastatic hormone-sensitive prostate cancer. Thus, patient-reported quality of life (QOL) data may guide treatment choices. METHODS A group of patients within the STAMPEDE trial were contemporaneously enrolled with the possibility of being randomly allocated to receive either docetaxel + SOC or AAP + SOC. A mixed-model assessed QOL in those who had completed at least one QLQ-C30 + PR25 questionnaire. The primary outcome measure was difference in global-QOL (QLQ-C30 Q29&30) between patients allocated to docetaxel + SOC or AAP + SOC over the 2 years after random assignment, with a predefined criterion for clinically meaningful difference of > 4.0 points. Secondary outcome measures included longitudinal comparison of functional domains, pain, and fatigue, plus global-QOL at defined timepoints. RESULTS Five hundred fifteen patients (173 docetaxel + SOC and 342 AAP + SOC) were included. Baseline characteristics, proportion of missing data, and mean baseline global-QOL scores (docetaxel + SOC 77.8 and AAP + SOC 78.0) were similar. Over the 2 years following random assignment, the mean modeled global-QOL score was +3.9 points (95% CI, +0.5 to +7.2; P = .022) higher in patients allocated to AAP + SOC. Global-QOL was higher for patients allocated to AAP + SOC over the first year (+5.7 points, 95% CI, +3.0 to +8.5; P < .001), particularly at 12 (+7.0 points, 95% CI, +3.0 to +11.0; P = .001) and 24 weeks (+8.3 points, 95% CI, +4.0 to +12.6; P < .001). CONCLUSION Patient-reported QOL was superior for patients allocated to receive AAP + SOC, compared with docetaxel + SOC over a 2-year period, narrowly missing the predefined value for clinical significance. Patients receiving AAP + SOC reported clinically meaningful higher global-QOL scores throughout the first year following random assignment.

Introduction /Objectives: The objectives were to conduct a survey of cardiologists on their recent experiences with cats that have dilated cardiomyopathy (DCM), and to retrospectively review individual cases of feline DCM. Animals, Materials and Methods Part One: A survey was distributed to cardiologists with questions regarding caseload and clinical management of cats with DCM diagnosed over the past two years. Part Two: Cardiologists completing the survey were invited to submit data from cats recently diagnosed with DCM. Data on signalment, clinical signs, diet, echocardiographic measurements, and outcome were recorded. Results Part One: From 52 completed surveys, many cardiologists responded that measuring and supplementing taurine and recommending a diet change in cats with DCM are common practices. Few (15%) cardiologists reported an increase in number of feline DCM cases over the past two years, although some had cases that improved even if taurine deficiency was not present. Part Two: Twenty of 37 (54%) cats ate low pea/lentil (low PL) diets and 14/37 (38%) ate high pea/lentil (high PL) diets at the time of diagnosis; three had incomplete diet information. Two of 13 cats (15%) in which taurine was measured had levels below the reference range. After adjusting for other variables, cats eating high PL diets that changed diets post-diagnosis had a significantly longer survival time compared to cats eating high PL diets that did not change diets post-diagnosis (P=0.025). Conclusions Additional research is warranted to determine whether there could be a possible association between diet and DCM in cats.

Ryan B Rush,1– 4 Sloan W Rush2,3 1Instituto de la Visión– Hospital La Carlota, Montemorelos, Nuevo León, 67530, México; 2Panhandle Eye Group, Amarillo, TX, 79106, USA; 3Department of Surgery, Texas Tech University Health Science Center, Amarillo, TX, 79106, USA; 4Southwest Retina Specialists, Amarillo, TX, 79106, USACorrespondence: Ryan B RushSouthwest Retina Specialists, 7411 Wallace Blvd, Amarillo, TX, 79106, USATel +1 806 351-1870Email ryan.rush.md@gmail.comPurpose: To report the outcomes in subjects undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for the management of treatment-naïve diabetic macular edema (DME).Methods: Ten treatment-naïve subjects with non-proliferative diabetic retinopathy prospectively underwent PPV with ILM peeling for the treatment of DME at a single university-affiliated institution. The preoperative features, intraoperative details and postoperative outcomes were collected and analyzed.Results: All 10 subjects underwent PPV with ILM peeling without significant intraoperative or postoperative complications at 6 months follow-up. Visual acuity improved from a baseline of 0.74 (95% CI: 0.48– 1.0) logMAR (Snellen 20/110) to 0.46 (95% CI: 0.3– 0.62) logMAR (Snellen 20/58) at 6 months follow-up (p=0.045). Optical coherence tomography central macular thickness reduced from a baseline of 456 (95% CI: 394.7– 516.4) microns to 316.8 (95% CI: 275.9– 357.7) microns at 6 months follow-up (p < 0.001).Conclusion: This pilot study suggests that PPV with ILM peeling may be a viable treatment option for the management of treatment naïve DME in subjects with non-proliferative diabetic retinopathy. Development of a randomized controlled trial may be justified to validate the results of this study.Clinicaltrials.gov Identifier #: NCT03660345.Keywords: vitrectomy, internal limiting membrane peeling, diabetic macular edema

PURPOSE To evaluate the benefits of internal limiting membrane peeling in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for the treatment of vitreous hemorrhage. METHODS Two hundred and fifty-eight proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for vitreous hemorrhage were enrolled into the trial. Patients were randomized into one of two cohorts: Group A patients underwent internal limiting membrane peeling, whereas Group B patients did not undergo internal limiting membrane peeling. The main outcome was best-corrected visual acuity at 6 months. Secondary outcomes were optical coherence tomography central macular thickness at 6 months, incidence of diabetic macular edema treatment during the postoperative trial period, and incidence of epiretinal membrane at 6 months. RESULTS Two hundred and seven patients were randomized and completed 6 months follow-up. Group A had better best-corrected visual acuity at 6 months than Group B (P < 0.01). Group A had a lower incidence of diabetic macular edema treatment during the postoperative trial period and a lower incidence of epiretinal membrane at 6 months than Group B (P = 0.02 and P < 0.001, respectively). There was a trend toward lower central macular thickness on optical coherence tomography in Group A than Group B (P = 0.09). There were no significant differences in baseline details or complications intraoperatively or postoperatively between cohorts. CONCLUSION This trial demonstrated better vision, fewer postoperative diabetic macular edema treatments, and a lower incidence of epiretinal membrane at 6 months when internal limiting membrane peeling was performed. Internal limiting membrane peeling may be considered a vital maneuver to perform in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for vitreous hemorrhage.

Sloan W Rush,1,2 Ryan B Rush1– 3 1Panhandle Eye Group, Amarillo, TX, 79106, USA; 2Texas Tech University Health Science Center, Department of Surgery, Amarillo, TX, 79106, USA; 3Southwest Retina Specialists, Amarillo, TX, 79106, USACorrespondence: Ryan B RushSouthwest Retina Specialists, 7411 Wallace Blvd., Amarillo, TX, 79106, USATel +1806 351-1870Email ryan.rush.md@gmail.comPurpose: To report the outcomes of femtosecond-assisted laser in situ keratomileusis (LASIK) in patients with previous corneal scarring using optical coherence tomography (OCT) imaging to determine flap depths.Methods: The charts of 11 eyes of 9 patients with previous off-visual axis corneal scarring that underwent femtosecond LASIK using OCT guidance for flap depth determination were retrospectively reviewed at a single private practice institution. The baseline characteristics, intraoperative findings and postoperative outcomes were analyzed.Results: All 11 eyes underwent femtosecond laser flap creation and LASIK without any significant intraoperative complications. Uncorrected visual acuity improved postoperatively (p< 0.0001) and remained stable at 3 months follow-up. None of the subjects lost any lines of best spectacle corrected visual acuity or developed any flap complications during the postoperative period.Conclusion: The OCT-guided femtosecond laser technique described in this report can provide a safe and effective method to deliver LASIK in the setting of previous corneal scarring. Future investigations are required to further validate the findings in this study.Keywords: LASIK, corneal scarring, optical coherence tomography

