Search

Zeenat SafdarDivision of Pulmonary-Critical Care Medicine, Baylor College of Medicine, Houston, Texas, USAIntroduction: Currently available endothelin receptor antagonists for treating pulmonary arterial hypertension block either the endothelin (ET) receptor A or both A and B receptors. Transition from one endothelin receptor antagonist to another may theoretically alter side-effects or efficacy. We report our experience of a transition from sitaxsentan to ambrisentan, both predominant ETA receptor antagonists, in pulmonary arterial hypertension patients.Methods: At Baylor Pulmonary Hypertension Center, 18 patients enrolled in the open-label extension phase of the original sitaxsentan studies (Sitaxsentan To Relieve ImpaireD Exercise) were transitioned to ambrisentan (from July 2007 to September 2007) at the time of study closure. Pre-transition (PreT), 1 month (1Mth) and 1 year (1Yr) post-transition assessments of 6-minute walk distance (6MWD), brain naturetic peptide (BNP) levels, WHO functional class (WHO FC), Borg dyspnea score (BDS), oxygen saturation, liver function, and peripheral edema were compared.Results: 6MWD was 356 ± 126 m at PreT, 361 ± 125 m at 1Mth, and 394 ± 114 m at 1Yr (mean ± SD). There was no difference in the walk distance at 1Mth and 1Yr post transition compared with PreT (P = 0.92, 0.41 respectively). Oxygen saturation was no different at 1Mth and 1Yr to PreT level (P = 0.49 and P = 0.06 respectively). BNP was 178 ± 244 pg/mL at PreT, 129 ± 144 pg/mL at 1Mth and 157 ± 201 at 1Yr. Peripheral edema was present in 7/18 patients at PreT, in 8/16 patients at 1Mth, and in 6/13 patients at 1Yr post transition. Proportions of patients with edema over these 3 time points did not change significantly (P = 0.803). At 1Yr, 2 patients had died, 1 had undergone lung transplantation, 1 had relocated, and 1 patient was started on intravenous prostacyclin therapy. Over 3 points (baseline, 1 month, and 1 year), there was no significant change in function class (P = 0.672).Conclusion: Our limited data suggest that ETA receptor antagonists can be switched from one to another with sustained exercise capacity and maintained WHO FC with no increase in incidence of peripheral edema.Keywords: right heart failure, 6-minute walk distance, endothelial receptor antagonist, echocardiogram

Crowdsourcing in general is an online distributed model for solving problems where the organizations use large number of contributions from Internet users for ideas and services towards problem solving. Crowdsourcing assists to divide work in tasks for contributors to achieve desired results and increase performance of platforms. Crowdsourcing embraces cheap labor that means less credible output and low quality products. Therefore, this study aims to propose a novel model in order to control the quality of the crowdsourced product. Exploratory mode of research has been adopted in order to explore the quality of crowdsourced software products. Furthermore, a roadmap is also formulated to lead crowdsource organizations in order to improve the quality of developed crowdsource product. [ABSTRACT FROM AUTHOR]

Emergency services contribute a lot for the wellbeing and comfort of the society by promoting the virtues of goodwill gestures. In Pakistan, emergency services took a long time to start in the form of Punjab Emergency Service (PES) Rescue 1122 in the year 2004. The PES has put its remarkable efforts to provide quality emergency services as acknowledged by the community. However, it still needs improvements from different perspectives. The inclusion and integration of Internet of Things (IoT) based apparatus and incorporation of emergency medical services (EMS) with e-health systems are the core aspects. The integration of call monitoring software (CMS) with the vehicle tracking system and the need for having a technology-based decision support system are other perspectives. The advancements in operational communication, safety and protection of rescuers during operations and the addition of helicopter emergency service, etc. are also considered. The state of the art literature is still deficient to comprehensively cover the topic under reference. The study successfully addresses this deficiency by thoroughly exploring different aspects of the PES in a critically constructive that leads towards technological and tactical improvements. The study also proposes an innovative IoT based EMS inclusive E-health Architecture and a Unified Emergency Operational Model to improve the service quality of the PES. These proposals set the basis for the optimal performance of the PES through various perspectives like collaborative quality emergency response with real-time monitoring and care, machine learning-based analysis of emergencies prevention, etc. along with the future research directions.. [ABSTRACT FROM AUTHOR]

