The use of combination therapy in pulmonary arterial hypertension: new developments

There is a strong clinical rationale for combination therapy in pulmonary arterial hypertension (PAH), as several pathological pathways have been implicated in its pathogenesis and no single agent has yet been shown to deliver completely satisfactory results. Registry data indicate that use of combination therapy is in fact common in existing clinical practice, even though support has been largely empirical or derived from small-scale observational studies. Data from large, adequately powered, randomised controlled trials of combination therapy in PAH are now emerging and suggest that combination therapy may be clinically beneficial. Studies of bosentan in combination with prostanoids and phosphodiesterase (PDE)-5 inhibitors show consistent evidence of improvements in exercise capacity compared with placebo. Similar improvements have been observed with PDE-5 inhibitors in combination with prostanoids. The appropriate timing of combination therapy requires further evaluation but goal-oriented therapy using combinations of oral and inhaled drugs has been shown to provide acceptable long-term results in patients with advanced PAH. Monitoring should be performed regularly and be based on repeatable, noninvasive, measurable parameters that have prognostic value

The Women’s Empowerment in Livestock Index

The empowerment of women in the livestock sector is fundamental to achieve gender equality. It also is instrumental for increased household productivity and improved household health and nutrition. Diverse strategies exist to empower women, yet these strategies are difficult to prioritize without a reliable and adapted means to measure women’s empowerment. One quantitative measure is the Women’s Empowerment in Agriculture Index (WEAI). Despite its reliability in certain agricultural contexts, the WEAI requires adaptation in settings where livestock farming is the dominant form of livelihood. Using the WEAI as a starting point, a multidisciplinary team of researchers developed the Women’s Empowerment in Livestock Index (WELI), a new index to assess the empowerment of women in the livestock sector. This paper presents the WELI and the dimensions of empowerment it includes: (1) decisions about agricultural production; (2) decisions related to nutrition; (3) access to and control over resources; (4) control and use of income; (5) access to and control of opportunities; and (6) workload and control over own time. The paper illustrates the use of the WELI by introducing pilot findings from dairy smallholders in four districts of northern Tanzania. The paper addresses considerations for the appropriate use and adaptation of the WELI to balance the needs for context specificity and cross-cultural comparisons; it also discusses its limitations. The paper recommends participatory and qualitative methods that are complementary to the WELI to provide context-specific insights on the processes of women’s empowerment in the livestock sector

Pregnancy in women with pulmonary hypertension

Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced therapies for pulmonary hypertension decrease the risk, though some promising results have been reported. However, pregnancy should still be regarded as contraindicated in women with pulmonary hypertension. When pregnancy occurs and termination is declined, pregnancy and delivery should be managed by multidisciplinary services with experience in the management of both pulmonary hypertension and high-risk pregnancies

Pulmonary arterial hypertension: an update

Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance and specific histological changes. It is a progressive disease finally resulting in right heart failure and premature death. Typical symptoms are dyspnoea at exercise, chest pain and syncope; furthermore clinical signs of right heart failure develop with disease progression. Echocardiography is the key investigation when pulmonary hypertension is suspected, but a reliable diagnosis of PAH and associated conditions requires an intense work-up including invasive measurement by right heart catheterisation. Treatment includes general measures and drugs targeting the pulmonary artery tone and vascular remodelling. This advanced medical therapy has significantly improved morbidity and mortality in patients with PAH in the last decade. Combinations of these drugs are indicated when treatment goals of disease stabilisation are not met. In patients refractory to medical therapy lung transplantation should be considered an option

A scoping review of market links between value chain actors and small-scale producers in developing regions

Sustainable Development Goal 2 aims to end hunger, achieve food and nutrition security and promote sustainable agriculture by 2030. This requires that small-scale producers be included in, and benefit from, the rapid growth and transformation under way in food systems. Small-scale producers interact with various actors when they link with markets, including product traders, logistics firms, processors and retailers. The literature has explored primarily how large firms interact with farmers through formal contracts and resource provision arrangements. Although important, contracts constitute a very small share of smallholder market interactions. There has been little exploration of whether non-contract interactions between small farmers and both small- and large-scale value chain actors have affected small farmers’ livelihoods. This scoping review covers 202 studies on that topic. We find that non-contract interactions, de facto mostly with small and medium enterprises, benefit small-scale producers via similar mechanisms that the literature has previously credited to large firms. Small and medium enterprises, not just large enterprises, address idiosyncratic market failures and asset shortfalls of small-scale producers by providing them, through informal arrangements, with complementary services such as input provision, credit, information and logistics. Providing these services directly supports Sustainable Development Goal 2 by improving farmer welfare through technology adoption and greater productivity

Relationship Between Time From Diagnosis and Morbidity/Mortality in Pulmonary Arterial Hypertension: Results From the Phase III GRIPHON Study