Sloan W Rush,1,2 Ryan B Rush1– 3 1Panhandle Eye Group, Amarillo, TX, 79106, USA; 2Department of Surgery, Texas Tech University Health Science Center, Amarillo, TX, 79106, USA; 3Southwest Retina Specialists, Amarillo, TX, 79106, USACorrespondence: Ryan B RushSouthwest Retina Specialists, 7411 Wallace Blvd, Amarillo, TX, 79106, USATel +1 806 351-1870Email ryan.rush.md@gmail.comPurpose: To report the outcomes of laser in situ keratomileusis (LASIK) in patients with previous microkeratome LASIK using a femtosecond laser platform to create a de novo flap.Methods: The charts of 17 patients that underwent femtosecond-assisted LASIK with de novo flap creation for consecutive refractive error following previous microkeratome LASIK were retrospectively reviewed at a single private practice institution. The baseline characteristics, intraoperative findings and postoperative outcomes were analyzed.Results: All 17 eyes underwent femtosecond-assisted LASIK with de novo flap creation without significant intraoperative or postoperative complications. Uncorrected visual acuity improved postoperatively (p< 0.0001) and remained stable at 6 months follow-up. None of the subjects lost any lines of best spectacle corrected visual acuity or developed epithelial ingrowth during the postoperative period.Conclusion: The femtosecond laser technique described in this report can provide a safe and effective method to deliver LASIK following previous microkeratome LASIK. Future investigations are required to further validate the findings in this study.Keywords: LASIK, cornea, optical coherence tomography

As of January 2021, there are more than 3.8 million women in the United States with a history of breast cancer. The current standard of care for breast cancer involves surgical resection, radiation therapy, adjuvant endocrine therapy, and/or adjuvant chemotherapy. Aromatase inhibitors (AIs) are the gold standard for endocrine therapy in postmenopausal women. Dermatologic adverse events (dAEs) associated with AIs are rare but have been reported in the literature. Commonly reported dAEs include unspecified rash, pruritus, alopecia, vulvovaginal atrophy, vasculitis, and autoimmune/connective tissue disorders. Appropriate preventative strategies and careful management considerations have the potential to optimize the comprehensive care of patients with cancer and improve quality of life. Furthermore, prevention of dAEs can lead to a reduction in cancer treatment interruptions and discontinuations. Herein, we characterize dAEs of AIs and discuss preventative management to reduce the incidence of AI therapy interruption.

Diagnostics tests used to identify the cause of infection using proteomics and genomics have revolutionised microbiology laboratories in recent times. However, approaches to build the capacity of clinical microbiology services in the rural tropics by simply transplanting these approaches have proven difficult to sustain. Tropical fever in the remote tropics is, by definition, a clinical diagnosis where the aetiology of fever is not known, treatment is empirical, guided by clinical suspicion with treatment failure often attributed to incorrect diagnosis or antimicrobial resistance. Tuberculosis (TB) in rural Papua New Guinea (PNG) is mostly diagnosed clinically, perhaps supported by microscopy. In fact, a ‘tuberculosis patient’ in rural PNG is included in the TB register upon commencement of TB treatment with or without any laboratory-based evidence of infection. The roll-out of GeneXpert is continuing to transform TB diagnostic certainty in TB endemic communities. Melioidosis is endemic in tropical regions and is increasingly reported to mimic TB. Isolation and identification of the causative agent Burkholderia pseudomallei remains the gold standard. Here, we discuss the increasing divide between rural and urban approaches to laboratory-based infection diagnosis using these two enigmatic tropical infectious diseases, in rural PNG, as examples.

Summary Background Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis. Methods MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18–50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2–15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5–6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit. Findings From July 16, 2012, until July 31, 2019, 144 patients were randomly assigned to first receive early intravenous infusion of autologous bone marrow-derived MSCs (n=69) or placebo (n=75). MSC treatment did not meet the primary endpoint of efficacy on the total number of GELs accumulated from baseline to week 24 (rate ratio [RR] 0·94, 95% CI 0·58–1·50; p=0·78). 213 adverse events were recorded, similarly distributed between groups (93 cases recorded in 35 [51%] of 69 patients treated first with MSCs vs 120 cases in 42 [56%] of 75 patients infused first with placebo). The most frequent adverse events reported were infection and infestations, with a total of 54 (25%) of 213 adverse events (18 [19%] of 93 in the early-MSC group and 36 [30%] of 120 in the delayed-MSC group). Nine serious adverse events were reported in seven patients treated with placebo versus none in the MSC group. All serious adverse events were considered to be unrelated to the treatment infusion. No deaths were reported during the study. Interpretation Bone marrow-derived MSC treatment was safe and well tolerated but did not show an effect on GELs, an MRI surrogate marker of acute inflammation, in patients with active forms of multiple sclerosis, at week 24. Thus, this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis. Further studies should address the effect of MSCs on parameters related to tissue repair. Funding Fondazione Italiana Sclerosi Multipla (FISM), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the Multiple Sclerosis International Federation (MSIF) for centralised activities. Individual trials participating in the MESEMS network are funded by the following agencies: FISM and Compagnia di San Paolo (Italy); The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark); the Spanish Health Research Institute Carlos 3 and the Andalusian Public Foundation Progreso y Salud (Spain); the Royan Institute for Stem Cell Biology and Technology (Iran); the Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, and Salzburg (Austria); the Fondation pour l’aide a la recherche sur la sclerose en plaques (ARSEP), French Muscular Dystrophy Association (AFM)-Telethon (France); the UK Multiple Sclerosis Society and the UK Stem Cell Foundation (UK); and the Multiple Sclerosis Society of Canada and The Multiple Sclerosis Scientific Research Foundation and Research Manitoba (Canada).

Introduction Kawasaki disease (KD) with coronary artery aneurysms (complex KD) presents relentless challenges for families. Psychosocial experiences and needs were explored. Method A descriptive, exploratory study of adolescents and parents using a needs survey and psychosocial instruments (anxiety, depression, and functional impairment). Results Fifty-one parents and 38 adolescents participated. Predominant interests were for information sheets, newsletters, Web sites, and phone applications. Gaps in disease-specific knowledge and awareness of coronary artery aneurysms between parents and adolescents were identified. Psychosocial concerns for adolescents included symptoms of anxiety (22%), depression (13%), and functional impairment (22%). Multivariable analyses indicated higher depression scores associated with longer travel distance from specialists (p = .04). Parent-reported social concerns for their adolescent were associated with higher anxiety (p = .005) and functional impairment (p = .005). Written commentary complemented the findings. Discussion Care protocols require psychosocial assessment/referral and the use of virtual platforms. The groundwork was laid for developing patient and family-centered strategies.

Background and Objectives Telehealth holds potential for inclusive and cost-saving health care; however, a better understanding of the use and acceptance of telehealth for health promotion among rural older adults is needed. This systematic review aimed to synthesize evidence for telehealth use among rural-living older adults and to explore cost-effectiveness for health systems and patients. Research Design and Methods This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study designs reporting health promotion telehealth interventions with rural-living adults aged 55 and older were eligible for review. Following screening and inclusion, articles were quality-rated and ranked by level of evidence. Data extraction was guided by the Technology Acceptance Model and organized into outcomes related to ease of use, usefulness, intention to use, and usage behavior along with cost-effectiveness. Results Of 2,247 articles screened, 42 were included. Positive findings for the usefulness of telehealth for promoting rural older adults’ health were reported in 37 studies. Evidence for ease of use and usage behavior was mixed. Five studies examined intention to continue to use telehealth and in 4 of these, patients preferred telehealth. Telehealth was cost-effective for health care delivery (as a process) compared to face to face. However, findings were mixed for cost-effectiveness with both reports of savings (e.g., reduced travel) and increased costs (e.g., insurance). Discussion and Implications Telehealth was useful for promoting health among rural-living older adults. Technological supports are needed to improve telehealth ease of use and adherence. Cost-effectiveness of telehealth needs more study, particularly targeting older adults.

