Primary and secondary care service use and costs associated with frailty in an ageing population: longitudinal analysis of an English primary care cohort of adults aged 50 and over, 2006-2017.

BACKGROUND: Frailty becomes more prevalent and healthcare needs increase with age. Information on the impact of frailty on population level use of health services and associated costs is needed to plan for ageing populations. AIM: To describe primary and secondary care service use and associated costs by electronic Frailty Index (eFI) category. DESIGN AND SETTING: Retrospective cohort using electronic health records. Participants aged ≥50 registered in primary care practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre, 2006-2017. METHODS: Primary and secondary care use (totals and means) were stratified by eFI category and age group. Standardised 2017 costs were used to calculate primary, secondary and overall costs. Generalised linear models explored associations between frailty, sociodemographic characteristics. Adjusted mean costs and cost ratios were produced. RESULTS: Individual mean annual use of primary and secondary care services increased with increasing frailty severity. Overall cohort care costs for were highest in mild frailty in all 12 years, followed by moderate and severe, although the proportion of the population with severe frailty can be expected to increase over time. After adjusting for sociodemographic factors, compared to the fit category, individual annual costs doubled in mild frailty, tripled in moderate and quadrupled in severe. CONCLUSIONS: Increasing levels of frailty are associated with an additional burden of individual service use. However, individuals with mild and moderate frailty contribute to higher overall costs. Earlier intervention may have the most potential to reduce service use and costs at population level.

Nocturnal temperature-controlled laminar airflow device for adults with severe allergic asthma: the LASER RCT.

BACKGROUND: Severe asthma exacerbations are costly to patients and the NHS, and occur frequently in severely allergic patients. OBJECTIVE: To ascertain whether or not nocturnal temperature-controlled laminar airflow (TLA) device usage over 12 months can reduce severe exacerbations and improve asthma control and quality of life compared with a placebo device, while being cost-effective and acceptable to adults with severe allergic asthma. DESIGN: A pragmatic, multicentre, randomised, double-blind, placebo-controlled, parallel-group, superiority trial with qualitative interviews. The trial included an internal pilot with qualitative focus groups. SETTING: Fourteen hospitals in the UK that manage patients with severe asthma. PARTICIPANTS: Adults (16-75 years) with severe, poorly controlled, exacerbation-prone asthma despite high-intensity treatment, and who are sensitised to a perennial indoor aeroallergen. INTERVENTION: Nocturnal, home-based TLA treatment using an Airsonett® (Airsonett AB, Ängelholm, Sweden) device. The comparator was a placebo device that was identical to the active device except that it did not deliver the laminar airflow. Participants were allocated 1 : 1 to TLA therapy or placebo, minimised by site, origin of case, baseline severe exacerbation frequency, maintenance oral corticosteroid use and pre-bronchodilator forced expiratory volume in 1 second. MAIN OUTCOME MEASURES: Primary outcome - frequency of severe asthma exacerbations occurring within the 12-month follow-up period, defined as worsening of asthma requiring systemic corticosteroids [≥ 30 mg of prednisolone or equivalent daily (or ≥ 50% increase in dose if on maintenance dose of ≥ 30 mg of prednisolone)] for ≥ 3 days. Secondary outcomes - changes in asthma control, lung function, asthma-specific and global quality of life for participants, adherence to the intervention, device acceptability, health-care resource use and cost-effectiveness. RESULTS: Between May 2014 and January 2016, 489 patients consented to participate in the trial, of whom 249 failed screening and 240 were randomised (n = 119 in the treatment group and n = 121 in the placebo group); all were analysed. In total, 202 participants (84%) reported use of the device for 9-12 months. Qualitative analyses showed high levels of acceptability. The mean [standard deviation (SD)] rate of severe exacerbations did not differ between groups [active 1.39 (1.57), placebo 1.48 (2.03); risk ratio 0.92, 95% CI 0.66 to 1.27; p = 0.616]. There were no significant differences in secondary outcomes for lung function, except for a reduction in mean daily peak expiratory flow [mean (SD) difference 14.7 l/minute (7.35 l/minute), 95% CI 0.32 to 29.1 l/minute; p = 0.045) for those in the active device group. There were no differences in asthma control or airway inflammation and no serious harms related to the device. No significant difference between the groups in quality-adjusted life-years gained over 1 year was observed. In addition, there was no difference in generic or disease-specific health-related quality of life overall, although statistically significant higher quality of life at month 6 was observed. Increases in quality of life were not sufficient to offset the annual costs associated with use of the TLA device. LIMITATIONS: Missing outcome data could have resulted in an underestimation of exacerbations and rendered the study inconclusive. CONCLUSIONS: Within the limits of the data, no consistent benefits of the active device were demonstrated, and the differences observed were not sufficient to make the device cost-effective. The types of patients who may benefit from the TLA device, and the reasons for large reductions in exacerbation frequency in severe asthma trials, which also incorporate other methods of recording exacerbations, need to be explored. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46346208. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 29. See the NIHR Journals Library website for further project information.

