The development and cognitive testing of the positive outcomes HIV PROM: a brief novel patient-reported outcome measure for adults living with HIV.

BACKGROUND: People living with HIV experience burdensome multidimensional symptoms and concerns requiring person-centred care. Routine use of patient reported outcome measures can improve outcomes. There is no brief patient reported outcome measure (PROM) that currently reflects the breadth of concerns for people living with HIV. This study aimed to develop and cognitively test a brief novel patient reported outcome measure for use within routine adult HIV care- the "Positive Outcomes" HIV PROM. METHODS: Development followed the COSMIN taxonomy and guidance for relevance and comprehensiveness, and Rothrock guidance on development of valid patient reported outcome measures. The Positive Outcomes HIV PROM was developed by a steering group (people living with HIV, HIV professionals and health services researchers) using findings from a previously reported qualitative study of priority outcomes for people living with HIV. The prototype measure was cognitively tested with a purposive sample of people living with HIV. RESULTS: The Positive Outcomes HIV PROM consists of 23 questions (22 structured, and one open question) informed by the priorities of key stakeholders (n = 28 people living with HIV, n = 21 HIV professionals and n = 8 HIV commissioners) to ensure face and content validity, and refined through cognitive testing (n = 6 people living with HIV). Cognitive testing demonstrated high levels of acceptability and accessibility. CONCLUSIONS: The Positive Outcomes HIV PROM is the first brief patient reported outcome measure reflecting the diverse needs of people living with HIV designed specifically for use in the clinical setting to support patient assessment and care, and drive service quality improvement. It is derived from primary data on the priority outcomes for people living with HIV and is comprehensive and acceptable. Further psychometric testing is required to ensure reliability and responsiveness.

Towards person-centred care for people living with HIV: what core outcomes matter, and how might we assess them? A cross-national multi-centre qualitative study with key stakeholders.

OBJECTIVES: People living with HIV (PLWH) have multidimensional concerns requiring person-centred care. Routine use of patient-reported outcome measures (PROMs) improves outcomes. No brief PROM currently reflects the breadth of concerns for PLWH. This study sought to identify priority outcomes for PLWH, model current practice, explore views on introducing PROMs into routine care, and devise a model for person-centred care incorporating the PROM. METHODS: A cross-national multi-centre study (London, Brighton and Dublin) was carried out. Semi-structured qualitative interviews with adult PLWH, HIV health care professionals and HIV commissioners (responsible for planning and commissioning services) were performed. Interviews were analysed using thematic and framework analysis. RESULTS: PLWH (n = 28), professionals (n = 21) and commissioners (n = 8) described concerns related to living with HIV across six domains: physical (e.g. pain and gastrointestinal symptoms), cognitive (e.g. memory and sleep), psychological (e.g. anxiety and depression), social (e.g. isolation and intimacy), welfare (e.g. finances and fears regarding change of immigration status), and information (e.g. long-term outcomes) needs. Themes were highly inter-related, impacting across domains of need (e.g. physical and cognitive problems impacting on psychological and social wellbeing). Perceived benefits of using PROMs in routine HIV care included improved person-centredness, patient empowerment, fewer missed concerns, increased engagement with services, and informed planning of services. Potential challenges included heterogeneity of PLWH, literacy, and utility for those who struggle to engage with care. CONCLUSIONS: This study presents a novel model of person-centred care incorporating an HIV-specific PROM. The model reflects priorities of key stakeholders. Explicit use of PROMs in routine HIV care could afford benefits for PLWH, clinical teams and commissioners.

Management dilemmas in pulmonary arterial hypertension associated with congenital heart disease.

There are few randomised controlled data to guide management of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). In this clinical review, common areas of uncertainty in the management of PAH-CHD are identified, the literature is summarised and discussed and a suggested approach offered for each clinical dilemma.

Employment characteristics of a complex adult congenital heart disease cohort.

