Comparative adherence of macitentan versus ambrisentan and bosentan in Australian patients with pulmonary arterial hypertension: a retrospective real-world database study.

AIM: Bosentan, ambrisentan, and macitentan are endothelin receptor antagonists (ERAs), currently available in Australia for treatment of pulmonary arterial hypertension (PAH). This study assessed the comparative adherence of these ERAs for PAH in Australian patients. METHODS: This retrospective, observational study used data for adults with PAH from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset (01/2006-10/2020). The primary outcome was treatment adherence (i.e. receiving ≥80% of ERA doses over 12 months). Secondary outcomes were time to treatment change (add-on or switch) and overall survival. RESULTS: The study included 436 patients who took bosentan (n = 200), ambrisentan (n = 69), or macitentan (n = 167). Treatment adherence was significantly greater in patients who received macitentan (65.3%) versus ambrisentan (56.5%) and bosentan (58.0%), with odds ratios (ORs; 95% CI) of 0.51 (0.30-0.88; p = 0.016) for bosentan versus macitentan and 0.48 (0.24-0.96; p = 0.037) for ambrisentan versus macitentan. The median time to treatment change was 47.2 and 43.4 months for bosentan and ambrisentan, respectively (not calculated for macitentan because of insufficient duration of data). LIMITATIONS AND CONCLUSIONS: Real-world data for Australian patients with PAH showed that treatment adherence for ERAs was suboptimal. Adherence was higher for macitentan compared with ambrisentan and bosentan.

Return to Sports Following Sports-Related Concussion in Collision Sports: An Expert Consensus Statement Using the Modified Delphi Technique.

PURPOSE: To perform a Delphi consensus for return to sports (RTS) following sports-related concussion (SRC). METHODS: Open-ended questions in rounds 1 and 2 were answered. The results of the first 2 rounds were used to develop a Likert-style questionnaire for round 3. If agreement at round 3 was ≤80% for an item, if panel members were outside consensus or there were >30% neither agree/disagree responses, the results were carried forward into round 4. The level of agreement and consensus was defined as 90%. RESULTS: Individualized graduated RTS protocols should be used. A normal clinical, ocular and balance examination with no more headaches, and asymptomatic exertional test allows RTS. Earlier RTS can be considered if athletes are symptom free. The Sports Concussion Assessment Tool 5 and vestibular and ocular motor screening are recognized as useful tools to assist in decision-making. Ultimately RTS is a clinical decision. Baseline assessments should be performed at both collegiate and professional level and a combination of neurocognitive and clinical tests should be used. A specific number of recurrent concussions for season-or career-ending decisions could not be determined but will affect decision making for RTS. CONCLUSIONS: Consensus was achieved for 10 of the 25 RTS criteria: early RTS can be considered earlier than 48 to 72 hours if athletes are completely symptom-free with no headaches, a normal clinical, ocular and balance examination. A graduated RTS should be used but should be individualized. Only 2 of the 9 assessment tools were considered to be useful: Sports Concussion Assessment Tool 5 and vestibular and ocular motor screening. RTS is mainly a clinical decision. Only 31% of the baseline assessment items achieved consensus: baseline assessments should be performed at collegiate and professional levels using a combination of neurocognitive and clinical tests. The panel disagreed on the number of recurrent concussions that should be season- or career-ending. LEVEL OF EVIDENCE: Level V, expert Opinion.

On-Field and Pitch-Side (Sideline) Assessment of Sports Concussion in Collision Sports: An Expert Consensus Statement Using the Modified Delphi Technique.

PURPOSE: To perform a Delphi consensus for on-field and pitch-side assessment of sports-related concussion (SRC). METHODS: Open-ended questions in rounds 1 and 2 were answered. The results of the first 2 rounds were used to develop a Likert-style questionnaire for round 3. If agreement at round 3 was ≤80% for an item, if panel members were outside consensus, or there were >30% neither agree/disagree responses, the results were carried forward into round 4. The level of agreement and consensus was defined as 90%. RESULTS: Loss of consciousness (LOC) or suspected LOC, motor incoordination/ataxia, balance disturbance, confusion/disorientation, memory disturbance/amnesia, blurred vision/light sensitivity, irritability, slurred speech, slow reaction time, lying motionless, dizziness, headaches/pressure in the head, falling to the ground with no protective action, slow to get up after a hit, dazed look, and posturing/seizures were clinical signs of SRC and indicate removal from play. Video assessment is helpful but should not replace clinical judgment. LOC/unresponsiveness, signs of cervical spine injury, suspicion of other fractures (skull/maxillo-facial), seizures, Glasgow Coma Scale score <14 and abnormal neurologic examination findings are indications for hospitalization. Return to play should only be considered when no clinical signs of SRC are present. Every suspected concussion should be referred to an experienced physician. CONCLUSIONS: Consensus was achieved for 85% of the clinical signs indicating concussion. On-field and pitch-side assessment should include the observation of the mechanism, a clinical examination, and cervical spine assessment. Of the 19 signs and red flags requiring removal from play, consensus was reached for 74%. Normal clinical examination and HIA with no signs of concussion allow return to play. Video assessment should be mandatory for professional games but should not replace clinical decision-making. Sports Concussion Assessment Tool, Glasgow Coma Scale, vestibular/ocular motor screening, Head Injury Assessment Criteria 1, and Maddocks questions are useful tools. Guidelines are helpful for non-health professionals. LEVEL OF EVIDENCE: Level V, expert opinion.