Allergies (along with viruses) are common triggers of asthma exacerbations or 'attacks', which can cause suffering and frequent visits to the general practitioner or hospital. A new machine known as a temperature-controlled laminar airflow device, which remains at the bedside and is switched on every night, filters out allergy particles in the air of a patient's breathing zone, allowing their lungs to rest in clean air overnight. We tested whether or not this machine could improve the lives of those with severe allergic asthma. We recruited 240 people across 14 centres that treat severe asthma across the UK; approximately half received the active device and the other half received a machine that looked exactly the same but did not remove the allergens (a 'placebo' machine). One in five participants was recruited using newer methods of social media such as Facebook (Facebook, Inc., Menlo Park, CA, USA) and Twitter (Twitter, Inc., San Francisco, CA, USA). Participants found the machine easy to use and to live with and there were no significant side effects. The number of attacks reduced a lot in both participants using the active device and those who used the placebo device ­ two participants in five did not suffer any attacks during the trial. However, there was no difference in the number of attacks between the two groups. This might have been because participants did not record everything that happened to them. There was no difference in measurements showing how well the lungs were working, nor in participants' quality of life after 1 year of participating in the trial. Those who were interviewed told us that the study visits and questionnaires could be burdensome, although it was helpful to think more about their asthma. An improvement was seen in one aspect of participants' breathing as well as in their quality of life after 6 months of using the machine, but these potential health benefits could not outweigh the cost of the machine.

A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.

BACKGROUND: Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. METHODS: This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. DISCUSSION: Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally. TRIAL REGISTRATION: Current controlled trials ISRCTN18955704. Date ISRCTN assigned: 31 January 2014.

Neuropsychiatric events with varenicline: a modified prescription-event monitoring study in general practice in England.

BACKGROUND: Varenicline (Champix(®)), launched in the UK in December 2006, is indicated for the treatment of smoking cessation in adults (≥18 years of age). In 2008, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK issued a warning suggesting that varenicline was associated with disparate neuropsychiatric symptoms, including depression, suicidal thoughts and behaviour. In response to this regulatory warning, the Drug Safety Research Unit conducted a modified prescription-event monitoring (M-PEM) study to monitor the safety of varenicline. OBJECTIVE: The aim of this study was to estimate the incidence and examine the pattern of neuropsychiatric events reported to general practitioners (GPs) in England during the immediate postmarketing period for varenicline. METHODS: A postmarketing surveillance study was conducted using the observational cohort technique of M-PEM. Patients were identified from dispensed prescriptions issued by primary care physicians between December 2006 and March 2007. Data on exposure, previous history of psychiatric illness and events reported during and after treatment were collected from questionnaires. In order to determine whether hazards for neuropsychiatric events of interest (depression, anxiety, aggression, suicidal ideation, non-fatal self-harm) were non-constant over time (which could indicate a possible association with the drug), the pattern of events was examined by plotting the smoothed hazard function estimate and then fitting a Weibull model. The Weibull model shape parameter (ß) and 95 % confidence interval were used as a test for a non-constant hazard function (where a value of 1 indicates a constant hazard over time). In addition to this analysis, the difference in incidence densities (IDs) between month 1 and months 2-3 were calculated and compared. RESULTS: The cohort comprised of 12,159 patients (median age 47 years [interquartile range 19]; 56.9 % [n = 6924 female]). The number of events reported during treatment, reason for stopping, adverse drug reactions (ADRs), and the p-value for the Weibull shape parameter were as follows: depression (n = 94; 42; 19; p = 0.144); anxiety (n = 94; 49; 9; p = 0.009); aggression (n = 7; 4; 2; p = 0.465); suicidal ideation (n = 8; 4; 1; p = 0.989) and non-fatal self-harm (n = 5; 1; 0; p = 0.771). No differences in the IDs between months 1 and months 2-3 were found for any of the events. CONCLUSION: Whilst between 7 and 17 % of neuropsychiatric events were attributed to the drug by GPs and approximately 20-50 % were given as reasons for stopping, no signal was raised using the ID differences approach, and only anxiety was flagged as a potential signal for an ADR using the Weibull model. The signal for anxiety requires further evaluation to determine whether the drug plays a part in the development of anxiety or whether it is a withdrawal symptom caused by smoking cessation. Analysis methods will lack power when the numbers of events are low even when a large number of participants are included in the study.

