Inside "Operation Change Agent": Mallinckrodt's Plan for Capturing the Opioid Market.

CONTEXT: The United States is deeply entangled in an opioid crisis that began with the overuse of prescription painkillers. At the height of the prescription opioid crisis (2006-2012), Mallinckrodt Pharmaceuticals was the nation's largest opioid manufacturer. This study explores Mallinckrodt's strategies for expanding its market share by promoting a new opioid. METHODS: The authors used the Opioid Industry Document Archive to analyze the incentive structures, sales contests, and rhetorical strategy behind Mallinckrodt's "Operation Change Agent," a campaign to switch patients from OxyContin to Mallinckrodt-manufactured painkillers. A structured search of the archive in October 2022 retrieved 464 documents dated between 2010 and 2020. FINDINGS: The authors identified a range of Mallinckrodt's sales force motivational techniques, including hypertargeting high-decile prescribers, providing free trial kits, using emotion-based language to connect with prescribers, and strategies for opposing prescriber resistance. Throughout, managers used specific incentivization metaphors to frame strategies in terms of sport and ultramarathons. CONCLUSIONS: This research on internal corporate strategy joins the growing challenges to industry claims that opioid sales teams simply educated providers and helped fill existing demand for their products. It has important implications for regulatory policy and consumer protections that can better protect health in the face of competitive market forces.

Autoimmunity Is a Significant Feature of Idiopathic Pulmonary Arterial Hypertension.

Rationale: Autoimmunity is believed to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear whether this is causative or a bystander of disease and if it carries any prognostic or treatment significance. Objectives: To study autoimmunity in IPAH using a large cross-sectional cohort. Methods: Assessment of the circulating immune cell phenotype was undertaken using flow cytometry, and the profile of serum immunoglobulins was generated using a standardized multiplex array of 19 clinically validated autoantibodies in 473 cases and 946 control subjects. Additional glutathione S-transferase fusion array and ELISA data were used to identify a serum autoantibody to BMPR2 (bone morphogenetic protein receptor type 2). Clustering analyses and clinical correlations were used to determine associations between immunogenicity and clinical outcomes. Measurements and Main Results: Flow cytometric immune profiling demonstrates that IPAH is associated with an altered humoral immune response in addition to raised IgG3. Multiplexed autoantibodies were significantly raised in IPAH, and clustering demonstrated three distinct clusters: "high autoantibody," "low autoantibody," and a small "intermediate" cluster exhibiting high concentrations of ribonucleic protein complex. The high-autoantibody cluster had worse hemodynamics but improved survival. A small subset of patients demonstrated immunoglobulin reactivity to BMPR2. Conclusions: This study establishes aberrant immune regulation and presence of autoantibodies as key features in the profile of a significant proportion of patients with IPAH and is associated with clinical outcomes.

Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action.

Cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and the Programmed Death Receptor 1 (PD-1) are immune checkpoint molecules that are well-established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies, Ipilimumab, Pembrolizumab, and Nivolumab, designed to interfere with T cell inhibitory signals to activate immune responses against tumors, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action. However, treatment with checkpoint inhibitor combinations also present significant clinical challenges and increased rates of immune-related adverse events. In this review, we discuss the potential mechanisms attributed to single and combined checkpoint inhibitor immunotherapies and clinical experience with their use.

Diagnostic accuracy of an automated artificial intelligence derived right ventricular to left ventricular diameter ratio tool on CT pulmonary angiography to predict pulmonary hypertension at right heart catheterisation.

