Vestibular rehabilitation in multiple sclerosis: study protocol for a randomised controlled trial and cost-effectiveness analysis comparing customised with booklet based vestibular rehabilitation for vestibulopathy and a 12 month observational cohort study of the symptom reduction and recurrence rate following treatment for benign paroxysmal positional vertigo.

BACKGROUND: Symptoms arising from vestibular system dysfunction are observed in 49-59% of people with Multiple Sclerosis (MS). Symptoms may include vertigo, dizziness and/or imbalance. These impact on functional ability, contribute to falls and significant health and social care costs. In people with MS, vestibular dysfunction can be due to peripheral pathology that may include Benign Paroxysmal Positional Vertigo (BPPV), as well as central or combined pathology. Vestibular symptoms may be treated with vestibular rehabilitation (VR), and with repositioning manoeuvres in the case of BPPV. However, there is a paucity of evidence about the rate and degree of symptom recovery with VR for people with MS and vestibulopathy. In addition, given the multiplicity of symptoms and underpinning vestibular pathologies often seen in people with MS, a customised VR approach may be more clinically appropriate and cost effective than generic booklet-based approaches. Likewise, BPPV should be identified and treated appropriately. METHODS/ DESIGN: People with MS and symptoms of vertigo, dizziness and/or imbalance will be screened for central and/or peripheral vestibulopathy and/or BPPV. Following consent, people with BPPV will be treated with re-positioning manoeuvres over 1-3 sessions and followed up at 6 and 12 months to assess for any re-occurrence of BPPV. People with central and/or peripheral vestibulopathy will be entered into a randomised controlled trial (RCT). Trial participants will be randomly allocated (1:1) to either a 12-week generic booklet-based home programme with telephone support or a 12-week VR programme consisting of customised treatment including 12 face-to-face sessions and a home exercise programme. Customised or booklet-based interventions will start 2 weeks after randomisation and all trial participants will be followed up 14 and 26 weeks from randomisation. The primary clinical outcome is the Dizziness Handicap Inventory at 26 weeks and the primary economic endpoint is quality-adjusted life-years. A range of secondary outcomes associated with vestibular function will be used. DISCUSSION: If customised VR is demonstrated to be clinically and cost-effective compared to generic booklet-based VR this will inform practice guidelines and the development of training packages for therapists in the diagnosis and treatment of vestibulopathy in people with MS. TRIAL REGISTRATION: ISRCTN Number: 27374299 Date of Registration 24/09/2018 Protocol Version 15 25/09/2019.

Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure.

BACKGROUND: This study determined whether evidence of congestion after 4 to 6 weeks of heart failure management predicted outcome for patients hospitalized with chronic New York Heart Association class IV symptoms. Class IV symptoms predict high mortality rates, but outcome is not known for patients who improve to establish freedom from congestion. Revised estimates at 1 month could facilitate decisions regarding transplantation and other high-risk interventions. METHODS: At 4 to 6 weeks after hospital discharge, 146 patients were evaluated for congestion by 5 criteria (orthopnea, jugular venous distention, edema, weight gain, and new increase in baseline diuretics). Heart failure management included inpatient therapy tailored to relieve congestion, followed by adjustments to maintain fluid balance during the next 4 weeks. RESULTS: Freedom from congestion was demonstrated at 4 to 6 weeks in 80 (54%) patients, who had 87% subsequent 2-year survival compared with 67% in 40 patients with 1 or 2 criteria of congestion and 41% in 26 patients with 3 to 5 criteria. The Cox proportional hazards model identified left ventricular dimension, pulmonary wedge pressure on therapy, and freedom from congestion as independent predictors of survival. Persistence of orthopnea itself predicted 38% 2-year survival (without urgent transplantation) versus 77% in 113 without orthopnea. Serum sodium was lower and blood urea nitrogen and heart rate higher when orthopnea persisted. CONCLUSIONS: The ability to maintain freedom from congestion identifies a population with good survival despite previous class IV symptoms. At 4 to 6 weeks, patients with persistent congestion may be considered for high-risk intervention.

