Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results.

BACKGROUND: Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population. METHODS: Patients with PH-COPD (mean pulmonary arterial pressure ≥30 mmHg and pulmonary vascular resistance ≥4 WU) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72 µg) 4 times daily or placebo. The primary efficacy end-point was change in peak 6-min walk distance (6MWD) at week 12. RESULTS: In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the data and safety monitoring committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure. CONCLUSIONS: The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.

Test-Retest reliability and preliminary reliable change estimates for Sway Balance tests administered remotely in community-dwelling adults.

Objective: Impaired balance and postural stability can occur with advanced age, following traumatic brain injury, in association with neurological disorders and diseases, and as the result of acute or chronic orthopedic problems. The remote assessment of balance and postural stability could be of value in clinical practice and research. We examined the test-retest reliability and reliable change estimates for Sway Balance Mobile Application tests (Sway Medical, Tulsa OK, USA) administered remotely from the participant's home. Method: Primarily young, healthy community-dwelling adults completed Sway Balance Mobile Application tests remotely on their personal mobile devices once per week for three consecutive weeks while being supervised with a video-based virtual connection. Sway Balance tests include five stances (i.e., feet together, tandem right foot forward, tandem left foot forward, single leg right foot, single leg left foot), which are averaged to compute a Sway Balance composite score from 0 to 100, with higher scores indicating better postural stability. We examined test-retest reliability (measured with intraclass correlation coefficients, ICCs) and preliminary reliable change estimates for 70%, 80%, and 90% confidence intervals. Results: Participants included 55 healthy adults (ages = 26.7 ± 9.9 years, interquartile range = 20-30, range = 18-58; 38 [69%] women). Test-retest reliability for the Sway Balance composite score across three weeks was.88. Test-retest reliability for individual stances ranged from 62 to 83 (all ps < 0.001). At the 80% confidence interval, preliminary reliable changes estimates were 9 points for the Sway Balance composite score. Conclusions: For a remote administration, test-retest reliability was moderate-to-good for all Sway Balance stances, as well as for the Sway Balance composite score. Reliable change estimates may allow clinicians to determine whether an improvement or decline in performance is greater than the expected improvement or decline due to measurement error in young adults.

Study design and rationale for the TETON phase 3, randomised, controlled clinical trials of inhaled treprostinil in the treatment of idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) greatly impacts quality of life and eventually leads to premature death from respiratory failure. Inhaled treprostinil was associated with improvements in forced vital capacity (FVC) and reduced exacerbations of underlying lung disease in post hoc analyses from a phase 3 study in patients with precapillary pulmonary hypertension due to interstitial lung disease. These results, combined with preclinical evidence of treprostinil's antifibrotic activity, support its investigation in the treatment of IPF. METHODS AND ANALYSIS: The TETON programme consists of two replicate, 52-week, randomised, double-blind placebo-controlled, phase 3 studies, each enrolling 396 subjects (NCT04708782, NCT05255991). Eligible subjects must have a diagnosis of IPF confirmed by central imaging review, along with an FVC ≥45%. Stable background use of pirfenidone or nintedanib is allowed. The primary endpoint is change in absolute FVC at week 52. Secondary endpoints include time to clinical worsening (first event of death, respiratory hospitalisation or ≥10% decline in % predicted FVC), time to first acute exacerbation of IPF, overall survival, change in % predicted FVC and change in the King's Brief Interstitial Lung Disease Questionnaire at week 52. Safety parameters include adverse events, hospitalisations, oxygenation and laboratory parameters. Patients who complete week 52 will be eligible to enter an open-label extension study. ETHICS AND DISSEMINATION: Studies will be conducted in accordance with the International Conference on Harmonisation Guideline for Good Clinical Practice, Declaration of Helsinki principles, and local regulatory, ethical and legal requirements. Results will be published in a peer-reviewed publication.

Test-Retest Reliability and Reliable Change Estimates for Four Mobile Cognitive Tests Administered Virtually in Community-Dwelling Adults.

