Pulmonary arterial hypertension outcomes upon endothelin-1 receptor antagonist switch to macitentan

Objectives: To assess whether switching patients with suboptimally controlled pulmonary arterial hypertension from bosentan or ambrisentan to macitentan would improve six-minute walk test (6MWT) distance and World Health Organization functional class. Methods: This was a retrospective cohort analysis of 37 patients from a single center. Patients were separated into three heterogeneous treatment groups and followed for 18 months: switch group (n¼14): patients switched to macitentan from bosentan/ambrisentan; added group (n¼11): patients who began macitentan as de novo therapy (n¼5) or who added macitentan to an existing sildenafil regimen (n¼6); and control group (n¼12): patients for whom sildenafil and/or bosentan/ambrisentan therapy was unchanged. Results: Mortality was observed in two patients (one each, switch and added groups). Patients in the control group had one hospital admission and 100% survival. There was significant improvement in functional class for the switch and added groups. Statistically significant improvement was observed in 6MWT distance in the added group alone. Overall, 92% of patients continued macitentan throughout the study. Conclusion: Macitentan was well tolerated. For bosentan/ambrisentan-treated patients with suboptimally controlled pulmonary arterial hypertension, switching to macitentan may facilitate an improvement in functional class

Review of bosentan in the management of pulmonary arterial hypertension

The dual endothelin receptor antagonist, bosentan, is an orally active therapy, which is effective in the treatment of pulmonary arterial hypertension (PAH). This review critically appraises the evidence for the efficacy of bosentan in idiopathic and familial PAH, in PAH associated with connective tissue disease and in PAH which may develop in association with other conditions. Data from the pivotal placebo controlled studies and their open labeled extensions as well as long term survival and quality of life data is presented. Data is also presented on the potential benefit of bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension. The safety and tolerability of bosentan as well as drug interactions are discussed. Dosage recommendations in adults and pediatrics are presented. An algorithm is provided to guide the reader in monitoring potential increases in alanine and aspartate transaminase levels that may occur with bosentan use and the dose adjustments that are recommended as a result of any increase in the levels of these enzymes are shown. Finally, the role of bosentan as part of combination therapy in PAH is examined

Advances in screening for undiagnosed atrial fibrillation for stroke prevention and implications for patients with obstructive sleep apnoea: A literature review and research agenda

Atrial fibrillation (AF) is the most common type of sustained cardiac arrhythmia encountered in clinical practice, and its burden is expected to increase in most developed countries over the next few decades. Because AF can be silent, it is often not diagnosed until an AF-related complication occurs, such as stroke. AF is also associated with increased risk of heart failure, lower quality of life, and death. Anticoagulation has been shown to dramatically decrease embolic risk in the setting of atrial fibrillation, resulting in growing interest in early detection of previously undiagnosed AF. Newly developed monitoring devices have improved the detection of AF and have been recommended in guidelines for screening of AF in individuals aged 65 years and over. While screening is currently targeted to these older individuals, younger patients with obstructive sleep apnoea (OSA) are at higher risk of AF and stroke than the general population, indicating a need for targeted early detection of AF in this group. Compared to individuals without OSA, those with OSA are four times more likely to develop AF, and the risk of AF is strongly associated with OSA severity. The overall prevalence of AF among individuals with OSA remains unknown because of limitations related to study design and to the conventional methods previously used for AF detection. Recent and emerging technological advances may improve the detection of undiagnosed AF in high-risk population groups, such as those with OSA. In this clinical review, we discuss the methods of screening for AF and the applications of newer technologies for AF detection in patients with OSA. We conclude the review with a brief description of our research agenda in this area

Exercise Intolerance in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is associated with symptoms of dyspnea and fatigue, which contribute to exercise limitation. The origins and significance of dyspnea and fatigue in PAH are not completely understood. This has created uncertainly among healthcare professionals regarding acceptable levels of these symptoms, on exertion, for patients with PAH. Dysfunction of the right ventricle (RV) contributes to functional limitation and mortality in PAH; however, the role of the RV in eliciting dyspnea and fatigue has not been thoroughly examined. This paper explores the contribution of the RV and systemic and peripheral abnormalities to exercise limitation and symptoms in PAH. Further, it explores the relationship between exercise abnormalities and symptoms, the utility of the cardiopulmonary exercise test in identifying RV dysfunction, and offers suggestions for further research

