The Miocene primate Pliobates is a pliopithecoid.

The systematic status of the small-bodied catarrhine primate Pliobates cataloniae, from the Miocene (11.6 Ma) of Spain, is controversial because it displays a mosaic of primitive and derived features compared with extant hominoids (apes and humans). Cladistic analyses have recovered Pliobates as either a stem hominoid or as a pliopithecoid stem catarrhine (i.e., preceding the cercopithecoid-hominoid divergence). Here, we describe additional dental remains of P. cataloniae from another locality that display unambiguous synapomorphies of crouzeliid pliopithecoids. Our cladistic analyses support a close phylogenetic link with poorly-known small crouzeliids from Europe based on (cranio)dental characters but recover pliopithecoids as stem hominoids when postcranial characters are included. We conclude that Pliobates is a derived stem catarrhine that shows postcranial convergences with modern apes in the elbow and wrist joints-thus clarifying pliopithecoid evolution and illustrating the plausibility of independent acquisition of postcranial similarities between hylobatids and hominids.

Recognition, diagnosis, and operability assessment of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Early recognition and diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is crucial for improving prognosis and reducing the disease burden. Established clinical practice guidelines describe interventions for the diagnosis and evaluation of CTEPH, yet limited insight remains into clinical practice variation and barriers to care. The CTEPH global cross-sectional scientific survey (CLARITY) was developed to gather insights into the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the recognition and diagnosis of CTEPH and the referral and evaluation of these patients. The survey was offered to hospital-based medical specialists through Scientific Societies and other medical organizations, from September 2021 to May 2022. Response data from 353 physicians showed that self-reported awareness of CTEPH increased over the past 10 years among 96% of respondents. Clinical practices in acute pulmonary embolism (PE) follow-up and CTEPH diagnosis differed among respondents. While 50% of respondents working in a nonexpert center reported to refer patients to an expert pulmonary hypertension/CTEPH center when CTEPH is suspected, 51% of these physicians did not report referral of patients with a confirmed diagnosis for further evaluation. Up to 50% of respondents involved in the evaluation of referred patients have concluded a different operability status than that indicated by the referring center. This study indicates that early diagnosis and timely treatment of CTEPH is challenged by suboptimal acute PE follow-up and patient referral practices. Nonadherence to guideline recommendations may be impacted by various barriers to care, which were shown to vary by geographical region.

Risk assessment and real-world outcomes in chronic thromboembolic pulmonary hypertension: insights from a UK pulmonary hypertension referral service.

OBJECTIVES: This study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Retrospective observational study. SETTING: Pulmonary hypertension referral centre in the UK. PARTICIPANTS: Adults diagnosed with CTEPH between 1 January 2012 and 30 June 2019 were included. Cohorts were retrospectively defined for operated patients (received pulmonary endarterectomy (PEA)) and not operated; further subgroups were defined based on risk score (low, intermediate or high risk for 1-year mortality) at diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographics, clinical characteristics, comorbidities, treatment patterns, HRQoL, HCRU, costs and survival outcomes were analysed. RESULTS: Overall, 683 patients were analysed (268 (39%) operated; 415 (61%) not operated). Most patients in the operated and not-operated cohorts were intermediate risk (63%; 53%) or high risk (23%; 31%) at diagnosis. Intermediate-risk and high-risk patients had higher HCRU and costs than low-risk patients. Outpatient and accident and emergency visits were lower postdiagnosis for both cohorts and all risk groups versus prediagnosis. HRQoL scores noticeably improved in the operated cohort post-PEA, and less so in the not-operated cohort at 6-18 months postdiagnosis. Survival at 5 years was 83% (operated) and 49% (not operated) and was lower for intermediate-risk and high-risk patients compared with low-risk patients. CONCLUSIONS: Findings from this study support that risk assessment at diagnosis is prognostic for mortality in patients with CTEPH. Low-risk patients have better survival and HRQoL and lower HCRU and costs compared with intermediate-risk and high-risk patients.

