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Biomedical subjects

Stephen Palmer

Publications and source records attributed to Stephen Palmer.

At least 19 recordsLinked to original sources

Places, people and mental health: a multilevel analysis of economic inactivity.

This paper investigates multilevel associations between the common mental disorders of anxiety, depression and economic inactivity measured at the level of the individual and the UK 2001 census ward. The data set comes from the Caerphilly Health & Social Needs study, in which a representative survey of adults aged 18-74 years was carried out to collect a wide range of information which included mental health status (using the Mental Health Inventory (MHI-5) scale of the Short Form-36 health status questionnaire), and socio-economic status (including employment status, social class, household income, housing tenure and property value). Ward level economic inactivity was measured using non-means tested benefits data from the Department of Work and Pensions (DWP) on long-term Incapacity Benefit and Severe Disablement Allowance. Estimates from multilevel linear regression models of 10,653 individuals nested within 36 census wards showed that individual mental health status was significantly associated with ward-level economic inactivity, after adjusting for individual-level variables, with a moderate effect size of -0.668 (standard error=0.258). There was a significant cross-level interaction between ward-level and individual economic inactivity from permanent sickness or disability, such that the effect of permanent sickness or disability on mental health was significantly greater for people living in wards with high levels of economic inactivity. This supports the hypothesis that living in a deprived neighbourhood has the most negative health effects on poorer individuals and is further evidence for a substantive effect of the place where you live on mental health.

Adolescent↗

Measuring health-related quality of life in bipolar disorder: relationship of the EuroQol (EQ-5D) to condition-specific measures.

UNLABELLED: Generic utility measures of health-related quality of life provide an independent net valuation of health states. They are increasingly used with condition-specific outcome measures in assessing treatments. In Bipolar Disorder, a few studies indicate poorer quality of life for depressed vs. euthymic patients. A single study suggests mania is less negative than depression. This analysis examines the relationship of one such scale, the EuroQol (EQ-5D), to objective and subjective measures of depression and mania in 221 Bipolar subjects, recently or still in an episode of illness. RESULTS: Depressed patients showed a very poor quality of life (median EQ-5D Index score 0.41). Index and Visual Analogue scores improved significantly as level of depression decreased (Jonckheere-Terpstra test p<0.001). Both scores were significantly negatively related to all depression measures. Patients reported problems across all areas of life covered by the EQ-5D. No such relationships were observed between EQ-5D scores and mania measures, though all mania measures were inter-related. However, the range of mania shown was quite restricted. CONCLUSIONS: The EQ-5D is a useful measure of quality of life for Bipolar patients suffering from depression. Conclusions about the role of the EQ-5D in mania are restricted by the limited range of mania observed.

Adult↗

Molecular properties and preclinical pharmacology of JNJ-1250132, a steroidal progesterone receptor modulator that inhibits binding of the receptor to DNA in vitro.

Progesterone receptor modulators have diverse potential therapeutic uses, including the treatment of endometriosis, uterine fibroids and breast cancer. Here we describe the molecular properties and preclinical pharmacology of a new steroidal progestin antagonist, JNJ-1250132. The compound is a high affinity ligand for the progesterone receptor, possessing cross-reactivity with other steroid receptors comparable to that of steroidal antagonists such as mifepristone. It inhibits progestin-inducible alkaline phosphatase gene expression in T47D human breast cancer cells, and also inhibits their in vitro proliferation. It inhibits gestation in rats and progesterone-dependent endometrial transformation in rabbits with efficacies comparable to mifepristone. Like mifepristone, it is a glucocorticoid antagonist in vivo. In cell-free DNA binding assays, the compound inhibits binding of the human progesterone receptor to a progesterone response element, and thus is similar to onapristone in this regard. In contrast, as judged by proteolytic analysis, JNJ-1250132 induces a receptor conformation more similar to that induced by mifepristone, which promotes receptor binding to DNA. Therefore, JNJ-1250132 has unique effects on the progesterone receptor that may translate into a novel clinical profile.

Animals↗

Perceptions of social capital and the built environment and mental health.