BACKGROUND: Early initiation of pulmonary arterial hypertension (PAH) therapies is associated with improved long-term outcomes, yet data on the early use of prostacyclin pathway agents are limited. In these post hoc analyses of the Prostacyclin (PGI(2)) Receptor Agonist In Pulmonary Arterial Hypertension (GRIPHON) study, the largest randomized controlled trial for PAH to date, the prognostic value of time from diagnosis and its impact on treatment response were examined. RESEARCH QUESTION: How does time from diagnosis impact morbidity/mortality events and response to selexipag treatment in patients with PAH? STUDY DESIGN AND METHODS: The GRIPHON study randomly assigned 1,156 patients with PAH to selexipag or placebo treatment. Patients were categorized post hoc into a time from diagnosis of ≤ 6 months and > 6 months at randomization. Hazard ratios (selexipag vs placebo) were calculated for the primary end point of morbidity/mortality by time from diagnosis using Cox proportional hazard models. RESULTS: Time from diagnosis was ≤ 6 months in 34.9% and > 6 months in 65.1% of patients. Time from diagnosis was prognostic of morbidity/mortality, with newly diagnosed patients having a poorer long-term outcome than patients diagnosed for longer. Compared with placebo, selexipag reduced the risk of morbidity/mortality in patients with a time from diagnosis of ≤ 6 months and > 6 months, with a more pronounced effect in newly diagnosed patients (hazard ratio, 0.45 [95% CI, 0.33-0.63] and 0.74 [95% CI, 0.57-0.96], respectively; P = .0219 for interaction). INTERPRETATION: In the GRIPHON study, newly diagnosed PAH patients had a worse prognosis than patients with a longer time from diagnosis. The benefit of selexipag treatment on disease progression was more pronounced in patients treated earlier than in patients treated later. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01106014; URL: www.clinicaltrials.gov

risk assessment in pulmonary arterial hypertension insights from the griphon study

BACKGROUND Approaches to risk assessment in pulmonary arterial hypertension (PAH) include the noninvasive French risk assessment approach (number of low-risk criteria based on the European Society of Cardiology and European Respiratory Society guidelines) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH. METHODS GRIPHON randomized 1,156 patients with PAH to selexipag or placebo. Post-hoc analyses were performed on the primary composite end-point of morbidity/mortality by the number of low-risk criteria (World Health Organization functional class I-II; 6-minute walk distance >440 m; N-terminal pro-brain natriuretic peptide RESULTS Both the number of low-risk criteria and the REVEAL 2.0 risk category were prognostic for morbidity/mortality at baseline and any time-point during the study. Patients with 3 low-risk criteria at baseline had a 94% reduced risk of morbidity/mortality compared to patients with 0 low-risk criteria and were all categorized as low-risk by REVEAL 2.0. The treatment effect of selexipag on morbidity/mortality was consistent irrespective of the number of low-risk criteria or the REVEAL 2.0 risk category at any time-point during the study. Selexipag-treated patients were more likely to increase their number of low-risk criteria from baseline to week 26 than placebo-treated patients (odds ratio 1.69, p = 0.0002); similar results were observed for REVEAL 2.0 risk score. CONCLUSIONS These results support the association between risk profile and long-term outcome and suggest that selexipag treatment may improve risk profile

High levels of healthcare utilization prior to diagnosis in idiopathic pulmonary arterial hypertension support the feasibility of an early diagnosis algorithm: the SPHInX project.

Idiopathic pulmonary arterial hypertension (iPAH) is a rare progressive, life-shortening disease, usually diagnosed at an advanced stage. We hypothesize that patients with iPAH exhibit patterns of health-seeking behavior before diagnosis that will allow the development of earlier identification tools. The Sheffield Pulmonary Hypertension IndeX (SPHInX) project aims to develop a predictive algorithm based on routinely collected healthcare resource utilization (HCRU) data. This report focuses on the initial feasibility of the project, examining whether Hospital Episode Statistics (HES) data from the National Health Service in England have sufficient richness to support the development of an early diagnosis algorithm. This is a two-stage study. First, hospital interactions during 2009-2014 captured in HES data identified 127,815 adult patients with pulmonary hypertension (PH) ICD-10 codes, containing a probable iPAH cohort with incidence and demographics similar to the reported literature. HCRU was high in the three years before diagnosis. Second, to examine HCRU in patients with a confirmed iPAH diagnosis, we built the SPHInX dataset incorporating all patients investigated for suspected PH in the Sheffield Pulmonary Vascular Disease Unit during 2008-2016 (n = 6674). For the SPHInX dataset, data could be linked to HES in 98.6% of cases and patients with confirmed iPAH had similar levels of pre-diagnosis HCRU. In conclusion, patients with probable iPAH identified using HES and patients with confirmed iPAH have high levels of HCRU for several years before diagnosis. Artificial intelligence models will now be used to develop the SPHInX algorithm to screen for undiagnosed iPAH in the general population