Skeletal Sarcoidosis

Osseous sarcoidosis is an uncommon manifestation, reported in 3–13% of patients with sarcoidosis. Although older literature suggested that hands and feet are most commonly affected, axial bone involvement may be more common than previously reported, since earlier studies relied mostly on plain X-rays, which may be less sensitive for axial bone lesions. Newer imaging modalities such as MRI and PET/CT scanning have demonstrated a larger incidence of vertebral involvement. Bone lesions are commonly asymptomatic and patients who have bone involvement may have higher incidences of multi-organ involvement. Osseous sarcoidosis appears to be mainly osteolytic in nature, but the radiographic appearance may be indistinguishable from other osteolytic lesions and therefore a biopsy is usually required to confirm the diagnosis. The histological findings of sarcoidosis in the bone are the same as in other tissues of the body. No general consensus exists for the treatment of bone sarcoidosis but corticosteroids are the most commonly prescribed first-line drugs. Methotrexate is the most widely studied steroid-sparing agent for sarcoidosis and it has been reported useful for a variety of organ symptoms, but especially where there is bone involvement

Dilemmas in anticoagulation and use of inferior vena cava filters in venous thromboembolism; A survey of respiratory physicians, haematologists and medical oncologists and a review of the literature

© The Author(s) 2021. Twenty percent of patients with Cancer Associated Thrombosis receive an inferior vena cava filter annually. Insertion is guided by practice guidelines, which do not specify or discuss the use of inferior vena cava filters in malignancy. Adherence to these guidelines is known to be variable. We aimed to see if there was consistent management of venous thromboembolism among Medical Oncologists/Haematologists and Respiratory Physicians, with respect to inferior vena cava filter use in the setting of suspected and confirmed malignancy. Medical Oncologists, Haematologists and Respiratory Physicians were surveyed with four theoretical cases. Case 1 concerns a patient who develops a pulmonary embolism following spinal surgery. Cases 2 and 4 explore the use of inferior vena cava filters in the setting of malignancy. Case 3 covers the role of inferior vena cava filters in recurrent thrombosis despite systemic anticoagulation. There were 56 responses, 32 (57%) Respiratory Physicians and 24 (43%) Haematologists/Oncologists. Respiratory Physicians were significantly more likely to insert an inferior vena cava filter in case 1 (p = 0.04) whilst Haematologists/Medical Oncologists were more likely to insert an inferior vena cava filter in case 3 (p = 0.03). No significant differences were found in cases 2 and 4. There were significant disparities in terms of type and timing of anticoagulation. Consistency of recommendations with guidelines was variable likely in part because guidelines are themselves inconsistent. The heterogeneity in responses highlights the variations in venous thromboembolism management, especially in Cancer Associated Thrombosis. International Societies should consider addressing inferior vena cava filter use specifically in the setting of Cancer Associated Thrombosis. Collaboration between interested specialities would assist in developing consistent, evidence-based guidelines for the use of inferior vena cava filters in the management of venous thromboembolism

Australian perspective regarding recommendations for physical activity and exercise rehabilitation in pulmonary arterial hypertension

Aim: To determine the opinion of health care professionals within Australia, regarding acceptable levels of exertion and symptoms, and referral for exercise rehabilitation in patients with pulmonary arterial hypertension (PAH). Method: In 2010, 76 health care professionals at a specialist pulmonary hypertension meeting in Australia were surveyed using a self-administered questionnaire. The questionnaire included case studies of patients with PAH in World Health Organization (WHO) functional classes II–IV. For each case study, respondents were asked to report their opinion regarding the acceptable level of exertion and symptoms during daily activities, and whether they would refer the patient for exercise rehabilitation. Three additional questions asked about advice in relation to four specific physical activities. Results: The response rate was 70% (n = 53). Overall, 58% of respondents recommended patients undertake daily activities 'as tolerated'. There was no consensus regarding acceptable levels of breathlessness or fatigue, but the majority of respondents considered patients should have no chest pain (73%) and no more than mild light-headedness (92%) during daily activities. Overall, 63% of respondents would have referred patients for exercise rehabilitation. There was little difference in opinion regarding the acceptable level of exertion or symptoms, or referral for exercise rehabilitation, according to functional class. However, the patients' functional class did influence the advice given regarding the specific physical activities. Conclusion: In 2010, there were inconsistencies between individual health care professionals within Australia regarding appropriate levels of physical exertion and acceptable symptoms during daily activities. Almost two-thirds of the respondents reported they would refer patients for exercise rehabilitation