Internet of things is novelemerging Internet based system for the exchange of information to provide efficient services regardless of time and place. IoT technology is playing a vital role in the current environment due to its wide spread applications in every domain of life like industrial, social, health care and domestic applications. IoT directly affects the security and privacy of all its involved entities as reported in the literature. Therefore, this study aims to propose a Security Enabled Model to provide secure end to end communication in IoT environment. Intensive literature review has been conducted to identify and investigate various security and privacy challenges encountered by the IoT environment. Proposed model ensures security at each layer of IoT. These layers includes I) perception layer which provides authentication process for the identification of fake objects ii) network layer that emphasis on data security process through cloud platform and iii) application layer which provides authentication for the end users. Results show that small sensing devices need to be highly focused in order to make them more secure and lightweight encryption techniques need to be developed. Furthermore, sensing devices are required to be more secure and protected from unauthorized access. [ABSTRACT FROM AUTHOR]

Introduction: Cystic fibrosis (CF) is a common lethal genetic disorder. The aim of this study was to determine the common chest radiograph (CXR) patterns in adult CF, and correlate disease distribution on CXRs with genotype, age, and gender. Methods: One hundred nine CF patients treated at Baylor Adult Cystic Fibrosis Center were identified. The intake CXR was reviewed and characterized as diffuse bilateral (DB), unilateral, upper lobe (UL), and lower lobe (LL) disease, or relatively normal. Lack of intake CXR, and/or genotype excluded 41 patients from analysis. Results: Of 68 patients, 38 were homozygous for DeltaF508 and 30 were heterozygous. Mean age of the population was 30 +/- 8 years (+/- SD) [range, 18 to 48 years]. The most common CXR pattern was DB; 62% had DB, 28% had UL, and 7% had LL predominance. This is in contrast to the UL-predominant CXR pattern commonly described in the pediatric population. In 18 DB patients, archived pediatric films were available, and the average patient age was 15.7 years. DB pattern was present in 16 of 18 CXRs that antedated adult intake CXRs by an average of 12.7 years. Homozygous DeltaF508 genotype was identified in 56% of patients and did not distinguish radiologic phenotypes. There was no association between radiograph pattern and identified infecting/colonizing organisms and percentage of predicted FEV(1). Conclusions: CF has commonly been reported as an UL disease. However, in this study of adult patients, the common pattern observed was DB. A small subgroup analysis suggests that DB disease was not a pattern of disease evolution but may be present from disease onset. [ABSTRACT FROM AUTHOR]

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic-organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin., (© 2024. The Author(s).)

Treatment modalities for pulmonary arterial hypertension (PAH) improve quality of life and walk distance. However, none of these therapies alter the structural/functional pulmonary vascular integrity that results in vascular remodeling. PAH smooth muscle cells share biological characteristics with cancer cells, which may be potential therapeutic targets for PAH. We present a case of a patient with connective tissue disease (CTD)-associated PAH treated on triple therapy who developed metastatic lung adenocarcinoma. While on PAH triple-therapy, she received a combination of carboplatin, pemetrexed, and pembrolizumab. She eventually had a complete pathologic response, no evidence of cancer recurrence, and significant improvement of PAH/overall clinical status. After discontinuation of neoplastic therapy, her clinical status worsened, she eventually passed away, and lung biopsy findings revealed evidence of severe pulmonary smooth muscle cell hypertrophy and pulmonary veno-occlusive disease. This report suggests that combined chemotherapy and immunotherapy may influence the efficacy of PAH therapies and improve clinical status., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Our retrospective study aimed to determine how pulmonary arterial hypertension (PAH) influences the clinical outcomes of COVID-19 admissions by using data from the 2020 nationwide inpatient sample (NIS). Among the 1,018,915 adults who were hospitalized with COVID-19 in 2020, 155 also had a PAH diagnosis. After adjusting for all baseline demographics and co-morbidities through multivariate analysis, we found that in patients admitted with a principal diagnosis of COVID-19, PAH was not associated with an increased risk of mortality compared to those without PAH. (adjusted OR 0.58 [95% CI 0.2-1.6] p=0.3). In addition, patients with both COVID-19 and PAH showed no statistically significant difference in the odds of requiring mechanical ventilation (adjusted OR 1.1 [95% CI 0.5-2.6] p=0.9), vasopressor needs (adjusted OR 0.4 [95% CI 0.1-3.5] p=0.4), acute kidney injury necessitating renal replacement therapy(adjusted OR 0.7 [95% CI 0.3-1.7] p=0.5), mean length of stay (LOS) (11.1 vs. 7.5 days), adjusted difference 3.1 [95% CI -3.8- 10.1] p=0.37) or mean total hospitalization charges ($195,815 vs $79,082, adjusted difference 107,146 [95% CI -93,939 - 308,232] p=0.29). Further studies are needed to investigate this subpopulation during the post-vaccination era to observe the effects of outcomes in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