Objective: Remote mobile cognitive testing (MCT) is an expanding area of research, but psychometric data supporting these measures are limited. We provide preliminary data on test-retest reliability and reliable change estimates in four MCTs from SWAY Medical, Inc. Methods: Fifty-five adults from the U.S. Midwest completed the MCTs remotely on their personal mobile devices once per week for 3 consecutive weeks, while being supervised with a video-based virtual connection. The cognitive assessment measured simple reaction time ("Reaction Time"), go/no-go response inhibition ("Impulse Control"), timed visual processing ("Inspection Time"), and working memory ("Working Memory"). For each cognitive test except Working Memory, we analyzed both millisecond (ms) responses and an overall SWAY composite score. Results: The mean age of the sample was 26.69years (SD=9.89; range=18-58). Of the 55 adults, 38 (69.1%) were women and 49 (89.1%) used an iPhone. Friedman's ANOVAs examining differences across testing sessions were nonsignificant (ps>0.31). Intraclass correlations for Weeks 1-3 were: Reaction Time (ms): 0.83, Reaction Time (SWAY): 0.83, Impulse Control (ms): 0.68, Impulse Control (SWAY): 0.80, Inspection Time (ms): 0.75, Inspection Time (SWAY): 0.75, and Working Memory (SWAY): 0.88. Intraclass correlations for Weeks 1-2 were: Reaction Time (ms): 0.75, Reaction Time (SWAY): 0.74, Impulse Control (ms): 0.60, Impulse Control (SWAY): 0.76, Inspection Time (ms): 0.79, Inspection Time (SWAY): 0.79, and Working Memory (SWAY): 0.83. Natural distributions of difference scores were calculated and reliable change estimates are presented for 70, 80, and 90% CIs. Conclusion: Test-retest reliability was adequate or better for the MCTs in this virtual remote testing study. Reliable change estimates allow for the determination of whether a particular level of improvement or decline in performance is within the range of probable measurement error. Additional reliability and validity data are needed in other age groups.

Accuracy of the SWAY Mobile Cognitive Assessment Application.

BACKGROUND: Mobile electronic devices have become integral tools in addressing the need for portable assessment of cognitive function following neurocognitive/motor injury. SWAY Medical, Inc., has employed mobile device motion-based technology in the SWAY Cognitive Assessment (SWAY CA) application to assess cognitive function. PURPOSE: The purpose of this study was to assess whether the SWAY CA application (reaction time, impulse control and inspective time) was able to reliably operate on different mobile devices and operating systems (iOS, Android). The study further sought to assess the validity of the SWAY CA application against the FDA approved ImPACT QT mobile device application. STUDY DESIGN: Original Research, observational study of validity. METHODS: 88 healthy, young adults, 18 to 48 years (mean= 22.09 ± sd=4.47 years) completed four, randomized and counter-balanced, reaction time tests (2- SWAY RT, 2- ImPACT QT) using different operating systems (iOS, Android) of 4 randomly assigned mobile devices. RESULTS: ANOVAs reported the SWAY CA application (reaction time, impulse control, inspection time) operated reliably with iPhone 6S, Samsung Galaxy S9, and iPad Pro 5 mobile devices (p > 0.05), respectively. Google Pixel 3 reliability with SWAY CA application remains undetermined. SWAY CA simple reaction motion measures were in agreement (r = -0.46 to 0.22, p ≤ 0.05) with several ImPACT QT reaction time measures. SWAY CA impulse control and inspection time measures are weakly correlated (r = -0.25 to -0.46, p ≤ 0.05) with five ImPACT QT reaction time measures. CONCLUSION: The motion-based SWAY CA mobile device application appears to reliably operate when being administered on different mobile devices and software operating systems. Furthermore, the SWAY CA application appears to be comparable to the ImPACT QT and serve as a valid tool for assessing reaction time measures. LEVEL OF EVIDENCE: Level 2b (observational study of validity).

Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease.

