A single-blinded, single-centre, controlled study in healthy adult smokers to identify the effects of a reduced toxicant prototype cigarette on biomarkers of exposure and of biological effect versus commercial cigarettes

BACKGROUND: Despite universal acceptance that smoking is harmful, a substantial number of adults continue to smoke. The development of potential reduced exposure products (more recently termed modified risk tobacco products) has been suggested as a way to reduce the risks of tobacco smoking. This trial is designed to investigate whether changes in toxicant exposure after switching from a commercial to reduced toxicant prototype (RTP) cigarette (7 mg International Organisation for Standardisation (ISO) tar yield) can be assessed by measurement of biomarkers and other factors. The primary objective is to descriptively assess changes in selected biomarkers of exposure (BoE) and biomarkers of biological effect (BoBE) within participants and within and between groups after switching. Secondary objectives are to assess similarly changes in other biomarkers, quality of life, smoking behaviours, physiological measures, mouth-level exposure to toxicants and sensory perception. METHODS/DESIGN: This trial will assess current smokers, ex-smokers and never-smokers in a single-centre single-blind, controlled clinical trial with a forced-switching design and in-clinic (residential) and ambulatory (non-residential) periods. Smokers will be aged 23–55 years (minimum legal smoking age plus 5 years) and non-smokers 28–55 years (minimum legal smoking age plus 5 years, plus minimum 5 years since last smoked). Smokers will be allowed to smoke freely at all times. We will assess changes in selected BoE and BoBE and effective dose in urine and blood after switching. Creatinine concentrations in serum, creatinine clearance in urine, cotinine concentration in saliva, diaries and collection of spent cigarette filters will be used to assess compliance with the study protocol. Mouth-level exposure to toxins will be assessed by filter analysis. DISCUSSION: Data from this study are expected to improve scientific understanding of the effects of RTP cigarettes on BoE and BoBE, and give insights into study design for clinical assessment of potential MRTPs. TRIAL REGISTRATION: The study was registered in the Current Controlled Trials database under the reference ISRCTN81286286

Hospital at Home admission avoidance with comprehensive geriatric assessment to maintain living at home for people aged 65 years and over: a RCT

Background Evidence is required to guide the redesign of health care for older people who require hospital admission. Objectives We assessed the clinical effectiveness and cost-effectiveness of geriatrician-led admission avoidance hospital at home with comprehensive geriatric assessment, the experiences of older people and their caregivers, and how the services differed. Design A multisite, randomised, open trial of comprehensive geriatric assessment hospital at home, compared with admission to hospital, using a 2 : 1 (hospital at home to hospital) ratio, and a parallel economic and process evaluation. Participants were randomised using a secure online system. Setting Participants were recruited from primary care or acute hospital assessment units from nine sites across the UK. Participants Older people who required hospital admission because of an acute change in health. Intervention Geriatrician-led admission avoidance hospital at home with comprehensive geriatric assessment. Main outcome measures The main outcome, ‘living at home’ (the inverse of death or living in a residential care setting), was measured at 6-month follow-up. Secondary outcomes at 6 months were the incidence of delirium, mortality, new long-term residential care, cognitive impairment, ability to perform activities of daily living, quality-adjusted survival, length of stay and transfer to hospital. Secondary outcomes at 12 months were living at home, new long-term residential care and mortality. Results Participants were allocated to hospital at home (n = 700) or to hospital (n = 355). All reported relative risks (RRs) were adjusted and are reported for hospital at home compared with hospital. There were no significant differences between the groups in the proportions of patients ‘living at home’ at 6 months [528/672 (78.6%) vs. 247/328 (75.3%), RR 1.05, 95% confidence interval (CI) 0.95 to 1.15; p = 0.36] or at 12 months [443/670 (66.1%) vs. 219/325 (67.4%), RR 0.99, 95% CI 0.89 to 1.10; p = 0.80]; mortality at 6 months [114/673 (16.9%) vs. 58/328 (17.7%), RR 0.98, 95% CI 0.65 to 1.47; p = 0.92] or at 12 months [188/670 (28.1%) vs. 82/325 (25.2%), RR 1.14, 95% CI 0.80 to 1.62]; the proportion of patients with cognitive impairment [273/407 (67.1%) vs. 115/183 (62.8%), RR 1.06, 95% CI 0.93 to 1.21; p = 0.36]; or in ability to perform the activities of daily living as measured by the Barthel Index (mean difference 0.24, 95% CI –0.33 to 0.80; p = 0.411; hospital at home, n = 521 patients contributed data; hospital, n = 256 patients contributed data) or Comorbidity Index (adjusted mean difference 0.0002, 95% CI –0.15 to 0.15; p = 0.10; hospital at home, n = 474 patients contributed data; hospital, n = 227 patients contributed data) at 6 months. The varying denominator reflects the number of participants who contributed data to the different outcomes. There was a significant reduction in the RR of living in residential care at 6 months [37/646 (5.7%) vs. 27/311 (8.7%), RR 0.58, 95% CI 0.45 to 0.76; p < 0.001] and 12 months [39/646 (6.0%) vs. 27/311 (8.7%), RR 0.61, 95% CI 0.46 to 0.82; p < 0.001], a significant reduction in risk of delirium at 1 month [10/602 (1.7%) vs. 13/295 (4.4%), RR 0.38, 95% CI 0.19 to 0.76; p = 0.006] and an increased risk of transfer to hospital at 1 month [173/672 (25.7%) vs. 64/330 (19.4%), RR 1.32, 95% CI 1.06 to 1.64; p = 0.012], but not at 6 months [343/631 (54.40%) vs. 171/302 (56.6%), RR 0.95, 95% CI 0.86 to 1.06; p = 0.40]. Patient satisfaction was in favour of hospital at home. An unexpected adverse event that might have been related to the research was reported to the Research Ethics Committee. At 6 months, there was a mean difference in NHS, personal social care and informal care costs (mean difference –£3017, 95% CI –£5765 to –£269), and no difference in quality-adjusted survival. Older people and caregivers played a crucial role in supporting the delivery of health care. In hospital at home this included monitoring a patient’s health and managing transitional care arrangements. Limitations The findings are most applicable to patients referred from an acute hospital assessment unit. Conclusions Comprehensive geriatric assessment hospital at home can provide a cost-effective alternative to hospitalisation for selected older people. Further research that includes a stronger element of carer support might generate evidence to improve health outcomes

