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OBJECTIVE The Osteoarthritis Research Society International (OARSI) recommends assessment of physical function using a performance-based test of stair negotiation, but was unable to recommend any specific test. We assessed the reliability, validity, responsiveness, measurement error, and minimum important change (MIC) of the 6-step timed Stair Climb Test (SCT). METHODS We used pooled data from 397 participants with hip or knee osteoarthritis (54% women) from four clinical trials (86% retained at 12-week follow-up). Construct validity was assessed by testing six a priori hypotheses against other OARSI-recommended physical function measures. A self-reported Global Rating of Change scale was used to classify participants as worsened, improved and stable. Participants who worsened in physical function were excluded from all analyses. Responsiveness and MIC were assessed using multiple anchor-based and distribution-based approaches. Test-retest reliability, standard error of measurement (SEM) and smallest detectable change (SDC) were assessed on stable participants. RESULTS Five of six hypotheses (83%) for construct validity were met. Test-retest reliability was excellent (intraclass correlation coefficient2,1 : 0.83; 95% confidence interval: 0.71, 0.90). The SEM and SDC values were 0.44 and 1.21 seconds respectively. We did not find adequate support for responsiveness. The MIC values ranged from 0.78 to 1.95 seconds using different approaches (median=1.37 seconds). CONCLUSION The 6-step timed SCT adequately assesses the construct of physical function in individuals with hip or knee osteoarthritis with excellent 12-week test-retest reliability. However, support for its responsiveness was inadequate to recommend its use as an outcome measure in people with osteoarthritis for research and clinical practice.

OBJECTIVE Life after transplant is often accompanied by a myriad of psychosocial and behavioral factors, such as medication adherence and depression, that impact quality of life and outcomes, including mortality. The current project sought to expand the breadth of psychosocial and behavioral care provided to heart transplant recipients during routine follow-up care within a heart transplant clinic housed within an urban academic medical center. METHOD A weekly half-day model of Cardiac Behavioral Medicine clinic integration (CBM-CI) was developed and implemented within an ongoing heart transplant clinic based off the primary care behavioral health (PCBH) model. After meetings with key leadership, the model was developed during a 3-week pilot, after which, clinic providers' expectations for integration were assessed. After the development phase, the CBM-CI was implemented into the weekly heart transplant clinic and a quality improvement (QI) process was engaged for the first 6 weeks. RESULTS Across 6 weeks of clinic implementation, 19 patients engaged with a behavioral medicine provider during routine transplant follow-up, with a wide range of psychosocial/behavioral issues. Overall, the CBM-CI was well-received, the integration was in many ways feasible, and the QI process allowed for iterative improvement that addressed issues related to space, scheduling, selection of patient served, and communication. CONCLUSIONS The CBM-CI for heart transplant enhances opportunity to address psychosocial and behavioral factors that negatively impact outcomes in all stages after heart transplant and highlights the unique role and contributions of clinical health psychologists in cardiology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

BACKGROUND Scalable knee osteoarthritis programs are needed to deliver recommended education, exercise, and weight loss interventions. OBJECTIVE To evaluate two 6-month, telehealth-delivered exercise programs, 1 with and 1 without dietary intervention. DESIGN 3-group, parallel randomized (5:5:2) trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000930280). SETTING Australian private health insurance members. PARTICIPANTS 415 persons with symptomatic knee osteoarthritis and a body mass index between 28 and 40 kg/m2 who were aged 45 to 80 years. INTERVENTION All groups received access to electronic osteoarthritis information (control). The exercise program comprised 6 physiotherapist consultations via videoconference for exercise, self-management advice, and behavioral counseling, plus exercise equipment and resources. The diet and exercise program included an additional 6 dietitian consultations for a ketogenic very-low-calorie diet (2 formulated meal replacements and a low-carbohydrate meal daily) followed by a transition to healthy eating, as well as nutrition and behavioral resources. MEASUREMENTS Primary outcomes were changes in knee pain (numerical rating scale [NRS] of 0 to 10, higher indicating worse) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]; scale, 0 to 68, higher indicating worse) at 6 months (primary time point) and 12 months. Secondary outcomes were weight, physical activity, quality of life, mental health, global change, satisfaction, willingness to have surgery, orthopedic appointments, and knee surgery. RESULTS A total of 379 participants (91%) provided 6-month primary outcomes, and 372 (90%) provided 12-month primary outcomes. At 6 months, both programs were superior to control for pain (between-group mean difference in change on NRS: diet and exercise, -1.5 [95% CI, -2.1 to -0.8]; exercise, -0.8 [CI, -1.5 to -0.2]) and function (between-group mean difference in change on WOMAC: diet and exercise, -9.8 [CI, -12.5 to -7.0]; exercise, -7.0 [CI, -9.7 to -4.2]). The diet and exercise program was superior to exercise (pain, -0.6 [CI, -1.1 to -0.2]; function, -2.8 [CI, -4.7 to -0.8]). Findings were similar at 12 months. LIMITATION Participants and clinicians were unblinded. CONCLUSION Telehealth-delivered exercise and diet programs improved pain and function in people with knee osteoarthritis and overweight or obesity. A dietary intervention conferred modest additional pain and function benefits over exercise. PRIMARY FUNDING SOURCE Medibank, the Medibank Better Health Foundation Research Fund, and a National Health and Medical Research Council Centre of Research Excellence.

OBJECTIVE This scoping review aims to identify and understand the different tools and methods used in studies in the field of human eating behavior to assess, measure, or classify participants' ambivalence towards food and diet, as well as to identify which tools and methods are most frequently employed. INTRODUCTION People's attitudes towards foods and eating behaviors are often ambivalent (simultaneously positive and negative), making it harder to change eating behaviors in favor of a healthier diet. This highlights the importance of resolving diet-related ambivalence. Identifying and understanding the different methods used in the literature to assess attitudinal ambivalence towards food and diet will provide researchers with a range of options to choose from for future studies. INCLUSION CRITERIA We will include peer-reviewed studies as well as preprints that assess the ambivalence of human participants towards food and diet, regardless of sex, age, or other sociodemographic factors. We will exclude studies in which the methods used to assess ambivalence aren't detailed or can't be reproduced, as well as studies that assessed the ambivalence of participants towards farming and agricultural methods or towards methods of food production and preparation. METHODS This review will follow JBI methodology for scoping reviews. Peer-reviewed studies will be retrieved from MEDLINE, PsycINFO, Web of Science, Food Science Source, FSTA, and CINAHL, and preprints will be retrieved from PsyArXiv and MedArXiv. Two independent reviewers will screen the articles. All relevant extracted information will be presented as tables and a descriptive summary of the findings.

Fused deposition modelling is the most popular method of 3D printing with a variety of polymers, but the raw materials are commonly in the filament form. Research has demonstrated the ability to use pellets for this process, which are easier to produce than filaments. Apart from the savings on the pre-processing, the approach also combines the good attributes of both injection moulding and 3D printing and referred to as extrusion 3D printing. Direct printing of pellets is especially suited for thermosensitive polymers, with which, repeated or excessive heating may lead to degeneration. Also, polymers that are too soft do not qualify for filament-based extrusion. PLA is a popular choice for fused deposition modelling in the filament form but is often too brittle. A softer version of PLA composite based on PBAT and cellulose fibres is proposed here for 3D printing. Considering the lack of stiffness of the filaments, direct extrusion from pellet form is evaluated. Regardless of form, the polymer material system satisfied the stringent conditions of consolidation as dictated by the dynamic combination of extrusion and rasterised material deposition. Experimental evaluation based on meso-structural and mechanical property analyses indicate the new pellet-based material system to be suitable and to perform well. The novelty of the material and process combination is that the printed samples were actually comparable mechanically to the injection moulded counterparts, which is an extraordinary achievement, considering the shortcomings typical of material consolidation in additive manufacturing.