BACKGROUND: No therapies are currently approved for the treatment of pulmonary hypertension in patients with interstitial lung disease. The safety and efficacy of inhaled treprostinil for patients with this condition are unclear. METHODS: We enrolled patients with interstitial lung disease and pulmonary hypertension (documented by right heart catheterization) in a multicenter, randomized, double-blind, placebo-controlled, 16-week trial. Patients were assigned in a 1:1 ratio to receive inhaled treprostinil, administered by means of an ultrasonic, pulsed-delivery nebulizer in up to 12 breaths (total, 72 µg) four times daily, or placebo. The primary efficacy end point was the difference between the two groups in the change in peak 6-minute walk distance from baseline to week 16. Secondary end points included the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level at week 16 and the time to clinical worsening. RESULTS: A total of 326 patients underwent randomization, with 163 assigned to inhaled treprostinil and 163 to placebo. Baseline characteristics were similar in the two groups. At week 16, the least-squares mean difference between the treprostinil group and the placebo group in the change from baseline in the 6-minute walk distance was 31.12 m (95% confidence interval [CI], 16.85 to 45.39; P<0.001). There was a reduction of 15% in NT-proBNP levels from baseline with inhaled treprostinil as compared with an increase of 46% with placebo (treatment ratio, 0.58; 95% CI, 0.47 to 0.72; P<0.001). Clinical worsening occurred in 37 patients (22.7%) in the treprostinil group as compared with 54 patients (33.1%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40 to 0.92; P = 0.04 by the log-rank test). The most frequently reported adverse events were cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. CONCLUSIONS: In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil improved exercise capacity from baseline, assessed with the use of a 6-minute walk test, as compared with placebo. (Funded by United Therapeutics; INCREASE ClinicalTrials.gov number, NCT02630316.).

A comparative study: tongue muscle performance in weightlifters and runners.

Exercise mode (i.e., resistance training, endurance training) is known to yield mode-specific effects on strength and endurance of muscles that are directly targeted during the exercise. Such mode-specific effects can also be observed in indirectly involved (i.e., nontargeted) muscles. Mode-specific muscle performance changes of nontargeted muscles, however, have only been investigated within the skeletal system. Therefore, as a first step, this study aimed to determine if bulbar muscle performance (tongue strength [TS], tongue endurance [TE]) differs between weightlifters and runners and if group differences are tongue region-specific. The Iowa Oral Performance Instrument (IOPI) was used to measure TS and TE of the anterior and posterior tongue regions in 21 weightlifters and 23 runners. In weightlifters anterior TS was significantly greater than posterior TS (P = 0.008), whereas in runners anterior and posterior TS were comparable. Furthermore, weightlifters produced significantly greater anterior TS than runners (P = 0.001). Finally, TE was overall significantly greater in runners than in weightlifters (P = 0.001). Findings suggest that exercise mode may differentially impact performance patterns of nontargeted bulbar muscles. More research is warranted to better understand the mechanisms underlying tongue muscle performance differences between weightlifters and runners.

Using Social Listening Data to Monitor Misuse and Nonmedical Use of Bupropion: A Content Analysis.

BACKGROUND: The nonmedical use of pharmaceutical products has become a significant public health concern. Traditionally, the evaluation of nonmedical use has focused on controlled substances with addiction risk. Currently, there is no effective means of evaluating the nonmedical use of noncontrolled antidepressants. OBJECTIVE: Social listening, in the context of public health sometimes called infodemiology or infoveillance, is the process of identifying and assessing what is being said about a company, product, brand, or individual, within forms of electronic interactive media. The objectives of this study were (1) to determine whether content analysis of social listening data could be utilized to identify posts discussing potential misuse or nonmedical use of bupropion and two comparators, amitriptyline and venlafaxine, and (2) to describe and characterize these posts. METHODS: Social listening was performed on all publicly available posts cumulative through July 29, 2015, from two harm-reduction Web forums, Bluelight and Opiophile, which mentioned the study drugs. The acquired data were stripped of personally identifiable identification (PII). A set of generic, brand, and vernacular product names was used to identify product references in posts. Posts were obtained using natural language processing tools to identify vernacular references to drug misuse-related Preferred Terms from the English Medical Dictionary for Regulatory Activities (MedDRA) version 18 terminology. Posts were reviewed manually by coders, who extracted relevant details. RESULTS: A total of 7756 references to at least one of the study antidepressants were identified within posts gathered for this study. Of these posts, 668 (8.61%, 668/7756) referenced misuse or nonmedical use of the drug, with bupropion accounting for 438 (65.6%, 438/668). Of the 668 posts, nonmedical use was discouraged by 40.6% (178/438), 22% (22/100), and 18.5% (24/130) and encouraged by 12.3% (54/438), 10% (10/100), and 10.8% (14/130) for bupropion, amitriptyline, and venlafaxine, respectively. The most commonly reported desired effects were similar to stimulants with bupropion, sedatives with amitriptyline, and dissociatives with venlafaxine. The nasal route of administration was most frequently reported for bupropion, whereas the oral route was most frequently reported for amitriptyline and venlafaxine. Bupropion and venlafaxine were most commonly procured from health care providers, whereas amitriptyline was most commonly obtained or stolen from a third party. The Fleiss kappa for interrater agreement among 20 items with 7 categorical response options evaluated by all 11 raters was 0.448 (95% CI 0.421-0.457). CONCLUSIONS: Social listening, conducted in collaboration with harm-reduction Web forums, offers a valuable new data source that can be used for monitoring nonmedical use of antidepressants. Additional work on the capabilities of social listening will help further delineate the benefits and limitations of this rapidly evolving data source.