Patient Preferences in Pulmonary Arterial Hypertension, a Latent Class Analysis to Identify Preference Heterogeneity.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a chronic, progressive disease of the pulmonary circulation characterized by vascular remodeling that, if untreated, can lead to right heart dysfunction and death. This analysis measured heterogeneity in patient preferences for PAH-specific treatment regimens. METHOD: Adult patients with PAH with slight to marked limitations during physical activity were recruited through a patient organization in Germany. Participants completed an online best-worst scaling case 3 survey. Patients chose among 3 hypothetical treatment profiles defined by 6 benefits and risks at varying levels. Participants completed 12 choice tasks. Preference heterogeneity was assessed using latent class analysis. RESULTS: A total of 83 participants (76% female) completed the survey. Best-fit model revealed 4 classes. Class 1 (19% of participants) assigned importance to multiple attributes particularly side effects, class 2 (34%) to physical activity limitations, class 3 (30%) to survival and physical activity limitations, and class 4 (17%) to survival. No differences in sociodemographic characteristics were observed across classes. Compared with other classes, class 4 was most likely to report having marked physical activity limitations (79%) and needing daily help (100%), while considering higher daily activity levels to be ordinary (walking >1 km [71%] or climbing several flights of stairs [50%]). CONCLUSION: This first patient preference study in a PAH population suggests that physical activity limitations in addition to survival matter most to patients; however, preference heterogeneity between groups of patients was observed. Patient preferences should be considered in treatment decision making to better balance patient's expectations regarding the known risk-benefit ratio of treatment.

What do brain endocasts tell us? A comparative analysis of the accuracy of sulcal identification by experts and perspectives in palaeoanthropology.

Palaeoneurology is a complex field as the object of study, the brain, does not fossilize. Studies rely therefore on the (brain) endocranial cast (often named endocast), the only available and reliable proxy for brain shape, size and details of surface. However, researchers debate whether or not specific marks found on endocasts correspond reliably to particular sulci and/or gyri of the brain that were imprinted in the braincase. The aim of this study is to measure the accuracy of sulcal identification through an experiment that reproduces the conditions that palaeoneurologists face when working with hominin endocasts. We asked 14 experts to manually identify well-known foldings in a proxy endocast that was obtained from an MRI of an actual in vivo Homo sapiens head. We observe clear differences in the results when comparing the non-corrected labels (the original labels proposed by each expert) with the corrected labels. This result illustrates that trying to reconstruct a sulcus following the very general known shape/position in the literature or from a mean specimen may induce a bias when looking at an endocast and trying to follow the marks observed there. We also observe that the identification of sulci appears to be better in the lower part of the endocast compared to the upper part. The results concerning specific anatomical traits have implications for highly debated topics in palaeoanthropology. Endocranial description of fossil specimens should in the future consider the variation in position and shape of sulci in addition to using models of mean brain shape. Moreover, it is clear from this study that researchers can perceive sulcal imprints with reasonably high accuracy, but their correct identification and labelling remains a challenge, particularly when dealing with extinct species for which we lack direct knowledge of the brain.

Use of the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events to assess treatment tolerability in pulmonary arterial hypertension: qualitative patient research findings in current and former users of oral selexipag.