Objective To explore the relationships between participant characteristics, perceptions of a short educational video about osteoarthritis and its management, and immediate changes in behavioural determinants for effective self-management behaviours. Methods Seventy-eight participants with knee OA (77% female, mean age 63.0 ± 8.7) watched the 9-min video that included evidence-based content and was designed to foster empowerment to self-manage effectively. Data were collected by online questionnaire at baseline and immediately after watching the video. Associations were tested between baseline health and information processing characteristics (health literacy, need for cognition), perceptions of the video (enjoyment, helpfulness, believability, novelty and relevance) and pre-post changes in behavioural determinants (self-efficacy for managing arthritis, attitude to self-management or ‘activation’, and importance/confidence for physical activity). Results All behavioural determinants improved immediately after watching the video. Positive perceptions were associated with greater improvements in self-efficacy for arthritis (Spearman’s rho, ρ = 0.26–0.47). Greater perceived relevance was associated with increased self-rated importance of being physically active (ρ = 0.43). There were small positive associations between health literacy domains related to health information and positive viewer perceptions of the video. People with higher need for cognition may achieve greater improvement in confidence to be physically active (ρ = 0.27). Conclusion The educational video may help achieve outcomes important for increasing self-management behaviours in people with knee osteoarthritis. Positive perceptions appear to be important in achieving these improvements. People with lower health literacy and lower need for cognition may respond less well to this information about knee osteoarthritis delivered in this way.

Background: The purpose of this study was to determine patient-reported outcome measures (PROMs) changes in: (1) pain, function and global health; and (2) predictors of PROMs in patients undergoing aseptic revision total hip arthroplasty (rTHA) using a multilevel model with patients nested within surgeon. Methods: A prospective cohort of 216 patients with baseline and 1-year PROMs who underwent aseptic rTHA between January 2016 and December 2017 were analysed. The most common indication for rTHA was aseptic loosening, instability, and implant failure. The PROMs included in this study were HOOS Pain and HOOS Physical Function Short-form (PS), Veterans RAND-12 Physical Component Score (VR-12 PCS), and VR-12 Mental Component Score (MCS). Multivariable linear regression models were constructed for predicting 1-year PROMs. Results: Mean 1-year PROMs improvement for aseptic revisions were 30.4 points for HOOS Pain and 22.1 points for HOOS PS. Predictors of better pain relief were patients with higher baseline pain scores. Predictors of better 1-year function were patients with higher baseline function and patients with a posterolateral hip surgical approach during revision. Although VR-12 PCS scores had an overall improvement, nearly 50% of patients saw no improvement or had worse physical component scores. Only 30.7% of patients reported improvements in VR-12 MCS. Conclusions: Overall, patients undergoing aseptic rTHA improved in pain and function PROMs at 1 year. Although global health assessment improved overall, nearly half of aseptic rTHA patients reported no change in physical/mental health status. The associations highlighted in this study can help guide the shared decision-making process by setting expectations before aseptic revision THA.

In March of 2020, the United States activated nationwide pandemic response protocols due to the swift spread of Novel Coronavirus Disease 2019, also known as COVID-19. Amidst the domestic response, urgency surrounded the need to build collective awareness of the signs, symptoms, and preventive measures of the virus. As the virus spread and historically marginalized communities were disproportionately impacted with rates of infection, the need to explore the presence of disparities in health communication, health education, and personal health literacy surfaced. The research contained within this study examines the root cause of the gap in health literacy for communities of color and presents actionable next steps to increase positive healthcare outcomes for all. Copyright © 2022, IGI Global.

PURPOSE: The precise timing of insemination after oocyte retrieval is sometimes challenging. In this study, we have assessed the effect of the variation in insemination timing on reproductive outcome for both conventional insemination (CI) and intracytoplasmic sperm injection (ICSI) cycles. METHODS: A single-center retrospective cohort data analysis was performed on 6559 patients (9575 oocyte retrievals) from January 2017 to July 2019. The main outcome measured was live birth rates. Secondary outcomes included fertilization rate per all oocytes retrieved, blastocyst utilization, clinical pregnancy, and miscarriage rates. The time interval between oocyte retrieval and insemination was analyzed in eight categories: 0 (0– 6.5 h, any detrimental effects are moderate on fertilization but do not affect blastocyst usage and birth rates. TRIAL REGISTRATION: Institutional Review Board Approval from the Beth Israel Deaconess Medical Centre [IRB Protocol #: 2015P000122]. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02299-7.

Background: Burnout, depression, and suicide among health care professionals and learners have reached a rampant level. This systematic review aimed to synthesize literature findings of nursing student burnout and its impact on psychological well-being and academic performance. Method: This systematic review followed PRISMA guidelines and included data-based studies on nursing student burnout published in peer-reviewed journals between January 2015 and January 2020. Results: This review included 17 articles. Four major themes were identified: 1) a negative relationship between burnout and student self-concept, 2) a negative association between burnout and student engagement, 3) risk factors contributing to student burnout, and 4) interventions to mitigate student burnout. Promoting positive self-concept, engagement, and resilience may alleviate student academic burnout. Conclusion: Student burnout has negative influences on health and academics, and interventions to mitigate burnout should be considered early in nursing programs. Nurse educators can create an engaging learning environment to build resilience and reduce burnout. [ J Nurs Educ . 2021;60(7):369–376.]

Question: What were the experiences of physiotherapists and patients who consulted via videoconference during the COVID-19 pandemic and how was it implemented? Design: Mixed methods study with cross-sectional national online surveys and qualitative analysis of free-text responses. Participants: A total of 207 physiotherapists in private practice or community settings and 401 patients aged ≥ 18 years who consulted (individual and/or group) via videoconference from April to November 2020. Methods: Separate customised online surveys were developed for physiotherapists and patients. Data were collected regarding the implementation of videoconferencing (cost, software used) and experience with videoconferencing (perceived effectiveness, safety, ease of use and comfort communicating, each scored on a 4-point ordinal scale). Qualitative content analysis was performed of physiotherapists’ free-text responses about perceived facilitators, barriers and safety issues. Results: Physiotherapists gave moderate-to-high ratings for the effectiveness of and their satisfaction with videoconferencing. Most intended to continue to offer individual consultations (81%) and group classes (60%) via videoconferencing beyond the pandemic. For individual consultations and group classes, respectively, most patients had moderately or extremely positive perceptions about ease of technology use (94%, 91%), comfort communicating (96%, 86%), satisfaction with management (92%, 93%), satisfaction with privacy/security (98%, 95%), safety (99% both) and effectiveness (83%, 89%). Compared with 68% for group classes, 47% of patients indicated they were moderately or extremely likely to choose videoconferencing for individual consultations in the future. Technology was predominant as both a facilitator and barrier. Falls risk was the main safety factor. Conclusion: Patients and physiotherapists had overall positive experiences using videoconferencing for individual consultations and group classes. The results suggest that videoconferencing is a viable option for the delivery of physiotherapy care in the future.