AIM: To determine the diagnostic accuracy of an automated artificial intelligence derived right ventricle/left ventricle diameter ratio (RV/LV) computed tomography pulmonary angiography (CTPA) analysis tool to detect pulmonary hypertension (PH) in patients with suspected PH referred to a specialist centre. MATERIALS AND METHODS: The present study was a retrospective analysis of a prospectively maintained database of 202 consecutive patients with suspected PH, who underwent CTPA within 12 months of right heart catheterisation (RHC). Automated ventricular segmentation and RV/LV calculation (Imbio LLC, Minneapolis, MN, USA) was undertaken on the CTPA images. PH diagnosis was made using the RHC reference standard. RESULTS: The automated RV/LV correlated more strongly with RHC metrics than main pulmonary artery (MPA) diameter and MPA to ascending aorta diameter ratio (MPA/AA) measured manually (mean pulmonary arterial pressure [mPAP] r=0.535, R2 = 0.287 p<0.001; pulmonary vascular resistance [PVR] r=0.607, R2 = 0.369 p<0.001). In the derivation cohort (n=100), the area under the receiver-operating curve for automated RV/LV discriminating PH was 0.752 (95% confidence interval [CI] 0.677-0.827, p<0.001). Using an optimised Youden's Index of ≥1.12 classified from derivation, automated RV/LV ratio analysis was more sensitive for the detection of PH with higher positive predictive value (PPV) when compared with manual MPA and MPA/AA in the validation cohort (n=102). Automated RV/LV compromise (1.12) and specific (1.335) thresholds were strongly predictive of mortality (log-rank 7.401, p=0.007 and log-rank 16.075, p<0.001 respectively). CONCLUSION: In suspected PH, automated RV/LV diameter thresholds have high sensitivity for PH, outperform manual MPA and MPA/AA and can predict survival.

Evaluation of 'Shisha No Thanks' - a co-design social marketing campaign on the harms of waterpipe smoking.

BACKGROUND: Waterpipe (shisha) is becoming increasingly popular worldwide, particularly among young people; and in some countries, it is one of the few forms of tobacco use that is increasing. While there is a growing body of evidence of the harms of waterpipe smoke, there is a scarcity of research of interventions to address this form of tobacco consumption. METHODS: The Shisha No Thanks project was a co-design social marketing campaign that aimed to raise awareness of the harms of waterpipe smoking among young people from an Arabic speaking background in Sydney, Australia. The campaign distributed material through social media and community events. We evaluated the project through an SMS community panel using a longitudinal study design. The cohort were sent questions before and after the project asking about their awareness of messages of harms, attitudes, intention to reduce waterpipe smoking, and awareness of support services. Data was analysed as matched pre- post- data. RESULTS: The evaluation recruited 133 people to the panel. There was a significantly greater proportion of people who reported seeing, hearing or reading something about the harms of waterpipe smoking after the campaign (67.5%) compared with before (45.0%) (p=0.003). Post-campaign, there were higher proportions of people who strongly agreed that waterpipe smoking causes damage, and that it contains cancer-causing substances, but these increases were not statistically significant. There was low awareness of waterpipe cessation services at baseline and post campaign (22.5%). CONCLUSIONS: The Shisha No Thanks project increased awareness of messages about the harms of waterpipe smoking. Although this is a small study, the longitudinal evaluation findings have international relevance and make a useful contribution to the understanding of the impact such interventions can have in addressing one of the few forms of tobacco use that is growing in both developed and developing countries.

Health-related quality of life trajectories in melanoma patients after electrochemotherapy: real-world insights from the InspECT register.

BACKGROUND: Electrochemotherapy (ECT) effectively controls skin metastases from cutaneous melanoma. OBJECTIVES: This study aimed to evaluate health-related quality of life (HRQoL) in melanoma patients pre-/post-ECT and its effect on treatment outcome. METHODS: The analysis included prospective data from the International Network for Sharing Practices of ECT register. Following the Standard Operating Procedures, patients received intravenous or intratumoural bleomycin (15,000 IU/m2 ; 1000 IU mL/cm3 ) followed by 100-microsecond, 1000-V/cm electric pulses. Endpoints included response (RECIST v3.0), local progression-free survival (LPFS), toxicity (CTCAE v5.0), and patient-reported HRQoL at baseline, one, two, four and ten months (EuroQol [EQ-5D-3L], including 5-item utility score [EQ-5D] and visual analogue scale for self-reported health state [EQ-VAS]). Comparisons within/between subgroups were made for statistical and minimal important differences (MID). HRQoL scores and clinical covariates were analysed to identify predictors of response in multivariate analysis. RESULTS: Median tumour size was 2 cm. Complete response rate, G3 toxicity and one-year LPFS in 378 patients (76% of the melanoma cohort) were 47%, 5%, and 78%. At baseline, age-paired HRQoL did not differ from the general European population. Following ECT, both EQ-5D and EQ-VAS scores remained within MID boundaries, particularly among complete responders. A subanalysis of the EQ-5D items revealed a statistically significant deterioration in pain/discomfort and mobility (restored within four months), and self-care and usual activities (throughout the follow-up) domains. Concomitant checkpoint inhibition correlated with better EQ-5D and EQ-VAS trajectories. Baseline EQ-5D was the exclusive independent predictor for complete response (RR 14.76, p=0.001). CONCLUSIONS: HRQoL of ECT melanoma patients parallels the general population and is preserved in complete responders. Transient deterioration in pain/discomfort and mobility and persistent decline in self-care and usual activities may warrant targeted support interventions. Combination with checkpoint inhibitors is associated with better QoL outcomes. Baseline HRQoL provides predictive information which can help identify patients most likely to respond.