A 67-year-old woman with pulmonary hypertension (PH) presented with a 1-day history of worsening shortness of breath and pleuritic chest pain and was found to have a troponin T level of 3755 ng/L (ref. range 0-19 ng/L). An initial diagnostic workup in the emergency department (ED) led to an urgent left heart catheterization which revealed a 90% occlusive right coronary artery blood clot, even though a recent heart catheterization less than a month prior was completely unremarkable. Further workup led to the discovery of a patent foramen ovale (PFO) and an aneurysmal interatrial septum, suggesting the presence of a paradoxical embolism. While typically asymptomatic, a PFO is an important clinical entity that can lead to irreversible cardiac damage. Suspicion should be high for this finding in the case of an acute myocardial infarction (MI) with no clear cause, especially in a patient with elevated right heart pressures., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Madeline Franke and Zeenat Safdar.)

Pulmonary hypertension (PH) is a complex cardiopulmonary disorder impacting the lung vasculature, resulting in increased pulmonary vascular resistance that leads to right ventricular dysfunction. Pulmonary hypertension comprises of 5 groups (PH group 1 to 5) where group 1 pulmonary arterial hypertension (PAH), results from alterations that directly affect the pulmonary arteries. Although PAH has a complex pathophysiology that is not completely understood, it is known to be a multifactorial disease that results from a combination of genetic, epigenetic and environmental factors, leading to a varied range of symptoms in PAH patients. PAH does not have a cure, its incidence and prevalence continue to increase every year, resulting in higher morbidity and mortality rates. In this review, we discuss the different pathologic mechanisms with a focus on epigenetic modifications and their roles in the development and progression of PAH. These modifications include DNA methylation, histone modifications, and microRNA dysregulation. Understanding these epigenetic modifications will improve our understanding of PAH and unveil novel therapeutic targets, thus steering research toward innovative treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ejikeme and Safdar.)

Background Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, enabling them to perform tasks. The advancements in AI have also improved virtual reality (VR), augmented reality (AR) and mixed reality (MR) experience allowing a greater opportunity for use in the field of medicine. Objective To evaluate the knowledge, attitude and practice of AI and types of realities among Pakistani healthcare professionals (HCPs). Materials and methods This was a prospective, nationwide study designed at the Department of Neurosurgery at Punjab Institute of Neurosciences (PINS), Lahore, was conducted between January 2024 to February 2024. More than 500 HCPs were approached, out of which 176 participated in this survey consensually. A pre-formed general questionnaire based on knowledge, attitude and practices of AI and types of realities was modified according to local conditions. Google Forms (Google Inc., USA) was used to conduct the one-time sign up response. Statistical Package for Social Sciences (IBM SPSS Statistics for Windows, Version 24, USA) was used to analyze submitted responses. Results About 69.9% respondents were male HCPs. Most of the respondents were from the fields of neurosurgery, medicine and general surgery, i.e., 10.80%, 10.20% and 4%, respectively. More than 90% HCPs used Internet and electronic devices daily. A majority of 62.50% respondents agreed that AI brings benefits for the patients, while at the same time, 45.50% agreed that they would not trust the assessment of AI more than that of HCPs. 61% HCPs feared that AI-based systems could be manipulated from the outside sources, like terrorists and hackers. Although 90% respondents knew the definition of AR and VR, a strikingly low 40% respondents could only identify the practical applications of these realities when asked in a mini-quiz. About 61.40% HCPs never used any AI-based application throughout their clinical practice, but Google Health was used by 29.50% respondents, followed by Remote Patient Monitoring AI application used by 3.4% individuals. Conclusion There is an evident under-utilization of AI and types of realities in clinical practice in Pakistan. Lack of awareness, paucity of resources and conventional clinical practices are the key reasons identified. Pakistan is on the path towards the point where the developed world is currently. There is a potential to move past the initial stages of AI implementation and into more advanced modes of adopting AI and types of realities., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mehmood Qadri et al.)