Comparative Treatment Persistence and Adherence to Endothelin Receptor Antagonists Among Patients with Pulmonary Arterial Hypertension in Japan: A Real-World Administrative Claims Database Study.

INTRODUCTION: Real-world data on the comparative effectiveness of endothelin receptor antagonists (ERAs; macitentan, bosentan, ambrisentan) for pulmonary arterial hypertension (PAH), particularly in Asian countries, are scarce. We evaluated the persistence of these ERAs before and after macitentan approval in Japan (2015). METHODS: We used real-world data from the Japanese Medical Data Vision administrative claims database between April 2008 and November 2020. Patients with PAH were identified from the dataset. Persistence to ERA treatment before and after approval of macitentan in Japan was defined as the time between start of the index ERA and treatment discontinuation or death. Propensity score adjustment was applied to minimize confounding effects among treatment groups. RESULTS: In the pre-macitentan approval cohort, 153 and 51 patients received bosentan and ambrisentan, respectively. In the post-macitentan approval cohort, 331, 284, and 91 patients received macitentan, bosentan, and ambrisentan, respectively. Unadjusted median persistence for ambrisentan- and bosentan-treated patients was 19 and 10 months, respectively (adjusted HR 0.87 [95% CI 0.61-1.24]; P = 0.434 [bosentan as reference]). In the post-macitentan approval cohort, unadjusted median persistence was 18 months for macitentan-treated patients versus 6 and 8 months for ambrisentan- and bosentan-treated patients, respectively. Adjusted HRs for ambrisentan and bosentan were 1.48 (95% CI 1.12-1.95; P = 0.006) and 1.63 (95% CI 1.30-2.04; P < 0.001 [macitentan as reference]), respectively. CONCLUSIONS: Real-world data for Japanese patients with PAH showed that persistence was significantly higher for macitentan, versus ambrisentan and bosentan, since its approval.

Risk Factors for Pulmonary Arterial Hypertension in Patients With Systemic Lupus Erythematosus: A Systematic Review and Expert Consensus.

OBJECTIVE: This study aimed to identify risk factors associated with the development of pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a systematic literature review of studies focusing on adult patients classified as having SLE-related PAH by searching the electronic databases Embase, Medline, Medline in-progress, Wanfang, China National Knowledge Infrastructure, Ichushi Web, Kmbase, and KoreaMed. Based on the findings, we conducted a Delphi survey to build expert consensus on issues related to screening for PAH in patients with SLE and on the importance and feasibility of measuring the identified factors in clinical practice. RESULTS: We included 21 eligible studies for data synthesis. Sixteen factors were associated with an increased risk of SLE-PAH: pericardial effusion, serositis, longer duration of SLE, arthritis, acute and subacute cutaneous lupus, scleroderma pattern on nailfold capillaroscopy, diffusion capacity of carbon monoxide in the lungs (DLCO) <70% predicted, interstitial lung disease, thrombocytopenia, and seven serological factors. Six factors were associated with a decreased risk of SLE-PAH: malar/acute rash, hematologic disorder, renal disorder, higher Systemic Lupus Erythematosus Disease Activity Index score, and two serological factors. Among these, there were six risk factors on which the panelists reached strong or general consensus (peak tricuspid regurgitation velocity on echocardiography >2.8 m/s, pericardial effusion, DLCO <70% predicted, scleroderma pattern on nailfold capillaroscopy, brain natriuretic peptide >50 ng/l, and N-terminal pro-brain natriuretic peptide >300 ng/l). The Delphi panel confirmed the need for a screening tool to identify patients with SLE at high risk of developing PAH and provided consensus on the importance and/or practicality of measuring the identified factors. CONCLUSION: The risk factors we identified could be used in a screening algorithm to identify patients with SLE with a high risk of developing PAH to facilitate early diagnosis, which could improve prognosis and management of these patients.