Preliminary Evaluation of a New German Translated Tobacco Quality of Life Impact Tool to Discriminate Between Healthy Current and Former Smokers and to Explore the Effect of Switching Smokers to a Reduced Toxicant Prototype Cigarette

BACKGROUND: Assessment of health-related quality of life (HRQoL) is well established in clinical research, but ceiling effects in validated tools might prevent detection of changes in well respondents. Tobacco Quality of Life Impact Tool (TQOLITv1) uses conceptual and psychometric advances to enhance detection of HRQoL changes. METHODS: In a 6-month, forced-switch study, the German TQOLITv1 was assessed in healthy adult (age 23-55 years) current and matched former-smokers. At baseline, smokers were switched to reduced toxicant prototype (RTP) or conventional cigarette for 6 months. TQOLITv1 responses were collected at baseline, 3 and 6 months from current smokers whilst former smokers completed it at the latter two time points. TQOLITv1 includes SF-36v2 and new smoking-specific, physical and general-health measures. RESULTS: Reliability at baseline was good (Cronbach\u27s coefficient alpha \u3e 0.70) for all measures. The baseline percentage with the best possible score (ceiling effect) for former and current smokers was substantially better for the new physical function than SF-36 physical function measure (35% vs. 59% at ceiling, respectively). New smoking-specific measures discriminated current from former smokers better than general health measures. Smoking-specific symptoms (r = 0.73) were more stable from baseline to 6 months than other measures (r = 0.38-0.54) particularly more than the SF-36 mental component score (r = 0.24). Although both product smoking groups worsened in most HRQoL measures, changes in general and smoking-specific HRQoL impact measures favored RTP smokers. CONCLUSIONS: The German TQOLITv1 is sufficiently reliable and valid to assess HRQoL and may be more useful than SF-36v2 in evaluation of interventions in well smoking populations including those consuming RTPs

Changes in levels of biomarkers of exposure and biological effect in a controlled study of smokers switched from conventional cigarettes to reduced-toxicant-prototype cigarettes

AbstractBackgroundDevelopment of cigarettes that reduce exposure to harmful smoke constituents is a suggested tobacco harm reduction strategy, but robust methods for measurement of change are required. We investigated whether changes in biomarkers of exposure (BoE), effective dose (BoED) and biological effect (BoBE) could be detected after switching from conventional cigarettes to a reduced-toxicant-prototype cigarette (RTP).MethodsRegular smokers of 6–8mg ISO tar yield cigarettes were recruited in Hamburg, Germany, and supplied with a conventional 7mg ISO tar yield cigarette for 2weeks then switched to the same cigarette with a different tipping paper (control) or the RTP for 6months. Subjects smoked mostly at home and attended five residential clinic visits where urine and blood samples were collected for analysis. Primary endpoints were changes in specific biomarker levels compared with non-smoker background levels. Changes in daily cigarette consumption were also investigated.ResultsBoE levels in controls generally increased over the study period, whereas most BoE and all BoED significantly declined in RTP smokers. Most BoBE data were similar across groups and/or too variable within individuals to detect changes. Increased daily cigarette consumption was affected by supply of free cigarettes, perceived shorter smoking time per cigarette than usual brands, and perceived reduced harm.ConclusionsDespite increased cigarette consumption, reductions in BoE and BoED were detectable