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by elevated pulmonary artery pressure and increased pulmonary vascular resistance. Females have a higher incidence of PAH, which is reflected globally across registries in the United States, Europe, and Asia. However, despite female predominance, women had better outcomes compared with male patients, a finding that has been labeled the "estrogen paradox." Special considerations should be given to women with PAH regarding sexual health, contraception, family planning, and treatment before, during, and after pregnancy. Pregnant women with PAH should be referred to a pulmonary hypertension care center; a multidisciplinary team approach is recommended, and Cesarean section is the preferred mode of delivery. While pregnancy outcomes have improved over the years with PAH-specific therapy, pregnancy portends a high-risk for those with PAH. Continued research is needed to tailor PAH treatment for women., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Introduction: Portopulmonary hypertension (PoPH) carries a worse prognosis than other forms of pulmonary arterial hypertension (PAH). Data regarding use of PAH-specific therapies in patients with PoPH are sparse as they are usually excluded from clinical trials. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles in patients with PoPH newly initiating macitentan in the USA using the OPUS/OrPHeUS combined dataset., Methods: OPUS was a prospective, US, multicenter, observational drug registry (April 2014-June 2020); OrPHeUS was a retrospective, US, multicenter chart review (October 2013-March 2017). Additional information regarding patients' liver disease was retrospectively collected for patients with PoPH in OPUS., Results: The OPUS/OrPHeUS dataset included 206 patients with PoPH (median age 58 years; 52.4% female), with baseline cirrhosis and liver test abnormalities reported in 72.8% and 31.6% of patients respectively. Macitentan was initiated as combination therapy in 74.8% of patients and median (Q1, Q3) exposure to macitentan was 11.9 (3.1, 26.0) months. One-year Kaplan-Meier estimates (95% confidence limit, CL) of patients free from all-cause hospitalization and survival were 48.6% (40.7, 56.0) and 82.2% (75.1, 87.4). Of the 96 patients with PoPH in OPUS, 29.2% were classified as in need of liver transplant due to underlying liver disease during the study; transplant waitlist registration was precluded because of PAH severity for 32.1% and 17.9% were transplanted. Hepatic adverse events (HAE) were experienced by 49.0% of patients; the most common being increased bilirubin (16.0%), ascites (7.3%), and hepatic encephalopathy (5.8%); 1.5% and 21.8% of patients discontinued macitentan as a result of HAE and non-hepatic adverse events., Conclusion: There were no unexpected safety findings in patients with PoPH treated with macitentan. These data add to the evidence supporting the safety and tolerability of macitentan in patients with PoPH. A graphical abstract is available with this article., Trial Registration: OPsumit® Users Registry (OPUS): NCT02126943; OPsumit® Historical Users cohort (OrPHeUS): NCT03197688; www., Clinicaltrials: gov ., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix in the pulmonary interstitium and progressive functional decline. We hypothesized that integration of multi-omics data would identify clinically meaningful molecular endotypes of IPF., Methods: The IPF-PRO Registry is a prospective registry of patients with IPF. Proteomic and transcriptomic (including total RNA [toRNA] and microRNA [miRNA]) analyses were performed using blood collected at enrollment. Molecular data were integrated using Similarity Network Fusion, followed by unsupervised spectral clustering to identify molecular subtypes. Cox proportional hazards models tested the relationship between these subtypes and progression-free and transplant-free survival. The molecular subtypes were compared to risk groups based on a previously described 52-gene (toRNA expression) signature. Biological characteristics of the molecular subtypes were evaluated via linear regression differential expression and canonical pathways (Ingenuity Pathway Analysis [IPA]) over-representation analyses., Results: Among 232 subjects, two molecular subtypes were identified. Subtype 1 (n = 105, 45.3%) and Subtype 2 (n = 127, 54.7%) had similar distributions of age (70.1 +/- 8.1 vs. 69.3 +/- 7.6 years; p = 0.31) and sex (79.1% vs. 70.1% males, p = 0.16). Subtype 1 had more severe disease based on composite physiologic index (CPI) (55.8 vs. 51.2; p = 0.002). After adjusting for CPI and antifibrotic treatment