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Biomedical subjects

Andrew Hutchings

Publications and source records attributed to Andrew Hutchings.

15 recordsLinked to original sources

Proteomic Profiling of the Large-Vessel Vasculitis Spectrum Identifying Shared Signatures of Innate Immune Activation and Stromal Remodeling.

OBJECTIVE: Takayasu arteritis (TAK) and giant cell arteritis (GCA), the most common forms of large-vessel vasculitis (LVV), can result in serious morbidity. Understanding the molecular basis of LVV should aid in developing better biomarkers and treatments. METHODS: Plasma proteomic profiling of 184 proteins was performed in two cohorts. Cohort 1 included patients with established TAK (n = 96) and large-vessel GCA (LV-GCA) (n = 35) in addition to healthy control participants (HCs) (n = 35). Cohort 2 comprised patients presenting acutely with possible cranial GCA (C-GCA) in whom the diagnosis was subsequently confirmed (C-GCA, n = 150) or excluded (Not C-GCA, n = 89). Proteomic findings were compared to published transcriptomic data from LVV-affected arteries. RESULTS: In cohort 1, comparison to HCs revealed 52 differentially abundant proteins (DAPs) in TAK and 72 DAPs in LV-GCA. Within-case analyses identified 16 and 18 disease activity-associated proteins in TAK and LV-GCA, respectively. In cohort 2, comparing C-GCA versus not C-GCA revealed 31 DAPs. Analysis within C-GCA cases suggested the presence of distinct endotypes, with more pronounced proteomic changes in the biopsy-proven subgroup. Cross-comparison of TAK, LV-GCA, and biopsy-proven C-GCA revealed highly similar plasma proteomic profiles, with 26 shared DAPs including interleukin 6 (IL-6), monocyte/macrophage-related proteins (CCL7, CSF1), tissue remodeling proteins (TIMP1, TNC), and novel associations (TNFSF14, IL-7R). Plasma proteomic findings reflected LVV arterial phenotype; for 42% of DAPs, the corresponding gene was differentially expressed in tissue. CONCLUSION: These findings suggest shared pathobiology across the LVV spectrum involving innate immunity, lymphocyte homeostasis, and tissue remodeling. Network-based analyses highlighted immune-stromal cross-talk and identified novel therapeutic targets (eg, TNFSF14).

Humans↗

Differences in review quality and recommendations for publication between peer reviewers suggested by authors or by editors.

CONTEXT: Many journals give authors who submit papers the opportunity to suggest reviewers. Use of these reviewers varies by journal and little is known about the quality of the reviews they produce. OBJECTIVE: To compare author- and editor-suggested reviewers to investigate differences in review quality and recommendations for publication. DESIGN, SETTING, AND PARTICIPANTS: Observational study of original research papers sent for external review at 10 biomedical journals. Editors were instructed to make decisions about their choice of reviewers in their usual manner. Journal administrators then requested additional reviews from the author's list of suggestions according to a strict protocol. MAIN OUTCOME MEASURE: Review quality using the Review Quality Instrument and the proportion of reviewers recommending acceptance (including minor revision), revision, or rejection. RESULTS: There were 788 reviews for 329 manuscripts. Review quality (mean difference in Review Quality Instrument score, -0.05; P = .27) did not differ significantly between author- and editor-suggested reviewers. The author-suggested reviewers were more likely to recommend acceptance (odds ratio, 1.64; 95% confidence interval, 1.02-2.66) or revise (odds ratio, 2.66; 95% confidence interval, 1.43-4.97). This difference was larger in the open reviews of BMJ than among the blinded reviews of other journals for acceptance (P = .02). Where author- and editor-suggested reviewers differed in their recommendations, the final editorial decision to accept or reject a study was evenly balanced (50.9% of decisions consistent with the preferences of the author-suggested reviewers). CONCLUSIONS: Author- and editor-suggested reviewers did not differ in the quality of their reviews, but author-suggested reviewers tended to make more favorable recommendations for publication. Editors can be confident that reviewers suggested by authors will complete adequate reviews of manuscripts, but should be cautious about relying on their recommendations for publication.

Authorship↗

A systematic review of factors affecting the judgments produced by formal consensus development methods in health care.