BACKGROUND: Understanding patients' perspectives regarding drug tolerability, in addition to effectiveness, provides a complete picture of the patient experience and supports more informed therapeutic decision-making. The item library of the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to measure patient-reported frequency, severity, and interference of adverse events (AEs) associated with cancer therapies. This qualitative interview study assessed the suitability of items selected from the PRO-CTCAE library for assessing tolerability of selexipag, a medication targeting the prostacyclin pathway for patients with pulmonary arterial hypertension (PAH). METHODS: Two rounds of 10 qualitative, web-assisted telephone interviews following a semi-structured guide were conducted in individuals with recent experience taking oral selexipag for PAH. Each interview included concept elicitation to gather participants' perspectives on symptomatic AEs (type, frequency, severity, and interference) and cognitive debriefing of PRO-CTCAE items addressing the most frequently reported AEs of oral selexipag. RESULTS: Interviews were conducted with 20 participants with PAH (mean [range] age 50 [24-68] years; 75% female; 85% in World Health Organization Functional Class II-III), comprising different races/ethnicities, levels of education, and employment status. Fifteen participants were currently treated with selexipag; five had taken selexipag for ≥ 6 months before discontinuing. The most frequently reported AEs included headache, jaw pain, and nausea (n = 15, 12, and 10 participants, respectively). Diarrhea and headache were identified as the most bothersome AEs by 5 and 4 participants, respectively. Some AEs were transitory (e.g., jaw pain); others were long-lasting (e.g., muscle pain). Based on findings from Round 1 interviews, a flushing item was added and the PRO-CTCAE general pain item was modified to be specific to jaw pain for testing in Round 2. Interview findings identified the following AEs as relevant to assess in a PAH clinical trial: nausea, vomiting, diarrhea, flushing, jaw pain, headache, aching muscles, and aching joints. CONCLUSIONS: The PRO-CTCAE items selected in this study and the additional symptomatic AEs identified as patient-relevant have the potential to be included in assessments capturing the patient perspective on tolerability in future studies of selexipag and possibly other PAH therapies.

Broca's area, variation and taxic diversity in early Homo from Koobi Fora (Kenya).

Because brain tissues rarely fossilize, pinpointing when and how modern human cerebral traits emerged in the hominin lineage is particularly challenging. The fragmentary nature of the fossil material, coupled with the difficulty of characterizing such a complex organ, has been the source of long-standing debates. Prominent among them are the uncertainties around the derived or primitive state of the brain organization in the earliest representatives of the genus Homo, more particularly in key regions such as the Broca's area. By revisiting a particularly well-preserved fossil endocast from the Turkana basin (Kenya), here we confirm that early Homo in Africa had a primitive organization of the Broca's area ca. 1.9 million years ago. Additionally, our description of KNM-ER 3732 adds further information about the variation pattern of the inferior frontal gyrus in fossil hominins, with implications for early Homo taxic diversity (i.e. one or two Homo species at Koobi Fora) and the nature of the mechanisms involved in the emergence of derived cerebral traits.

A Health State Utility Study to Elicit Societal Values Associated with Pulmonary Hypertension.

Aim: Pulmonary hypertension (PH) is a rare, severe, and progressive pulmonary vascular disease, which includes five subgroups with similar presentation. Symptoms include dyspnea, and fatigue, and can significantly impact one's health-related quality of life (HRQL). Although treatments are mainly medical, PH group 4, chronic thromboembolic pulmonary hypertension (CTEPH), can be managed with procedures, ie pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA). Currently, drugs in Europe are only approved for pulmonary arterial hypertension (PAH), and CTEPH therefore the aim of this study was to elicit novel societal health state utilities in the UK for PAH and CTEPH based on disease severity, functional class (FC), clinical events, and treatment procedures specifically for CTEPH. Material and Methods: Six health states were defined: World Health Organization (WHO)-FC II, WHO-FC III, and WHO-FC IV [defined by the New York Heart Association (NYHA)]; PH-related hospitalization; and "BPA procedure and recovery" and "PEA surgery and recovery". Health states were based on a targeted literature review and two rounds of interviews with clinical experts (N = 4) and patients (N = 6). Draft health states were validated in cognitive debriefing interviews with clinical experts (N = 3). Health states were valued by the UK general public (n = 200), using a visual analogue scale (VAS) and time trade-off (TTO) assessment with the lead time method. Results: The mean TTO values/utilities were 0.81 (FC II), 0.80 (BPA), 0.78 (PEA), 0.59 (FC III), 0.28 (FC IV), and 0.25 (PH-related hospitalization). Each progression in FC was associated with worse TTO scores. Conclusion: This study reports societal utility values for PAH and CTEPH in the UK. It provides first utility estimates for states such as BPA procedure and recovery, PEA surgery and recovery and PH-related hospitalization for this population. The results show important distinctions between FC, treatment procedures, and hospitalization, and the significant burden of disease on HRQL.