There has been much speculation about a possible association between the social and built environment and health, but the empirical evidence is still elusive. The social and built environments are best seen as contextual concepts but they are usually estimated as an aggregation of individual compositional measures, such as perceptions on trust or the desirability to live in an area. If these aggregated compositional measures were valid measures, one would expect that they would evince correlations at higher levels of data collection (e.g., neighbourhood). The aims of this paper are: (1) to investigate the factor structure of a self-administered questionnaire measuring individual perceptions of trust, social participation, social cohesion, social control, and the built environment; (2) to investigate variation in these factors at higher than the individual level (households and postcodes) in order to assess if these constructs reflect some contextual effect; and (3) to study the association between mental health, as measured by the General Health Questionnaire-12 (GHQ-12), and these derived factors. A cross-sectional household survey was undertaken during May-August 2001 in a district of South Wales with a population of 140,000. We found that factor analysis grouped our questions in factors similar to the theoretical ones we had previously envisaged. We also found that approximately one-third of the variance for neighbourhood quality and 10% for social control was explained at postcode (neighbourhood) level after adjusting for individual variables, thus suggesting that some of our compositional measures capture contextual characteristics of the built and social environment. After adjusting for individual variables, trust and social cohesion, two key social capital components were the only factors to show statistically significant associations with GHQ-12 scores. However, these factors also showed little variation at postcode levels, suggesting a stronger individual determination. We conclude that our results provide some evidence in support of an association between mental health (GHQ-12 scores) and perceptions of social capital, but less support for the contextual nature of social capital.

Adult↗

A systematic review of measures of effectiveness in screening for oral cancer and precancer.

Nine databases were searched for studies reporting a range of measures on the effectiveness of screening for oral cancer and precancer in primary care. Of 1114 papers generated in a search of nine databases, full texts of 90 were scrutinised by two reviewers to ensure that they were concerned with oral cancer/precancer, reported an oral cancer screening programme/exercise and included at least one effectiveness outcome. Criteria for considering studies for the review covered types of studies, participants, interventions and outcome measures. The latter included measures of both end point and interim outcome and also process. Of 90 full text articles screened, examiners agreed on the inclusion of 28 (initial agreement -- kappa=0.60). The remaining 62 were excluded and the reasons recorded. The studies included showed substantial heterogeneity regarding objectives and study design, location and setting, numbers and characteristics of participants, screening personnel, methods of recruitment and types of data collected. Only one study, from the Indian sub-continent, reported a randomised controlled trial: interim results showed 14.9% of intervention subjects died after 3 years compared with 56.3% of non-intervention controls. The review overall produced no evidence in favour of or against the potential benefits associated with an oral cancer screening programme. It was concluded that there are insufficient available data to make an unequivocal determination as to the effectiveness of oral cancer screening programmes at the present time. However, a recent further report on the Indian study published after completion of the review, provides some evidence that screening for oral cancer may be effective, at least in developing countries with a high incidence of the disease.

Humans↗

Priority setting for research in health care: an application of value of information analysis to glycoprotein IIb/Illa antagonists in non-ST elevation acute coronary syndrome.

The purpose of this study is to explain the rationale for the value of information approach to priority setting for research and to describe the methods intuitively for those familiar with basic decision analytical modeling. A policy-relevant case study is used to show the feasibility of the method and to illustrate the type of output that is generated and how these might be used to frame research recommendations. The case study relates to the use of glycoprotein Ilb/Illa antagonists for the treatment of patients with non-ST elevation acute coronary syndrome. This is an area that recently has been appraised by the National Institute for Health and Clinical Excellence.

Acute Disease↗

A randomized controlled trial of cognitive behavior therapy for borderline personality disorder: rationale for trial, method, and description of sample.

This paper describes the rationale for a randomized controlled trial, comparing cognitive behavior therapy in addition to treatment as usual with treatment as usual alone, for borderline personality disorder. Previous pioneering randomized controlled trials of psychotherapies have suffered from methodological weaknesses and have not always been reported clearly to allow adequate evaluation of either the individual study or comparisons across studies to be undertaken. We report on the recruitment and randomization, design, and conduct of an ongoing randomized controlled trial of one hundred and six patients with borderline personality disorder. Primary and secondary hypotheses and their planned analyses are stated. The baseline characteristics of 106 patients meeting diagnostic criteria for borderline personality disorder are described.

Adult↗

The effectiveness of cognitive behavior therapy for borderline personality disorder: results from the borderline personality disorder study of cognitive therapy (BOSCOT) trial.