Objective To conduct a comprehensive review of racial and ethnic health disparities in infertility care and treatment. Evidence Review Systematic literature searches were performed in PubMed and Embase from inception to April 2021. Studies were eligible for inclusion if they were original research performed in humans, observational study design, focused on circumstances contributing to infertility, access to infertility care, or outcomes of infertility treatment, and provided relevant information on racial or ethnic groups. Titles and abstracts were reviewed independently by two reviewers to identify pertinent articles. In addition, references of included articles were screened. Result(s) The PubMed search yielded 2,113 articles. An additional 2,301 articles were found in the Embase search. In total, 4,414 articles were screened on the basis of title and, where necessary, abstract. Thirty-four were found to meet the inclusion criteria and included in this review. Three additional studies were found from searching references of the included articles, resulting in 37 articles for discussion: 26 retrospective cohort studies, 2 prospective cohort studies, and 9 cross-sectional studies. The overall consensus in the literature is that reproductive health disparities on the basis of race and ethnicity impact fertility, access to care, and fertility treatment outcomes. Conclusion(s) Racial and ethnic differences in access to full-spectrum reproductive care, including infertility evaluation and treatment, remain. Despite access to infertility treatment, disparate treatment outcomes persist. Intrinsic and extrinsic factors, such as the institutionalization of racism and discrimination within medicine, remain influential in the diagnosis, care, and treatment outcomes of individuals with infertility. To address these inequities, we should mitigate provider bias, fund high-quality health disparity research, improve patient reproductive health knowledge, and advocate for increased access to treatment for all.

The purpose of this study was to compare (1) operative time, (2) in-hospital pain scores, (3) opioid medication use, (4) length of stay (LOS), (5) discharge disposition at 90-day postoperative, (6) range of motion (ROM), (7) number of physical therapy (PT) visits, (8) emergency department (ED) visits, (9) readmissions, (10) reoperations, (11) complications, and (12) 1-year patient-reported outcome measures (PROMs) in propensity matched patient cohorts who underwent robotic arm-assisted (RA) versus manual total knee arthroplasty (TKA). Using a prospectively collected institutional database, patients who underwent RA- and manual TKA were the nearest neighbor propensity score matched 3:1 (255 manual TKA:85 RA-TKA), accounting for various preoperative characteristics. Data were compared using analysis of variance (ANOVA), Kruskal–Wallis, Pearson's Chi-squared, and Fisher's exact tests, when appropriate. Postoperative pain scores, opioid use, ED visits, readmissions, and 1-year PROMs were similar between the cohorts. Manual TKA patients achieved higher maximum flexion ROM (120.3 ± 9.9 versus 117.8 ± 10.2, p = 0.043) with no statistical differences in other ROM parameters. Manual TKA had shorter operative time (105 vs.113 minutes, p

Supplemental Digital Content is available in the text., After deployment to Southwest Asia, some soldiers develop persistent respiratory symptoms, including exercise intolerance and exertional dyspnea. We identified 50 soldiers with a history of deployment to Southwest Asia who presented with unexplained dyspnea and underwent an unrevealing clinical evaluation followed by surgical lung biopsy. Lung tissue specimens from 17 age-matched, nonsmoking subjects were used as controls. Quantitative histomorphometry was performed for evaluation of inflammation and pathologic remodeling of small airways, pulmonary vasculature, alveolar tissue and visceral pleura. Compared with control subjects, lung biopsies from affected soldiers revealed a variety of pathologic changes involving their distal lungs, particularly related to bronchovascular bundles. Bronchioles from soldiers had increased thickness of the lamina propria, smooth muscle hypertrophy, and increased collagen content. In adjacent arteries, smooth muscle hypertrophy and adventitial thickening resulted in increased wall-to-lumen ratio in affected soldiers. Infiltration of CD4 and CD8 T lymphocytes was noted within airway walls, along with increased formation of lymphoid follicles. In alveolar parenchyma, collagen and elastin content were increased and capillary density was reduced in interalveolar septa from soldiers compared to control subjects. In addition, pleural involvement with inflammation and/or fibrosis was present in the majority (92%) of soldiers. Clinical follow-up of 29 soldiers (ranging from 1 to 15 y) showed persistence of exertional dyspnea in all individuals and a decline in total lung capacity. Susceptible soldiers develop a postdeployment respiratory syndrome that includes exertional dyspnea and complex pathologic changes affecting small airways, pulmonary vasculature, alveolar tissue, and visceral pleura.

BACKGROUND: Expanding on research that has identified nonsuicidal self-injury (NSSI) as a strong predictor of suicide risk, the present study examined NSSI disorder (NSSID) and borderline personality disorder (BPD) as unique contributors to lifetime suicide attempts. To our knowledge, the present study represents the first exploration of these associations among veterans. METHODS: Participants included 124 male (74%) and female (26%) veterans diagnosed with at least one mental health disorder. Posttraumatic stress disorder (93%) and major depression (86%) were the most common mental health diagnoses. Large proportions of the sample met criteria for NSSID (48%) and BPD (40%). Suicide attempts were reported by 28% of the sample. Chi-square tests determined the bivariate associations among NSSID, BPD, history of suicide attempts, and other variables. Significant diagnostic (i.e., MDD, BPD, and NSSID) and demographic (i.e., age) characteristics were included as covariates in a logistic regression model examining the associations of BPD and NSSID with suicide attempts. RESULTS: BPD, X(2)=11.1, p

Asthma guided self-management enhances patients' control of their condition under the guidance of the treating physician. The aim of the present study was to understand how physicians perceive, endorse, uptake, and support asthma guided self-management.We conducted a secondary supplementary analysis of data originally collected as part of a multicenter collective case study in which physicians treating patients with asthma were interviewed. Using reflective thematic analysis, we aimed to explore physicians' understanding of guided asthma self-management as related to four ideas, namely: (a) understanding of the disease management and treatment goals; (b) defining medical frame and guidance; (c) describing the importance of patient-physician relationship; and (d) implementing asthma guided self-management.Evidence indicates that physicians perceived optimal guided self-management as related to patients' adherence to physician's instructions and recommendations, supported by the adjustment of prescribed pharmaceutical therapy contingent upon patient's symptoms. Some physicians also perceived behavior change and environmental control along with the medical recommendations. While physicians' perception of asthma and its treatment were aligned with the recommended guidelines-i.e., patient-centered care approach based on guided self-management, the actual guidance offered to patients remained primarily directive and paternalistic. Non-pharmacological approaches, such as exercise, smoking cessation, patient self-monitoring, and self-management supported by education and written self-management plans, were given little consideration in the context of the recommended treatment plan.

We examine how people’s emotional reactions to gun violence public service announcements (PSAs) influence information acquisition, policy preferences, and political engagement. Utilizing a non-student sample of more than 100 participants, we look people’s emotional reactions (i.e., anger, sadness, contempt, and fear) to two Sandy Hook Promise PSAs. We assess people’s emotional reactions by relying on two complimentary measures: the traditional self-report measures as well as facial expression analysis. We demonstrate that when people are feeling sad after watching the Sandy Hook Promise PSAs, they are significantly more likely to retain information from a news article about school violence. Furthermore, feelings of contempt and fear lead people to seek out additional information about gun violence. In addition, we find when people feel anger, contempt, and fear after watching the PSAs, they change their views of gun policies. Finally, fear and contempt increase people’s likelihood of becoming politically mobilized.

