In the past 2 decades, major changes have occurred in the epidemiological and treatment landscape of pulmonary arterial hypertension (PAH). Previously regarded as a disease of the young and ...middle-aged, contemporary registries from the Western world have demonstrated an increase in the age of patients with PAH, many of whom are elderly with multiple comorbidities. Another important observation is the improvement in survival of patients with PAH in the modern treatment era compared with historical cohorts, before the availability of advanced therapy. The management of PAH has also become more complex, and numerous drugs are now approved that target the endothelin 1, nitric oxide, and prostacyclin pathways. Combining drugs from different classes is now considered the standard of care and has been demonstrated to improve outcomes. Furthermore, the current treatment paradigm is the early use of combination therapy, often at the time of diagnosis, particularly in patients with severe disease. This Review provides a comprehensive update on the epidemiology and pharmacotherapy of PAH.
The first World Health Organization (WHO) Symposium on Pulmonary Hypertension was held in 1973 in response to the sudden increase in the number of patients with primary pulmonary hypertension (PPH) ...1. This epidemic was related to the intake of appetite-suppressing drugs and only 17 clinicians and scientists convened at the landmark first WHO meeting. Back then, PPH was a mysterious condition without any known therapy. Two decades later, in 1993, the first consensus guideline on PPH endorsed by a specialist society was published 2. The chairman of the 1993 consensus document, Lewis Rubin (University of California, San Diego, CA, USA), recognised the limited knowledge and science in the field at the time, and remarked some years later that "our task was relatively easy...since the published literature was fairly limited. Accordingly, our guidelines were largely driven by expert opinion" 3. Since then, we have witnessed dramatic leaps in our knowledge of both the basic and clinical science of pulmonary hypertension. Intravenous epoprostenol, the first of many targeted pulmonary arterial hypertension (PAH) therapies that are currently available, gained US Food and Drug Administration approval in 1995. The turn of the 21st century saw the emergence of efficacious oral therapies that have altered the care of patients with PAH.
Pulmonary arterial hypertension (PAH) remains an incurable disease associated with an unacceptably high early mortality, despite advances in therapeutic options. The disease is clinically silent ...until late in its natural history, when most of the distal pulmonary arteries have been obliterated. Early diagnosis of PAH is associated with improved long-term survival, and screening of at-risk populations is, therefore, a rational strategy to improve outcomes in this condition. Doppler echocardiography is the most widely used screening tool in current clinical practice. The role of evidence-based screening strategies has been clarified by research such as the DETECT study in patients with systemic sclerosis. A multimodal approach, using a range of noninvasive tests, improves the performance of screening algorithms. Right heart catheterization is mandatory to confirm a diagnosis of PAH. Uncertainties exist about the definition and prognostic relevance of pulmonary hypertension during exercise, but accumulating evidence suggests that stress testing of the pulmonary circulation can unmask clinically important early disease. Novel tools for the early detection of pulmonary vascular disease are urgently needed, given the substantial limitations of currently available techniques.
Right ventricular adaptation to the increased pulmonary arterial load is a key determinant of outcomes in pulmonary hypertension (PH). Pulmonary vascular resistance (PVR) and total arterial ...compliance (C) quantify resistive and elastic properties of pulmonary arteries that modulate the steady and pulsatile components of pulmonary arterial load, respectively. PVR is commonly calculated as transpulmonary pressure gradient over pulmonary flow and total arterial compliance as stroke volume over pulmonary arterial pulse pressure (SV/PApp). Assuming that there is an inverse, hyperbolic relationship between PVR and C, recent studies have popularised the concept that their product (RC-time of the pulmonary circulation, in seconds) is "constant" in health and diseases. However, emerging evidence suggests that this concept should be challenged, with shortened RC-times documented in post-capillary PH and normotensive subjects. Furthermore, reported RC-times in the literature have consistently demonstrated significant scatter around the mean. In precapillary PH, the true PVR can be overestimated if one uses the standard PVR equation because the zero-flow pressure may be significantly higher than pulmonary arterial wedge pressure. Furthermore, SV/PApp may also overestimate true C. Further studies are needed to clarify some of the inconsistencies of pulmonary RC-time, as this has major implications for our understanding of the arterial load in diseases of the pulmonary circulation.
Pulmonary arterial hypertension (PAH) can be a rapidly progressive disorder and is associated with high rate of mortality, despite medical intervention. With the availability of effective therapy, ...early disease detection is an important strategic objective to improve treatment outcomes. Resting echocardiography is currently the recommended screening modality for high-risk population groups. However, it is clear that derangements in resting haemodynamics (and symptoms) are late sequelae of the pathobiological processes that begin in the distal pulmonary arteries. Exercise stress may unmask early pulmonary vascular dysfunction but the definition, clinical significance, and natural history of 'exercise PAH' remain undefined. We will review the currently available and potential future strategies aimed at early disease detection, and propose that ultimately the way forward is to detect disease at a stage prior to the rise in resting pulmonary artery pressure.
Abstract This study characterizes the patient and clinical factors influencing the economic burden of periprosthetic joint infection (PJI) in the United States. The 2001-2009 Nationwide Inpatient ...Sample was used to identify total hip and knee arthroplasties using International Classification of Diseases, Ninth Revision , procedure codes. The relative incidence of PJI ranged between 2.0% and 2.4% of total hip arthroplasties and total knee arthroplasties and increased over time. The mean cost to treat hip PJIs was $5965 greater than the mean cost for knee PJIs. The annual cost of infected revisions to US hospitals increased from $320 million to $566 million during the study period and was projected to exceed $1.62 billion by 2020. As the demand for joint arthroplasty is expected to increase substantially over the coming decade, so too will the economic burden of prosthetic infections.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Periprosthetic joint infection (PJI) is a potentially deadly complication of total joint arthroplasty. This study was designed to address how the incidence of PJI and outcome of treatment, including ...mortality, are changing in the population over time.
Primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients with PJI from the 100% Medicare inpatient data set (2005-2015) were identified. Cox proportional hazards regression models for risk of PJI after THA/TKA (accounting for competing risks) or risk of all-cause mortality after PJI were adjusted for patient and clinical factors, with year included as a covariate to test for time trends.
The unadjusted 1-year and 5-year risk of PJI was 0.69% and 1.09% for THA and 0.74% and 1.38% for TKA, respectively. After adjustment, PJI risk did not change significantly by year for THA (P = .63) or TKA (P = .96). The unadjusted 1-year and 5-year overall survival after PJI diagnosis was 88.7% and 67.2% for THA and 91.7% and 71.7% for TKA, respectively. After adjustment, the risk of mortality after PJI decreased significantly by year for THA (hazard ratio = 0.97; P < .001) and TKA (hazard ratio = 0.97; P < .001).
Despite recent clinical focus on preventing PJI, we are unable to detect substantial decline in the risk of PJI over time, although mortality after PJI has declined. Because PJI risk appears not to be changing over time, the incidence of PJI is anticipated to scale up proportionately with the demand for THA and TKA, which is projected to increase substantially in the coming decade.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved ...outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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