OBJECTIVES: Formal consensus development methods are ways of obtaining and synthesising views of experts, opinion leaders and other stakeholders, and are increasingly being used to develop clinical practice guidelines. Our objective was to examine the impact that the characteristics of individual participants, groups and the consensus process have on the judgments produced by formal consensus development methods in health care. METHODS: Studies were identified from an earlier methodological review and a search of five bibliographic databases for the period January 1996 to December 2004. Studies were eligible if they involved formal consensus development methods and reported differences in judgments between groups or participants. For studies comparing two or more groups overall percentage agreement, the kappa coefficient and the odds ratio for differences in judgments were calculated. RESULTS: There were 22 studies comparing the impact of the characteristics of individual participants within groups and 30 studies comparing the results produced by two or more groups. Practitioners who perform a procedure tend to emphasise the appropriateness of the procedure compared with non-performing practitioners, and individuals from groups that were subject to performance criteria are more critical of those criteria than individuals from other groups. There was no clear pattern for the differences in judgments produced by participants and groups from different countries. CONCLUSIONS: Except for participant specialty there is little general evidence for how the characteristics of participants and groups influence the judgments produced in formal consensus development methods. Multi-specialty groups are preferable to single-specialty groups because of their potential for taking account of a wider range of opinions.

Consensus↗

A comparison of formal consensus methods used for developing clinical guidelines.

OBJECTIVES: To compare two consensus development methods commonly used for developing clinical guidelines in terms of the judgments produced, closeness of consensus, amount of change between rounds, concordance with research evidence and reliability. METHODS: In all, 213 general practitioners and mental health professionals from England participated in four Delphi and four nominal groups. They rated the appropriateness of four treatments (cognitive behavioural therapy [CBT], behavioural therapy [BT], brief psychodynamic interpersonal therapy [BPIT] and antidepressants) for three conditions. First, participants rated the appropriateness of interventions independently, using a postal questionnaire. For nominal groups, the ratings were fed back and discussed at a meeting, and then group members privately completed the questionnaire again. For Delphi groups, there was feedback but no discussion, and the entire process was conducted by postal questionnaire. RESULTS: The effect of consensus method on final ratings varied with therapeutic intervention, with nominal groups rating CBT and antidepressants more favourably than Delphi groups. Consensus was closer in the nominal than in the Delphi groups in both rounds. There was no overall difference between groups in their concordance with research evidence (odds ratio 1.13, 95% confidence interval 0.79-1.61). In this study, the Delphi method was more reliable (kappa coefficients 0.88 and 0.89 compared with 0.41 and 0.65 for nominal groups). CONCLUSIONS: The advantages of nominal groups (more consensus; greater understanding of reasons for disagreement) could be combined with the greater reliability of the Delphi approach by developing a hybrid method.

Chronic Disease↗

Challenges to implementing the national programme for information technology (NPfIT): a qualitative study.

OBJECTIVES: To describe the context for implementing the national programme for information technology (NPfIT) in England, actual and perceived barriers, and opportunities to facilitate implementation. DESIGN: Case studies and in depth interviews, with themes identified using a framework developed from grounded theory. SETTING: Four acute NHS trusts in England. PARTICIPANTS: Senior trust managers and clinicians, including chief executives, directors of information technology, medical directors, and directors of nursing. RESULTS: The trusts varied in their circumstances, which may affect their ability to implement the NPfIT. The process of implementation has been suboptimal, leading to reports of low morale by the NHS staff responsible for implementation. The overall timetable is unrealistic, and trusts are uncertain about their implementation schedules. Short term benefits alone are unlikely to persuade NHS staff to adopt the national programme enthusiastically, and some may experience a loss of electronic functionality in the short term. CONCLUSIONS: The sociocultural challenges to implementing the NPfIT are as daunting as the technical and logistical ones. Senior NHS staff feel these have been neglected. We recommend that national programme managers prioritise strategies to improve communication with, and to gain the cooperation of, front line staff.

Attitude of Health Personnel↗

Changing organisations: a study of the context and processes of mergers of health care providers in England.

This paper presents findings from a study of the context and processes of provider mergers in the NHS in England. Mergers are an example of organisational restructuring, a key lever for change in the UK health care sector and elsewhere, although it is only one strategy for organisational change. The framework for the study is key themes from the organisational change literature: the complexity of the effects of change; the importance of context; and the role of organisational culture. The drivers for health care mergers and the evidence for these are analysed. Using documentary analysis and in-depth qualitative interviews with internal and external stakeholders, the first part of the paper reports on stated and unstated drivers in nine mergers. This provides the context for four in-depth case studies of the process of merger in the second and third years post-merger. Our study shows that the contexts of mergers, including drivers of change, are important. Merger is a process without clear boundaries, and this study shows problems persisting into the third year post-merger. Loss of management control and focus led to delays in service developments. Difficulties in the merger process included perceived differences in organisational culture and perceptions of 'takeover' which limited sharing of 'good practice' across newly merged organisations. Merger policy was based on simplistic assumptions about processes of organisational change that do not take into account the dynamic relationship between the organisation and its context and between the organisation and individuals within it. Understanding the process of merger better should lead to a more cautious approach to the likely gains, provide understanding of the problems that are likely in the period of change, and anticipate and avoid harmful consequences.

England↗

Is publicly funded health care really distributed according to need? The example of cardiac rehabilitation in the UK.