Sport Concussion Assessment Tool-5th Edition (SCAT5): Normative Reference Values for the National Rugby League Women's Premiership.

Objective: To establish normative reference values for the Sport Concussion Assessment Tool-5th Edition (SCAT5) for the new National Rugby League Women's Premiership. Methods: Preseason SCAT5 baseline testing was administered individually to all National Rugby League Women's Premiership players (N = 117). Testing was completed by the medical staff. Normative reference values were calculated for the components of the SCAT5, including the Standardized Assessment of Concussion, modified Balance Error Scoring System, and the Symptom Scale. A small case series of players who sustained concussions were included to illustrate the use of the new normative data. Results: The median Standardized Assessment of Concussion total score was 27.0 (M = 26.9, SD = 2.1). The median modified Balance Error Scoring System score was 2.0 (M = 2.4, SD = 2.2). The median number of symptoms score was 1.0 (M = 3.2, SD = 4.7) and the median symptom severity score was 2.0 (M = 5.4, SD = 8.2). The most common baseline symptom was fatigue or low energy (33%), followed by trouble sleeping (24%), headache (23%), neck pain (22%), and difficulty remembering (21%). In the total sample, 41% reported no symptoms. The clinical interpretation of these new normative data to a case series of women with concussions is provided. Conclusions: Normative reference values are provided for the SCAT5 for women who are professional rugby league players. Using these normative data will improve clinical interpretation of SCAT5 scores following a concussion.

Concussion Guidelines in National and International Professional and Elite Sports.

The Berlin statement on sport-related concussion was published in 2017 using evidence-based recommendations. We aimed to examine (1) the implementation of, distribution and education based on the Berlin recommendations, and the development of sport-specific protocols/guidelines among professional and elite sports, (2) the implementation of guidelines at the community level, (3) translation of guidelines into different languages, and (4) research activities. Senior medical advisers and chief medical officers from Australian Football League, All Japan Judo Federation, British Horseracing Authority, Cricket Australia, Fédération Equestre Internationale, Football Association, Gaelic Athletic Association, International Boxing Association, Irish Horseracing Regulatory Board, Major League Baseball, National Football League, National Hockey League, National Rugby League, and World Rugby completed a questionnaire. The results demonstrated that all 14 sporting organizations have published concussion protocols/guidelines based on the Berlin recommendations, including Recognize, Removal from play, Re-evaluation, Rest, Recovery, and Return to play. There is variable inclusion of Prolonged symptoms. Prevention and Risk reduction and Long-term effects are addressed in the guidelines, rules and regulations, and/or sport-specific research. There is variability in education programs, monitoring compliance with guidelines, and publication in other languages. All sporting bodies are actively involved in concussion research. We conclude that the Berlin recommendations have been included in concussion protocols/guidelines by all the sporting bodies, with consistency in the essential components of the recommendations, whilst also allowing for sport- and regional-specific variations. Education at the elite, community, and junior levels remains an ongoing challenge, and future iterations of guidelines may consider multiple language versions, and community- and junior-level guidelines.

International consensus definitions of video signs of concussion in professional sports.

BACKGROUND: The use of video to assist professional sporting bodies with the diagnosis of sport-related concussion (SRC) has been well established; however, there has been little consistency across sporting codes with regards to which video signs should be used, and the definitions of each of these signs. AIM: The aims of this study were to develop a consensus for the video signs considered to be most useful in the identification of a possible SRC and to develop a consensus definition for each of these video signs across the sporting codes. METHODS: A brief questionnaire was used to assess which video signs were considered to be most useful in the identification of a possible concussion. Consensus was defined as >90% agreement by respondents. Existing definitions of these video signs from individual sports were collated, and individual components of the definitions were assessed and ranked. A modified Delphi approach was then used to create a consensus definition for each of the video signs. RESULTS: Respondents representing seven sporting bodies (Australian Football League, Cricket Australia, Major League Baseball, NFL, NHL, National Rugby League, World Rugby) reached consensus on eight video signs of concussion. Thirteen representatives from the seven professional sports ranked the definition components. Consolidation and refinement of the video signs and their definitions resulted in consensus definitions for six video signs of possible concussion: lying motionless, motor incoordination, impact seizure, tonic posturing, no protective action-floppy and blank/vacant look. CONCLUSIONS: These video signs and definitions have reached international consensus, are indicated for use by professional sporting bodies and will form the basis for further collaborative research.

International study of video review of concussion in professional sports.