Transthoracic echocardiography (TTE) is increasingly utilized for guiding transcatheter closure of patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. The objectives of this study were to compare PDA size measurements by TTE with angiographic measurements and to describe TTE techniques used in guiding transcatheter PDA closure (TCPC) in ELBW infants.One hundred twenty-five consecutive ELBW infants (gestational age 27 weeks, birth weight 1 kg) who underwent TCPC before 8 weeks of age under TTE guidance were included. Patent ductus arteriosus sizes were measured from the procedural TTE and angiograms retrospectively by blinded observers. The TTE PDA diameters at the aortic (ED1) and pulmonary end (ED2) were compared with the corresponding angiographic diameters (CD1 and CD2). The TTE PDA lengths, obtained by two techniques (EL1, a straight line between ED1 and ED2; and EL2, a curvilinear line along the PDA), were compared with the PDA length by angiography (CL). Transthoracic echocardiography was used to guide accurate device positioning within the PDA.The procedure weight was 600-1,460 g. The TTE and angiographic PDA diameters were comparable (mean ED1 vs CD1 = 4.5 ± 0.68 vs 4.4 ± 0.85 mm, P = .26; and mean ED2 vs CD2 = 3.1 ± 0.72 vs 3.2 ± 0.94 mm, P = .14). The angiographic length was underestimated by EL1 by 2.6 ± 1.6 mm (P .0001), while EL2 estimated it better (mean EL2 vs CL = 11.0 ± 1.83 vs 10.8 ± 2.15 mm; P = .40). Transcatheter PDA closure was successful in 100% of the cases using TTE guidance. There were no intraprocedural complications.Transthoracic echocardiography guidance during TCPC in ELBW infants eliminates the need for aortograms via femoral arterial access, preventing the complications associated with it. Transthoracic echocardiography PDA measurements are comparable to angiographic measurements, thereby assisting in appropriate device size selection.

Aim To report the outcomes of patients undergoing anterior segment optical coherence tomography-guided transepithelial phototherapeutic keratectomy (ASOCT T-PTK) for central corneal scarring after pterygium excision. Methods The charts of 11 eyes of 10 patients that underwent ASOCT T-PTK following excision of visual axis-involving pterygia were retrospectively reviewed from a single private practice institution. The visual outcomes and corneal topographic findings were evaluated 4±1mo after pterygium excision and 6±2mo after transepithelial phototherapeutic keratectomy (T-PTK). Results All 11 eyes tolerated both the pterygium excision and T-PTK procedure well without any significant intraoperative or postoperative complications. Uncorrected distance visual acuity (UDVA) and manifest refraction corrected distance visual acuity (CDVA) improved after pterygium excision (P=0.03 and P=0.05, respectively). The UDVA and CDVA improved further after T-PTK (P=0.004 and P=0.002, respectively). The topographic surface asymmetry index, topographic surface regularity index, and topographic projected visual acuity significantly improved after T-PTK (P=0.0092, P=0.0022, and P=0.0002, respectively). None of the subjects lost any lines of CDVA, developed recurrence of pterygia or required keratoplasty during the postoperative period. Conclusion ASOCT T-PTK can provide excellent visual and anatomic outcomes in patients with central corneal scarring after excision of visual axis-involving pterygia.

INTRODUCTION Per-oral endoscopic myotomy (POEM) has been widely adopted for the treatment of achalasia as it provides a precise, tailored myotomy in a minimally invasive endoscopic procedure. Several short-term studies and a few long-term studies have confirmed that POEM is a safe and effective treatment for achalasia. However, the long-term outcome of POEM performed by trainees is unknown. MATERIALS AND METHODS We conducted a retrospective study of all patients who underwent POEM for achalasia at our tertiary care center during December 2012 and January 2019. All procedures performed with trainees were included. The primary outcome was the clinical response to POEM, defined as an Eckardt score of

First responders encounter many hazards in the execution of their duties, and exposure to hazardous materials such as opioids is a primary safety concern. The ongoing opioid crisis in the United States continues to be a major public health issue, with overdose deaths from opioids reaching epidemic levels. Although responders frequently encounter opioids, available data on safety and risk are not always well-communicated, and we identified a need for refresher and just-in-time training products on this topic. In response, we created a training video series that is informative, concise, and visually appealing. The video series, available on YouTube, was tested with a small initial population, with findings suggesting key questions for a larger study focused on integration of the refresher training with existing programs to optimize retention and adoption of safety practices.

During the COVID-19 pandemic, educators around the globe seek to understand how to support students whose academic performance is impacted by mental health challenges. This article presents a co-operative inquiry undertaken by colleagues in Canada and Australia, responding to the question; what insights can the existing Carleton University framework of reflective questions offer to educators responding to student mental health challenges in social work education during the COVID-19 pandemic? The risks and complexities of attending to student mental health needs are illustrated by a pandemic-informed case study that extends the framework into this unique context and illustrates the importance of respecting learning requirements, combating discrimination, protecting students' rights, and honouring the professional and legislative mandates of social work within all responses aimed at supporting student mental health resilience during COVID-19. This article acknowledges the limitations of previous practices guiding work with students with mental health needs during any period of crisis or disaster and demonstrates that the Carleton University framework assists in developing improved processes and policy grounded in social work's commitment to social justice and critical reflection.

Background Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment. Objective The objective of this study was to determine the effect of HSCT on disease progression. Methods We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board-certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI). Results Our patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow-up time (median, 11; range, 2-27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden. Conclusions This is the largest series of patients with CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to be considered when evaluating a patient's candidacy for transplant. HSCT appears to be the first disease-modifying therapy for CSF1R-related leukoencephalopathy. This milestone may serve as a foothold toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease-specific therapies. © 2021 International Parkinson and Movement Disorder Society.

There is a need to identify brain connectivity alterations predictive of transdiagnostic processes that may confer vulnerability for affective symptomology. Here, we tested whether amygdala resting-state functional connectivity (rsFC) mediated the relationship between catastrophizing (negative threat appraisals and predicting poorer functioning) and altered threat-safety discrimination learning (critical to flexibly adapt to new and changing environments) in adolescents with persistent pain. We examined amygdala rsFC in 46 youth with chronic pain and 29 healthy peers (age M = 15.8, SD = 2.9; 64 females) and its relationship with catastrophizing and threat-safety learning. We used a developmentally appropriate threat-safety learning paradigm and performed amygdala seed-based rsFC and whole-brain mediation analyses. Patients exhibited enhanced connectivity between the left amygdala and right supramarginal gyrus (SMG) (cluster-level P-FDR < 0.05), whereas right amygdala rsFC showed no group differences. Only in patients, elevated catastrophizing was associated with facilitated threat-safety learning (CS+>CS-; rp = 0.49, P = 0.001). Furthermore, in patients, elevated catastrophizing was associated with reduced left amygdala connectivity with SMG / parietal operculum, and increased left amygdala connectivity with hippocampus, dorsal striatum, paracingulate, and motor regions (P < 0.001). In addition, blunted left amygdala rsFC with right SMG/parietal operculum mediated the association between catastrophizing and threat-safety learning (P < 0.001). To conclude, rsFC between the left amygdala (a core emotion hub) and inferior parietal lobe (involved in appraisal and integration of bodily signals and attentional reorienting) explains associations between daily-life relevant catastrophizing and threat-safety learning. Findings provide a putative model for understanding pathophysiology involved in core psychological processes that cut across diagnoses, including disabling pain, and are relevant for their etiology.