Characterization of GDF2 Mutations and Levels of BMP9 and BMP10 in Pulmonary Arterial Hypertension.

Rationale: Recently, rare heterozygous mutations in GDF2 were identified in patients with pulmonary arterial hypertension (PAH). GDF2 encodes the circulating BMP (bone morphogenetic protein) type 9, which is a ligand for the BMP2 receptor.Objectives: Here we determined the functional impact of GDF2 mutations and characterized plasma BMP9 and BMP10 levels in patients with idiopathic PAH.Methods: Missense BMP9 mutant proteins were expressed in vitro and the impact on BMP9 protein processing and secretion, endothelial signaling, and functional activity was assessed. Plasma BMP9 and BMP10 levels and activity were assayed in patients with PAH with GDF2 variants and in control subjects. Levels were also measured in a larger cohort of control subjects (n = 120) and patients with idiopathic PAH (n = 260).Measurements and Main Results: We identified a novel rare variation at the GDF2 and BMP10 loci, including copy number variation. In vitro, BMP9 missense proteins demonstrated impaired cellular processing and secretion. Patients with PAH who carried these mutations exhibited reduced plasma levels of BMP9 and reduced BMP activity. Unexpectedly, plasma BMP10 levels were also markedly reduced in these individuals. Although overall BMP9 and BMP10 levels did not differ between patients with PAH and control subjects, BMP10 levels were lower in PAH females. A subset of patients with PAH had markedly reduced plasma levels of BMP9 and BMP10 in the absence of GDF2 mutations.Conclusions: Our findings demonstrate that GDF2 mutations result in BMP9 loss of function and are likely causal. These mutations lead to reduced circulating levels of both BMP9 and BMP10. These findings support therapeutic strategies to enhance BMP9 or BMP10 signaling in PAH.

The Swine Flu Pandemic - Should We Be Concerned?

As I write this review, we are in the midst of the 2009 influenza A (H1N1) pandemic. The extent and impact of this pandemic is still unknown. Although daily reports on confirmed cases and deaths provide a constant stream of detailed information, it is not possible to predict with any degree of precision the impact the outbreak will have in society in general or on the life insurance industry in particular.1 The epidemiology of such disease outbreaks has been likened to a jigsaw puzzle, and we are now at the stage where the picture is intriguing even if we are not sure what we are seeing.2.

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).

Traffic exposures, air pollution and outcomes in pulmonary arterial hypertension: a UK cohort study analysis.

