Bridging the age gap in breast cancer: impact of omission of breast cancer surgery in older women with oestrogen receptor-positive early breast cancer on quality-of-life outcomes.

BACKGROUND: Primary endocrine therapy may be an alternative treatment for less fit women with oestrogen receptor (ER)-positive breast cancer. This study compared quality-of-life (QoL) outcomes in older women treated with surgery or primary endocrine therapy. METHODS: This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer. QoL was assessed using European Organisation for Research and Treatment of cancer QoL questionnaires QLQ-C30, -BR23, and -ELD14, and the EuroQol Five Dimensions 5L score at baseline, 6 weeks, and 6, 12, 18, and 24 months. Propensity score matching was used to adjust for baseline variation in health, fitness, and tumour stage. RESULTS: The study recruited 3416 women (median age 77 (range 69-102) years) from 56 breast units. Of these, 2979 (87.2 per cent) had ER-positive breast cancer; 2354 women had surgery and 500 received primary endocrine therapy (125 were excluded from analysis due to inadequate data or non-standard therapy). Median follow-up was 52 months. The primary endocrine therapy group was older and less fit. Baseline QoL differed between the groups; the mean(s.d.) QLQ-C30 global health status score was 66.2(21.1) in patients who received primary endocrine therapy versus 77.1(17.8) among those who had surgery plus endocrine therapy. In the unmatched analysis, changes in QoL between 6 weeks and baseline were noted in several domains, but by 24 months most scores had returned to baseline levels. In the matched analysis, major surgery (mastectomy or axillary clearance) had a more pronounced adverse impact than primary endocrine therapy in several domains. CONCLUSION: Adverse effects on QoL are seen in the first few months after surgery, but by 24 months these have largely resolved. Women considering surgery should be informed of these effects.

Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices.

BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).

Rehabilitation of older patients: day hospital compared with rehabilitation at home. Clinical outcomes.

OBJECTIVES: to test the hypothesis that older people and their informal carers are not disadvantaged by home-based rehabilitation (HBR) relative to day hospital rehabilitation (DHR). DESIGN: pragmatic randomised controlled trial. SETTING: four geriatric day hospitals and four home rehabilitation teams in England. PARTICIPANTS: eighty-nine patients referred for multidisciplinary rehabilitation. The target sample size was 460. INTERVENTION: multidisciplinary rehabilitation either in the home or in the day hospital. MEASUREMENTS: the primary outcome measure was the Nottingham extended activities of daily living scale (NEADL). Secondary outcome measures included EQ-5D, hospital anxiety and depression scale, therapy outcome measures, hospital admissions and the General Health Questionnaire for carers. RESULTS: at the primary end point of 6 months NEADL scores were not significantly in favour of HBR cf. DHR; mean difference -2.139 (95% confidence interval -6.87 to 2.59, P = 0.37). A post hoc analysis suggested non-inferiority for HBR for NEADL but there was considerable statistical uncertainty. CONCLUSION: taken together the statistical analyses and lack of power of the trial outcomes do not provide sufficient evidence to conclude that patients in receipt of HBR are disadvantaged compared with those receiving DHR.

Voltage- and temperature-dependent gating of heterologously expressed channelrhodopsin-2.

Channelrhodopsins are light-activated channels originally isolated from algae that are being used increasingly as tools to non-invasively stimulate neurones. Despite their widespread use some aspects of their biophysical properties have not been fully characterised. Here we report detailed investigation of the gating kinetics and voltage-dependence of ChR2 transiently expressed in HEK-293 cells. Currents were elicited using light pulses of defined duration and intensity generated by a blue LED. Datasets were gathered both at room temperature (RT, ∼22°C) and 37°C. Current responses to light rose rapidly to a peak and then desensitized to a steady state plateau. When illumination was terminated currents rapidly deactivated. Recovery from desensitization at -85 mV was slow with half-times of 1.4 and 3.1s at 37°C and ∼22°C, respectively. At both temperatures, the reversal potential of ChR2 responses was a few mV positive to 0 mV. Both the peak and plateau phases of ChR2 responses exhibited strong inward rectification with only small outward currents at positive membrane potentials. The rates of ChR2 activation, deactivation and desensitization were ∼2 times faster at 37°C than at ∼22°C. Both the activation and deactivation kinetics of ChR2 were significantly slowed by depolarization at both temperatures. Additionally, the degree of steady state desensitization was greater at more depolarized potentials. The macroscopic desensitization kinetics were not voltage-dependent, but recovery from desensitization was slowed by depolarization. These gating behaviour data provide an important basis for more detailed analysis of the properties and limitations of ChR2 use in more complex systems.

Epidemiology of critically ill children in England and Wales: incidence, mortality, deprivation and ethnicity.