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is an intervention that targets common mechanisms that maintain symptoms across multiple disorders. The UP has been shown to be effective across many disorders, including generalized anxiety disorder, major depressive episode (MDE), and panic disorder, that commonly codevelop following trauma exposure. The present study represented the first randomized controlled trial of the UP in the treatment of trauma-related psychopathology, including posttraumatic stress disorder (PTSD), depression, and anxiety symptoms. Adults (N = 43) who developed posttraumatic psychopathology that included PTSD, MDE, or an anxiety disorder after sustaining a severe injury were randomly assigned to receive 10-14 weekly, 60-min sessions of UP (n = 22) or usual care (n = 21). The primary treatment outcome was PTSD symptom severity, with secondary outcomes of depression and anxiety symptom severity and loss of diagnosis for any trauma-related psychiatric disorder. Assessments were conducted at intake, posttreatment, and 6-month follow-up. Posttreatment, participants who received the UP showed significantly larger reductions in PTSD, Hedges' g = 1.27; anxiety, Hedges' g = 1.20; and depression symptom severity, Hedges' g = 1.40, compared to those receiving usual care. These treatment effects were maintained at 6-month follow-up for PTSD, anxiety, and depressive symptom severity. Statistically significant posttreatment loss of PTSD, MDE, and agoraphobia diagnoses was observed for participants who received the UP but not usual care. This study provides preliminary evidence that the UP may be an effective non-trauma-focused treatment for PTSD and other trauma-related psychopathology.

BackgroundA systems-level approach to smoking cessation treatment may optimize healthcare provider adherence to guidelines. Institutions such as the Veterans Health Administration (VHA) are unique in their systematic approach, but comparisons of provider behavior in different healthcare systems are limited.MethodsWe surveyed general medicine providers and specialists in a large academic health center (AHC) and its affiliated VHA in the Mid-South in 2017 to determine the cross-sectional association of healthcare system in which the provider practiced (exposure: AHC versus VHA) with self-reported provision of evidence-based smoking cessation treatment (delivery of counseling plus smoking cessation medication or referral) at least once in the past 12 months (composite outcome). Multivariable logistic regression with adjustment for specialty was performed in 2017–2019.ResultsOf 625 healthcare providers surveyed, 407 (65%) responded, and 366 (59%) were analyzed. Most respondents practiced at the AHC (273[75%] vs VHA 93[25%]) and were general internists (215[59%]); pulmonologists (39[11%]); hematologists/oncologists (69[19%]); and gynecologists (43[12%]). Most respondents (328[90%]) reported the primary outcome. The adjusted odds of evidence-based smoking cessation treatment were higher among VHA vs. AHC healthcare providers (aOR = 4.3; 95% CI 1.3–14.4;p = .02). Health systems differed by provision of individual treatment components, including smoking cessation medication use (98% VHA vs. 90% AHC,p = 0.02) and referral to smoking cessation services (91% VHA vs. 65% AHCp = 0.001).ConclusionsVHA healthcare providers were significantly more likely to provide evidence-based smoking cessation treatment compared to AHC healthcare providers. Healthcare systems’ prioritization of and investment in smoking cessation treatment is critical to improving providers’ adherence to guidelines.

Trauma-focused cognitive behavior therapy (TF-CBT) is the gold standard treatment for posttraumatic stress disorder (PTSD), up to one-half of PTSD patients remain treatment non-responders. Although studies have used functional MRI to understand the neurobiology of treatment response, there is less understanding of the role of white matter brain structures in response to TF-CBT. Thirty-six treatment-seeking PTSD patients and 33 age-gender matched healthy controls completed diffusion-weighted imaging scans at baseline. Patients underwent nine sessions of TF-CBT treatment and PTSD symptom severity was assessed with the Clinician-Administered PTSD Scale before and after completing treatment. Patients were assessed to estimate the reduction in overall symptoms and also specifically fear and dysphoric symptoms of PTSD. Tract-based spatial statistical analyses were performed for the PTSD group to evaluate whole-brain correlations of fractional anisotropy (FA) with improvement in overall, fear, and dysphoric symptoms using non-parametric permutation inference testing (pFWE

Background Low back pain (LBP) and knee osteoarthritis (OA) are major contributors to disability worldwide. These conditions result in a significant burden at both individual and societal levels. Engagement in regular physical activity and exercise programs are known to improve physical function in both chronic LBP and knee OA populations. For people residing in rural areas, musculoskeletal conditions are often more frequent and disabling compared to urban populations, which could be the result of reduced access to appropriate health services and resources in rural settings. EHealth is an innovative solution to help provide equitable access to treatment for people with musculoskeletal pain living in rural settings. Methods/design We will conduct a randomised clinical trial investigating the effects of an eHealth intervention compared to usual care, for people with chronic non-specific LBP or knee OA in rural Australia. We will recruit 156 participants with non-specific chronic LBP or knee OA. Following the completion of baseline questionnaires, participants will be randomly allocated to either the eHealth intervention group, involving a tailored physical activity and progressive resistance exercise program remotely delivered by a physiotherapist (n = 78), or usual care (n = 78) involving referral to a range of care practices in the community. Outcomes will be measured at baseline, 3 and 6 months post-randomisation. The primary outcome will be physical function assessed by the Patient-Specific Functional Scale (PSFS). Secondary outcomes include pain intensity, physical activity levels, activity limitations, quality of life, pain coping. We will also collect process evaluation data such as recruitment rate, attendance and adherence, follow-up rate, participants’ opinions and any barriers encountered throughout the trial. Discussion The findings from this trial will establish the effectiveness of eHealth-delivered interventions that are known to be beneficial for people with LBP and knee OA when delivered in person. As a result, this trial will help to inform health care policy and clinical practice in Australia and beyond for those living in non-urban areas. Trial registration This study was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12618001494224) registered 09.05.2018.

Objective To qualitatively explore the perceptions and experiences of people with knee osteoarthritis (OA) who used an online automated pain coping skills training program (PCST). Methods This was a descriptive qualitative study (based on interpretivist methodology) embedded within a randomized controlled trial. Individual semistructured interviews were conducted with 12 people with knee OA who had participated in an 8-week automated online PCST program while also receiving exercise advice and support from a physical therapist via Skype. Interviews in this study focused specifically on the online PCST program, rather than the physical therapy component. Interviews were audiorecorded, transcribed verbatim, and thematically analyzed. Results Five themes arose: 1) easy to understand and follow (clearly explained, presented well), 2) better able to cope with pain (controlling pain, helping relax, pacing self, incorporating skills into exercise program), 3) anonymity and flexibility (no judgement by clinician, work at own pace, accessibility), 4) not always relatable or engaging (some techniques not useful, Americanization of the program, annoying character examples, time consuming and slow-paced), and 5) support from clinician desirable (follow-up from a clinician would be beneficial, worked in tandem with physical therapist-prescribed exercise, desire referral to the program by a trusted source). Conclusion People with knee OA had generally positive experiences using an online PCST program, suggesting that online PCST is a broadly acceptable and accessible way to help people with OA to manage their pain. User engagement may be enhanced by redesigning some aspects of the program and by provision of support from a clinician.

BackgroundIntersectoral collaboration in the context of the prevention and control of vector-borne diseases has been broadly described in both the literature and the current global strategy by the World Health Organization. Our aim was to develop a framework that will distill the currently known multiple models of collaboration.MethodsQualitative content analysis and logic modeling of data abstracted from 69 studies included in a scoping review done by the authors were used to develop 9 recommendation statements that summarized the composition and attributes of multisectoral approaches, which were then subjected to a modified Delphi process with 6 experts in the fields of health policy and infectious diseases.ResultsConsensus for all statements was achieved during the first round. The recommendation statements were on (1–3) sectoral engagement to supplement government efforts and augment public financing; (4) development of interventions for most systems levels; (5–6) investment in human resource, including training; (7–8) intersectoral action to implement strategies and ensure sustainability of initiatives; and (9) research to support prevention and control efforts.ConclusionsThe core of intersectoral action to prevent vector-borne diseases is collaboration among multiple stakeholders to develop, implement, and evaluate initiatives at multiple levels of intervention.