While traffic and air pollution exposure is associated with increased mortality in numerous diseases, its association with disease severity and outcomes in pulmonary arterial hypertension (PAH) remains unknown.Exposure to particulate matter with a 50% cut-off aerodynamic diameter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2) and indirect measures of traffic-related air pollution (distance to main road and length of roads within buffer zones surrounding residential addresses) were estimated for 301 patients with idiopathic/heritable PAH recruited in the UK National Cohort Study of Idiopathic and Heritable PAH. Associations with transplant-free survival and pulmonary haemodynamic severity at baseline were assessed, adjusting for confounding variables defined a prioriHigher estimated exposure to PM2.5 was associated with higher risk of death or lung transplant (unadjusted hazard ratio (HR) 2.68 (95% CI 1.11-6.47) per 3 µg·m-3; p=0.028). This association remained similar when adjusted for potential confounding variables (HR 4.38 (95% CI 1.44-13.36) per 3 µg·m-3; p=0.009). No associations were found between NO2 exposure or other traffic pollution indicators and transplant-free survival. Conversely, indirect measures of exposure to traffic-related air pollution within the 500-1000 m buffer zones correlated with the European Society of Cardiology/European Respiratory Society risk categories as well as pulmonary haemodynamics at baseline. This association was strongest for pulmonary vascular resistance.In idiopathic/heritable PAH, indirect measures of exposure to traffic-related air pollution were associated with disease severity at baseline, whereas higher PM2.5 exposure may independently predict shorter transplant-free survival.

Smoking Cessation Care in Cardiothoracic Surgery: A Qualitative Study Exploring the Views of Australian Clinicians.

BACKGROUND: Smoking cessation (SC) care in the perioperative period of cardiothoracic surgery is important to reduce surgical risk and help achieve long-term smoking abstinence in patients who continue to smoke. The implementation of clinical guidelines for SC care in the perioperative period has proved challenging, yet little is known of what influences the inter-disciplinary team involved in the cardiothoracic area. This qualitative study explored the views of the clinicians involved in perioperative period of cardiothoracic surgery in Australia on their SC advice and support. METHODS: Semi-structured interviews were conducted with 52 cardiothoracic surgeons, anaesthetists, nurses and physiotherapists in three public tertiary referral hospitals and three private hospitals in New South Wales (NSW). Data was thematically analysed, and categorised using the Behaviour Change Wheel "Capabilities, Opportunity, Motivation & Behaviour" (COM-B) analysis framework to understand the factors that influence clinicians' views and perceived abilities to provide SC care. RESULTS: Barriers and facilitators to providing SC care were identified. The most commonly identified barriers in capability were the lack of knowledge, training and institutional engagement. Opportunity was hindered by lack of time, hospital support and resources, yet facilitated by the existence of a collaborative, multidisciplinary team and the ability to follow-up patients long term. In motivation, clinicians' attitudes and experience negatively influenced the initiation of the cessation conversation, while intrinsic attributes of empathy and positivity were drivers to provide SC care. CONCLUSIONS: Clinicians' views, together with inadequate SC training, resources and engagement to implement clinical guidelines, contribute to inconsistent SC care. There is a need for hospitals to provide adequate SC resources and training to all clinicians to improve SC care to cardiothoracic surgery patients throughout the perioperative period.

All-Cause Mortality for Life Insurance Applicants with the Presence of Bundle Branch Block.

Objective.-To determine the all-cause mortality of life insurance applicants who have a bundle branch block. Background.-Bundle branch block is an electrocardiographic pattern that has variable prognostic implications. Research studies have shown that both left and right bundle branch block are associated with increased mortality among cases that have heart disease. In the general population and life insurance applicant population, the prevalence of bundle branch block is relatively low, and its effects on long-term prognosis are not as well established. Methodology.-Life insurance applicants with reported bundle branch block were extracted from data covering United States residents between October 2009 and October 2016. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2009 to 2012 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2009 to 2016 to determine vital status. Actual to expected (A/E) mortality ratios were calculated using the Society of Actuaries 2015 Valuation Basic Table (2015VBT), select and ultimate table (age last birthday). All expected bases were not smoker distinct. Confidence bands around these mortality ratios were calculated. The variables of interest were applicant age, gender, location of the bundle branch block, and the presence of cardiac or cardiovascular conditions. Results.-There were 258,529.85 person-years exposure for applicants with bundle branch block. Of the applicants, 57.2% had right bundle branch block. Of person-years exposure, 11.5% had a cardiac condition along with the bundle branch block, and 4.4% had an underlying cardiovascular condition. Female mortality ratios were higher than those for males, but due to the low number of deaths, this difference was not significant. Left bundle branch block mortality ratios (1.01) were 1.4 times higher than those with right (0.74). Those applicants with a cardiac condition along with their bundle branch block had between 1.6 to 1.8 times the mortality ratio depending on the bundle branch block location, and those with a cardiovascular condition had between 1.5 to 1.7 times the mortality ratio over those applicants with just bundle branch block alone. Conclusion.-The presence of bundle branch block in an insurance applicant may be associated with increased all-cause mortality. In this study, life insurance applicants overall had a mortality slightly lower than the expected mortality based on the 2015 VBT. However, applicants with bundle branch block and a cardiac or cardiovascular comorbid condition had a significantly higher mortality ratio.

