Point of care testing: randomised controlled trial of clinical outcome

Objectives: To describe the proportion of patients attending an accident and emergency department for whom blood analysis at the point of care brought about a change in management; to measure the extent to which point of care testing resulted in differences in clinical outcome for these patients when compared with patients whose samples were tested by the hospital laboratory.

Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial

BACKGROUND The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. METHODS The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. DISCUSSION This is the first randomised trial to investigate the effect of the duration of TTM at 33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients. TRIAL REGISTRATION NCT01689077.

Randomised masked clinical trial of the MGDRx eyebag for the treatment of meibomian gland dysfunction-related evaporative dry eye

Background/aims To investigate the efficacy and safety of the MGDRx EyeBag (The Eyebag Company, Halifax, UK) eyelid warming device. Methods Twenty-five patients with confirmed meibomian gland dysfunction (MGD)-related evaporative dry eye were enrolled into a randomised, single masked, contralateral clinical trial. Test eyes received a heated device; control eyes a non-heated device for 5 min twice a day for 2 weeks. Efficacy (ocular symptomology, noninvasive break-up time, lipid layer thickness, osmolarity, meibomian gland dropout and function) and safety (visual acuity, corneal topography, conjunctival hyperaemia and staining) measurements were taken at baseline and follow-up. Subsequent patient device usage and ocular comfort was ascertained at 6 months. Results Differences between test and control eyes at baseline were not statistically signi ficant for all measurements ( p>0.05). After 2 weeks, statistically significant improvements occurred in all efficacy measurements in test eyes ( p<0.05). Visual acuity and corneal topography were unaffected (p>0.05). All patients maintained higher ocular comfort after 6 months ( p<0.05), although the bene fit was greater in those who continued usage 1-8 times a month (p<0.001). Conclusions The MGDRx EyeBag is a safe and effective device for the treatment of MGD-related evaporative dry eye. Subjective benefit lasts at least 6 months, aided by occasional retreatment. Trial registration number NCT01870180.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia:the ECLIPSE trial

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena(®), Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment. DESIGN: A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. SETTING: Women who presented in primary care. PARTICIPANTS: A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. INTERVENTIONS: LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. OUTCOME MEASURES: The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. RESULTS: The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women's experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. CONCLUSIONS: The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women's assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86566246. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information.

The functional and clinical outcomes of exercise training following a very low energy diet for severely obese women: study protocol for a randomised controlled trial

BACKGROUND: Clinical practice guidelines globally recommend lifestyle modification including diet and exercise training as first-line treatment for obesity. The clinical benefits of exercise training in adults with obesity is well-documented; however, there is no strong evidence for the effectiveness of exercise training for weight loss in class II and class III obesity. The purpose of the randomised controlled trial described in this protocol article is to examine the effect of exercise training, in addition to a very low energy diet (VLED), in clinically severe obese women for changes in body composition, physical function, quality of life, and markers of cardiometabolic risk.

METHODS/DESIGN: Sixty women, aged 18-50 years with a body mass index (BMI) greater than 34.9 kg.m(2) and at least one obesity-related co-morbidity, will be recruited for this 12-month study. Participants will be randomised to either exercise plus energy restriction (n = 30), or energy restriction alone (n = 30). All participants will follow an energy-restricted individualised diet incorporating a VLED component. The exercise intervention group will also receive exercise by supervised aerobic and resistance training and a home-based exercise programme totalling 300 minutes per week. Primary outcome measures include body composition and aerobic fitness. Secondary outcome measures include: physical function, cardiometabolic risk factors, quality of life, physical activity, and mental health. All outcome measures will be conducted at baseline, 3, 6 and 12 months.

DISCUSSION: Previous research demonstrates various health benefits of including exercise training as part of a healthy lifestyle at all BMI ranges. Although clinical practice guidelines recommend exercise training as part of first-line treatment for overweight and obesity, there are few studies that demonstrate the effectiveness of exercise in class II and class III obesity. The study aims to determine whether the addition of exercise training to a VLED provides more favourable improvements in body composition, physical function, quality of life, and markers of cardiometabolic risk for women with clinically severe obesity, compared to VLED alone.

