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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).

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.

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.

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.

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.

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

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.

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.

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.

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.com View the original paper by Dr Rush and colleagues This is in response to the Letter to the Editor

Purpose The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment-resistant, chronic mood disorder, i.e., difficult-to-treat depression (DTD). This review distills some of the implications of this research for future therapeutic trials in this population. Methods A narrative review is provided on VNS in DTD. Protocols for a new, large, sham-controlled trial and a global, longitudinal observational study are described. Results Following encouraging results in open studies, a randomized, masked, sham-controlled trial of VNS for DTD failed to demonstrate an effect on the primary outcome. The negative results may have been partly due to inadequate treatment duration (10 weeks). In long-term observational studies, adjunctive VNS, combined with treatment-as-usual (VNS+TAU), was administered to more than 1100 DTD patients and compared with TAU alone in more than 400 patients. VNS+TAU had superior antidepressant effects, but maximal symptom reduction was often observed after 12 months or longer of stimulation. VNS+TAU had also marked superiority in durability of benefit. Sustained levels of symptom reduction below the traditional cutoff for response (i.e. < 50%) were associated with improved quality of life. Limitations Most comparisons of VNS+TAU and TAU were derived from observational, open label studies. Conclusion The history of VNS in DTD has implications for interventional studies in this population, and perhaps other chronic medical disorders. The slow onset of benefit with VNS necessitates considerably longer controlled observation periods to establish efficacy. Durability of benefit should be routinely incorporated in efficacy assessment. New outcome metrics are needed to both categorically identify clinically meaningful benefit and to integrate information on symptom burden over time.

Cardiac hemangiosarcoma, especially primary, is infrequently reported in the horse and remains a diagnostic challenge because of vague clinical signs and difficulty to reach an antemortem diagnosis. A 17-year-old American Quarter Horse gelding was presented with a history of tongue swelling and secondary aspiration pneumonia. Initial assessment indicated dehydration, and thoracic ultrasound revealed an abnormal structure within the myocardium alongside the previously suspected aspiration pneumonia. A subsequent, complete echocardiogram identified a large, heterogeneous, ill-defined mass invading and replacing the normal myocardium of the right ventricular free wall. Because of lack of improvement the horse was euthanized, and postmortem examination confirmed primary cardiac hemangiosarcoma with no further masses identified in other organs. This case is an unusual presentation of primary cardiac hemangiosarcoma for which echocardiography played a significant role in identifying a cardiac mass.

Background The United States Food and Drug Administration is investigating possible diet‐associated dilated cardiomyopathy (DCM) in dogs and cats. Objectives To retrospectively review DCM cases for signalment, diet information, echocardiographic changes, and survival. Animals Client‐owned dogs (n = 71). Methods Medical records of dogs diagnosed with DCM between January 1, 2014 and September 30, 2018 were reviewed. Dogs were grouped into “traditional” or “nontraditional” diet categories and whether or not diet was changed after diagnosis. Results For dogs eating nontraditional diets, those that had their diets changed had a larger percentage decrease in normalized systolic left ventricular internal dimension (P = .03) and left atrial:aorta ratio (P

Context: Altered quadriceps activation is common following anterior cruciate ligament reconstruction (ACLR), and can persist for years after surgery. These neural deficits are due, in part, to chronic central nervous system alterations. Transcranial direct current stimulation (tDCS) is a noninvasive modality, that is, believed to immediately increase motor neuron activity by stimulating the primary motor cortex, making it a promising modality to use improve outcomes in the ACLR population. Objective: To determine if a single treatment of tDCS would result in increased quadriceps activity and decreased levels of self-reported pain and dysfunction during exercise. Design: Randomized crossover design. Setting: Controlled laboratory. Patients: Ten participants with a history of ACLR (5 males/5 females, 22.9 [4.23] y, 176.57 [12.01] cm, 80.87 [16.86] kg, 68.1 [39.37] mo since ACLR). Interventions: Active tDCS and Sham tDCS. Main Outcome Measures: Percentage of maximum electromyographic data of vastus medialis and lateralis, voluntary isometric strength, percentage of voluntary activation, and self-reported pain and symptom scores were measured. The 2 × 2 repeated-measures analysis of variance by limb were performed to explain the differences between time points (pre and post) and condition (tDCS and sham). Results: There was a significant time main effect for quadriceps percentage of maximum electromyographic of vastus medialis (F9,1 = 11.931, P = .01) and vastus lateralis (F9,1 = 9.132, P = .01), isometric strength (F9,1 = 5.343, P = .046), and subjective scores for pain (F9,1 = 15.499, P = .04) and symptoms (F9,1 = 15.499, P = .04). Quadriceps percentage of maximum electromyographic, isometric strength, and voluntary activation showed an immediate decline from pre to post regardless of tDCS condition. Subjective scores improved slightly after each condition. Conclusions: One session of active tDCS did not have an immediate effect on quadriceps activity and subjective scores of pain and symptoms. To determine if tDCS is a valid modality for this patient population, a larger scale investigation with multiple treatments of active tDCS is warranted.