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation.

An Irregular Rhythm with Missing P Waves.

An electrocardiogram on a life insurance applicant with a history of surgically repaired congenital heart disease displays an irregular rhythm with occasional missing P waves.

All-Cause Mortality for Life Insurance Applicants with a Family History of Coronary Artery Disease Before 60.

OBJECTIVE: -To determine the all-cause mortality of life insurance applicants having a family history of coronary artery disease (CAD) before age 60. BACKGROUND: -Epidemiological studies have shown that a family history of premature CAD is an independent risk factor for CAD events. The strength of the association between family history and CAD is greatest with earlier age of presentation of CAD in the family member and when multiple family members are affected. Despite earlier insurance studies on this relationship, there is sparse current data on the association between family history of CAD and all-cause mortality in life insurance applicants. METHODOLOGY: -Life insurance applicants with reported family history of Coronary Artery Disease (CAD) were extracted from data covering United States residents between October 2009 and October 2016. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2009 to 2012 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2009 to 2016 to determine vital status. Actual to Expected (A/E) mortality ratios were calculated using the Society of Actuaries 2015 Valuation Basic Table (2015VBT), select and ultimate table (age last birthday). All expected bases were not smoker distinct. Confidence bands around these mortality ratios were calculated. The variables of interest were applicant age, gender, number of family members with CAD before age 60, and the presence of cardiac or cardiovascular conditions. RESULTS: -Overall, the mortality of applicants with family members with a history of CAD before age 60 was slightly lower than expected mortality based on the 2015 VBT. Applicants with a cardiac or cardiovascular comorbid condition had a significantly higher mortality ratio. For applicants aged 25-54 and 65-75 with cardiac comorbid conditions, the mortality ratio was 2 times that of those without a cardiac comorbid condition. For those aged 55-64 with cardiovascular comorbid conditions, the mortality ratio was 2.9 times that of those without a cardiovascular comorbid condition. Females had a slightly higher mortality ratio for all age groups, number of family members with CAD before age 60, and cardiovascular conditions. CONCLUSION: -A family history of CAD before the age of 60 in an insurance applicant may be associated with increased all-cause mortality. Overall in this study, life insurance applicants had a mortality slightly lower than the expected mortality based on the 2015 VBT. However, applicants with a positive family history and a cardiac or cardiovascular comorbid condition had a significantly higher mortality ratio.

Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort.

BACKGROUND: Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA. METHODS AND RESULTS: Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s(-1)·cm(-5) at reassessment correlated with worse long-term survival. CONCLUSIONS: Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.

A Comparison of Heat Wave Response Plans From an Aged Care Facility Perspective.

Heat waves result in significant excess mortality, particularly amongst elderly people. This article examines selected heat wave response plans at national, state/provincial, and municipal levels, with a particular focus on specific responses aimed at residents of aged care facilities. We sourced heat wave response plans from several countries that are experiencing a demographic transition that features a growing aging population. We collected a total of 23 heat wave response plans; most of those plans were from Australia, with only three plans each available from Canada and the UK, and only two available from the U.S. Key components found across the plans were analysis of temperature thresholds, heat stress prevention measures, and communication strategies. Only three heat wave response plans that were analyzed included specific guidance for aged care facilities. Projected increases in frequency and duration of heat waves in coming decades underline the need for governments to implement effective guidelines that include specific provisions for aged care facilities.

Infarction or Pseudo-infarction?

An applicant with a history of paroxysmal atrial fibrillation is found to have QS waves in leads III and AVF suggestive of a prior inferior wall myocardial infarction. Using the relationship between Q wave and T wave vectors in the inferior leads, an alternative explanation is explored.