Sodium chloride (NaCl) 23.4% solution has been shown to reduce intracranial pressure (ICP) and reverse transtentorial herniation. A limitation of 23.4% NaCl is its high osmolarity (8008 mOsm/l) and the concern for tissue injury or necrosis following extravasation when administered via peripheral venous access. The use of this agent is therefore often limited to central venous or intraosseous routes of administration. Our objective was to evaluate the safety and efficacy of administration of 23.4% NaCl via peripheral venous access compared with administration via central venous access. We reviewed pharmacy records to identify all administrations of 23.4% NaCl at our institution between December 2017 and February 2020. Medical records were then reviewed to identify complications, such as extravasation, soft tissue injury or necrosis, hypotension (mean arterial pressure less than 65 mm Hg), pulmonary edema, hemolysis, and osmotic demyelination. We also compared the change in physiological variables, such as ICP, mean arterial pressure, cerebral perfusion pressure, and heart rate, as well as laboratory values, such as sodium, chloride, bicarbonate, creatinine, and hemoglobin, following administration of 23.4% NaCl via the peripheral and central venous routes. We identified 299 administrations of 23.4% NaCl (242 central and 57 peripheral) in 141 patients during the study period. There was no documented occurrence of soft tissue injury or necrosis in any patient. One patient developed hypotension following central administration. Among the 38 patients with ICP monitoring at the time of drug administration, there was no significant difference in median ICP reduction (− 13 mm Hg [central] vs. − 24 mm Hg [peripheral], p = 0.21) or cerebral perfusion pressure augmentation (16 mm Hg [central] vs. 15 mm Hg [peripheral], p = 0.87) based on route of administration. Peripheral venous administration of 23.4% NaCl is safe and achieves a reduction in ICP equivalent to that achieved by administration via central venous access.

Emerging adults experience increased morbidity as a result of psychological distress and risky sexual behavior. This study examines how sexual behaviors (e.g., condom use inconsistency and past yea...

Background Hypophosphatasia (HPP), a rare metabolic disease, can be inherited in an autosomal recessive (biallelic) or an autosomal dominant (monoallelic) manner. Most of the severe, early-onset, frequently lethal HPP in infants is acquired through recessive inheritance; less severe, later-onset, typically nonlethal HPP phenotypes are acquired through either dominant or recessive inheritance. HPP's variable clinical presentation arises from >400 identified ALPL pathogenic variants with likely variable penetrance, especially with autosomal dominant inheritance. This post hoc analysis investigated the relationship between ALPL variant state (biallelic and monoallelic) and clinical outcomes with asfotase alfa in HPP. Methods Data were pooled from two phase 2, randomized, open-label studies in adolescents and adults with HPP; one study evaluated the efficacy and safety of different doses of asfotase alfa (n = 25), and the other assessed the pharmacodynamics and safety of asfotase alfa (n = 19). Patients were grouped by ALPL variant state (biallelic or monoallelic). Available data from both studies included ALPL pathogenic variant state, Baseline characteristics, HPP-specific medical history, and Baseline TNSALP substrate levels (inorganic pyrophosphate [PPi] and pyridoxal 5′-phosphate [PLP]) concentrations). Clinical outcomes over 5 years of treatment were available from only the efficacy and safety study. Results In total, 44 patients with known variant status were included in the pooled analysis (biallelic, n = 30; monoallelic, n = 14). The most common pathogenic variant was c.571G > A (p.Glu191Lys) in biallelic patients (allele frequency: 19/60) and c.1133A > T (p.Asp378Val) in monoallelic patients (allele frequency: 7/28). Median (min, max) Baseline PPi concentrations were significantly higher in patients with a biallelic vs monoallelic variant state (5.3 [2.2, 12.1] vs 4.3 [3.5, 7.4] μM; P = 0.0113), as were Baseline PLP concentrations (221.4 [62.4, 1590.0] vs 75.1 [28.8, 577.0] ng/mL; P = 0.0022). HPP-specific medical history was generally similar between biallelic and monoallelic patients in terms of incidence and type of manifestations; notable exceptions included fractures, which were more common among monoallelic patients, and delayed walking and bone deformities such as abnormally shaped chest and head and bowing of arms or legs, which were more common among biallelic patients. Data from the efficacy and safety study (n = 19) showed that median PPi and PLP concentrations were normalized over 5 years of treatment in patients with both variant states. Median % predicted distance walked on the 6-Minute Walk Test remained within the normal range for monoallelic patients over 4 years of treatment, and improved from below normal ( Conclusions Although patients with biallelic variants had significantly higher Baseline PPi and PLP levels than monoallelic variants, both groups generally showed similar pretreatment Baseline clinical characteristics. Treatment with asfotase alfa for up to 5 years normalized TNSALP substrate concentrations and improved functional outcomes, with no clear differences between biallelic and monoallelic variant states. This study suggests that patients with HPP have significant disease burden, regardless of ALPL variant state.

Background: Whether advances in identification and management of atrial fibrillation and atrial flutter (collectively, AF) have led to improved outcomes is unclear. We sought to study trends in clinical outcomes selected as quality indicators for nonvalvular AF in Canada. Methods: We identified hospitalized patients with a first diagnosis of nonvalvular AF between April 2006 and March 2015, in all of Canada except Quebec. We assessed trends in 1-year incidence of stroke/systemic embolism (SSE), major bleeding, and initial heart failure (HF) hospitalization. Results: The cohort included 466,476 patients. The median age was 77 years (interquartile range, 68-84 years), 46% were female, and 68% had a Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score > 3. Within 1 year of discharge, 3.5% were hospitalized for stroke or SSE, 1.6% for major bleeding, and 8.6% for new HF. Over the study period, the crude rate of SSE declined from 3.6% to 3.3% (P = 0.002), whereas the rates of hospitalization for new HF and for major bleeding did not significantly change. After adjustment for CHA2DS2-VASc score, the yearly rates of incident SSE (risk ratio, 0.99; 95% confidence interval [CI], 0.98-0.99; P = 0.002) and HF (risk ratio, 0.99; 95% CI, 0.99-1.00; P = 0.001) declined ≤ 1% absolute, whereas major bleeding remained unchanged (risk ratio, 1.00; 95% CI, 0.99-1.00; P = 0.28). Conclusions: Among hospitalized patients with nonvalvular AF in Canada, the rate of SSE and new HF decreased modestly over a 10-year period, with no significant change in major bleeding. Efforts to study process-based quality indicators, with increased focus on HF prevention, are needed. Résumé: Contexte: On ne sait pas si les avancées en matière de détection et de prise en charge de la fibrillation auriculaire et du flutter auriculaire (collectivement appelés « FA » ci-après) ont permis d’améliorer les résultats pour les patients. Nous avons donc étudié les tendances à l’égard de résultats cliniques particuliers pris comme indicateurs de qualité relatifs à la FA non valvulaire au Canada. Méthodologie: Nous avons recensé les patients hospitalisés au Canada (sauf au Québec) entre avril 2006 et mars 2015 en raison d’une FA non valvulaire nouvellement diagnostiquée. Nous avons évalué les tendances quant à la survenue d’un accident vasculaire cérébral ou d’une embolie systémique (AVC/ES), d’une hémorragie majeure et d’une première hospitalisation pour insuffisance cardiaque. Résultats: La cohorte comprenait 466 476 patients, dont l’âge médian était de 77 ans (intervalle interquartile : 68 à 84 ans); 46 % des patients étaient des femmes, et 68 % avaient un score CHA2DS2-VASc (Congestive Heart Failure [insuffisance cardiaque congestive], hypertension, âge [≥ 75 ans], diabète, Stroke/Transient Ischemic Attack [AVC/accident ischémique transitoire] – maladie vasculaire, âge [65-74 ans], sexe [femmes]) supérieur à 3. Dans l’année suivant la sortie de l’hôpital, 3,5 % des patients ont été hospitalisés en raison d’un AVC ou d’un AVC/ES, 1,6 %, en raison d’une hémorragie majeure et 8,6 %, en raison d’une nouvelle insuffisance cardiaque. Au cours de la période étudiée, le taux brut d’AVC/ES est passé de 3,6 % à 3,3 % (p = 0,002), tandis que les taux d’hospitalisation en raison d’une nouvelle insuffisance cardiaque ou d’une hémorragie majeure n’ont pas changé de manière significative. Après correction pour tenir compte du score CHA2DS2-VASc, les taux annuels de survenue d’un AVC/ES (rapport des risques de 0,99; intervalle de confiance [IC] à 95 % : de 0,98 à 0,99; p = 0,002) et d’une insuffisance cardiaque (rapport des risques de 0,99; IC à 95 % : de 0,99 à 1,00; p = 0,001) ont diminué de ≤ 1 % en valeur absolue, tandis que le taux de survenue d’une hémorragie majeure n’a pas changé (rapport des risques : 1,00; IC à 95 % : de 0,99 à 1,00; p = 0,28). Conclusions: Parmi les patients hospitalisés au Canada en raison d’une FA non valvulaire, les taux d’AVC/ES et de nouvelle insuffisance cardiaque ont affiché une réduction modeste sur une période de 10 ans, tandis que le taux d’hémorragie majeure n’a pas changé de manière significative. D’autres études évaluant les indicateurs de qualité fondés sur les procédés, notamment en matière de prévention de l’insuffisance cardiaque, s’imposent.