BACKGROUND: Video review has become an important tool in professional sporting codes to help sideline identification and management of players with a potential concussion. AIM: To assess current practices related to video review of concussion in professional sports internationally, and compare protocols and diagnostic criteria used to identify and manage potential concussions. METHODS: Current concussion management guidelines from professional national and international sporting codes were reviewed. Specific criteria and definitions of video signs associated with concussion were compared between codes. Rules and regulations adopted across the codes for processes around video review were also assessed. RESULTS: Six sports with specific diagnostic criteria and definitions for signs of concussion identified on video review participated in this study (Australian football, American football, world rugby, cricket, rugby league and ice hockey). Video signs common to all sports include lying motionless/loss of responsiveness and motor incoordination. The video signs considered by the majority of sports as most predictive of a diagnosis of concussion include motor incoordination, impact seizure, tonic posturing and lying motionless. Regulatory requirements, sideline availability of video, medical expertise of video reviewers and use of spotters differ across sports and geographical boundaries. By and large, these differences reflect a pragmatic approach from each sport, with limited underlying research and development of the video review process in some instances. CONCLUSIONS: The use of video analysis in assisting medical staff with the diagnosis or identification of potential concussion is well established across different sports internationally. The diagnostic criteria used and the expertise of the video review personnel are not clearly established, and research efforts would benefit from a collaborative harmonisation across sporting codes.

Implementation of the 2017 Berlin Concussion in Sport Group Consensus Statement in contact and collision sports: a joint position statement from 11 national and international sports organisations.

The 2017 Berlin Concussion in Sport Group Consensus Statement provides a global summary of best practice in concussion prevention, diagnosis and management, underpinned by systematic reviews and expert consensus. Due to their different settings and rules, individual sports need to adapt concussion guidelines according to their specific regulatory environment. At the same time, consistent application of the Berlin Consensus Statement's themes across sporting codes is likely to facilitate superior and uniform diagnosis and management, improve concussion education and highlight collaborative research opportunities. This document summarises the approaches discussed by medical representatives from the governing bodies of 10 different contact and collision sports in Dublin, Ireland in July 2017. Those sports are: American football, Australian football, basketball, cricket, equestrian sports, football/soccer, ice hockey, rugby league, rugby union and skiing. This document had been endorsed by 11 sport governing bodies/national federations at the time of being published.

Lung Function Abnormalities in Smokers with Ischemic Heart Disease.

RATIONALE: The aim of the ALICE (Airflow Limitation in Cardiac Diseases in Europe) study was to investigate the prevalence of airflow limitation in patients with ischemic heart disease and the effects on quality of life, healthcare use, and future health risk. OBJECTIVES: To examine prebronchodilator and post-bronchodilator spirometry in outpatients aged greater than or equal to 40 years with clinically documented ischemic heart disease who were current or former smokers. METHODS: This multicenter, cross-sectional study was conducted in 15 cardiovascular outpatient clinics in nine European countries. Airflow limitation was defined as post-bronchodilator FEV1/FVC less than 0.70. MEASUREMENTS AND MAIN RESULTS: Among the 3,103 patients with ischemic heart disease who were recruited, lung function was defined for 2,730 patients. Airflow limitation was observed in 30.5% of patients with ischemic heart disease: 11.3% had mild airflow limitation, 15.8% moderate airflow limitation, 3.3% severe airflow limitation, and 0.1% very severe airflow limitation. Most patients with airflow limitation (70.6%) had no previous spirometry testing or diagnosed pulmonary disease. Airflow limitation was associated with greater respiratory symptomatology, impaired health status, and more frequent emergency room visits (P < 0.05). CONCLUSIONS: Airflow limitation compatible with chronic obstructive pulmonary disease affects almost one-third of patients with ischemic heart disease. Although airflow limitation is associated with additional morbidity and societal burden, it is largely undiagnosed and untreated. Clinical trial registered with www.clinicaltrials.gov (NCT 01485159).

Iliotibial band release as an adjunct to the surgical management of patellar stress fracture in the athlete: a case report and review of the literature.

Stress fracture of the patella is rare. In this report, a case of patellar stress fracture occurring in an amateur athlete is presented, and an operative adjunct to the surgical management of this condition is proposed.A review of the English literature identified 21 previous cases of stress fracture of the patella, the majority in young athletes. None of these reports discussed treatment addressing the pathological process contributing to patellar stress fracture.The subject of this case report is a young male netballer who presented with a transverse stress fracture in the inferior third of his patella, on a background of patellofemoral overload. The patient underwent open reduction and internal fixation of his patella, combined with release of the iliotibial band. He returned to training after 6 weeks.The previous literature suggests that operative fixation is indicated for the treatment of displaced patellar stress fractures. Iliotibial band release, as a surgical adjunct to this treatment, may address the pathology of these fractures, and facilitate a return to sport at the highest level.