Tongue strength and endurance: Comparison in active and non-active young and older adults.

PURPOSE: Tongue strength and endurance are important for swallowing and upper airway patency. Physical activity positively affects targeted and non-targeted skeletal muscles; however, little is known about the indirect effect of physical activity on tongue muscles. This study sought to determine if tongue muscle performance differs between highly active and non-active individuals and if such an effect varies with age. METHOD: Forty-eight healthy adults were divided into two age groups (24 young, 20.96 ± 3.22 years; 24 older, 65 ± 3.72 years) and further divided into highly active and non-active based on The General Practice Physical Activity Questionnaire. Tongue strength (TS) and tongue endurance (TE) were obtained using the Iowa Oral Performance Instrument. RESULT: A significant main effect of activity level on TS and TE was found. Although the main effect of age on TS and TE and age × activity level interactions were not significant, the effect of activity level on TS and TE was more pronounced in older adults than younger adults. CONCLUSION: Findings suggest physical activity may affect TS and TE, particularly in older adults. Future research is warranted to understand the underlying mechanisms contributing to these group differences. Clinical implications of these findings are discussed.

Social Media Listening for Routine Post-Marketing Safety Surveillance.

INTRODUCTION: Post-marketing safety surveillance primarily relies on data from spontaneous adverse event reports, medical literature, and observational databases. Limitations of these data sources include potential under-reporting, lack of geographic diversity, and time lag between event occurrence and discovery. There is growing interest in exploring the use of social media ('social listening') to supplement established approaches for pharmacovigilance. Although social listening is commonly used for commercial purposes, there are only anecdotal reports of its use in pharmacovigilance. Health information posted online by patients is often publicly available, representing an untapped source of post-marketing safety data that could supplement data from existing sources. OBJECTIVES: The objective of this paper is to describe one methodology that could help unlock the potential of social media for safety surveillance. METHODS: A third-party vendor acquired 24 months of publicly available Facebook and Twitter data, then processed the data by standardizing drug names and vernacular symptoms, removing duplicates and noise, masking personally identifiable information, and adding supplemental data to facilitate the review process. The resulting dataset was analyzed for safety and benefit information. RESULTS: In Twitter, a total of 6,441,679 Medical Dictionary for Regulatory Activities (MedDRA(®)) Preferred Terms (PTs) representing 702 individual PTs were discussed in the same post as a drug compared with 15,650,108 total PTs representing 946 individual PTs in Facebook. Further analysis revealed that 26 % of posts also contained benefit information. CONCLUSION: Social media listening is an important tool to augment post-marketing safety surveillance. Much work remains to determine best practices for using this rapidly evolving data source.

Postpartum prolapsed leiomyoma with uterine inversion managed by vaginal hysterectomy.