Societal costs associated to chronic thromboembolic pulmonary hypertension: A study utilizing linked national registries.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but serious complication after a pulmonary embolism. Healthcare resource utilization (HCRU; hospitalization, outpatient visits, and drug utilization) as well as productivity loss (sick leave and disability pension) before and after the CTEPH diagnosis is sparsely studied. By linking several Swedish national databases, this study estimated the societal costs in a national CTEPH cohort (n = 369, diagnosed with CTEPH in 2008-2019) 5 years before and 5 years after diagnosis (index date) and compared to an age, sex, and geographically matched control group (n = 1845, 1:5 match). HCRU and productivity loss were estimated per patient per year. Patients were stratified as operated with pulmonary endarterectomy (PEA group) or not operated (non-PEA group). Direct and indirect societal costs were 2.1 times higher before, and 8.1 times higher after the index date for patients with CTEPH compared to the matched control groups. The higher costs were evident already several years preceding the index date. The main cost driver before the index date in both the PEA and the non-PEA groups was productivity loss. The productivity loss remained high for both groups in the 5-year period following the index date, but the main cost drivers were prescribed drugs and hospitalizations for patients that underwent PEA and prescribed drugs in the non-PEA group. In conclusion, CTEPH was associated with large societal costs related to healthcare consumption and productivity loss, both before and after diagnosis.

From fossils to mind.

Fossil endocasts record features of brains from the past: size, shape, vasculature, and gyrification. These data, alongside experimental and comparative evidence, are needed to resolve questions about brain energetics, cognitive specializations, and developmental plasticity. Through the application of interdisciplinary techniques to the fossil record, paleoneurology has been leading major innovations. Neuroimaging is shedding light on fossil brain organization and behaviors. Inferences about the development and physiology of the brains of extinct species can be experimentally investigated through brain organoids and transgenic models based on ancient DNA. Phylogenetic comparative methods integrate data across species and associate genotypes to phenotypes, and brains to behaviors. Meanwhile, fossil and archeological discoveries continuously contribute new knowledge. Through cooperation, the scientific community can accelerate knowledge acquisition. Sharing digitized museum collections improves the availability of rare fossils and artifacts. Comparative neuroanatomical data are available through online databases, along with tools for their measurement and analysis. In the context of these advances, the paleoneurological record provides ample opportunity for future research. Biomedical and ecological sciences can benefit from paleoneurology's approach to understanding the mind as well as its novel research pipelines that establish connections between neuroanatomy, genes and behavior.

Comparative evaluation of costs and healthcare resource utilization of oral selexipag versus inhaled treprostinil or oral treprostinil in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), a rare vasculopathy progressively leading to right heart failure and death, is associated with considerable economic burden. Oral prostacyclin pathway agents (PPAs) like selexipag and treprostinil address an underlying PAH pathway, yet are often under-utilized. Data on head-to-head cost comparison of various PPAs is lacking. METHODS: In this retrospective study using a large health claims database, we compared the per-patient-per-year (PPPY) costs and healthcare resource utilization (HRU) among PAH patients taking either oral selexipag, inhaled treprostinil or oral treprostinil in the United States between July 2015 and March 2020. Patients with ≥1 prescription for one of the drugs of interest, ≥1 in-patient pulmonary hypertension (PH) diagnosis, or ≥ 2 outpatient PH diagnoses were included in this study. Baseline differences between the three groups were adjusted using an inverse probability of treatment weighting approach. 411 patients were selected for the final study cohorts. RESULTS: All-cause hospitalization costs were highest for oral treprostinil ($39,983) compared to oral selexipag ($20,635) and inhaled treprostinil ($16,548; p = .037). Total PAH-related medical costs were 40% lower for patients on oral selexipag compared to patients on oral and inhaled treprostinil ($24,351 vs. $40,398 and $40,339, respectively; p = .006). PAH-related outpatient visits were lowest for patients on oral selexipag (14 PPPY visits) compared to oral treprostinil (16 PPPY visits) and inhaled treprostinil (22 PPPY visits; p = .001). CONCLUSIONS: Compared to oral and inhaled treprostinil, oral selexipag may incur lower medical costs and reduce PAH related outpatient visits for patients with PAH.