OBJECTIVES: To demonstrate the importance of measuring both the horizontal and vertical components of equity in order to examine whether patients are receiving the health care that they need. METHODS DESIGN: A theoretical demonstration followed by analysis of a prospectively collected national random sample of acute cardiac admissions to 94 hospitals in the UK. PATIENTS: 1064 patients under 70 years old. ANALYSIS: The association between use of cardiac rehabilitation and gender (after adjusting for clinical need) was measured using multivariable analysis with effect modification. RESULTS: Hypertensive males were nearly twice as likely to undergo rehabilitation compared to hypertensive females (OR 1.76, 95% CI 1.03-3.02). Hyertensive patients were less likely to undergo rehabilitation than normotensive patients (OR 0.67, 95% CI 0.50-0.89) but this treatment difference did not apply in the same way to both men and women. Hypertensive women were half as likely to undergo rehabilitation compared with normotensive women (OR 0.48, 95% CI 0.30-0.78), whereas hypertensive men were as likely as normotensive men to receive rehabilitation (OR 1.00. 95% CI 0.63-1.60). CONCLUSIONS: Horizontal inequity was demonstrated because male and female hypertensive patients with equal needs were not treated equally. There was also vertical inequity because although patients with hypertension were treated differently to normotensive patients, this treatment difference was not the same for men and women.

Coronary Artery Disease↗

Socioeconomic status and outcome from intensive care in England and Wales.

OBJECTIVE: The objective of this study was to estimate the association between socioeconomic status (SES) and outcome for admissions to intensive care. RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: We studied 51,572 admissions to 99 intensive-care units in England and Wales between 1995 and 2000. MEASURES: The SES of admissions was measured using Carstairs deprivation scores. Outcome was hospital mortality after adjustment for case mix using the APACHE II method. RESULTS: Admissions of lower SES were, on average, younger and less likely to be following surgery. There was evidence of a SES gradient for hospital mortality in admissions after elective surgery after adjusting for case mix (test for trend P <0.001), with higher SES associated with lower mortality. In the least-deprived quintile of SES, the odds ratio for hospital mortality was 0.70 (95% confidence interval, 0.58-0.84) compared with the most deprived quintile. There was no evidence of a SES gradient for hospital mortality in nonsurgical or emergency surgical admissions, and the decision to withdraw active treatment did not differ by SES. CONCLUSIONS: There is a SES gradient for hospital mortality in elective surgical admissions that is not explained by differences in case mix or the withdrawal of active treatment. Further research is required to establish if this finding can be explained by unmeasured differences in health status at admission to an intensive-care unit or differences in care and to establish the potential impact these results may have on interpreting comparative surgical performance data.

APACHE↗

Is publicly funded health care really distributed according to need? The example of cardiac rehabilitation in the UK.

OBJECTIVES: To demonstrate the importance of measuring both the horizontal and vertical components of equity in order to examine whether patients are receiving the health care that they need. METHODS DESIGN: A theoretical demonstration followed by analysis of a prospectively collected national random sample of acute cardiac admissions to 94 hospitals in the UK. PATIENTS: One thousand and sixty-four patients under 70 years old. ANALYSIS: The association between use of cardiac rehabilitation and gender (after adjusting for clinical need) was measured using multivariable analysis with effect modification. RESULTS: Hypertensive males were nearly twice as likely to undergo rehabilitation compared with hypertensive females (OR 1.76, 95%CI 1.03-3.02). Hyertensive patients were less likely to undergo rehabilitation than normotensive patients (OR 0.67, 95% CI 0.50-0.89) but this treatment difference did not apply in the same way to both men and women. Hypertensive women were half as likely to undergo rehabilitation compared with normotensive women (OR 0.48, 95% CI 0.30-0.78), whereas hypertensive men were as likely as normotensive men to receive rehabilitation (OR 1.00. 95%CI 0.63-1.60). CONCLUSIONS: Horizontal inequity was demonstrated because male and female hypertensive patients with equal needs were not treated equally. There was also vertical inequity because although patients with hypertension were treated differently to normotensive patients, this treatment difference was not the same for men and women.

Acute Disease↗

Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care?

