Withdrawal from treatment as an outcome in the Isolde study of COPD

Objectives: To investigate the determinants of patient withdrawal from our study, and the effect of these withdrawals on the outcome of treatment with inhaled corticosteroids in patients with COPD. Design: A double-blind, placebo-controlled, randomized trial. Setting: Eighteen outpatient centers in the United Kingdom. Participants: Seven hundred fifty-one patients with stable COPD defined clinically as baseline postbronchodilator FEV1 > 0.8 L and < 85% predicted, FEV1/FVC ratio < 70%, and FEV1 change after albuterol < 10% of predicted. Intervention: Random assignment of either 500 micrograms bid of inhaled fluticasone propionate (FP)using a spacer device or an identical placebo inhaler. Treatment was continued for 3 years or until patients withdrew from follow-up. Measurements and results: Postbronchodilator FEV1 was measured on three occasions before randomization and every 3 months thereafter. Health status was assessed by the disease-specific St. George Respiratory Questionnaire (SGRQ) and the modified short-form 36 questionnaire (SF-36) at baseline and every 6 months. Three hundred thirty-nine patients withdrew, of whom 156 patients received FP. Prescription of frequent courses of oral prednisolone was the most common reason for withdrawing as specified in the protocol (69 patients in the FP group withdrew due to respiratory symptoms, compared with 93 patients in the placebo group). This explained the significantly greater dropout of placebo-treated patients that was most evident when FEV1 was < 50% predicted. Patients withdrawing had a significantly more rapid decline in health status, measured by both the SGRQ and the SF-36 (p < 0.001). Those withdrawing from the placebo group had a more rapid decline in FEV1 and more exacerbations than the FP-treated groups. Baseline FEV1 was lower in dropouts than in patients completing the study receiving placebo, but there was no difference between the respective groups receiving FP. Conclusions: Patients who withdrew from follow-up were those with the most rapidly deteriorating health status and lung function. Losing these patients from the final analysis can reduce the power of a study to achieve its primary end point

Spatial sampling of the thermospheric vertical wind field at auroral latitudes

Results are presented from two nights of bistatic Doppler measurements of neutral thermospheric winds using Fabry!Perot spectrometers at Mawson and Davis stations in Antarctica. A scanning Doppler imager (SDI) at Mawson and a narrow-field Fabry-Perot spectrometer (FPS) at Davis have been used to estimate the vertical wind at three locations along the great circle joining the two stations, in addition to the vertical wind routinely observed above each station. These data were obtained from observations of the 630.0 nm airglow line of atomic oxygen, at a nominal altitude of 240 km. Low!resolution all-sky images produced by the Mawson SDI have been used to relate disturbances in the measured vertical wind field to auroral activity and divergence in the horizontal wind field. Correlated vertical wind responses were observed on a range of horizontal scales from ~150 to 480 km. In general, the behavior of the vertical wind was in agreement with earlier studies, with strong upward winds observed poleward of the optical aurora and sustained, though weak, downward winds observed early in the night. The relation between vertical wind and horizontal divergence was seen to follow the general trend predicted by Burnside et al. (1981), whereby upward vertical winds were associated with positive divergence and vice versa; however, a scale height approximately 3–4 times greater than that modeled by NRLMSISE-00 was required to best fit the data using this relation

The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

Current and Emerging Uses of Statins in Clinical Therapeutics: A Review

Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug–drug and drug–food interactions associated with statin use are presented. Furthermore, we discuss the pleiotropic effects associated with statins with regard to the onset and progression of autoimmune and inflammatory diseases, cancer, neurodegenerative disorders, strokes, bacterial infections, and human immunodeficiency virus. Understanding these issues will improve the prognosis of patients who are administered statins and potentially expand our ability to treat a wide variety of diseases

Preventing male suicide through a psychosocial intervention that provides psychological support and tackles financial difficulties:a mixed method evaluation

BACKGROUND: To help resolve high suicide rates in Bristol, North Somerset and South Gloucestershire, the charity Second Step was commissioned to roll-out the Hope service offering a psychosocial intervention for men, supporting them through acute distress and addressing financial difficulties. This study evaluated the impact of the Hope service on men at risk of suicide experiencing financial and other difficulties. METHODS: Mixed methods study using: (i) a prospective cohort study design to compare depression, suicidal ideation and financial self-efficacy scores of men aged 30–64, referred to the service between October 2018 and July 2020, at baseline and 6 months follow-up and between low and moderate to high-intensity service users; and (ii) a qualitative interview study to evaluate the acceptability and impact of the Hope service to Hope service users. RESULTS: There was a 49% reduction in depression score (mean reduction − 10.0, 95% CI − 11.7 to − 8.3) and in the proportion of service users with suicidal ideation (percent reduction − 52.5, 95% CI − 64.1% to − 40.9%) at 6 months follow-up compared to baseline. Financial self-efficacy scores increased by 26% (mean increase 2.9, 95% CI 1.8 to 3.9). Qualitative accounts illustrated how ‘Hope saved my life’ for several men interviewed; most respondents described being able to move forward and tackle challenges with more confidence following the Hope intervention. Professional advice to tackle financial and other difficulties such as housing helped to relieve anxiety and stress and enable practical issues to be resolved. CONCLUSIONS: The Hope service offered practical and emotional support to men who have experienced suicidal feelings, redundancy, homelessness and poverty and occupies an important space between mental health and social care provision. Hope demonstrates the value of an intervention which cuts across traditional boundaries between psychiatric care and social advice agencies to provide, what is, in effect, an integrated care service. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-022-03973-5