Summary The incidence and relevance of histological findings in removed allografts is unknown. In this study, we investigated the outcome of routine histopathological examination of removed allografts. We performed a retrospective cohort study in patients with kidney graft failure ≥3 months after transplantation. In this cohort, 244 allograft nephrectomies were performed. We routinely sent removed grafts for histopathological examination. In 197 cases, a pathology report was available for analysis. In 21 of the 197 grafts, gross necrosis precluded adequate interpretation. Signs of rejection were reported in 163 of the remaining 176 allografts. Recurrences of the original disease were found in 13 cases. These were all known from prior biopsies. Relevant secondary findings were present in eight cases: renal cell carcinoma (n = 2), urothelial cell carcinoma, candida pyelonephritis (n = 2), post‐transplant lymphoproliferative disease, polyomavirus inclusions, and membranous nephropathy. All conditions were diagnosed before graft nephrectomy, except for one case of papillary renal cell carcinoma of 0.8 cm. As expected, signs of acute and/or chronic rejection are the main histopathological finding in grafts that are removed after late graft failure. Unexpected secondary findings are very rare. Therefore, it is justifiable to restrict histopathological examination of removed kidney allografts to specific cases.

Questions What are the experiences of physiotherapists delivering care for people with knee osteoarthritis? How do these experiences align with the national Clinical Care Standard? Design A qualitative study using individual interviews. Participants Twenty-two Australian physiotherapists (mean age 34 years, 50% female) with experience in providing care for people with knee osteoarthritis. Methods Physiotherapists participated in semi-structured individual telephone interviews. Questions were informed by seven quality statements from the national Knee Osteoarthritis Clinical Care Standard. Thematic analysis was undertaken, with themes/subthemes inductively derived. Interview data were also deductively analysed according to the Clinical Care Standard. Results Five themes emerged. First, physiotherapists focused on biomedical assessment with little psychosocial consideration. They managed ‘mechanical’ aspects of knee osteoarthritis, aiming to restore functional ability. Second, physiotherapists’ perceived their role as primarily providing goal-orientated personalised exercise via short-term episodic care. Knee surgery was considered a last option, but physiotherapists ‘prepped’ patients who decided on surgery. Third, clinical challenges included patient comorbidity, unsatisfactory patient adherence and a patient’s desire for a ‘quick fix’. The other two themes were: physiotherapists described a mismatch between what they know and what they do regarding imaging, weight management and manual therapy; and physiotherapists viewed weight loss, medication and surgical advice as outside of their professional role. Conclusion Physiotherapists’ reported experiences of delivering care for people with knee osteoarthritis were mostly consistent with the quality care standard. Care may be improved by increasing the focus on psychosocial aspects of care, offering longer-term reviews, and being more proactive with advice and/or referral regarding weight loss, pain medications and knee surgery. By describing the potential benefits and harms of common osteoarthritis medications and surgical interventions, physiotherapists will ensure that their patients are fully informed about all their treatment options.

ObjectivesTo evaluate the association between psychological factors and pain exacerbations in people with hip OA.MethodsEligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10 days over a 90-day follow-up period. In addition, they were required to complete the questionnaire whenever they perceived they were experiencing a hip pain exacerbation. Hip pain exacerbation was defined as an increase of 2 points in pain intensity compared with baseline on an 11-point numeric rating scale (0–10). The Depression, Anxiety and Stress Scale–21 Items, Positive and Negative Affect Schedule, Pain Catastrophizing Scale and Pain Self-Efficacy Questionnaire were used to evaluate psychological factors. The associations of these with risk of hip pain exacerbation were examined by conditional logistic regression.ResultsOf 252 participants recruited, 131 (52.0%) contributed both case and control period data and were included in the analysis. A significant association was found between Pain Catastrophizing Scale overall score (1 point increase) with hip pain exacerbations (odds ratio: 1.07, 95% CI: 1.04, 1.11). An increase of a minimal important change (5.5 points) of Pain Self-Efficacy Questionnaire score was associated with a lower odds of pain exacerbations (odds ratio: 0.74, 95% CI: 0.65, 0.85). No significant associations were found between Depression, Anxiety and Stress Scale–21 Items or Positive and Negative Affect Schedule scores with hip pain exacerbations.ConclusionBoth pain catastrophizing and pain self-efficacy beliefs were associated with pain exacerbations in people with hip OA, but other psychological factors including depression, anxiety and stress or positive and negative affects, were not associated with pain exacerbations.

ObjectivesOsteoarthritis is a leading cause of immobility and joint replacement, two strong risk factors for venous thromboembolism (VTE). We aimed to examine the relation of knee, hip and hand osteoarthritis to the risk of VTE and investigate joint replacement as a potential mediator.MethodsWe conducted three cohort studies using data from The Health Improvement Network. Up to five individuals without osteoarthritis were matched to each case of incident knee (n=20 696), hip (n=10 411) or hand (n=6329) osteoarthritis by age, sex, entry time and body mass index. We examined the relation of osteoarthritis to VTE (pulmonary embolism and deep vein thrombosis) using a multivariable Cox proportional hazard model.ResultsVTE developed in 327 individuals with knee osteoarthritis and 951 individuals without osteoarthritis (2.7 vs 2.0 per 1000 person-years), with multivariable-adjusted HR being 1.38 (95% CI 1.23 to 1.56). The indirect effect (HR) of knee osteoarthritis on VTE through knee replacement was 1.07 (95% CI 1.01 to 1.15), explaining 24.8% of its total effect on VTE. Risk of VTE was higher in hip osteoarthritis than non-osteoarthritis (3.3 vs 1.8 per 1000 person-years; multivariable-adjusted HR=1.83, 95% CI 1.56 to 2.13). The indirect effect through hip replacement yielded an HR of 1.14 (95% CI 1.04 to 1.25), explaining 28.1% of the total effect. No statistically significant difference in VTE risk was observed between hand osteoarthritis and non-osteoarthritis (1.5 vs 1.6 per 1000 person-years; multivariable-adjusted HR=0.88, 95% CI 0.67 to 1.16).ConclusionOur large population-based cohort study provides the first evidence that knee or hip osteoarthritis, but not hand osteoarthritis, was associated with an increased risk of VTE, and such an association was partially mediated through knee or hip replacement.

Patients with autosomal dominant polycystic kidney disease (ADPKD) exhibit enhanced susceptibility to tolvaptan hepatotoxicity relative to other patient populations. In a rodent model of ADPKD, the expression and function of the biliary efflux transporter multidrug resistance-associated protein (Mrp) 2 was reduced, and biliary excretion of a major tolvaptan metabolite (DM-4103) was decreased. The current study investigated whether reduced biliary efflux could contribute to increased susceptibility to tolvaptan-associated hepatotoxicity using a quantitative systems toxicology (QST) model (DILIsym® ). QST simulations revealed that decreased biliary excretion of DM-4103, but not tolvaptan, resulted in substantial hepatic accumulation of bile acids, decreased electron transport chain activity, reduced hepatic adenosine triphosphate concentrations, and an increased incidence of hepatotoxicity. In vitro experiments (C-DILI™) with sandwich-cultured human hepatocytes and HepaRG™ cells were performed to assess tolvaptan-associated hepatotoxic effects when MRP2 was impaired by chemical inhibition (MK571, 50µM) or genetic knockout, respectively. Tolvaptan (64µM, 24hr) treatment of these cells increased cytotoxicity markers up to 27.9-fold and 1.6-fold, respectively, when MRP2 was impaired, indicating that MRP2 dysfunction may be involved in tolvaptan-associated cytotoxicity. In conclusion, QST modeling supported the hypothesis that reduced biliary efflux of tolvaptan and/or DM-4103 could account for increased susceptibility to tolvaptan-associated hepatotoxicity; in vitro experiments implicated MRP2 dysfunction as a key factor in susceptibility. QST simulations revealed that DM-4103 may contribute to hepatotoxicity more than the parent compound. ADPKD progression and gradual reduction in MRP2 activity may explain why acute liver events can occur well after one year of tolvaptan treatment.