Safety profile of oxcarbazepine: results from a prescription-event monitoring study.

PURPOSE: To monitor safety of oxcarbazepine, prescribed in primary care in England, using prescription-event monitoring (PEM). METHODS: Postmarketing surveillance using observational cohort technique of PEM. Exposure data were obtained from dispensed British National Health Service prescriptions issued by general practitioners (GPs) March 2000-July 2003. Demographic, drug utilization, and clinical event data were collected from questionnaires posted to GPs at least 6 months after first prescription date for each patient. Incidence densities (IDs) (number of first reports per 1,000 patient-months of treatment) were calculated and differences for events reported in month 1 (ID(1)) and months 2-6 (ID(2-6)) (99% confidence intervals) were examined for changes in event rates. Follow-up and causality assessment of medically significant events were undertaken. RESULTS: The cohort comprised 2,243 patients [mean age 40.4 years; range 2-99 years; standard deviation (SD) 18.8; 46.3% (n = 1,038) male]. Most frequently reported primary indications were epilepsy, convulsion (n = 1,111; 49.5%, n = 209; 9.3%, respectively). GPs recorded 932 reasons for stopping medication in 698 (31.1%) patients; most frequent clinical reason "drowsiness/sedation" (n = 57; 2.5% of cohort). Clinical events (excluding indication) associated with starting treatment (lower 99% CI > 0) included: "drowsiness/sedation" (ID(1)-ID(2-6) = 14.2), "nausea/vomiting" (ID(1)-ID(2-6) = 13.0), and dizziness (ID(1)-ID(2-6) = 11.6). Events followed up and assessed as probably related to oxcarbazepine use included rash (7 of 11) and hyponatremia (15 of 38). DISCUSSION: There were no serious adverse drug reactions reported during this study. Results of the study should be taken in context with other epidemiologic studies.

Assessment of three new parasite lactate dehydrogenase (pan-pLDH) tests for diagnosis of uncomplicated malaria.

A study to assess the diagnostic capabilities of three parasite lactate dehydrogenase (pan-pLDH) tests, Vistapan), Carestart and Parabank), was conducted in Uganda. An HRP2 test, Paracheck-Pf), and a Giemsa-stained blood film were performed with the pLDH tests for outpatients with suspected malaria. In total, 460 subjects were recruited: 248 with positive blood films and 212 with negative blood films. Plasmodium falciparum was present in 95% of infections. Sensitivity above 90% was shown by two pLDH tests, Carestart (95.6%) and Vistapan (91.9%), and specificity above 90% by Parabank (94.3%) and Carestart (91.5%). Sensitivity decreased with low parasitaemia (chi(2) trend, P<0.001); however, all tests achieved sensitivity >90% with parasitaemia > or =100/microl. All tests had good inter-reader reliability (kappa>0.95). Two weeks after diagnosis, 4-10% of pLDH tests were still positive compared with 69.7% of the HRP2 tests. All tests had similar ease of use. In conclusion, two pLDH tests performed well in diagnosing P. falciparum malaria, and all pLDH tests became negative after treatment more quickly than the HRP2. Therefore the rapid test of choice for use with artemisinin-combination therapies in this area would be one of these new pLDH tests.