A validation study comparing accelerator MS and liquid scintillation counting for analysis of 14C-labelled drugs in plasma, urine and faecal extracts.

A comparison has been made between accelerator mass spectrometry (AMS) analysis and liquid scintillation counting (LSC) of plasma, urine and faecal samples containing 14C-labelled drugs. In an in vitro study in which human plasma was spiked (the term spiked is used in Section 2.6) with 14C-Fluconazole (14C-FL) over a concentration range of 0.1-2.5 dpm/ml, a correlation coefficient of 0.999 was determined for AMS analysis versus extrapolated LSC data. No significant day to day (or inter-day)variation was seen (P < 0.05 by ANOVA). Coefficients of variation for these analyses ranged from 2.68 to 6.50%. In vivo studies in which rats were given a high (11.5 microCi/kg) or low (18.1 nCi/kg) radioactive dose (to model an exposure of 0.9 microSievert to man) of 14C-Fluticasone propionate(14C-FP) showed that there was also a good correspondence between AMS and LSC data. A mass balance study in a single the faeces by 96 h; less than 1% of the administered dose was excreted in the urine. The limit of reliable measurement of drug related material, above background concentrations, by AMS analysis in this study was approximately 0.1 dpm/ml for plasma, 0.01 dpm/ml for urine without any sample extraction or concentration and 0.01 dpm/ml for faecal extracts. The data reported here demonstrate that AMS is an ultrasensitive and reliable method for analysing 14C-labelled drugs in human and animal body fluids.

Relationship between right and left-sided filling pressures in 1000 patients with advanced heart failure.

BACKGROUND: Elevated left ventricular filling pressures present a major target of therapy for symptomatic heart failure but are difficult to assess directly. Because the relationship of left- and right-sided pressures remains ill defined in chronic heart failure, this study compared 3 right-sided measurements (right atrial [RA] pressure, pulmonary artery systolic [PAS] pressure, and severity of tricuspid regurgitation [TR]) to the pulmonary capillary wedge (PCW) pressure. METHODS: Hemodynamic measurements and echocardiography were available from 1000 patients undergoing transplant evaluation. Right atrial and PAS pressure, and TR severity were compared to PCW pressure. For 754 patients undergoing repeat measurements, changes in RA and PAS pressures were compared to PCW changes. RESULTS: Right atrial pressure correlated with PCW pressure (r = 0.64), regardless of etiology or TR severity. Right atrial pressure changes correlated with PCW changes (r = 0.62). Discordance was defined as either RA > or = 10 mm Hg despite PCW < 22 mm Hg (6%) or RA < 10 mm Hg despite PCW > or = 22 mm Hg (15%). For detection of PCW > or = 22 mm Hg, positive predictive values were 88% for RA > or = 10 mm Hg, 95% for PAS > or = 60 mm Hg, and 79% for > or = moderate TR. Pulmonary artery systolic pressure correlated very closely with PCW (r = 0.79), and could be estimated as 2 x PCW. Reduction in PAS pressure during therapy was strongly determined by PCW pressure reduction (r = 0.67). CONCLUSIONS: Accurate estimation of RA pressure can potentially guide therapy of left ventricular filling pressures in approximately 80% of chronic heart failure patients without obvious non-cardiac disease. In this population, elevated PAS pressures are largely determined by elevated left-sided filling pressures.

Women and coronary heart disease.

Research in the diagnosis and treatment of coronary heart disease has largely excluded women despite an increasing incidence, morbidity and mortality in women. This article outlines gender differences in cardiac anatomy and physiology; identifies risk factors in women; reviews primary prevention trials; discusses diagnostic techniques and therapeutic interventions in women. Understanding the strengths and weaknesses of the current knowledge of coronary heart disease in women is essential to planning effective, individualized nursing care.