BACKGROUND: Differences in the susceptibility of preterm infants to develop necrotizing enterocolitis (NEC) implicate potential genetic differences in response to the inflammatory stimuli leading to NEC. Dual specificity phosphatases (DUSPs) are a key suppressor pathway of the mitogen-activated protein kinase (MAPK) pro-inflammatory signaling pathway. We hypothesized that inherited single nucleotide polymorphisms (SNPs) in DUSP genes contribute to NEC susceptibility in premature infants. METHODS: Patients admitted between 2010 and 2015 born at < 32 weeks GA and≤1,500 g BW with stage II+NEC (cases; n = 50) and age, weight-matched controls (n = 38) were included. Blood samples were collected for DNA isolation. Agena Mass Array assay was used to examine 31 SNPs in 9 different DUSP genes. Calculated minor allele frequencies (MAF) for cases and controls were compared using χ2 and logistic regression. RESULTS: The presence of the rs704074 SNP was associated with a 48% decreased risk of developing NEC (OR 0.52; 95% CI 0.27– 1.01, p = 0.04). The odds of surgical NEC decreased by 78% (OR 0.22; 95% CI 0.06– 0.84, p = 0.027) for each copy of rs704074/G allele in patients with NEC. CONCLUSION: In this small single-center pilot study, DUSP-6 SNP (rs704074) was associated with a lower risk of developing NEC and surgical NEC, the most severe form of NEC, in preterm infants.

PURPOSE For individuals with cancer, palliative care improves quality of life, mood, and survival. Rural residents experience limited access to palliative care. In eastern North Carolina, a rural area, little is known about access to inpatient cancer-related palliative care. This study describes access to inpatient palliative care and developed a predictive model of who was most likely to be admitted to an inpatient facility without a palliative care provider. METHODS A descriptive, exploratory design was used to examine demographics, clinical variables, and inpatient admissions from 2017 and 2018, in a major regional teaching hospital system that included 8 hospitals (7 rural hospitals). Descriptive statistics and a binary logistic regression were used to analyze data. FINDINGS The mean age was 62.2 years (N = 2,161, range: 18-88, SD = 15.52): 49.4% were female, 54% lived in a rural county, and 44.4% were black. The outlying rural hospitals, with no palliative care providers on staff, had 388 admissions (18%). Only gender (P = .0128), county (P < .0001), and age (P < .05) contributed to the logistic model. The predicted probability of being admitted to an inpatient facility with a palliative care provider is higher for younger males living in urban counties. That probability decreases with age regardless of the gender or type of county. CONCLUSIONS These findings highlight the limited availability of inpatient palliative care for those with cancer. Women, older adults, and rural residents are more likely to be admitted to 1 of the 7 rural hospitals with no palliative care provider on staff.

There is an increasing interest in transporter induction (i.e., decreased systemic drug exposure due to increased efflux-limited absorption or transporter-mediated clearance) as a mechanism of drug-drug interactions (DDIs), although evidence of clinical relevance is still evolving. Intestinal P-glycoprotein (P-gp) and hepatic organic anion transporting polypeptides 1B (OATP1B) can be important determinants of drug absorption and disposition, as well as targets for DDIs. Current data indicate that intestinal P-gp protein levels can be induced up to threefold to fourfold in humans primarily with pregnane X receptor (PXR) activators, and that this induction can decrease the systemic exposure of drugs with P-gp efflux-limited absorption (e.g., ≤ 67% decrease in the exposure of total dabigatran following rifampin multiple oral dosing). Evaluation of the clinical relevance of P-gp induction as a DDI mechanism must consider the induction potential of the perpetrator drug for P-gp and attenuation of exposure of the victim drug in the context of its therapeutic window. Practical drug development recommendations are provided herein. Reports are contradictory on OATP1B induction by PXR activators in human hepatocytes and liver biopsies. Some clinical investigations demonstrated that rifampin pretreatment decreased exposure of OATP1B substrates, while other studies found no differences, and the potential involvement of other mechanisms in these observed DDIs cannot be definitively ruled out. Thus, further studies are needed to understand hepatic OATP1B induction and potential involvement of other mechanisms contributing to reduced exposure of OATP1B substrates. This review critically summarizes the state-of-the-art on intestinal P-gp and hepatic OATP1B induction, and highlights implications for drug development.

With the rapid development of image acquisition and storage, multiple images per class are commonly available for computer vision tasks (e.g., face recognition, object detection, medical imaging, etc.). Recently, the recurrent neural network (RNN) has been widely integrated with convolutional neural networks (CNN) to perform image classification on ordered (sequential) data. In this paper, by permutating multiple images as multiple dummy orders, we generalize the ordered “RNN+CNN” design (longitudinal) to a novel unordered fashion, called Multi-path x-D Recurrent Neural Network (MxDRNN) for image classification. To the best of our knowledge, few (if any) existing studies have deployed the RNN framework to unordered intra-class images to leverage classification performance. Specifically, multiple learning paths are introduced in the MxDRNN to extract discriminative features by permutating input dummy orders. Eight datasets from five different fields (MNIST, 3D-MNIST, CIFAR, VGGFace2, and lung screening computed tomography) are included to evaluate the performance of our method. The proposed MxDRNN improves the baseline performance by a large margin across the different application fields (e.g., accuracy from 46.40% to 76.54% in VGGFace2 test pose set, AUC from 0.7418 to 0.8162 in NLST lung dataset). Additionally, empirical experiments show the MxDRNN is more robust to category-irrelevant attributes (e.g., expression, pose in face images), which may introduce difficulties for image classification and algorithm generalizability. The code is publicly available.

Objectives The purpose of this systematic review was to describe psychiatric presentations observed among Takotsubo syndrome (TS) patients, how psychiatric conditions and associated treatments impact TS events, and how psychiatric conditions are managed alongside TS medical treatment and follow-up. Methods We searched MEDLINE, Cochrane Database of Systematic Reviews, Embase, PsycInfo, CINAHL, and Web of Science between 1990 and 2019 for case reports of TS with comorbid psychiatric conditions, behaviors, or substance use. Results Of 2403 records, we included 243 records comprising 252 total cases. Common psychiatric conditions included depression (n = 98; 39%), anxiety (n = 44, 17%), alcohol use (n = 35, 14%), suicidality (n = 30, 12%), and severe mental illness (n = 25, 10%). Psychiatric conditions were frequently associated with triggering TS events (61%). Less than one-third of cases reported providing psychiatric care during hospitalization (n = 80, 32%). Only 33 cases (13%) described psychiatric functioning at follow-up. All case studies were assessed to be of low quality; patterns of reporting bias were observed. Conclusions Despite heterogeneous psychiatric presentations among TS patients, psychiatric treatment was rarely incorporated into the medical care or addressed at follow-up. This gap may be better attended to by integrating psychiatrists and psychologists into the multidisciplinary treatment team. PROSPERO registration number CRD42019119998.