OBJECTIVES: To determine the strength of evidence for the effectiveness of mental health interventions for patients with three common somatic conditions (chronic fatigue syndrome, irritable bowel syndrome, and chronic back pain). To assess whether results obtained in secondary care can be extrapolated to primary care and suggest how future trials should be designed to provide more rigorous evidence. DESIGN: Systematic review. DATA SOURCES: Five electronic databases, key texts, references in the articles identified, and citations from expert clinicians. STUDY SELECTION: Randomised controlled trials including participants with one of the three conditions for which no physical cause could be found. Two reviewers screened sources and independently extracted data and assessed quality. RESULTS: Sixty one studies were identified; 20 were classified as primary care and 41 as secondary care. For some interventions, such as brief psychodynamic interpersonal therapy, little research was identified. However, results of meta-analyses and of randomised controlled trials suggest that cognitive behaviour therapy and behaviour therapy are effective for chronic back pain and chronic fatigue syndrome and that antidepressants are effective for irritable bowel syndrome. Cognitive behaviour therapy and behaviour therapy were effective in both primary and secondary care in patients with back pain, although the evidence is more consistent and the effect size larger for secondary care. Antidepressants seem effective in irritable bowel syndrome in both settings but ineffective in chronic fatigue syndrome. CONCLUSIONS: Treatment seems to be more effective in patients in secondary care than in primary care. This may be because secondary care patients have more severe disease, they receive a different treatment regimen, or the intervention is more closely supervised. However, conclusions of effectiveness should be considered in the light of the methodological weaknesses of the studies. Large pragmatic trials are needed of interventions delivered in primary care by appropriately trained primary care staff.

Antidepressive Agents↗

Process and impact of mergers of NHS trusts: multicentre case study and management cost analysis.

OBJECTIVE: To study the processes involved in and impact of mergers between NHS trusts, including the effect on management costs. DESIGN: Cross sectional study involving in depth interviews and documentary analysis; case study to compare savings in management costs between case trusts and control trusts. SETTING: Nine trusts (cross sectional study) and four trusts (case study) in London. PARTICIPANTS: 96 interviews with trust board members, other senior managers, clinicians, service managers, and representatives of health authorities, regional office, community health councils, local authorities, other trusts in the area, and primary care groups and trusts. MAIN OUTCOME MEASURES: Stated and unstated drivers, and impact of merger on delivery and development of services, management structures, and staff recruitment, retention, and morale. Effects of difference in trust size before and after the merger. Savings in management costs two years after merger. RESULTS: Some important drivers for merger are not publicly stated. Mergers had a negative effect on delivery of services because of a loss of managerial focus on services. Planned developments in services were delayed by at least 18 months. Trusts' larger sizes after mergers had unintended negative consequences, as well as predicted advantages. The tendency for one trust's management team to dominate over the other resulted in tension. No improvement in recruitment or retention of clinical and managerial staff was reported. Perceived differences in organisational culture were an important barrier to bringing together two or more organisations. Two years after merger, merged trusts had not achieved the objective of saving pound 500 000 a year in management costs. CONCLUSIONS: Important unintended consequences need to be accounted for when mergers are planned. Mergers can cause considerable disruptions to services, and require greater management support than previously acknowledged. Other organisations undergoing restructuring, such as primary care groups developing into primary care trusts and health authorities merging into strategic health authorities, should take these findings into account.

Attitude of Health Personnel↗

Cost data for individual patients included in clinical studies: no amount of statistical analysis can compensate for inadequate costing methods.

This work examines the quality of the cost methods used to derive patient level costs in 45 economic evaluations conducted alongside randomised controlled trials. The perspective of the cost analysis, the methods used to determine quantities and values of resources and how the cost data were reported are examined. The reported costing methods were found to be of poor quality, highlighting the need for greater rigour. Researchers to date appear more concerned with whether cost data have been subjected to the appropriate statistical analysis. For the results of clinical studies to be valid both cost methods and the methods used for the statistical analysis of cost data should be of a high quality.

Cost-Benefit Analysis↗

An experimental study of determinants of group judgments in clinical guideline development.

BACKGROUND: Clinical guidelines for improving the quality of care are a familiar part of clinical practice. Formal consensus methods such as the nominal group technique are often used as part of guideline development, but little is known about factors that affect the statements produced by nominal groups, and on their consistency with the research evidence. METHODS: Cognitive behavioural therapy, behavioural therapy, brief psychodynamic interpersonal therapy, and antidepressants for irritable bowel syndrome, chronic fatigue syndrome, and chronic back pain were selected for study. 16 nominal groups in a factorial design allowed comparison of GP-only with mixed groups of GPs and specialists, provision of a literature review with no provision, and ratings made in the context of realistic or ideal levels of health-care resources. Participants rated appropriateness independently, and again after a facilitated meeting. Audiotapes of four group discussions were analysed. FINDINGS: There was agreement with the research evidence for 51% of 192 scenarios. Agreement was more likely if the group was GP-only, if a literature review was provided, or if the evidence was in accordance with clinicians' beliefs. Assumptions about the level of resources available had no impact. Clinical and social cues had mixed effects, irrespective of the research evidence. Qualitative analysis showed the modifying effect of clinical experience and beliefs about research evidence. INTERPRETATION: Guidelines cannot be based on data alone; judgment is unavoidable. The nominal group technique is a method of eliciting and aggregating judgments in a transparent and structured way. It can provide important information on levels of agreement between experts. However, conclusions can be at odds with the published literature. If they are, reasons need to be explicit.

Back Pain↗