at enrollment, subtype 1 experienced shorter progression-free survival (HR 1.79, 95% CI 1.28,2.56; p = 0.0008) and similar transplant-free survival (HR 1.30, 95% CI 0.87,1.96; p = 0.20) as subtype 2. There was little agreement in the distribution of subjects to the molecular subtypes and the risk groups based on 52-gene signature (kappa = 0.04, 95% CI= -0.08, 0.17), and the 52-gene signature risk groups were associated with differences in transplant-free but not progression-free survival. Based on heatmaps and differential expression analyses, proteins and miRNAs (but not toRNA) contributed to classification of subjects to the molecular subtypes. The IPA showed enrichment in pulmonary fibrosis-relevant pathways, including mTOR, VEGF, PDGF, and B-cell receptor signaling., Conclusions: Integration of transcriptomic and proteomic data from blood enabled identification of clinically meaningful molecular endotypes of IPF. If validated, these endotypes could facilitate identification of individuals likely to experience disease progression and enrichment of clinical trials., Trial Registration: NCT01915511., (© 2023. The Author(s).)

Purpose: Real-world studies have reported reduced mortality in patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotic therapy; however, the initiation or discontinuation of therapy during these studies may have introduced bias. This study investigated the effect of antifibrotic therapy on mortality and other outcomes in patients with IPF using causal inference methodology., Methods: Data from a multicenter US registry of patients with IPF were used to assess the effect of antifibrotic therapy (nintedanib or pirfenidone) on death, death or lung transplant, respiratory-related hospitalization, and acute worsening of IPF (defined as any health care encounter deemed due to acute worsening of IPF). This study used the Gran method, which accounts for differences in patient characteristics and for treatment initiations and discontinuations during follow-up. The analysis cohort was limited to patients who started antifibrotic therapy on or after the day of enrollment or had never taken it., Findings: Among the 499 patients analyzed, 352 (70.5%) received antifibrotic therapy. Estimated event rates of death at 1 year were 6.6% (95% CI, 6.1-7.1) for treated patients and 10.2% (95% CI, 9.5-10.9) for control patients. There was a numerical reduction in the risk of death (hazard ratio [HR], 0.53; 95% CI, 0.28-1.03; P = 0.060) but numerical increases in risks of respiratory-related hospitalization (HR, 1.88; 95% CI, 0.90-3.92; P = 0.091) and acute worsening of IPF (HR, 1.71; 95% CI, 0.36-8.09; P = 0.496) in treated versus control patients., Implications: Analyses based on causal inference methodology suggest that patients with IPF who receive antifibrotic therapy have improved survival., Competing Interests: Declaration of Interest JAdeA is a member of the Steering Committee for the IPF-PRO/ILD-PRO Registry; has received speaker fees from Boehringer Ingelheim (BI); has served on a Data Safety Monitoring Board for Respivant Sciences, Roche/Genentech, the National Institutes of Health; and is a Scientific Advisory Committee member for the Pulmonary Fibrosis Foundation. MLN, ASH, LS and SMP are employees of DCRI, which receives funding support from BIPI to coordinate the IPF-PRO/ILD-PRO Registry. In addition, SMP has received research funding paid to Duke/DCRI from AstraZeneca, Bristol Myers Squibb, CareDx; royalties from UpToDate; and speaker fees from Altavant Sciences and Bristol Myers Squibb. DAC is a member of the Steering Committee and Publication Committee for the IPF-PRO/ILD-PRO Registry and reports consulting and speaker fees from BI and Genentech. HJK is a member of the Publication Committee for the IPF-PRO/ILD-PRO Registry and has received a grant for a Patient Education Day from Roche/Genentech. TL, LJL, MR have no disclosures. ZS reports consulting fees and honoraria for lectures from BI and Genentech. SB was an employee of BIPI at the time that this study was conducted. TBL and CSC are employees of BIPI., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Interstitial lung disease (ILD) results in profound symptom burden and carries high mortality. Palliative care (PC) is dedicated to improving quality of life in patients with serious illness. Early PC provision improves rates of advance care planning and symptom management in patients with ILD., Research Question: What are the current perspectives on PC among ILD providers, and what are the barriers to PC in ILD specialty centers?, Study Design and Methods: A 24-question electronic survey was