Kristin Martin-Cook,1 Lucy Palmer,1 Larry Thornton,1 A John Rush,2 Carol A Tamminga,1 Hicham M Ibrahim1 1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2National University of Singapore, Singapore; Department of Psychiatry, Duke University School of Medicine, Durham, NC, USA; Department of Psychiatry, Texas Tech Health Sciences Center, Midland, TX, USACorrespondence: Kristin Martin-CookDepartment of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75235, USATel +1-214-648-1983Fax +1-214-648-4947Email Kristin.Martin-Cook@UTSouthwestern.eduAbstract: Measurement-based care (MBC) involves the systematic use of standardized measurements to inform treatment decisions. MBC can enhance clinical decision-making and quality of care by prompting personalized changes in treatment based on measured patient outcomes. MBC can also promote more precise communications between patients and clinicians around individual patient care. While commonly employed in psychiatric clinical research, the use of MBC in everyday practice can be complicated by clinic operations and variability across patients. We implemented MBC in the UT Southwestern Psychiatry Multispecialty Outpatient Clinic during the expansion of our general psychiatry clinic and subspecialty targeted programs. This article describes the top 10 lessons we learned as we confronted practical obstacles around implementing the ideals of MBC into a pre-existing, busy psychiatric clinical practice and how doing so impacts care, provider engagement, patient engagement, and research opportunity.Keywords: measurement-based care, clinic operations, quality improvement, quality care, screening, outpatient

Objective:This systematic review and meta-analysis evaluated the effect of telehealth (TH) weight management interventions compared to usual care on anthropometric outcomes in children and adolesce...

Purpose: To describe the use of the internal mammary vein as an alternative access for central venous catheters. Methods: We performed a retrospective review of patients who underwent placement of central venous catheters via the internal mammary vein. Patient demographics, indication for venous access, technical success, catheter type, dwell time and indication for exchange or removal were recorded. Results: Placement of central venous catheters via the internal mammary vein was attempted in 11 patients including 8 children (4 males, mean age 5.7 years) and 3 adults. The most common indication was parenteral nutrition in patients with intestinal failure (7/11). Initial needle access of the vein was successful in all patients. Catheter placement was successful in 9 and unsuccessful in 2 patients due to occlusion of the superior vena cava. There were no immediate complications. A total of 20 catheters of various sizes (3–14.5 French) and lengths (8–23 cm) were either placed (n = 12) or exchanged (n = 8). The most common indications for catheter exchange were poor function and malposition (7/8). Four catheters were removed for infection and 4 were accidentally removed. The mean dwell time was 141 days (range 0–963 days) per catheter for a total of 2829 catheter days. The total mean dwell time per patient, including primarily placed and exchanged catheters, was 314 days (range 5–963 days). CONCLUSIONS: The internal mammary vein may provide a safe alternative route for patients who have lost their traditional access veins.

Atrial fibrillation (AF) is the most common arrhythmia in the world. Despite the increasing prevalence, there remains a limited understanding of how the pre-diagnosis symptom experience varies by gender. The purpose of this study was to retrospectively explore gender differences/similarities in the pre-diagnosis period of AF. Twenty-six adults (13 men and 13 women) were interviewed guided by the Symptom Experience in AF (SEAF). Data were analyzed using a two-step approach to thematic analysis. Women had greater challenges receiving a timely diagnosis, with 10 women (77%) experiencing symptoms ≥1 year prior to their diagnosis, in comparison to only three (23%) of the men. Women also reported more severe symptoms, less AF-related knowledge, viewed themselves as low risk for cardiovascular disease, and described how their comorbid conditions confused AF symptom evaluation. This study provides a foundational understanding of differences/similarities in the AF symptom experience by gender.

Background Associations of diet with dilated cardiomyopathy are under investigation. Objectives That cardiac assessment would show abnormalities in healthy dogs eating grain‐free (GF) diets or diets with Food and Drug Administration (FDA)‐listed ingredients of concern (peas, lentils, or potatoes) as top 10 ingredients (FDA‐PLP), but not in dogs eating grain‐inclusive (GI) diets or diets without FDA‐listed ingredients of concern (PLP) in the top 10 ingredients (NoFDA‐PLP). Animals One hundred eighty‐eight healthy Doberman Pinschers, Golden Retrievers, Miniature Schnauzers, and Whippets. Methods This study was an observational cross‐sectional study. Echocardiograms, cardiac biomarkers, and blood and plasma taurine concentrations were compared between dogs eating GF (n = 26) and GI (n = 162) diets, and between FDA‐PLP (n = 39) and NoFDA‐PLP (n = 149) diets, controlling for age and breed. Demographic characteristics, murmurs, genetic status, and ventricular premature complexes (VPCs) during examination were compared between dogs eating different diet types. Results No differences in echocardiographic variables, N‐terminal pro‐B‐type natriuretic peptide or whole blood taurine were noted between dogs eating different diet types. Dogs eating GF diets had higher median high‐sensitivity cardiac troponin I (hs‐cTnI) (GF 0.076 ng/mL [Interquartile range (IQR), 0.028‐0.156] vs. GI 0.048 [IQR, 0.0026‐0.080]; P

Using pre-treatment biomarkers to guide patients to the preferred antidepressant medication treatment could be a promising approach to enhance its current modest response and remission rates. This open-label prospective study assessed the feasibility of using such pre-treatment biomarkers, by using previously identified EEG features (paroxysmal activity; alpha peak frequency; frontal alpha asymmetry) to inform the clinician in selecting among three different antidepressants (ADs; escitalopram, sertraline, venlafaxine) as compared to Treatment As Usual (TAU). EEG data were obtained from 195 outpatients with major depressive disorder prior to eight weeks of AD treatment. Primary outcome measure was the percentage change between before and after treatment on the Beck Depression Inventory-II (BDI-II). We compared TAU and EEG-informed prescription through AN(C)OVAs. Recruitment started with patients receiving TAU to establish baseline effectiveness, after which we recruited patients receiving EEG-informed prescription. 108 patients received EEG-informed prescription and 87 patients received TAU. Clinicians and patients were satisfied with the protocol. Overall, 70 (65%) of the EEG-informed clinicians followed recommendations (compared to 52 (60%) following prescriptions in the TAU group), establishing feasibility. We here confirm that treatment allocation informed by EEG variables previously reported in correlational studies, was feasible.