Methods for the thematic synthesis of qualitative research in systematic reviews

<p>Abstract</p> <p>Background</p> <p>There is a growing recognition of the value of synthesising qualitative research in the evidence base in order to facilitate effective and appropriate health care. In response to this, methods for undertaking these syntheses are currently being developed. Thematic analysis is a method that is often used to analyse data in primary qualitative research. This paper reports on the use of this type of analysis in systematic reviews to bring together and integrate the findings of multiple qualitative studies.</p> <p>Methods</p> <p>We describe thematic synthesis, outline several steps for its conduct and illustrate the process and outcome of this approach using a completed review of health promotion research. Thematic synthesis has three stages: the coding of text 'line-by-line'; the development of 'descriptive themes'; and the generation of 'analytical themes'. While the development of descriptive themes remains 'close' to the primary studies, the analytical themes represent a stage of interpretation whereby the reviewers 'go beyond' the primary studies and generate new interpretive constructs, explanations or hypotheses. The use of computer software can facilitate this method of synthesis; detailed guidance is given on how this can be achieved.</p> <p>Results</p> <p>We used thematic synthesis to combine the studies of children's views and identified key themes to explore in the intervention studies. Most interventions were based in school and often combined learning about health benefits with 'hands-on' experience. The studies of children's views suggested that fruit and vegetables should be treated in different ways, and that messages should not focus on health warnings. Interventions that were in line with these suggestions tended to be more effective. Thematic synthesis enabled us to stay 'close' to the results of the primary studies, synthesising them in a transparent way, and facilitating the explicit production of new concepts and hypotheses.</p> <p>Conclusion</p> <p>We compare thematic synthesis to other methods for the synthesis of qualitative research, discussing issues of context and rigour. Thematic synthesis is presented as a tried and tested method that preserves an explicit and transparent link between conclusions and the text of primary studies; as such it preserves principles that have traditionally been important to systematic reviewing.</p

Life path analysis: scaling indicates priming effects of social and habitat factors on dispersal distances

1. Movements of many animals along a life-path can be separated into repetitive ones within home ranges and transitions between home ranges. We sought relationships of social and environmental factors with initiation and distance of transition movements in 114 buzzards Buteo buteo that were marked as nestlings with long-life radio tags. 2. Ex-natal dispersal movements of 51 buzzards in autumn were longer than for 30 later in their first year and than 35 extra-natal movements between home ranges after leaving nest areas. In the second and third springs, distances moved from winter focal points by birds that paired were the same or less than for unpaired birds. No post-nuptial movement exceeded 2 km. 3. Initiation of early ex-natal dispersal was enhanced by presence of many sibs, but also by lack of worm-rich loam soils. Distances travelled were greatest for birds from small broods and with relatively little short grass-feeding habitat near the nest. Later movements were generally enhanced by the absence of loam soils and short grassland, especially with abundance of other buzzards and probable poor feeding habitats (heathland, long grass). 4. Buzzards tended to persist in their first autumn where arable land was abundant, but subsequently showed a strong tendency to move from this habitat. 5. Factors that acted most strongly in ½-km buffers round nests, or round subsequent focal points, usually promoted movement compared with factors acting at a larger scale. Strong relationships between movement distances and environmental characteristics in ½-km buffers, especially during early ex-natal dispersal, suggested that buzzards became primed by these factors to travel far. 6. Movements were also farthest for buzzards that had already moved far from their natal nests, perhaps reflecting genetic predisposition, long-term priming or poor habitat beyond the study area

Evidence-based planning and costing palliative care services for children : novel multi-method epidemiological and economic exemplar

Background: Children’s palliative care is a relatively new clinical specialty. Its nature is multi-dimensional and its delivery necessarily multi-professional. Numerous diverse public and not-for-profit organisations typically provide services and support. Because services are not centrally coordinated, they are provided in a manner that is inconsistent and incoherent. Since the first children’s hospice opened in 1982, the epidemiology of life-limiting conditions has changed with more children living longer, and many requiring transfer to adult services. Very little is known about the number of children living within any given geographical locality, costs of care, or experiences of children with ongoing palliative care needs and their families. We integrated evidence, and undertook and used novel methodological epidemiological work to develop the first evidence-based and costed commissioning exemplar. Methods: Multi-method epidemiological and economic exemplar from a health and not-for-profit organisation perspective, to estimate numbers of children under 19 years with life-limiting conditions, cost current services, determine child/parent care preferences, and cost choice of end-of-life care at home. Results: The exemplar locality (North Wales) had important gaps in service provision and the clinical network. The estimated annual total cost of current children’s palliative care was about £5.5 million; average annual care cost per child was £22,771 using 2007 prevalence estimates and £2,437- £11,045 using new 2012/13 population-based prevalence estimates. Using population-based prevalence, we estimate 2271 children with a life-limiting condition in the general exemplar population and around 501 children per year with ongoing palliative care needs in contact with hospital services. Around 24 children with a wide range of life-limiting conditions require end-of-life care per year. Choice of end-of-life care at home was requested, which is not currently universally available. We estimated a minimum (based on 1 week of end-of-life care) additional cost of £336,000 per year to provide end-of-life support at home. Were end-of-life care to span 4 weeks, the total annual additional costs increases to £536,500 (2010/11 prices). Conclusions: Findings make a significant contribution to population-based needs assessment and commissioning methodology in children’s palliative care. Further work is needed to determine with greater precision which children in the total population require access to services and when. Half of children who died 2002-7 did not have conditions that met the globally used children's palliative care condition categories, which need revision in light of findings