BACKGROUND: Due to advances in surgical techniques and subsequent management, there have been remarkable improvements in the survival of patients with congenital heart disease. In particular, larger numbers of patients with complex disease are now living into adulthood and are entering the workforce. AIMS: To establish the types of employment complex adult congenital heart disease (ACHD) patients are engaged in, based on the largest cohort of patients with a single-ventricle circulation in the UK. METHODS: Records of all patients with a univentricular (Fontan) circulation at the Queen Elizabeth Hospital were reviewed. Employment status was categorized according to the Standard Occupational Classification criteria (2010). RESULTS: A total of 210 patient records were reviewed. There was the same proportion of professionals in our cohort compared to the rest of the UK (20% versus 20%). There were greater proportions working in the caring, leisure and other service occupations (15% versus 9%), the elementary occupations (17% versus 11%), sales and customer service occupations (14% versus 8%) and administrative and secretarial occupations (12% versus 11%). The reverse trend was observed for associate professions and technical occupations (7% versus 14%), skilled trades (10% versus 11%), process, plant and machine operatives (3% versus 6%) and managers, directors and senior officials (2% versus 10%). CONCLUSIONS: The data show that ACHD patients with a single ventricle are engaged in a diverse range of occupations. It is essential that early education and employment advice are given to this cohort to maximize future employment potential.

Assessment of the Physiological Adaptations to Chronic Hypoxemia in Eisenmenger Syndrome.

OBJECTIVE: Eisenmenger syndrome is characterized by severe and lifelong hypoxemia and pulmonary hypertension. Despite this, patients do surprisingly well and report a reasonable quality of life. The aim of this study was to investigate whether these patients undergo adaptation of their skeletal and cardiac muscle energy metabolism which would help explain this paradox. DESIGN AND SETTING: Ten patients with Eisenmenger syndrome and eight age- and sex-matched healthy volunteers underwent symptom-limited treadmill cardiopulmonary exercise testing, transthoracic echocardiography and (31) P magnetic resonance spectroscopy of cardiac and skeletal muscle. Five subjects from each group also underwent near infrared spectroscopy to assess muscle oxygenation. RESULTS: Despite having a significantly lower peak VO2 , patients with Eisenmenger syndrome have a similar skeletal muscle phosphocreatine (PCr) recovery, a measure of oxidative capacity, when compared to healthy controls (34.9 s ± 2.9 s vs. 35.2 s ± 1.7 s, P = .9). Furthermore their intracellular pH falls to similar levels during exercise suggesting they are not reliant on early anaerobic metabolism (0.3 ± 0.06 vs. 0.28 ± 0.04, P = .7). While their right ventricular systolic function remained good, the Eisenmenger group had a lower cardiac PCr/ATP ratio compared to the control group (1.55 ± 0.10 vs. 2.17 ± 0.15, P < .05). CONCLUSIONS: These results show that adult patients with Eisenmenger syndrome have undergone beneficial physiological adaptations of both skeletal and cardiac muscle. This may, in part, explain their surprisingly good survival despite a lifetime of severe hypoxemia and adverse cardiopulmonary hemodynamics.

Cross-sectional imaging of the Fontan circuit in adult congenital heart disease.

The Fontan circuit is the result of a palliative surgical procedure that is performed in patients with a functionally single ventricle cardiac anomaly. The success of this operation has resulted in an increasing population of adults with this anatomy and physiology. The purpose of this article is to familiarize the general radiologist with the expected anatomy and cross-sectional imaging findings, highlight special imaging considerations, and examine the common complications that are encountered in this group of patients.

Percutaneous device closure of a pseudoaneurysm of the left ventricular wall.

The percutaneous device closure of a left ventricular pseudoaneurysm is described in a 60 year old man with a history of myocardial infarction complicated by ventricular tachycardia and left ventricular aneurysm treated by coronary artery bypass grafting and aneursymectomy with ventricular tachycardia ablation. He subsequently developed a vast pseudoaneurysm of the left ventricle with New York Heart Association functional class II heart failure symptoms. The selection of the approach and type of device used to close the neck of the pseudoaneurysm are discussed.

Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia.