BACKGROUND: Recommended first-line management of lower limb osteoarthritis (OA) includes support for self-management, exercise and weight loss. However, many Australians with OA do not receive these. A National Osteoarthritis Strategy (the Strategy) was developed to outline a national plan to achieve optimal health outcomes for people at risk of, or with, OA. OBJECTIVE: The aim of this article is to identify priorities for action for Australians living with OA. DISCUSSION: The Strategy was developed in consultation with a leadership group, thematic working groups, an implementation advisory committee, multisectoral stakeholders and the public. Two priorities were identified by the 'living well with OA' working group: 1) support primary care practitioners in the delivery of high-value care to Australians with OA, and 2) enhance the uptake of high-value care by Australians with OA. Evidence-informed strategies and implementation plans were developed through consultation to address these priorities.

Summary Objective Different exercise types may yield different outcomes in osteoarthritis (OA) subgroups. The objective was to directly compare effectiveness of two exercise programs for people with medial knee OA and co-morbid obesity. Design We performed a participant- and assessor-blinded randomized controlled trial. 128 people ≥50 years with medial knee OA and body mass index ≥30 kg/m2 were recruited from the community. Interventions were home-based non-weight bearing (NWB) quadriceps strengthening or weight bearing (WB) functional exercise for 12 weeks. Primary outcomes were change in overall knee pain (numeric rating scale, range 0–10) and difficulty with physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0–68) over 12 weeks. Secondary outcomes included other pain measures, physical function, quality-of-life, global changes, physical performance, and lower-limb muscle strength. Results 123 (96%) participants were retained. There was no evidence of a between-group difference in change in pain (mean difference 0.73 units (95% confidence intervals (0.05,1.50)) or function (2.80 units (−1.17,6.76)), with both groups reporting improvements. For secondary outcomes, the WB group had greater improvement in quality-of-life (−0.043 units (−0.085,-0.001)) and more participants reporting global improvement (overall: relative risk 1.40 (0.98,2.01); pain 1.47 (0.97,2.24); function 1.43 (1.04,1.98). Although adverse events were minor, more NWB group participants reported ≥1 adverse event (26/66 (39%) vs 14/62 (23%), p = 0.04). Conclusions Both exercise types similarly improved primary outcomes of pain and function and can be recommended for people with knee OA and obesity. WB exercise may be preferred given fewer adverse events and potential additional benefits on some secondary outcomes. Registration Prospectively registered (Australian New Zealand Clinical Trials Registry #12617001013358, 14/7/2017).

Aims Thresholds for operative eligibility based on body mass index (BMI) alone may restrict patient access to the benefits of arthroplasty. The purpose of this study was to evaluate the relationship between BMI and improvements in patient-reported outcome measures (PROMs), and to determine how many patients would have been denied improvements in PROMs if BMI cut-offs were to be implemented. Methods A prospective cohort of 3,449 primary total hip arthroplasties (THAs) performed between 2015 and 2018 were analyzed. The following one-year PROMs were evaluated: hip injury and osteoarthritis outcome score (HOOS) pain, HOOS Physical Function Shortform (PS), University of California, Los Angeles (UCLA) activity, Veterans Rand-12 Physical Component Score (VR-12 PCS), and VR-12 Mental Component Score (VR-12 MCS). Positive predictive values for failure to improve and the number of patients denied surgery in order to avoid a failed improvement were calculated for each PROM at different BMI cut-offs. Results There was a trend to improved outcomes in terms of pain and function improvements with higher BMI. Patients with BMI ≥ 40 kg/m2 had median (Q1, Q3) HOOS pain improvements of 58 points (interquartile range (IQR) 41 to 70) and those with BMI 35 to 40 kg/m2 had median improvements of 55 (IQR 40 to 68). With a BMI cut-off of 30 kg/m2, 21 patients would have been denied a meaningful improvement in HOOS pain score in order to avoid one failed improvement. At a 35 kg/m2 cut-off, 18 patients would be denied improvement, at a 40 kg/m2 cut-off 21 patients would be denied improvement, and at a 45 kg/m2 cut-off 21 patients would be denied improvement. Similar findings were observed for HOOS-PS, UCLA, and VR-12 scores. Conclusion Patients with higher BMIs show greater improvements in PROMs. Using BMI alone to determine eligibility criteria did not improve the rate of clinically meaningful improvements. BMI thresholds prevent patients who may benefit the most from surgery from undergoing THA. Surgeons should consider PROMs improvements in determining eligibility for THA while balancing traditional metrics of preoperative risk stratification. Cite this article: Bone Joint J 2020;102-B(6):683–692.

This study investigated the associations between various financial hardship and debt indicators and mental health status among older adults.Using data from the Health and Retirement Study (HRS), we considered the association between different forms of financial hardship and debt of those who were identified as having high levels of depressive symptoms (Participants who had difficulty paying bills were more likely to have high levels of depressive symptoms (RR = 2.06, CI = 1.75-2.42,Indicators of financial hardship and medical debt were associated with depressive symptoms and anxiety in a cohort of older adults. In contrast, the influence of credit card debt appeared to be more complex and vary by individual. These findings indicate that doing without meeting personal salient needs has a particularly adverse effect on psychological well-being.

BackgroundAlthough trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), one-third of patients are treatment non-responders. To identify neural markers of treatment response to TF-CBT when participants are reappraising aversive material.MethodsThis study assessed PTSD patients (n = 37) prior to TF-CBT during functional magnetic brain resonance imaging (fMRI) when they reappraised or watched traumatic images. Patients then underwent nine sessions of TF-CBT, and were then assessed for symptom severity on the Clinician-Administered PTSD Scale. FMRI responses for cognitive reappraisal and emotional reactivity contrasts of traumatic images were correlated with the reduction of PTSD severity from pretreatment to post-treatment.ResultsSymptom improvement was associated with decreased activation of the left amygdala during reappraisal, but increased activation of bilateral amygdala and hippocampus during emotional reactivity prior to treatment. Lower connectivity of the left amygdala to the subgenual anterior cingulate cortex, pregenual anterior cingulate cortex, and right insula, and that between the left hippocampus and right amygdala were also associated with symptom improvement.ConclusionsThese findings provide evidence that optimal treatment response to TF-CBT involves the capacity to engage emotional networks during emotional processing, and also to reduce the engagement of these networks when down-regulating emotions.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

In spite of the substantial amount of work that has been done to date, cardiovascular disease (CVD) is still the leading global cause of mortality and morbidity ([1][1]). In addition, to the human burden of CVD, there is a significant financial burden. For example, in the United States, it is

Administration of intrathecal chemotherapy for leukemia is a common procedure in pediatric oncology. The direct delivery of drug into the cerebral spinal fluid requires that no preservative be used. Preserved drugs administered in error can result in significant neurotoxicity. A case series is described where preservative-containing methotrexate was incidentally administered intrathecally. All patients were treated at Children's Hospitals and Clinics of Minnesota. Medical records of the patients affected were reviewed and abstracted for this report. Four children with acute lymphoblastic leukemia received 1 dose of intrathecal methotrexate that contained 0.07% benzyl alcohol in January 2019. Overall, minimal to no symptoms were seen after dosing. The error was traced to a drug shortage in which benzyl alcohol–containing methotrexate was obtained and incorrectly stocked. A novel replacement drug procurement process was developed within our institution. The process includes sequestered queues where a drug awaits evaluation and independent double check of entry accuracy in the electronic health record and pharmacy parenteral dose preparation software prior to release and use. In contrast to IV administration, intrathecal benzyl alcohol at concentrations ≥ 0.9% can cause significant neurotoxicity. Although minimal, if any, neurotoxicity was seen in patients who received a 10-fold lower concentration of benzyl alcohol than previously associated with complications, all institutions should recognize the potential for this error and implement similar safety precautions to ensure that this type of error will not occur.