Hamstrings muscle morphology is determinant of muscle function (i.e. strength). Among individuals with ACL reconstruction (ACLR), less cross-sectional area (CSA) and volume in the ACLR-limb are associated with muscle weakness, and may contribute to lower rates of return to preinjury activity level and an increased risk for long-term sequelae. To effectively treat muscular impairments, an accurate understanding of differences in hamstrings morphology following ACLR is needed. A systematic review and meta-analysis were undertaken to describe the morphology of the hamstring muscle complex after ACLR. We searched five databases for studies evaluating the difference between hamstrings size and architecture in individuals with ACLR. Two independent reviewers assessed each paper for inclusion and quality. Means and standard deviations were extracted from each included study to allow fixed-effect size meta-analysis calculations for comparison of results. Twenty-four studies were included for final review. Eight categories of morphological outcomes were identified, and studies were grouped accordingly: (1) volume, (2) cross-sectional area (CSA), (3) muscle length, (4) muscle thickness, (5) fascicle length, (6) pennation angle, (7) fiber area, and (8) fiber type. Meta-analysis demonstrated lower hamstrings volume in the ACLR-limb in both contralateral and control group comparisons, and lower CSA, length, and thickness in the ACLR-limb in contralateral comparisons. The semitendinosus and gracilis were most profoundly impacted. Limited moderate evidence demonstrated greater biceps femoris pennation angle in the ACLR-limb. Individuals with ACLR demonstrated large deficits in semitendinosus and gracilis muscle CSA and volume in the ACLR-limb compared contralaterally, with no differences observed in the biceps femoris or semimembranosus. Clinical implications regarding assessment and treatment of individuals with ACLR are discussed.

Nager syndrome epitomizes the acrofacial dysostoses, which are characterized by craniofacial and limb defects. The craniofacial defects include midfacial retrusion, downslanting palpebral fissures, prominent nasal bridge, and micrognathia. Limb malformations typically include hypoplasia or aplasia of radial elements including the thumb. Nager syndrome is caused by haploinsufficiency of SF3B4, encoding a spliceosomal protein called SAP49. Here, we report a patient with a loss of function variant in SF3B4 without acrofacial dysostosis or limb defects, whose reason for referral was developmental and growth delay. This patient is evidence of a broader phenotypic spectrum associated with SF3B4 variants than previously appreciated.

Background: The benefits of pimobendan in the treatment of congestive heart failure (CHF) in cats with hypertrophic cardiomyopathy (HCM) have not been evaluated prospectively. Hypothesis/objectives: To investigate the effects of pimobendan in cats with HCM and recent CHF and to identify possible endpoints for a pivotal study. We hypothesized that pimobendan would be well-tolerated and associated with improved outcome. Animals: Eighty-three cats with HCM and recently controlled CHF: 30 with and 53 without left ventricular outflow tract obstruction. Methods: Prospective randomized placebo-controlled double-blind multicenter nonpivotal field study. Cats received either pimobendan (0.30 mg/kg q12h, n = 43), placebo (n = 39), or no medication (n = 1) together with furosemide (

About half of pediatric blunt trauma patients undergo an abdominopelvic computed tomographic (CT) scan, while few of these require intervention for an intraabdominal injury. We evaluated the effectiveness of an evidence-based guideline for blunt abdominal trauma at a Level I pediatric trauma center.Pediatric blunt trauma patients (n = 998) age 0-15 years who presented from the injury scene were evaluated over a 10 year period. After five years, we implemented our guideline in which the decision for CT was standardized based on mental status, abdominal examination, and laboratory results (alanine aminotransferase, aspartate aminotransferase, hemoglobin, urinalysis).There were no differences in age, GCS, SIPA or ISS scores between the patients before or after guideline implementation. Nearly half of the patients (48.3%) underwent CT scan before guideline implementation compared to 36.7% after (p 0.0002). There was no difference in ISS (p = 0.44) between CT scanned patients in either group. No statistical differences were found in rate of intervention (p = 0.20), length of stay (p = 0.65), or readmission rate (0.2%) before versus after guideline implementation. There were no missed injuries.Implementation of an evidence-based clinical guideline for pediatric patients with blunt abdominal trauma decreases the rate of CT utilization while accurately identifying significant injuries.III.

Characterising the risk of the fire spread in informal settlements relies on the ability to understand compartment fires with boundary conditions that are significantly different to normal residential compartments. Informal settlement dwellings frequently have thermally thin and leaky boundaries. Due to the unique design of these compartments, detailed experimental studies were conducted to understand their fire dynamics. This paper presents the ability of FDS to model these under-ventilated steel sheeted fire tests. Four compartment fire tests were modelled with different wall boundary conditions, namely sealed walls (no leakage), non-sealed walls (leaky), leaky walls with cardboard lining, and highly insulated walls; with wood cribs as fuel and ISO-9705 room dimensions. FDS managed to capture the main fire dynamics and trends both qualitatively and quantitatively. However, using a cell size of 6 cm, the ability of FDS to accurately model the combustion at locations with high turbulent flows (using the infinitely fast chemistry mixing controlled combustion model), and the effect of leakage, was relatively poor and both factors should be further studied with finer LES filter width. Using the validated FDS models, new flashover criteria for thermally thin compartments were defined as a combination of critical hot gas layer and wall temperatures. Additionally, a parametric study was conducted to propose an empirical correlation to estimate the onset Heat Release Rate required for flashover, as current knowledge fails to account properly for large scale compartments with thermally thin boundaries. The empirical correlation is demonstrated to have an accuracy of ≈ ± 10% compared with the FDS models.

Low reward responsiveness (RR) is associated with poor psychological well-being, psychiatric disorder risk, and psychotropic treatment resistance. Functional MRI studies have reported decreased activity within the brain's reward network in individuals with RR deficits, however the neurochemistry underlying network hypofunction in those with low RR remains unclear. This study employed ultra-high field glutamate chemical exchange saturation transfer (GluCEST) imaging to investigate the hypothesis that glutamatergic deficits within the reward network contribute to low RR. GluCEST images were acquired at 7.0 T from 45 participants (ages 15-29, 30 females) including 15 healthy individuals, 11 with depression, and 19 with psychosis spectrum symptoms. The GluCEST contrast, a measure sensitive to local glutamate concentration, was quantified in a meta-analytically defined reward network comprised of cortical, subcortical, and brainstem regions. Associations between brain GluCEST contrast and Behavioral Activation System Scale RR scores were assessed using multiple linear regressions. Analyses revealed that reward network GluCEST contrast was positively and selectively associated with RR, but not other clinical features. Follow-up investigations identified that this association was driven by the subcortical reward network and network areas that encode the salience of valenced stimuli. We observed no association between RR and the GluCEST contrast within non-reward cortex. This study thus provides new evidence that reward network glutamate levels contribute to individual differences in RR. Decreased reward network excitatory neurotransmission or metabolism may be mechanisms driving reward network hypofunction and RR deficits. These findings provide a framework for understanding the efficacy of glutamate-modulating psychotropics such as ketamine for treating anhedonia.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone–bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone–bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone–bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone–bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone–bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P

Morbidity and mortality from opioid use disorders (OUD) and other substance use disorders (SUD) is a major public health crisis, yet there are few medications to treat them. There is an urgency to accelerate SUD medication development. We present an integrated drug repurposing strategy that combines computational prediction, clinical corroboration using electronic health records (EHRs) of over 72.9 million patients and mechanisms of action analysis. Among top-ranked repurposed candidate drugs, tramadol, olanzapine, mirtazapine, bupropion, and atomoxetine were associated with increased odds of OUD remission (adjusted odds ratio: 1.51 [1.38–1.66], 1.90 [1.66–2.18], 1.38 [1.31–1.46], 1.37 [1.29–1.46], 1.48 [1.25–1.76], p value < 0.001, respectively). Genetic and functional analyses showed these five candidate drugs directly target multiple OUD-associated genes including BDNF, CYP2D6, OPRD1, OPRK1, OPRM1, HTR1B, POMC, SLC6A4 and OUD-associated pathways, including opioid signaling, G-protein activation, serotonin receptors, and GPCR signaling. In summary, we developed an integrated drug repurposing approach and identified five repurposed candidate drugs that might be of value for treating OUD patients, including those suffering from comorbid conditions.