Improving long‐term kidney transplant outcomes requires novel treatment strategies, including delayed calcineurin inhibitor (CNI) substitution, tested using informative trial designs. An alternative approach to the usual superiority‐based trial is a noninferiority trial design that tests whether an investigational agent is not unacceptably worse than standard of care. An informative noninferiority design, with biopsy‐proven acute rejection (BPAR) as the endpoint, requires determination of a prespecified, evidence‐based noninferiority margin for BPAR. No such information is available for delayed CNI substitution in kidney transplantation. Herein we analyzed data from recent kidney transplant trials of CNI withdrawal and “real world” CNI‐ based standard of care, containing subjects with well‐documented evidence of immune quiescence at 6 months posttransplant—ideal candidates for delayed CNI substitution. Our analysis indicates an evidence‐based noninferiority margin of 13.8% for the United States Food and Drug Administration's composite definition of BPAR between 6 and 24 months posttransplant. Sample size estimation determined that ~225 randomized subjects would be required to evaluate noninferiority for this primary clinical efficacy endpoint, and superiority for a renal function safety endpoint. Our findings provide the basis for future delayed CNI substitution noninferiority trials, thereby increasing the likelihood they will provide clinically implementable results and achieve regulatory approval., This meta‐analysis defines a noninferiority margin to use in the design of a phase II/III delayed calcineurin inhibitor substitution trial in kidney transplantation.

OBJECTIVE In this study, we took advantage of a natural experiment that occurred within a substance use disorders (SUD) treatment setting which first saw the implementation of an evidence-based practice (EBP) for tobacco cessation, followed by the implementation of a tobacco-free policy (TFP) that included a campus-wide tobacco ban. We sought to examine how implementation of the EBP and TFP was associated with substances use outcomes, in addition to tobacco use, up to 3-months posttreatment. METHODS Data were collected from patients in a substance use disorders treatment program at baseline, discharge, 1-, and 3-months posttreatment. Using a quasi-experimental design and generalized estimating equations, we modelled how patients' (N = 480) exposure to one of 3 interventions (1: treatment as usual [TAU], 2: EBP, and 3: EBP + TFP) was associated with overall abstinence from tobacco, alcohol, and other substances over time. Measures of tobacco use frequency, amount, and quit attempts were also modelled among a sub-sample of participants who self-reported using tobacco before treatment. RESULT Exposure to the EBP + TFP was associated with increased tobacco abstinence (odds ratio [OR] = 1.93, 95% confidence interval [CI] [1.29, 2.90]) over time, including decreases in tobacco use frequency (OR = 0.78, 95% CI [0.68, 0.89]) and amount (OR = 0.80, 95% CI [0.67, 0.96]), and increased in likelihood of making a quit attempt (OR = 1.75, 95% CI [1.10, 2.80]) compared to TAU. Exposure was not associated with alcohol and/or other substance use. CONCLUSIONS Comprehensive tobacco interventions that include EBP + TFP can promote tobacco cessation and reduced tobacco use following inpatient SUD treatment, without adversely affecting the use of other substances.