Patterns of immunotherapy-induced pneumonitis in patients with non-small-cell lung cancer: A case series

Background: Immunotherapy has become an efficacious option in the management of solid organ malignancies. Immune-related adverse events including pneumonitis are well described and may be particularly of concern in patients receiving immunotherapy for non-small-cell lung cancer. Case presentations: In this paper, we describe three cases of immunotherapy-induced pneumonitis occurring in the management of lung malignancy. Our cases include a 54-year-old Caucasian woman with squamous cell lung cancer who was successfully rechallenged with immunotherapy after prior significant pneumonitis, a 65-year-old Caucasian man with metastatic squamous cell lung cancer who developed pneumonitis after multiple cycles of uneventful immunotherapy, and a 73-year-old Caucasian man with squamous cell lung cancer who developed early-onset pneumonitis with rebound on steroid taper. Conclusions: This case series has provided further insight into the presentation and risk factors for pneumonitis in patients with non-small-cell lung cancer. Each of the cases of immunotherapy-induced pneumonitis illustrates the different potential patterns that may arise when immunotherapy-induced pneumonitis develops. This case series provides key learning points that may assist physicians managing non-small-cell lung cancer with immunotherapy

Patterns of immunotherapy-induced pneumonitis in patients with non-small-cell lung cancer: A case series

Background: Immunotherapy has become an efficacious option in the management of solid organ malignancies. Immune-related adverse events including pneumonitis are well described and may be particularly of concern in patients receiving immunotherapy for non-small-cell lung cancer. Case presentations: In this paper, we describe three cases of immunotherapy-induced pneumonitis occurring in the management of lung malignancy. Our cases include a 54-year-old Caucasian woman with squamous cell lung cancer who was successfully rechallenged with immunotherapy after prior significant pneumonitis, a 65-year-old Caucasian man with metastatic squamous cell lung cancer who developed pneumonitis after multiple cycles of uneventful immunotherapy, and a 73-year-old Caucasian man with squamous cell lung cancer who developed early-onset pneumonitis with rebound on steroid taper. Conclusions: This case series has provided further insight into the presentation and risk factors for pneumonitis in patients with non-small-cell lung cancer. Each of the cases of immunotherapy-induced pneumonitis illustrates the different potential patterns that may arise when immunotherapy-induced pneumonitis develops. This case series provides key learning points that may assist physicians managing non-small-cell lung cancer with immunotherapy

Inferior vena cava filters (IVCFs): A review of uses and application to international guidelines at a single Australian center; implications of venous thromboembolism associated with malignancy

Venous thromboembolism (VTE) is a potentially lethal event. Anticoagulation is the cornerstone of treatment. Inferior vena cava filters (IVCFs) may be used in circumstances when anticoagulation is contraindicated or as an adjunct to anticoagulation. IVCF use is not without controversy due to concerns over their safety profile, differences in guidelines from international societies, and a limited randomized control trial evidence. We retrospectively undertook a review of IVCF use over a three-year period (2014–2016) at our center, which has a large oncology service but no trauma unit. There were 44 patients with successful IVCF insertion and one patient with an unsuccessful attempt. Indications for insertion included: a contraindication to anticoagulation (n¼28); recurrent VTE on anticoagulation (n¼10); and extensive VTE (n¼7). There were 13 retrieval attempts, of which ten were successful. There were five documented IVCF complications (tilting: n¼2, IVC thrombus: n¼3) with one episode of IVCF failure and two episodes of deep vein thrombosis during the follow-up period. Of the patients, 71% had an active malignancy (of whom 71% had metastatic disease). Seventeen patients died due to progressive malignancy during the study period. There were no life-threatening VTEs or IVCF associated mortalities. Adherence with published international guidelines was variable. Patients with malignancy were less likely to undergo IVCF retrieval and had a reduced rate of retrieval success. None of the international guidelines comment on the use of IVCFs in patients with malignancy despite being commonly used. IVCF use may be an underappreciated tool in this group