disseminated to providers at the 68 Pulmonary Fibrosis Foundation Care Centers across the United States from October 2020 to December 2020., Results: The survey was completed by 128 participants representing all 68 Pulmonary Fibrosis Foundation Care Center Network sites. Most respondents were physicians. Most providers exhibit good knowledge of, feel comfortable assessing a patient's readiness for, and agree with the need for PC for patients with ILD. Providers are most likely to refer to PC at objective disease and/or symptomatic progression rather than at initial diagnosis. In comparison with providers who report referring their patients to PC, providers who report rare referral are more likely to cite lack local PC availability (P < .01) and less likely to feel comfortable discussing prognosis/disease trajectory (P = .03) or feel it is important to address advance directives in ILD clinic (P = .02). There is a lack of standardized measures used to assess specific symptoms, overall symptom burden, or health-related quality of life across institutions. Discordance exists between self-reported and actual access to local inpatient and outpatient PC services., Interpretation: Most ILD providers use PC and are comfortable discussing PC. Barriers to PC identified in this survey include the following: perceived lack of local access to PC, lack of systematic tools to assess symptom burden, lack of established optimal timing of PC referral, and unclear need for specialized PC delivery., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD) and is associated with worse outcomes and increased mortality. Evaluation of PH is recommended in lung transplant candidates, but there are currently no standardized screening approaches. Trials have identified therapies that are effective in this setting, providing another rationale to routinely screen patients with ILD for PH., Research Question: What screening strategies for identifying PH in patients with ILD are supported by expert consensus?, Study Design and Methods: The study convened a panel of 16 pulmonologists with expertise in PH and ILD, and used a modified Delphi consensus process with three surveys to identify PH screening strategies. Survey 1 consisted primarily of open-ended questions. Surveys 2 and 3 were developed from responses to survey 1 and contained statements about PH screening that panelists rated from -5 (strongly disagree) to 5 (strongly agree)., Results: Panelists reached consensus on several triggers for suspicion of PH including the following: symptoms, clinical signs, findings on chest CT scan or other imaging, abnormalities in pulse oximetry, elevations in brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP), and unexplained worsening in pulmonary function tests or 6-min walk distance. Echocardiography and BNP/NT-proBNP were identified as screening tools for PH. Right heart catheterization was deemed essential for confirming PH., Interpretation: Many patients with ILD may benefit from early evaluation of PH now that an approved therapy is available. Protocols to evaluate patients with ILD often overlap with evaluations for pulmonary hypertension-interstitial lung disease and can be used to assess the risk of PH. Because standardized approaches are lacking, this consensus statement is intended to aid physicians in the identification of patients with ILD and possible PH, and provide guidance for timely right heart catheterization., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate-risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined. We developed an expert consensus statement on the transition to sGC and other treatment escalations and transitions in PAH using a modified Delphi process. The Delphi process used a panel of 20 physicians with expertise in PAH. Panelists answered three questionnaires on the management of treatment escalations and transitions in PAH. The initial questionnaire included open-ended questions. Later questionnaires consolidated the responses into statements that panelists rated on a Likert scale from -5 ( strongly disagree ) to +5 ( strongly agree ) to determine consensus. The Delphi process produced several consensus recommendations. Escalation should be considered for patients who are at high risk or not achieving treatment goals, by adding an agent from a new class, switching from oral to parenteral prostacyclins, or increasing the dose. Switching to a new class or within a class should be considered if tolerability or other considerations unrelated to efficacy are affecting adherence. Switching from a PDE5i to an SGC activator may benefit patients with intermediate risk