BackgroundAtrial fibrillation is a complex condition associated with a broad spectrum of symptoms, coupled with variability in the frequency, duration and severity of symptoms. Early treatment seeking is important to reduce the risk of stroke, heart failure and dementia. Despite the increasing prevalence, there remains a limited understanding of the symptom experience prior to an atrial fibrillation diagnosis, and how these experiences influence treatment-related decisions and time frames.AimsThis qualitative study aimed to explore the symptom experiences of patients receiving an early diagnosis of less than 48 hours and a late diagnosis of 48 hours or more after symptom awareness.MethodsTwenty-six adults were interviewed guided by the symptom experience model. The symptom checklist was used to probe patient’s symptoms further. Data were analysed using a two-step approach to thematic analysis utilising concepts from the symptom experience model.ResultsThe two groups differed in their perception, evaluation and response to symptoms. The early diagnosis group (n = 6) experienced traumatic, severe and persistent symptoms, evoking concern and urgent treatment seeking. Conversely, the late diagnosis group (n = 20) reported more vague, paroxysmal symptoms that were readily ignored, self-theorised as non-illness related, and engaged in non-treatment strategies. Healthy self-perceptions, past experiences, atrial fibrillation knowledge and healthcare provider interactions influenced early or late treatment seeking.ConclusionFor many, the atrial fibrillation pre-diagnosis was a tumultuous period, requiring prolonged periods to recognise symptoms and formulate treatment-seeking responses. This study may promote future research and strategies aimed at facilitating the early identification and response to symptoms among atrial fibrillation patients.

BACKGROUND Racial and ethnic disparities are a barrier in delivery of healthcare across the USA. Care for minority patients tends to be clustered into a small number of providers at minority hospitals, which has been associated with worse clinical outcomes in several conditions. However, the outcomes of treatment in patients with end-stage liver disease (ESLD) at predominately minority hospitals are unknown. We investigated the burden of the problem. METHODS We utilized the nationwide in-patient sample (NIS) to conduct a retrospective nationwide cohort analysis. All patients >18 years of age admitted with ESLD were included in the analysis. A multivariate logistic regression model was used to study the mortality rate among patients with ESLD treated at minority hospitals compared to nonminority hospitals. RESULTS A total of 53 281 467 hospitalizations from the 2008 to 2014 NIS were analyzed. There were 163 470 patients with ESLD that met inclusion criteria. In-hospital mortality rates for all races were 8.0 and 8.1% in black and Hispanic minority hospitals, respectively, compared to 7.3% in nonminority hospitals (P

Background Since 2004, Sport Waikato has delivered Project Energize, a through-school nutrition and physical activity program to primary schools in the Waikato. As part of the program’s continued assessment and quality control, the programme was evaluated in 2011 and 2015. This paper’s aim was to compare the cardiorespiratory fitness (time to run 550 m (T550)) levels of children participating in Project Energize in 2011 and 2015. Methods In the 2011 evaluation of Project Energize, gender specific- T550-for-age Z scores (T550AZ) were derived from the T550 of 4832 Waikato children (2527 girls; 2305 boys; 36% Māori) aged between 6 and 12 years. In 2015, T550 was measured for 4798 (2361 girls; 2437 boys; 32% Māori) children, representative of age, gender and school socioeconomic status (SES). The T550AZ for every child in the 2015 study and 2011 evaluation were derived and differences in T550 between 2015 and 2011 by gender, SES and age were determined using independent t-tests. Multiple regression analysis predicted T550 Z score and run time, using year of measurement, gender, ethnicity, age and school SES. Results With and without adjustment, children in 2015 ran 550 m faster than in 2011 (adjusted Z score 0.06, time 11 s). Specifically, girls ran at a similar speed in 2015 as 2011 but boys were faster than in 2011 (Z score comparison P Conclusions The findings from this study support the continuation of the delivery of Project Energize in the Waikato region of New Zealand, as cardiorespiratory fitness scores in 2015, compared to 2011, were improved, particularly for lower SES schools and for Māori children. Ethnically diverse populations, schools with higher deprivation and girls, continue to warrant further attention to help achieve equity.