These practice recommendations for the management of moderate-to-severe UC were developed using the GRADE framework and in adherence to the standards established by the Institute of Medicine for the development of trustworthy guidelines12, 13. The goal of this guideline is to promote high quality, high value evidence-based care for patients with moderate-to-severe UC. Current evidence supports use of infliximab, adalimumab, golimumab, vedolizumab, and tofacitinib for the induction and maintenance of remission in moderate-severe UC. Thiopurine monotherapy should not be used for induction of remission but may be considered for maintenance of remission; in contrast, methotrexate monotherapy, orally or subcutaneously, should not be used for induction or maintenance of remission. Network meta-analysis suggests that infliximab and vedolizumab may be preferred first-line therapy in biologic-naive patients, rather than standard-dose adalimumab or golimumab, with limited evidence to inform appropriate positioning of tofacitinib. In patients with prior exposure to infliximab, particularly those with primary non-response to induction therapy, vedolizumab or tofacitinib may be preferred over adalimumab or golimumab. Combination therapy of a biologic agent with an immunomodulator is more effective than monotherapy with either agent, though patients, particularly those with less severe disease and those averse to side effects from medications, may opt for monotherapy. In patients with moderate-severe disease activity, at high risk of colectomy, biologic agents with or without an immunomodulator, or tofacitinib, should be used early rather than gradual step up therapy after failure of 5-aminosalicylates. Patients in remission with biologic agents and/or immunomodulators or tofacitinib after prior failure of 5-ASA, may discontinue 5-aminosalicylates. Among hospitalized patients with ASUC, after excluding alternative etiologies, intravenous methylprednisolone doses of 40–60mg/day or equivalent are mainstay of therapy. Routine use of adjunctive antibiotics in patients without infections is not recommended. Patients who are refractory to 3–5 days trial of intravenous corticosteroids, who prefer ongoing medical management, may be treated with either infliximab or cyclosporine. In patients being treated with infliximab, no recommendation can be made regarding routine use of intensive vs. standard infliximab dosing.

Background First metatarsophalangeal (MTP) joint osteoarthritis (OA) is a common and painful problem that causes significant disability. There is limited research on assessment and treatment options, and the efficacy of current management strategies is unknown. The aim of this study was to determine how podiatrists and physical therapists in Australia and the United Kingdom (UK) manage people with first MTP joint OA. Methods A survey of podiatrists and physiotherapists was conducted. Potential respondents were recruited through professional representative organisations in Australia and the UK. Participants completed a bespoke online survey regarding the assessment and treatment approaches they most commonly use for patients with first MTP joint OA. Descriptive statistics were calculated and differences between professions compared using chi-square. Results Two hundred respondents (n = 113 (57%) podiatrists and n = 140 (70%) from Australia) completed the survey. Assessment tests were similar between professions and included x-ray (n = 151/164; 92%), range of motion (n = 127/141; 90%), and a pain scale (n = 78/99; 79%). Podiatrists were more likely than physical therapists to discuss over-the-counter medication (42% vs 17%; p p p p p p p Conclusion Podiatrists and physical therapists use an array of assessment and treatment approaches for people with first MTP joint OA, albeit there is limited evidence to support their clinical utility. Treatment strategies differ between professions, particularly with respect to medication, orthoses and exercise. It is unclear whether these commonly-used strategies improve symptoms associated with first MTP joint OA.

Objective To investigate the feasibility of progressive resistance training for people with Prader-Willi syndrome (PWS), who have muscle weakness and very low muscle mass. Design Randomised controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis. Setting Community gymnasium. Participants Sixteen participants with PWS (eight female; mean age 25 years) were randomly assigned with 1:1 allocation to an experimental (n = 8) or control group (n = 8). Intervention Progressive resistance training was performed twice a week for 10 weeks. The training was supervised one-to-one by a physiotherapist and comprised seven exercises. The control group continued their usual activities and were offered the training after follow-up assessment. Main outcome measures Three domains of feasibility were evaluated: implementation (attendance and adherence), practicality (safety) and limited efficacy testing. Muscle strength (one repetition maximum for chest and leg press), physical function (box stacking test, timed stairs climb), muscle composition (US) and body composition (whole-body DXA scan) were measured before and after the intervention. Results Participants attended 92% of scheduled sessions and adhered by progressing their training resistance by 82% (range 60–140%). There was one unexpected serious adverse event unrelated to the intervention and several non-serious expected adverse events related to the intervention. Estimates of standardised mean differences indicated moderate to large effects in favour of the experimental group for arm (0.92, 95%CI −0.11 to 1.95) and leg strength (0.78, 95%CI −0.27 to 1.83). The effect was uncertain for secondary outcomes. Conclusions There is preliminary evidence showing progressive resistance training is feasible for people with Prader-Willi syndrome and may increase muscle strength. Clinical Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12616000107426.

Background Although education, exercise, and weight loss are recommended for management of knee osteoarthritis, the additional benefits of incorporating weight loss strategies into exercise interventions have not been well investigated. The aim of this study is to compare, in a private health insurance setting, the clinical- and cost-effectiveness of a remotely-delivered, evidence- and theory-informed, behaviour change intervention targeting exercise and self-management (Exercise intervention), with the same intervention plus active weight management (Exercise plus weight management intervention), and with an information-only control group for people with knee osteoarthritis who are overweight or obese. Methods Three-arm, pragmatic parallel-design randomised controlled trial involving 415 people aged ≥45 and ≤ 80 years, with body mass index ≥28 kg/m2 and 2 and painful knee osteoarthritis. Recruitment is Australia-wide amongst Medibank private health insurance members. All three groups receive access to a bespoke website containing information about osteoarthritis and self-management. Participants in the Exercise group also receive six consultations with a physiotherapist via videoconferencing over 6 months, including prescription of a strengthening exercise and physical activity program, advice about management, and additional educational resources. The Exercise plus weight management group receive six consultations with a dietitian via videoconferencing over 6 months, which include a very low calorie ketogenic diet with meal replacements and resources to support behaviour change, in addition to the interventions of the Exercise group. Outcomes are measured at baseline, 6 and 12 months. Primary outcomes are self-reported knee pain and physical function at 6 months. Secondary outcomes include weight, physical activity levels, quality of life, global rating of change, satisfaction with care, knee surgery and/or appointments with an orthopaedic surgeon, and willingness to undergo surgery. Additional measures include adherence, adverse events, self-efficacy, and perceived usefulness of intervention components. Cost-effectiveness of each intervention will also be assessed. Discussion This pragmatic study will determine whether a scalable remotely-delivered service combining weight management with exercise is more effective than a service with exercise alone, and with both compared to an information-only control group. Findings will inform development and implementation of future remotely-delivered services for people with knee osteoarthritis. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12618000930280 (01/06/2018).

Background & Aims Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown. Methods microRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative polymerase chain reaction in colonic IECs. Functional characterization of activin receptor-like kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan–Meier estimator. Results ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3’-untranslated region reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in a 5-ethynyl-2-deoxyuridine proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling increased colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared with healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a transepithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and was associated with a higher risk of endoscopic relapse in CD patients. Conclusions Decreased colonic ALK1 disrupted colonic IEC barrier integrity and was associated with poor clinical outcomes in CD patients., Graphical abstract

Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management. (c) 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.