Chronic hypoxia leads to a greater degree of pulmonary hypertension in the Wistar-Kyoto (WKY) rat than in the Fischer 344 (F-344) rat. We questioned whether this difference is associated with baseline differences in pulmonary artery anatomy, a greater degree of hypoxia-induced pulmonary vascular remodeling in the WKY rat, and/or differences in expression of endothelin (ET)-1. Male F-344 and WKY rats were maintained in normoxia or normobaric hypoxia for 21 days. Morphometry revealed that baseline pulmonary artery anatomy was similar in the two strains. However, during chronic hypoxia, the WKY rats developed a greater degree of muscularization of small pulmonary arteries. Baseline plasma and lung immunoreactive ET-1 levels were similar in the WKY and F-344 rats and increased significantly during hypoxia in the WKY rats. Northern analysis demonstrated increased lung preproET-1 mRNA during hypoxia in both strains, with a greater increase in WKY rats. Immunostaining demonstrated increased ET-1 in bronchial epithelium and peripheral pulmonary arteries during hypoxia, although to a greater degree in the WKY rats. We conclude that the WKY strain demonstrates increased susceptibility to hypoxia-induced pulmonary vascular remodeling compared with the F-344 strain and that increased lung and circulating ET-1 levels during hypoxia may partly explain this difference.

Membrane action of chloramphenicol measured by protozoan motility inhibition.

The mechanism of the grey baby syndrome produced by chloramphenicol overdose is poorly understood. The present study assessed the membrane toxicity of this agent by means of its depressant effect on excitable tissues. The inhibition by drugs of protozoan motility was used as a toxicity endpoint, measured by the swimming speed of Tetrahymena pyriformis using an image analysis system. The n-octanol/water partition coefficient at pH 7.4, 37 degrees C was determined as a measure of the hydrophobicity of the drugs. Chloramphenicol dose-dependently depressed the motility of the test organism with an IC50 value (the concentration reducing the mean swimming speed to 50% of control) of 2.95 +/- 0.25 mM, in contrast to a significantly weaker effect of its succinate salt with an IC50 of 28.2 +/- 1.93 mM. Thiamphenicol, a drug with similar properties to chloramphenicol, produced little effect on protozoan motility. Several other antibiotics either in free or salt forms were also ineffective. A series of agents known to possess membrane stabilising action also tested for comparison showed that chloramphenicol possesses the ability to reduce protozoan motility. Measurement of the n-octanol/water partition coefficient revealed a value for chloramphenicol of 11.9 +/- 0.66. This property was correlated with protozoan immobilising potency among a series of heterogeneous compounds, suggesting that the mechanism involved a hydrophobic interaction with the excitable membrane. These results show that chloramphenicol has a depressant effect on protozoan motility comparable to agents with known toxicity effects on cell membranes. This suggests that chloramphenicol has the potential to cause membrane-mediated toxic effects, a mode of action that may underlie its acute toxicity to excitable tissues.

Seven million years of glaciation in greenland.

Glacial till, glaciomarine diamictites, and ice-rafted detritus found in marine cores collected off the shore of southeast Greenland record multiple Late Cenozoic glaciations beginning in the Late Miocene. Distinct rock assemblages and seismic stratigraphic control correlate the diamictites with glaciation of the southeast Greenland margin. Glaciers advanced to the sea during several intervals in the Pliocene and Pleistocene. North Atlantic glaciation may have nucleated in southern Greenland rather than further north because of the high mountains and the high levels of precipitation in this region.

Posttraining effects of amphetamine, chlorpromazine, ketamine, and scopolamine on the acquisition and extinction of the rabbit's conditioned nictitating membrane response.

Four experiments examined whether posttraining deliveries of drugs modified the performance of the rabbit's conditioned nictitating membrane response (NMR) during acquisition and extinction. The results show that ketamine accelerated, but that amphetamine, chlorpromazine, and scopolamine retarded, conditioning when the drugs were injected immediately after the completion of daily training sessions. However, all conditioning effects of the drugs were lost when their deliveries were delayed by 2 hr after the end of training. During extinction, the only drug that altered conditioned performance was ketamine. Specifically, ketamine retarded the rate of extinction when the drug was given immediately after training. However, delaying ketamine by 2 hr after training neutralized the drug's influence. These findings indicate that the NMR preparation should be useful in examining how the posttraining delivery of drugs influences associative processes in conditioning.