Background Patients with a history of opioid use disorder (OUD) tend to have more complications, higher readmission rates, and increased costs following orthopaedic procedures. This study evaluated patients undergoing hallux valgus correction for their odds of increased (1) readmission rates, (2) emergency room (ER) visits, and (3) costs. Methods Patients undergoing hallux valgus corrections with OUD history were identified using a national Medicare administrative claims database of approximately 24 million orthopaedic surgery patients. OUD patients were matched to non–opioid use disorder (NUD) patients in a 1:4 ratio by age, sex, Elixhauser-Comorbidity Index (ECI), diabetes mellitus, hyperlipidemia, hypertension, and tobacco use. The query yielded 6318 patients (OUD = 1276; NUD = 5042) who underwent a hallux valgus correction. Primary outcomes analyzed included odds of 90-day readmission rates, 30-day ER visits, and 90-day episode-of-care costs. Demographics, odds ratios (ORs), ECI, and cost were assessed as appropriate using a Pearson χ2 test, logistic regression, and a t test. A P value Results There were no significant differences in demographics between OUD and NUD patients. OUD patients had higher incidence and odds of 90-day readmission (9.56% vs 6.04%; OR = 1.55; P < .001) and 30-day ER visits (0.86% vs 0.35%; OR = 2.42; P = .021) and incurred greater 90-day episode-of-care costs ($7208.28 vs $6134.75; P < .001) compared with NUD patient controls. Conclusion The study demonstrates the possible influence of OUD on higher odds of readmission, ER visits, and costs following a hallux valgus correction. Levels of Evidence Level III: Retrospective cohort study

PURPOSE To evaluate outcome data of patients undergoing DeJour sulcus-deepening trochleoplasty with medial patellofemoral ligament reconstruction (MPFLR) for high-grade trochlear dysplasia at a single institution in the United States. METHODS A total of 67 patients (76 knees) with severe trochlear dysplasia and recurrent patellar instability were prospectively enrolled and underwent DeJour sulcus-deepening trochleoplasty with MPFLR from 2011 to 2019. Inclusion criteria included recurrent lateral patellar instability following failure of conservative treatment with radiographic evidence of severe trochlear dysplasia (DeJour types B or D). Patients with less than 2-year follow-up were excluded. Radiographic analysis, physical examination, clinical follow-up, patient demographics, and patient-reported outcome measures were obtained for all patients at each visit. RESULTS Forty patients (44 knees) had complete 2-year or longer follow-up and were included. The majority of patients were female (81.8%) with a mean age of 19.2 years (standard deviation [SD] 6.7; range 13.2-47.0). Follow-up ranged from 2.0 years to 6.8 years (mean 3.6 years, SD 1.35). In total, 45.5% had failed previous surgery for patellar instability. Eight knees developed arthrofibrosis and the overall reoperation rate was 27.3%. No patients had fixation failure and no further surgery was required for instability. The mean preoperative International Knee Documentation Committee score of 50.8 improved to 79.1 (P < .001), and the mean preoperative Kujala score of 56.4 improved to 86.5 (P < .001). Patients reported high satisfaction rates (mean 9.1 of 10). When applicable, 100% of patients returned to work, whereas 84.8% returned to sport. There was no significant radiographic progression of patellofemoral arthritis at a mean of 2.4 years after surgery (SD 1.7). CONCLUSIONS DeJour sulcus-deepening trochleoplasty combined with MPFLR and used with tibial tubercle osteotomy and lateral release is a reliable and effective treatment for recurrent patellar instability due to severe trochlear dysplasia, even in this group with many revisions of previous procedures. LEVEL OF EVIDENCE IV, case series.

Acute kidney injury (AKI) is a risk factor for the development of chronic kidney disease (CKD). One mechanism for this phenomenon is renal microvascular rarefaction and subsequent chronic impairment in perfusion. However, diagnostic tools to monitor the renal microvasculature in a noninvasive and quantitative manner are still lacking. Ultrasound super-resolution imaging is an emerging technology that can identify microvessels with unprecedented resolution. Here, we applied this imaging technique to identify microvessels in the unilateral ischemia-reperfusion injury mouse model of AKI-to-CKD progression in vivo. Kidneys from 21 and 42 day post- ischemia-reperfusion injury, the contralateral uninjured kidneys, and kidneys from sham-operated mice were examined by ultrasound super-resolution and histology. Renal microvessels were successfully identified by this imaging modality with a resolution down to 32 μm. Renal fibrosis was observed in all kidneys with ischemia-reperfusion injury and was associated with a significant reduction in kidney size, cortical thickness, relative blood volume, and microvascular density as assessed by this imaging. Tortuosity of the cortical microvasculature was also significantly increased at 42 days compared to sham. These vessel density measurements correlated significantly with CD31 immunohistochemistry (R(2)=0.77). Thus, ultrasound super-resolution imaging provides unprecedented resolution and is capable of noninvasive quantification of renal vasculature changes associated with AKI-to-CKD progression in mice. Hence, this technique could be a promising diagnostic tool for monitoring progressive kidney disease.