Creating a therapeutic environment : a non-randomised controlled trial of a quiet time intervention for patients in acute care

Background: Noise is a significant barrier to sleep for acute care hospital patients, and sleep has been shown to be therapeutic for health, healing and recovery. Scheduled quiet time interventions to promote inpatient rest and sleep have been successfully trialled in critical care but not in acute care settings. Objectives: The study aim was to evaluate as cheduled quiet time intervention in an acute care setting. The study measured the effect of a scheduled quiet time on noise levels, inpatients’ rest and sleep behaviour, and wellbeing. The study also examined the impact of the intervention on patients’, visitors’ and health professionals’ satisfaction, and organisational functioning. Design: The study was a multi-centred non-randomised parallel group trial. Settings: The research was conducted in the acute orthopaedic wards of two major urban public hospitals in Brisbane, Australia. Participants: All patientsadmitted to the two wards in the5-month period of the study were invited to participate, withafinalsample of 299 participants recruited. This sample produced an effect size of 0.89 for an increase in the number of patients asleep during the quiet time. Methods: Demographic data were collected to enable comparison between groups. Data for noise level, sleep status, sleepiness and well being were collected using previously validated instruments: a Castle Model 824 digital sound level indicator; a three point sleep status scale; the Epworth Sleepiness Scale; and the SF12 V2 questionnaire. The staff, patient and visitor surveys on the experimental ward were adapted from published instruments. Results: Significant differences were found between the two groups in mean decibel level and numbers of patients awake and asleep. The difference in mean measured noise levels between the two environments corresponded to a ‘perceived’ difference of 2 to 1. There were significant correlations between average decibel level and number of patients awake and asleep in the experimental group, and between average decibel level and number of patients awake in the control group. Overall, patients, visitors and health professionals were satisfied with the quiet time intervention. Conclusions: The findings show that a quiet time intervention on an acute care hospital ward can affect noise level and patient sleep/wake patterns during the intervention period. The overall strongly positive response from surveys suggests that scheduled quiet time would be a positively perceived intervention with therapeutic benefit.

Mailed treatment to augment primary care for alcohol disorders : a randomised controlled trial

Introduction and Aims: Remote delivery of interventions is needed to address large numbers of people with alcohol use disorders who are spread over large areas. Previous correspondence trials typically examined its effects as stand-alone treatment. This study aimed to test whether adding postal treatment to general practitioner (GP) support would lower alcohol use more than GP intervention alone. Design and Methods: A single-blind, randomised controlled trial with a crossover design was conducted over 12 months on 204 people with alcohol use disorders. Participants in an immediate correspondence condition received treatment over the first 3 months; those receiving delayed treatment received it in months 3–6. Results: Few participants were referred from GPs, and little intervention was offered by them. At 3 months, 78% of participants remained in the study. Those in immediate treatment showed greater reductions in alcohol per week, drinking days, anxiety, depression and distress than those in the delayed condition. However, post-treatment and follow-up outcomes still showed elevated alcohol use, depression, anxiety and distress. Greater baseline anxiety predicted better alcohol outcomes, although more mental distress at baseline predicted dropout. Discussion and Conclusions: The study gave consistent results with those from previous research on correspondence treatments, and showed that high levels of participant engagement over 3 months can be obtained. Substantial reductions in alcohol use are seen, with indications that they are well maintained. However, many participants continue to show high-risk alcohol use and psychological distress.

Improved functional ability and independence in activities of daily living for older adults at high risk of hospital readmission : a randomised controlled trial

Objective: During hospitalisation older people often experience functional decline which impacts on their future independence. The objective of this study was to evaluate a multifaceted transitional care intervention including home-based exercise strategies for at-risk older people on functional status, independence in activities of daily living, and walking ability. Methods: A randomised controlled trial was undertaken in a metropolitan hospital in Australia with 128 patients (64 intervention, 64 control) aged over 65 years with an acute medical admission and at least one risk factor for hospital readmission. The intervention group received an individually tailored program for exercise and follow-up care which was commenced in hospital and included regular visits in hospital by a physiotherapist and a Registered Nurse, a home visit following discharge, and regular telephone follow-up for 24 weeks following discharge. The program was designed to improve health promoting behaviours, strength, stability, endurance and mobility. Data were collected at baseline, then 4, 12 and 24 weeks following discharge using the Index of Activities of Daily Living (ADL), Instrumental Index of Activities of Daily Living (IADL), and the Walking Impairment Questionnaire (Modified). Results: Significant improvements were found in the intervention group in IADL scores (p<.001), ADL scores (p<.001), and WIQ scale scores (p<.001) in comparison to the control group. The greatest improvements were found in the first four weeks following discharge. Conclusions: Early introduction of a transitional model of care incorporating a tailored exercise program and regular telephone follow-up for hospitalised at-risk older adults can improve independence and functional ability.