who are not improving on their present therapy. These consensus-based recommendations may be helpful to clinicians and beneficial for patients when evidence-based guidance is unavailable., Competing Interests: Franck F. Rahaghi reports consultation, research, and speakership honoraria from Bayer and Janssen, consultation and speakership from United Therapeutics, and consultation fees from Acceleron. Vijay P. Balasubramanian reports a research grant from United Therapeutics and serves on a speakers bureau for Bayer. Robert C. Bourge reports research grant support to my institution from United Therapeutics and Bayer, and service on a Scientific Advisory Board at United Therapeutics. Murali M. Chakinala reports grants or contracts from Actelion/Janssen, Bayer, Medtronic, NIH, Reata, Liquidia, Phase Bio, Complexa, United Therapeutics, Altavant, Trio Health Analytics, Reata, Acceleron, Arena, and Gossamer; consulting fees from Altavant, Vaderis Therapeutics, Aerovate, Reata, VWave, and Arena; honoraria from Bayer, Gilead, Simply Speaking, WebMD, and United Therapeutics; support for attending meetings and/or travel from Actelion/Janssen, United Therapeutics, Bayer, Acceleron, Reata, and Gilead; participation on a Data Safety Monitoring Board or Advisory Board for Actelion/Janssen, Express Scripts, Phase Bio, Altavant, Gossamer, United Therapeutics, Bayer, Acceleron, and Liquidia; and leadership or a fiduciary role in the Pulmonary Hypertension Association and the Cure HHT Global Research and Medical Advisory Board. Michael S. Eggert reports research contracts with United Therapeutics (BREEZE and ADVANCE Outcomes), Acceleron, and Actelion. Jean M. Elwing reports grants from Actelion, Acceleron, Reata, United Therapeutics, Liquidia, Phase Bio, Complexa, Gossamer Bio, Bayer, Arena, Eiger, Akros, Bellerophon, and Lung LLC and consulting fees from United Therapeutics, Acceleron, Liquidia, Altavant, Bayer, Gossamer Bio, Actelion, Bayer. Jeremy Feldman reports consulting and giving talks for Bayer, United Therapeutics, and Jansen. Christopher King reports personal fees from Actelion, personal fees from Genentech, United Therapeutics, and Boehringer Ingelheim; has served on advisory boards for and is on the Speakers’ Bureau of Actelion, Boehringer‐Ingelheim Pharmaceuticals, and United Therapeutics. James R. Klinger reports that his institution receives research funding from United Technologies, service on a Steering Committee and a Clinical Outcomes Committee for Bayer, and a leadership role in the Pulmonary Hypertension Association. Stephen C. Mathai reports personal fees from United Therapeutics; participation on a data safety monitoring board or advisory board from United Therapeutics, Actelion, and Bayer, and leadership or a fiduciary role in the PCORI Rare Disease Advisory Panel and the World Symposium on Pulmonary Hypertension. John Wesley McConnell reports consulting fees from Actelion, Bayer, Gossamer, Altavant, and Liquidia; honoraria from Actelion, Bayer, Simply Speaking, Impact PH, and Reata, and participation on a data safety monitoring board or advisory board for Actelion, Liquidia, Gossamer, and Altavant. Harold I. Palevsky reports honoraria for serving on scientific advisory boards for Acceleron, Actelion/Janssen, PhaseBio and United Therapeutics, and serving on a DSMB for United Therapeutics. Ricardo Restrepo‐Jaramillo reports serving on speaker's bureau for United Therapeutics, Bayer, and Actelion. Zeenat Safdar reports serving on a speakers bureau, consultation and advisory boards for Actelion, United Therapeutics, Boehringer Ingelheim, Bayer, and Roche. Jeffrey S. Sager reports personal fees from Bayer pharmaceuticals, grants and personal fees from United Therapeutics, grants and personal fees from Janssen (J and J), and grants from Reata outside the submitted work. Namita Sood reports a speaking fee from Bayer. Roxana Sulica reports research grants from Bayer, United Therapeutics, Complexa, and Reata, and serves on advisory boards for Actelion, Bayer, United Therapeutics, and Reata. R. James White reports research grants from United Therapeutics, Reata, Bayer, Merck, and Janssen and consulting fees from Merck and Bayer. Nicholas S. Hill reports honoraria from Axon Research for this study; grants to his institution from Actelion, Bayer, Gilead, and United Therapeutics; consulting fees from United Therapeutics; and participation in Data Safety Monitoring Boards for United Therapeutics and Pfizer. All authors had access to the Delphi questionnaire analysis and data and participated in the review, revision, and approval of the content of the manuscript for submission. Charles