Background. Uterine inversion is a rare, but life threatening, obstetrical emergency which occurs when the uterine fundus collapses into the endometrial cavity. Various conservative and surgical therapies have been outlined in the literature for the management of uterine inversions. Case. We present a case of a chronic, recurrent uterine inversion, which was diagnosed following spontaneous vaginal delivery and recurred seven weeks later. The uterine inversion was likely due to a leiomyoma. This late-presenting, chronic, recurring uterine inversion was treated with a vaginal hysterectomy. Conclusion. Uterine inversions can occur in both acute and chronic phases. Persistent vaginal bleeding with the appearance of a prolapsing fibroid should prompt further investigation for uterine inversion and may require surgical therapy. A vaginal hysterectomy may be an appropriate management option in select populations and may be considered in women who do not desire to maintain reproductive function.

Impact of electronic medical record on physician practice in office settings: a systematic review.

BACKGROUND: Increased investments are being made for electronic medical records (EMRs) in Canada. There is a need to learn from earlier EMR studies on their impact on physician practice in office settings. To address this need, we conducted a systematic review to examine the impact of EMRs in the physician office, factors that influenced their success, and the lessons learned. RESULTS: For this review we included publications cited in Medline and CINAHL between 2000 and 2009 on physician office EMRs. Studies were included if they evaluated the impact of EMR on physician practice in office settings. The Clinical Adoption Framework provided a conceptual scheme to make sense of the findings and allow for future comparison/alignment to other Canadian eHealth initiatives.In the final selection, we included 27 controlled and 16 descriptive studies. We examined six areas: prescribing support, disease management, clinical documentation, work practice, preventive care, and patient-physician interaction. Overall, 22/43 studies (51.2%) and 50/109 individual measures (45.9%) showed positive impacts, 18.6% studies and 18.3% measures had negative impacts, while the remaining had no effect. Forty-eight distinct factors were identified that influenced EMR success. Several lessons learned were repeated across studies: (a) having robust EMR features that support clinical use; (b) redesigning EMR-supported work practices for optimal fit; (c) demonstrating value for money; (d) having realistic expectations on implementation; and (e) engaging patients in the process. CONCLUSIONS: Currently there is limited positive EMR impact in the physician office. To improve EMR success one needs to draw on the lessons from previous studies such as those in this review.

Development and implementation of coral reef biocriteria in U.S. jurisdictions.

Coral reefs worldwide are declining at an alarming rate and are under continuous threat from both natural and anthropogenic environmental stressors. Warmer sea temperatures attributed to global climate change and numerous human activities at local scales place these valuable ecosystems at risk. Reefs provide numerous services, including shoreline protection, fishing, tourism and biological diversity, which are lost through physical damage, overfishing, and pollution. Pollution can be controlled under provisions of the Clean Water Act, but these options have not been fully employed to protect coral reefs. No U.S. jurisdiction has implemented coral reef biocriteria, which are narrative or quantitative water quality standards based on the condition of a biological resource or assemblage. The President's Ocean Action Plan directs the U.S. Environmental Protection Agency (EPA) to develop biological assessment methods and biological criteria for evaluating and maintaining the health of coral reef ecosystems. EPA has formed the Coral Reef Biocriteria Working Group (CRBWG) to foster development of coral reef biocriteria through focused research, evaluation and communication among Agency partners and U.S. jurisdictions. Ongoing CRBWG activities include development and evaluation of a rapid bioassessment protocol for application in biocriteria programs; development of a survey design and monitoring strategy for the U.S. Virgin Islands; comprehensive reviews of biocriteria approaches proposed by states and territories; and assembly of data from a variety of monitoring programs for additional metrics. Guidance documents are being prepared to assist U.S. jurisdictions in reaching protective and defensible biocriteria.

A pan-Canadian health informatics education strategy.

Despite the fact that health informatics (HI) educational opportunities in Canada have increased by 40% over the last 3 years, there are few opportunities for advanced research or credentialing at the MSc and PhD levels. Existing programs are also not easily accessible to working health care professionals, who require flexible, non-traditional delivery options for basic to advanced HI training. This strategy report proposes an overall vision, 3 goals, 4 tactical initiatives and a set of action items to improve the effectiveness of HI education in Canada