Approximately one billion people across the globe are living in informal settlements with a large potential fire risk. Due to the high dwelling density, a single informal settlement dwelling fire may result in a very serious fire disaster leaving thousands of people homeless. In this work, a simple physics-based theoretical model was employed to assess the critical fire separation distance between dwellings. The heat flux and ejected flame length were obtained from a full-scale dwelling tests with ISO 9705 dimension (3.6 m × 2.4 m × 2.4 m) to estimate the radiation decay coefficient of the radiation heat flux away from the open door. The ignition potential of combustible materials in adjacent dwellings are analyzed based on the critical heat flux from cone calorimeter tests. To verify the critical distance in real informal settlement fire, a parallel method using aerial photography within geographic information systems (GIS), was employed to determine the critical separation distances in four real informal settlement fires of 2014–2015 in Masiphumelele, Cape Town, South Africa. The fire-spread distances were obtained as well through the real fires. The probabilistic analysis was conducted by Weibull distribution and logistic regression, and the corresponding separation distances were given with different fire spread probabilities. From the experiments with the assumption of no interventions and open doors and windows, it was established that the heat flux would decay from around 36 kW/m2 within a distance of 1.0 m to a value smaller than 5 kW/m2 at a distance of 4.0 m. Both experiments and GIS results agree well and suggest the ignition probabilities at distances of 1.0 m, 2.0 m and 3.0 m are 97%, 52% and 5% respectively. While wind is not explicitly considered in the work, it is implicit within the GIS analyses of fire spread risk, therefore, it is reasonable to say that there is a relatively low fire spread risk at distances greater than 3 m. The distance of 1.0 m in GIS is verified to well and conservatively predict the fire spread risk in the informal settlements.

Differences in the excitability of motor generating neural pathways are reported following anterior cruciate ligament reconstruction (ACLR) that is associated with quadriceps dysfunction and theorized to prevent the full recovery of muscle function. The aims of this systematic review and meta-analysis were to compare quadriceps neural excitability between the involved ACLR limb, the uninvolved limb, and uninjured controls, and to determine at what time intervals these differences are present after surgery. We conducted a search of PubMed, SPORTDiscus, Embase, and Web of Science, and extracted measures assessing difference of quadriceps spinal-reflexive, corticospinal, and intracortical excitability from studies that compared (1) involved limb to the uninvolved limb, (2) involved limb to a control limb, or (3) uninvolved limb to a control limb. We stratified time at 24 months, since this represents a period of heightened risk for reinjury. A modified Downs and Black checklist and Egger’s test were used to determine the methodological quality of individual studies and risk of bias between studies. Fourteen studies comprising 611 participants (371 individuals with a history of ACLR; median time from surgery: 31.5 months; range 0.5–221.1 months) were included in the review. Overall, the involved (g = 0.60, 95% CI [0.24, 0.96]) and uninvolved (g = 0.49, 95% CI [0.00, 0.98]) limbs exhibited greater motor threshold (MT) in comparison to uninjured controls. Motor-evoked potential (MEP) amplitudes were greater in the uninvolved limb in comparison to uninjured controls (g = 0.31, 95% CI [0.03, 0.59]). Lesser intracortical inhibition was exhibited in the uninvolved limb compared to uninjured controls (g = 0.54, 95% CI [0.14, 0.93]). When stratified by time from surgery, MEP amplitudes were greater in the uninvolved limb compared to uninjured controls (g = 0.33, 95% CI [0.03, 0.63]) within the first 24 months after surgery. When evaluated more than 24 months after surgery, the involved limb exhibited greater Hoffmann reflex (H-reflex) compared to uninjured controls (g = 0.38, 95% CI [0.00, 0.77]). MT were greater in the involved limb (g = 0.93, 95% CI [− 0.01, 1.88]) and uninvolved limb (g = 0.57, 95% CI [0.13, 1.02]) compared to uninjured controls. MEP amplitudes in the involved limb were lesser compared to uninjured controls when evaluated more than 24 months after ACLR (g = -1.11, 95% CI [− 2.03, − 0.20]). The available evidence supports that there are neural excitability differences within the corticospinal tract in individuals with ACLR when compared to uninjured controls. Future research should focus further on longitudinal assessments of neural excitability prior to and following ACLR. Identifying interventions aimed to facilitate corticospinal excitability after ACLR appears to be warranted to improve quadriceps function. Registered through PROSPERO CRD42020158714.

Background Personal health records (PHR) provide opportunities for improved patient engagement, collection of patient-generated data, and overcome health-system inefficiencies. While PHR use is increasing, uptake in rural populations is lower than in urban areas. Objectives The study aimed to identify priorities for PHR functionality and gain insights into meaning, value, and use of patient-generated data for rural primary care providers. Methods We performed PHR preimplementation focus groups with rural providers and their health care teams from five primary care clinics in a sparsely populated mountainous region of British Columbia, Canada to obtain their understanding of PHR functionality, needs, and perceived challenges. Results Eight general practitioners (GP), five medical office assistants, two nurse practitioners (NP), and two registered nurses (14 females and 3 males) participated in focus groups held at their respective clinics. Providers (GPs, NPs, and RNs) had been practicing for a median of 9.5 (range = 1–38) years and had used an electronic medical record for 7.0 (1–20) years. Participants expressed interest in incorporating functionality around two-way communication and appointment scheduling, previsit data gathering, patient and provider data sharing, virtual care including visits using videoconferencing tools, and postvisit sharing of educational materials. Three further themes emerged from the focus groups: (1) the context in which the providers' practice matters, (2) the need for providing patients and providers with choice (e.g., which data to share, who gets to initiate/respond in communications, and processes around virtual care visits), and (3) perceived risks of system use (e.g., increased complexity for older patients and workload barriers for the health care team). Conclusion Rural primary care teams perceived PHR opportunities for increased patient engagement and access to patient-generated data, while worries about changes in workflow were the biggest perceived risk. Recommendations for PHR adoption in a rural primary health network include setting provider-patient expectations about response times, ability to share notes selectively, and automatically augmented note-taking from virtual-care visits.