D. Burger reports no disclosures or conflicts of interest., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Considering that antimicrobial resistance (AMR) is a global challenge, there is a dire need to assess the knowledge, attitude, and practice (KAP) of clinicians in AMR endemic countries. The current multicenter, cross-sectional study aimed at highlighting gaps in antimicrobial (AM) stewardship and AMR among practicing doctors working in public tertiary care teaching hospitals of Lahore, Pakistan. A KAP survey, based on a self-administered questionnaire containing 45 questions, was distributed among 336 clinicians in 6 randomly selected hospitals. Overall, 92% of the clinicians considered AMR as a worldwide problem but only 66% disagreed that cold and flu symptoms require antibiotics. Moreover, around 68% of the doctors felt confident about their practice in AM but still, 96% felt the need to get more knowledge about AM drugs. The need for refresher courses on rational antibiotic use was expressed by 84% of the participants. The main contributing factors considered for AMR by the doctors included excessive AM usage in the medical profession (87.1%) and multiple antibiotics per prescription (76.4%). Pharmacologically, AM spectrum was accurately chosen by 1.4% for Ampicillin, 0.003% for Erythromycin and 0% for Levofloxacin. Clinically, more than 50% of the clinicians used miscellaneous AM for empirical therapy of respiratory tract infection and cholecystitis. The data was analyzed using Statistical Package for Social Sciences (SPSS) version 25. It is concluded that the knowledge of clinicians is relatively poor for AM spectrum and drugs of choice for certain infections. However, the clinicians are aware of their shortcomings and desire for improvement., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Real-world dosing and titration of parenteral (subcutaneous, SC; intravenous, IV) prostacyclin, a mainstay of pulmonary arterial hypertension (PAH) treatment, is not always consistent with prescribing information or randomized trials and has yet to be adequately characterized. The current study describes real-world outpatient dosing and titration patterns over time, in PAH patients initiated on SC or IV treprostinil. A longitudinal, cross-sectional analysis of medication shipment records from US specialty pharmacy services between 2009 and 2018 was conducted to determine dosing and titration patterns of SC or IV treprostinil in the outpatient setting beginning with the patient's first shipment. The sample for analysis included shipment records for 2647 patients (IV = 1040, SC = 1607). Although more patients were started on SC treprostinil than IV, median initial outpatient IV treprostinil dose (11 ng/kg/min at month on therapy one [MOT1]) was consistently and statistically significantly higher than initial outpatient SC dose (7.5 ng/kg/min at MOT1; p  < 0.01). However, the SC treprostinil dose acceleration rate (DAR) was more aggressive from MOT1 to MOT6, MOT12, and MOT24, leading to a higher dose achieved at later timepoints. All between-group DAR differences were statistically significant ( p  < 0.001). This study provides evidence that real-world prescribing patterns of parenteral treprostinil in the outpatient setting differs from dosing described in pivotal trials, with important differences between SC and IV administration. Although initial outpatient IV treprostinil dosing was higher, SC titration was accelerated more aggressively and a higher dose was achieved by MOT3 suggesting that factors specific to SC administration (e.g., site pain) may not limit dosing and titration as previously thought., Competing Interests: Lana Melendres‐Groves has received honoraria and/or fees for consultancy and advisory committees from United Therapeutics Corporation, outside of the submitted work; Zeenat Safdar has received honoraria and/or fees for consultancy and advisory committees from United Therapeutics Corporation, Bayer Pharmaceuticals, Actelion Pharmaceuticals, Boehringer Ingelheim, and Genentech, outside the submitted work. Margaret R. Sketch, Meredith Broderick, and Andrew C. Nelsen are employees of United Therapeutics Corporation. Dasom Lee has nothing to disclose. Vijay P. Balasubramanian has received research support, honoraria, and/or fees for consultancy and an advisory committee from United Therapeutics Corporation, speaker bureau, and advisory committee honoraria and/or fees from Bayer Pharmaceuticals, and speaker bureau honoraria and/or fees from Boehringer Ingelheim, outside the submitted work., (© 2021 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)