OBJECTIVE: The purpose of this work was to investigate the incidence rate for admission and mortality of children receiving paediatric intensive care in relation to socioeconomic status and ethnicity in England and Wales. DESIGN: National cohort of sequential hospital admissions. SETTING: Twenty nine paediatric intensive care units in England and Wales. PARTICIPANTS: All children aged under 16 years admitted to paediatric intensive care in the 4 years 2004-2007. MAIN OUTCOME MEASURES: Incidence rates for admission and odds ratios (OR) for risk-adjusted mortality by an area based measure of deprivation (Townsend score) and ethnic group (south Asian vs non-south Asian determined using two-name analysis algorithms). RESULTS: The incidence for south Asian children was higher than that of non-south Asian children (138 vs 95/100,000, incidence rate ratio 1.36, 95% CI 1.32 to 1.40). The age-sex standardised incidence for children admitted to paediatric intensive care ranged from 69/100,000 in the least deprived fifth of the population to 124/100,000 in the most deprived fifth. The risk-adjusted OR for mortality for south Asian children was 1.36 (95% CI 1.18 to 1.57) overall, rising to 2.40 (95% CI 1.40 to 4.10) in the least deprived fifth of the population when a statistical interaction term for deprivation was included. CONCLUSIONS: In England and Wales, the admission rate to paediatric intensive care is higher for children from more deprived areas and 36% higher for children from the south Asian population. Risk-adjusted mortality increases in south Asian children as deprivation decreases.

Rehabilitation of older patients: day hospital compared with rehabilitation at home. A randomised controlled trial.

OBJECTIVES: To test the hypotheses that older people and their informal carers are not disadvantaged by home-based rehabilitation (HBR) relative to day hospital rehabilitation (DHR) and that HBR is less costly. DESIGN: Two-arm randomised controlled trial. SETTING: Four trusts in England providing both HBR and DHR. PARTICIPANTS: Clinical staff reviewed consecutive referrals to identify subjects who were potentially suitable for randomisation according to the defined inclusion criteria. INTERVENTIONS: Patients were randomised to receive either HBR or DHR. MAIN OUTCOME MEASURES: The primary outcome measure was the Nottingham Extended Activities of Daily Living (NEADL) scale. Secondary outcome measures included the EuroQol 5 dimensions (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Therapy Outcome Measures (TOMs), hospital admissions and the General Health Questionnaire (GHQ-30) for carers. RESULTS: Overall, 89 subjects were randomised and 42 received rehabilitation in each arm of the trial. At the primary end point of 6 months there were 32 and 33 patients in the HBR and DHR arms respectively. Estimated mean scores on the NEADL scale at 6 months, after adjustment for baseline, were not significantly in favour of either HBR or DHR [DHR 30.78 (SD 15.01), HBR 32.11 (SD 16.89), p = 0.37; mean difference -2.139 (95% CI -6.870 to 2.592)]. Analysis of the non-inferiority of HBR over DHR using a 'non-inferiority' limit (10%) applied to the confidence interval estimates for the different outcome measures at 6 months' follow-up demonstrated non-inferiority for the NEADL scale, EQ-5D and HADS anxiety scale and some advantage for HBR on the HADS depression scale, of borderline statistical significance. Similar results were seen at 3 and 12 months' follow-up, with a statistically significant difference in the mean EQ-5D(index) score in favour of DHR at 3 months (p = 0.047). At the end of rehabilitation, a greater proportion of the DHR group showed a positive direction of change from their initial assessment with respect to therapist-rated clinical outcomes; however, a lower proportion of HBR patients showed a negative direction of change and, overall, median scores on the TOMs scales did not differ between the two groups. Fewer patients in the HBR group were admitted to hospital on any occasion over the 12-month observation period [18 (43%) versus 22 (52%)]; however, this difference was not statistically significant. The psychological well-being of patients' carers, measured at 3, 6 and 12 months, was unaffected by whether rehabilitation took place at day hospital or at home. As the primary outcome measure and EQ-5D(index) scores at 6 months showed no significant differences between the two arms of the trial, a cost-minimisation analysis was undertaken. Neither the public costs nor the total costs at the 6-month follow-up point (an average of 213 days' total follow-up) or the 12-month follow-up point (an average of 395 days' total follow-up) were significantly different between the groups. CONCLUSIONS: Compared with DHR, providing rehabilitation in patients' own homes confers no particular disadvantage for patients and carers. The cost of providing HBR does not appear to be significantly different from that of providing DHR. Rehabilitation providers and purchasers need to consider the place of care in the light of local needs, to provide the benefits of both kinds of services. Caution is required when interpreting the results of the RCT because a large proportion of potentially eligible subjects were not recruited to the trial, the required sample size was not achieved and there was a relatively large loss to follow-up. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71801032.