Fang Liu-Walsh,1 Neena K Tierney,1 James Hauschild,2 Allison K Rush,1 John Masucci,3 Gregory C Leo,3 Kimberly A Capone1 1Johnson & Johnson Consumer Inc., Skillman, NJ, USA; 2Johnson & Johnson Microbiological Quality & Sterility Assurance, Johnson & Johnson Inc., Raritan, NJ, USA; 3Janssen R&D Companies of Johnson & Johnson, Springhouse, PA, USACorrespondence: Fang Liu-Walsh; Kimberly A CaponeJohnson & Johnson Consumer Inc., 199 Grandview Road, Skillman, NJ 08558-9418, USAEmail fliuwals@ITS.JNJ.com; KCapone@its.jnj.comBackground: Multiple skin conditions have been associated with alterations in the diversity and composition of the skin microbiome, including dry skin and atopic dermatitis. In these conditions, a number of commensal skin bacteria have been implicated in supporting a healthy skin barrier, including Staphylococcus epidermidis. Recent clinical studies in patients with mild-to-moderate atopic dermatitis and dry/itchy skin have shown significantly improved skin barrier function and microbial diversity upon treatment with moisturizers containing 1% colloidal oat. We hypothesized that direct use of colloidal oat by skin microbes contributes to these therapeutic benefits.Methods: Skin bacterial growth was assessed using the BacT/ALERT system. Staphylococcus aureus and S. epidermidis growth rates and metabolism were compared in an in vitro competition assay. The effect of a 1% colloidal oat–containing moisturizer on lactic acid content of the stratum corneum was clinically assessed in subjects with moderate-to-severe dry skin. S. epidermidis gene expression was evaluated by next-generation mRNA sequencing. Short-chain fatty acids were quantified in bacterial culture supernatants.Results: In vitro, colloidal oat increased the growth rate of S. epidermidis vs S. aureus, as well as the metabolism of S. epidermidis. Colloidal oat also significantly increased lactic acid concentrations in supernatants of both strains and decreased pH, consistent with clinical findings that 6-week use of a 1% colloidal oat–containing lotion significantly increased lactic acid on dry skin. Further analyses suggest that colloidal oat alters the gene expression profile of S. epidermidis.Conclusion: Colloidal oat directly affects the growth, metabolism, lactic acid production, and gene expression of skin commensal bacteria, as shown via in vitro studies. The increased production of lactic acid reflects clinical observations with colloidal oat–containing skin moisturizers. Our findings suggest a new mechanism for colloidal oat as a skin prebiotic, which may contribute to improvements in skin and microbiome diversity in various skin conditions, including dry/itchy skin and atopic dermatitis.Keywords: atopic dermatitis, dry skin, colloidal oat, skin barrier function, skin microbiome, skin moisturizer, S. epidermidis

Custom 3D printed total talus implants have been used successfully as a functional alternative to arthrodesis or amputation in cases of severe talar destruction or loss. However, the ideal material and construct still remains to be elucidated. Current models have been made from aluminum ceramic, cobalt chrome, stainless steel, titanium, or metal combinations. The implants may be constrained (subtalar arthrodesis) or unconstrained (press fit within mortise). They may also be combined with a tibial prosthesis or used in isolation. The majority of currently published case studies examine unconstrained and isolated implants. This case study presents satisfactory 1-y outcomes in 3 cobalt chrome constrained total talar implants used in combination with a tibial prosthesis, and a literature review of total talus replacements.

Heterogeneity in the clinical presentation of major depressive disorder and response to antidepressants limits clinicians’ ability to accurately predict a specific patient’s eventual response to therapy. Validated depressive symptom profiles may be an important tool for identifying poor outcomes early in the course of treatment. To derive these symptom profiles, we first examined data from 947 depressed subjects treated with selective serotonin reuptake inhibitors (SSRIs) to delineate the heterogeneity of antidepressant response using probabilistic graphical models (PGMs). We then used unsupervised machine learning to identify specific depressive symptoms and thresholds of improvement that were predictive of antidepressant response by 4 weeks for a patient to achieve remission, response, or nonresponse by 8 weeks. Four depressive symptoms (depressed mood, guilt feelings and delusion, work and activities and psychic anxiety) and specific thresholds of change in each at 4 weeks predicted eventual outcome at 8 weeks to SSRI therapy with an average accuracy of 77% (p = 5.5E-08). The same four symptoms and prognostic thresholds derived from patients treated with SSRIs correctly predicted outcomes in 72% (p = 1.25E-05) of 1996 patients treated with other antidepressants in both inpatient and outpatient settings in independent publicly-available datasets. These predictive accuracies were higher than the accuracy of 53% for predicting SSRI response achieved using approaches that (i) incorporated only baseline clinical and sociodemographic factors, or (ii) used 4-week nonresponse status to predict likely outcomes at 8 weeks. The present findings suggest that PGMs providing interpretable predictions have the potential to enhance clinical treatment of depression and reduce the time burden associated with trials of ineffective antidepressants. Prospective trials examining this approach are forthcoming.

The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway upregulates key cellular defenses. Clinical trials are utilizing pharmacologic Nrf2 inducers such as bardoxolone methyl to treat chronic kidney disease, but Nrf2 activation has been linked to a paradoxical increase in proteinuria. To understand this effect, we examined genetically engineered mice with elevated Nrf2 signaling due to reduced expression of the Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1). These Keap1FA/FA mice lacked baseline proteinuria but exhibited increased proteinuria in experimental models evoked by adriamycin, angiotensin II, or protein overload. After injury, Keap1FA/FA mice had increased glomerulosclerosis, nephrin disruption and shedding, podocyte injury, foot process effacement, and interstitial fibrosis. Keap1FA/FA mice also had higher daytime blood pressures and lower heart rates measured by radiotelemetry. Conversely, Nrf2 knockout mice were protected from proteinuria. We also examined the pharmacologic Nrf2 inducer CDDO-Im. Compared to angiotensin II alone, the combination of angiotensin II and CDDO-Im significantly increased proteinuria, a phenomenon not observed in Nrf2 knockout mice. This effect was not accompanied by additional increases in blood pressure. Finally, Nrf2 was found to be upregulated in the glomeruli of patients with focal segmental glomerulosclerosis, diabetic nephropathy, fibrillary glomerulonephritis, and membranous nephropathy. Thus, our studies demonstrate that Nrf2 induction in mice may exacerbate proteinuria in chronic kidney disease.

Pharmacists are increasingly expected to communicate skillfully, yet few Doctor of Pharmacy (PharmD) curricula include theoretically-derived or evidence-based communication training. The 12 Fundamentals of Highly Effective Communicators is a pedagogical tool that we developed to teach principles of communication to two consecutive cohorts of PharmD students in their second year (P2). Students were asked to reflect on which of the 12 Fundamentals they found most helpful in their pharmacy training and practice. The most frequently selected Fundamental was “There is no ‘one size fits all’ message that will work in EVERY situation.” Students provided specific examples of how they perceived that these Fundamentals could help them have effective and appropriate interactions with patients and colleagues.

PURPOSE To evaluate the outcomes of delay in care secondary to the coronavirus pandemic in patients requiring intravitreal anti-vascular endothelial growth factor therapy. METHODS A retrospective review was performed, and subjects were divided into two groups: 1) a study group of patients who experienced a treatment delay of ≥6 weeks from the intended follow-up during the coronavirus pandemic and resumed treatment with ≥2 anti-vascular endothelial growth factor injections over 6 months following treatment delay, and 2) a control group of patients who received regular care throughout the coronavirus pandemic. RESULTS Totally, 234 subjects were analyzed. The mean treatment delay from the intended follow-up in the study group was 11.8 (±4.0) weeks. Visual acuity and central macular thickness worsened from baseline to 6 months after resuming anti-vascular endothelial growth factor therapy in the study group (P < 0.0001 and P = 0.001, respectively). Visual acuity and central macular thickness were better in the control group compared with the study group at the end of the 6-month study period (P < 0.0001 for both). CONCLUSION Treatment delay in subjects undergoing anti-vascular endothelial growth factor therapy for retina disease during the coronavirus pandemic had worse visual and anatomical outcomes despite reinitiating treatment over 6 months compared with a control group, suggesting irreversibility and permanence of outcomes.