BACKGROUND AND AIM: The impact of household income, a surrogate of socioeconomic status, on hospital readmission rates for patients with decompensated cirrhosis has not been well characterized. METHODS: The Nationwide Readmission Database from 2012 to 2014 was used to study the association of lower median household income on 30-, 90-, and 180-day hospital readmission rates for patients with decompensated cirrhosis. RESULTS: From the 42 679 001 hospital admissions contained in the sample, there were 82 598 patients with decompensated cirrhosis who survived a hospital admission in the first 6 months of the year. During a uniform 6-month follow-up period, 25 914 (31.4%), 39 928 (48.3%), and 47 496 (57.5%) patients were readmitted at 30, 90, and 180 days, respectively. After controlling for demographic and clinical confounders, patients residing in the three lowest income quartiles were significantly more likely to be readmitted at 30 days than those in the fourth quartile (first quartile, odds ratio [OR] 1.32 [95% confidence interval, CI, 1.17–1.47, P < 0.01]; second quartile, OR 1.25 [95% CI 1.13–1.38, P < 0.01]; and third quartile, OR 1.08 [95% CI 0.97–1.20, P = 0.07]). The association between lower socioeconomic status and the higher risk of readmissions persisted at 90 days (first quartile, OR 1.21 [95% CI 1.14–1.30, P < 0.01]) and 180 days (first quartile, OR 1.32 [95% CI 1.20–1.44, P < 0.01]). CONCLUSION: Patients with decompensated cirrhosis residing in the lowest income quartile had a 32% higher odds of hospital readmissions at 30, 90, and 180 days compared with those in the highest income quartile.

Objective Following percutaneous liver biopsy performed at our institution on an outpatient basis, children traditionally were observed for 4 hours then discharged after verifying a stable hematocrit level. In June 2015, we adopted a quality improvement project with shorter 2-hour observation for patients with no known risks and the hematocrit test was abandoned.The purpose of this study is to evaluate the clinical and economic outcomes of early discharge of children following liver biopsy. Methods We analyzed data on 2 groups of children who underwent ultrasound-guided nontargeted core needle liver biopsy performed on outpatient basis. Group A (100 procedures with 4-hour postprocedural observation time and hematocrit test) was compared with group B (100 procedures with 2-hour observation without hematocrit test). Results Group A consisted of 92 patients (43 boys; 49 girls) with a mean age of 11.1 years and mean weight of 52.6 kg. Group B had 92 patients (47 boys; 45 girls) with a mean age of 8.9 years and mean weight of 40.5 kg. The mean length of observation was 281 minutes (range 204-540 minutes) and 147 minutes (range 86-332 minutes) for groups A and B, respectively. The mean recovery charges were reduced by 35% per procedure in group B. The tissue obtained was sufficient for pathologic diagnosis in all procedures. There were no biopsy-related complications in either group. Conclusions Enhanced recovery with early discharge of low-risk children after 2-hour observation following percutaneous liver biopsy can be safely implemented without adversely affecting the outcome. Shorter postbiopsy observation can be cost-saving and may potentially improve patient satisfaction.

The management of high-grade acromioclavicular separations remains unclear. The surgical interventions have shifted to more anatomic, less invasive techniques. The purpose of this study was to systematically review the outcomes and complications of anatomic coracoclavicular ligament reconstruction using a tendon graft.Twenty-one studies (n = 460 patients) met the criteria for inclusion. A double clavicle tunnel tendon graft construct was used in 348 patients (75.7%), whereas a single clavicle tunnel technique was used in 112 patients (24.3%). No significant difference in loss of reduction was found between the 2 techniques. Of 460 patients, 96 (20.9%) demonstrated some form of radiographic displacement at the final follow-up. The overall complication rate was 21.3% (98 of 460), and a higher complication rate was found in the double clavicle tunnel technique (P.001). The overall reoperation rate was 7.6% (37 of 460). The most common reason for reoperation was clavicle fracture (8 of 37). There was a statistically significant increase in reoperation when allograft was used (P = .003).The results of this study suggest that despite newer techniques, approximately 20% of patients develop loss of reduction and/or experience a surgical complication. Attempts to minimize trauma to the clavicle and use autograft tendon may reduce the risk of reoperation.