Digital methods to enhance the usefulness of patient experience data in services for long-term conditions: the DEPEND mixed-methods study

Background Collecting NHS patient experience data is critical to ensure the delivery of high-quality services. Data are obtained from multiple sources, including service-specific surveys and widely used generic surveys. There are concerns about the timeliness of feedback, that some groups of patients and carers do not give feedback and that free-text feedback may be useful but is difficult to analyse. Objective To understand how to improve the collection and usefulness of patient experience data in services for people with long-term conditions using digital data capture and improved analysis of comments. Design The DEPEND study is a mixed-methods study with four parts: qualitative research to explore the perspectives of patients, carers and staff; use of computer science text-analytics methods to analyse comments; co-design of new tools to improve data collection and usefulness; and implementation and process evaluation to assess use of the tools and any impacts. Setting Services for people with severe mental illness and musculoskeletal conditions at four sites as exemplars to reflect both mental health and physical long-terms conditions: an acute trust (site A), a mental health trust (site B) and two general practices (sites C1 and C2). Participants A total of 100 staff members with diverse roles in patient experience management, clinical practice and information technology; 59 patients and 21 carers participated in the qualitative research components. Interventions The tools comprised a digital survey completed using a tablet device (kiosk) or a pen and paper/online version; guidance and information for patients, carers and staff; text-mining programs; reporting templates; and a process for eliciting and recording verbal feedback in community mental health services. Results We found a lack of understanding and experience of the process of giving feedback. People wanted more meaningful and informal feedback to suit local contexts. Text mining enabled systematic analysis, although challenges remained, and qualitative analysis provided additional insights. All sites managed to collect feedback digitally; however, there was a perceived need for additional resources, and engagement varied. Observation indicated that patients were apprehensive about using kiosks but often would participate with support. The process for collecting and recording verbal feedback in mental health services made sense to participants, but was not successfully adopted, with staff workload and technical problems often highlighted as barriers. Staff thought that new methods were insightful, but observation did not reveal changes in services during the testing period. Conclusions The use of digital methods can produce some improvements in the collection and usefulness of feedback. Context and flexibility are important, and digital methods need to be complemented with alternative methods. Text mining can provide useful analysis for reporting on large data sets within large organisations, but qualitative analysis may be more useful for small data sets and in small organisations. Limitations New practices need time and support to be adopted and this study had limited resources and a limited testing time. Future work Further research is needed to improve text-analysis methods for routine use in services and to evaluate the impact of methods (digital and non-digital) on service improvement in varied contexts and among diverse patients and carers. Funding This project was funded by the NIHR Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 28. See the NIHR Journals Library website for further project information

6-hydroxydopamine-mediated release of norepinephrine increases faecal excretion of Salmonella enterica serovar Typhimurium in pigs

Salmonella enterica serovar Typhimurium is an animal and zoonotic pathogen of worldwide importance. In pigs, transport and social stress are associated with reactivation and spread of Salmonella Typhimurium infection. The stress-related catecholamine norepinephrine (NE) has been reported to activate growth and virulence factor expression in Salmonella; however the extent to which NE contributes to stress-associated salmonellosis is unclear. We studied the impact of releasing NE from endogenous stores during Salmonella Typhimurium infection of pigs by administration of 6-hydroxydopamine (6-OHDA), which selectively destroys noradrenergic nerve terminals. Treatment of pigs with 6-OHDA 7 or 16 days post-oral inoculation with Salmonella Typhimurium produced elevated plasma NE levels and transiently, but significantly, increased faecal excretion of the challenge strain. Oral administration of NE to Salmonella Typhimurium-infected pigs also transiently and significantly increased shedding; however pre-culture of the bacteria with NE did not alter the outcome of infection. Salmonella has been proposed to sense and respond to NE via a homologue of the adrenergic sensor kinase QseC. A ΔqseC mutant of Salmonella Typhimurium was consistently excreted in lower numbers than the parent strain post-oral inoculation of pigs, though not significantly so. 6-OHDA treatment of pigs infected with the ΔqseC mutant also increased faecal excretion of the mutant strain, albeit to a lesser extent than observed upon 6-OHDA treatment of pigs infected with the parent strain. Our data support the notion that stress-related catecholamines modulate the interaction of enteric bacterial pathogens with their hosts