Brain evolution and language: A comparative 3D analysis of Wernicke's area in extant and fossil hominids.

The spoken word does not fossilize. Despite this, scientists have long sought to unearth the origins of language within the human lineage. One of the lines of evidence they have pursued is functional brain areas, such as Broca's and Wernicke's areas, which are associated with speech production and comprehension, respectively. Sulcal layout of Broca's area clearly differs between humans and our closest living relatives, the chimpanzees, enabling its homolog in fossil hominins to be deemed more chimpanzee-like (i.e., closer to the ancestral form) or more human-like (i.e., derived form) with relative ease. Yet, no such differences have been found for Wernicke's area. This study compares sulcal and gyral organization of Wernicke's area across extant human brains (n=4), extant chimpanzee brains (n=5) and fossil hominin endocasts (n=4). Some chimpanzee brains had indications of leftward Wernicke's area asymmetry in the form of a shorter Sylvian fissure and/or caudal superior temporal gyral bulging in the left hemisphere. Overlap between the superior and middle temporal sulci in human but not chimpanzee brains may be due to a relatively larger Wernicke's area in humans. Fragmentation of the main body of the superior temporal sulcus exclusively in human left hemispheres was ascribed to a leftward Wernicke's area asymmetry in this species. Endocast examination found that, while Paranthropus robustus exhibit human-like overlap between the superior and middle temporal sulci, Australopithecus africanus do not, although they do exhibit chimpanzee-like caudal superior temporal gyral bulging. Such findings signal, albeit loosely, a more human-like Wernicke's area in Paranthropus than Australopithecus.

Evolutionary history of hominin brain size and phylogenetic comparative methods.

An absolutely and relatively large brain has traditionally been viewed as a distinctive characteristic of the Homo genus, with anatomically modern humans presented at the apex of a long line of progressive increases in encephalization. Many studies continue to focus attention on increasing brain size in the Homo genus, while excluding measures of absolute and relative brain size of more geologically recent, smaller brained, hominins such as Homo floresiensis, and Homo naledi and smaller brained Homo erectus specimens. This review discusses the benefits of using phylogenetic comparative methods to trace the diverse changes in hominin brain evolution and the drawbacks of not doing so.

The Australopithecus assemblage from Sterkfontein Member 4 (South Africa) and the concept of variation in palaeontology.

Interpreting morphological variation within the early hominin fossil record is particularly challenging. Apart from the fact that there is no absolute threshold for defining species boundaries in palaeontology, the degree of variation related to sexual dimorphism, temporal depth, geographic variation or ontogeny is difficult to appreciate in a fossil taxon mainly represented by fragmentary specimens, and such variation could easily be conflated with taxonomic diversity. One of the most emblematic examples in paleoanthropology is the Australopithecus assemblage from the Sterkfontein Caves in South Africa. Whereas some studies support the presence of multiple Australopithecus species at Sterkfontein, others explore alternative hypotheses to explain the morphological variation within the hominin assemblage. In this review, I briefly summarize the ongoing debates surrounding the interpretation of morphological variation at Sterkfontein Member 4 before exploring two promising avenues that would deserve specific attention in the future, that is, temporal depth and nonhuman primate diversity.

Societal costs associated with pulmonary arterial hypertension: A study utilizing linked national registries.

Pulmonary arterial hypertension (PAH) is a progressive disease with no cure. Healthcare resource utilization (HCRU; hospitalization, outpatient visits, and drug utilization) before diagnosis and productivity loss (sick leave and disability pension) before and after PAH diagnosis are not well known. By linking several Swedish national databases, this study have estimated the societal costs in a national PAH cohort (n = 749, diagnosed with PAH in 2008-2019) 5 years before and 5 years after diagnosis and compared to an age, sex, and geographically matched control group (n = 3745, 1:5 match). HCRU and productivity loss were estimated per patient per year. The PAH group had significantly higher HCRU and productivity loss compared to the control group starting already 3 and 5 years before diagnosis, respectively. HCRU peaked the year after diagnosis in the PAH group with hospitalizations (mean ± standard deviation; 2.0 ± 0.1 vs. 0.2 ± 0.0), outpatient visits (5.3 ± 0.3 vs. 0.9 ± 0.1), and days on sick leave (130 ± 10 vs. 13 ± 1) significantly higher compared to controls. Total costs during the entire 10-year period were six times higher for the PAH group than the control group. In the 5 years before diagnosis the higher costs were driven by productivity loss (76%) and hospitalizations (15%), while the 5 years after diagnosis the main cost drivers were drugs (63%), hospitalizations (16%), and productivity loss (16%). In conclusion, PAH was associated with large societal costs due to high HCRU and productivity loss, starting several years before diagnosis. The economic and clinical burden of PAH suggests that strategies for earlier diagnosis and more effective treatments are warranted.

The brain of Homo habilis: Three decades of paleoneurology.

In 1987, Phillip Tobias published a comprehensive anatomical analysis of the endocasts attributed to Homo habilis, discussing issues dealing with brain size, sulcal patterns, and vascular traces. He suggested that the neuroanatomy of this species evidenced a clear change toward many cerebral traits associated with our genus, mostly when concerning the morphology of the frontal and parietal cortex. After more than 30 years, the fossil record associated with this taxon has not grown that much, but we have much more information on cranial and brain biology, and we are using a larger array of digital methods to investigate the paleoneurological variation observed in the human genus. Brain volume, the size of the frontal lobe, or the gross hemispheric asymmetries are still relevant issues, but they are considered to be less central than before. More attention is instead being paid to the cortical organization, the relationships with the cranial architecture, and the influence of molecular or ecological factors. Although the field of paleoneurology can currently count on a larger range of tools and principles, there is still a general lack of anatomical information on many endocranial traits. This aspect is probably crucial for the agenda of paleoneurology. More importantly, the whole science is undergoing a delicate change, because of the growing influence of the social environment. In this sense, the disciplines working with fossils (and, in particular, with brain evolution) should take particular care to maintain a healthy professional situation, avoiding an excess of speculation and overstatement.

Healthcare resource utilization and quality of life in patients with sarcoidosis-associated pulmonary hypertension.

A retrospective, observational cohort study was conducted to generate real-world evidence in adult patients diagnosed with sarcoidosis-associated pulmonary hypertension (SAPH) at a referral center in England between 2012 and 2019. Data from the referral center electronic medical record database were linked to the National Health Service Hospital Episode Statistics database to collect and analyze patient demographics, clinical characteristics, comorbidities, treatment patterns, health-related quality of life (HRQoL; assessed using the EmPHasis-10 questionnaire), healthcare resource utilization (HCRU), costs, and survival. Sixty-two patients with SAPH were identified. At diagnosis, 84% were in WHO functional class III and presented with significant pulmonary hemodynamic impairment. Cardiovascular and respiratory comorbidities were commonly reported prediagnosis. Median EmPHasis-10 score at diagnosis was 34, indicative of poor HRQoL. In the 1st year after diagnosis, median (Q1, Q3) per-patient HCRU was 1 (0, 2) all-cause inpatient hospitalizations; 3 (2, 4) same-day hospitalizations; and 9 (6, 11) outpatient consultations. In 24 patients who were hospitalized longer than 1 day in the 1st year after diagnosis, the median duration of hospitalization was 4 days. With a median follow-up of 1.8 years, the median overall survival was 2.9 years. In this cohort of patients with SAPH, poor HRQoL and high HCRU were observed following diagnosis. To our knowledge, this is the first study to report on HRQoL and HCRU in patients with SAPH. More research is needed on treatment options for this population with high unmet needs.

Frontal sinuses and human evolution.

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species' holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species.

Five year risk assessment and treatment patterns in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period. METHODS AND RESULTS: Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008-2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1-Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51-71) years, 37% female] used PH-specific treatment and 20, 69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65-77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment. CONCLUSIONS: Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group.