The outcome of a randomized controlled trial of cognitive behavior therapy in addition to treatment as usual (CBT plus TAU) compared with TAU alone (TAU) in one hundred and six participants meeting diagnostic criteria for borderline personality disorder is described. We anticipated that CBT plus TAU would decrease the number of participants with in-patient psychiatric hospitalizations or accident and emergency room contact or suicidal acts over twelve months treatment and twelve months follow-up, compared with TAU. We also anticipated that CBT plus TAU would lead to improvement in a range of secondary outcomes of mental health and social functioning compared to TAU. Of the 106 participants randomized, follow-up data on 102 (96%) was obtained at two years. Those randomized to CBT were offered an average of 27 sessions over 12 months and attended on average 16 (range 0 to 35). We found that the global odds ratio of a participant in the CBT plus TAU group compared with the TAU alone group having any of the outcomes of a suicidal act, in-patient hospitalization, or accident and emergency contact in the 24 months following randomization was 0.86 (95% confidence interval [CI] 0.45 to 1.66, p = 0.66). The corresponding global odds ratio, excluding accident and emergency room contact, was 0.75 (95% CI 0.37 to 1.54, p = 0.44). In terms of the number of suicidal acts, there was a significant reduction over the two years in favor of CBT plus TAU over TAU, with a mean difference of -0.91 (95% CI -1.67 to -0.15, p = 0.020). Across both treatment arms there was gradual and sustained improvement in both primary and secondary outcomes, with evidence of benefit for the addition of CBT on the positive symptom distress index at one year, and on state anxiety, dysfunctional beliefs and the quantity of suicidal acts at two year follow-up. CBT can deliver clinically important changes in relatively few clinical sessions in real clinical settings.

Adult↗

The cost-effectiveness of cognitive behavior therapy for borderline personality disorder: results from the BOSCOT trial.

Borderline personality disorder places a significant burden on healthcare providers and other agencies. This study evaluated the cost-effectiveness of cognitive behavior therapy plus treatment as usual compared to treatment as usual alone for patients with borderline personality disorder. The economic analysis was conducted alongside a multi-center, randomized controlled trial. The costs of primary and secondary healthcare utilization, alongside the wider economic costs, were estimated from medical records and patient self-report. The primary outcome measure used was the quality-adjusted life year (QALY), assessed using EuroQol. On average, total costs per patient in the cognitive behavior therapy group were lower than patients receiving usual care alone (-689 pounds sterling), although this group also reported a lower quality of life (-0.11 QALYs). These differences were small and did not approach conventional levels of statistical significance. The use of cognitive therapy for borderline personality disorder does not appear to demonstrate any significant cost-effective advantage based on the results of this study.

Adult↗

Antibiotic-resistant infections in primary care are symptomatic for longer and increase workload: outcomes for patients with E. coli UTIs.

BACKGROUND: Antimicrobial resistance is considered to be one of the major threats to public health. However, the practical implications for patients and workload in primary care are largely unknown. AIM: To determine outcomes for patients managed in primary care with an antibiotic resistant compared to an antibiotic sensitive Escherichia coli (E. coli) urinary tract infection (UTI). DESIGN: Nested case control study with prospective measurement of outcomes. SETTING: Ten general practices in South Wales. METHOD: Patients consulting with symptoms suggestive of UTI identified through systematic sampling, and with a laboratory proven E. coli infection, were followed up by interview 1 month after their consultations and by searching of their medical records. RESULTS: Nine hundred and thirty-two patients were interviewed and had their medical records reviewed. The risk of patients reporting 'feeling poorly', 'frequency or pain on urinating' and being 'out of action' for more than 5 days after consulting was significantly increased for patients with resistant compared to sensitive infections. After adjusting for risk factors, there was an increased risk of 'frequency or pain on urinating' and 'being out of action' for those infected with a resistant E. coli. The median number of maximum reported days with at least one symptom was 12 days for patients with E. coli infections resistant to trimethoprim, 7 days for infections resistant to ampicillin, 7 days for infections resistant to any antibiotic, and 5 days for infections sensitive to all tested antibiotics. Even if treated with an appropriate antibiotic, infections caused by a resistant strain were symptomatic for longer. For those infected with an organism resistant to at least one antibiotic, the odds ratio (OR) for re-visiting their GP within the next 30 days for the UTI was 1.47 (95% confidence interval [CI] = 1.10 to 1.95). The OR was 1.49 (95% CI = 1.11 to 2.00) for ampicillin resistance and 2.48 (95% CI = 1.70 to 3.59) for trimethoprim resistance. CONCLUSIONS: Resistant E. coli UTIs are symptomatic for longer and cause increased work load in general practice.

Adult↗

Management of non-ST-elevation acute coronary syndromes: how cost-effective are glycoprotein IIb/IIIA antagonists in the UK National Health Service?

BACKGROUND: The glycoprotein IIb/IIIa antagonists (GPAs) represent a new class of drugs to prevent platelet aggregation in the acute treatment of non-ST-elevation acute coronary syndromes (NSTE-ACS). Systematic reviews have identified serious limitations in published cost-effectiveness analyses, including a lack of UK-specific studies and an absence of studies comparing different protocols for the use of GPAs. METHODS: A model was developed to assess the cost effectiveness of a variety of protocols employing GPAs for patients presenting with NSTE-ACS in the UK. The perspective of the UK National Health Service was adopted, with outcomes in terms of quality-adjusted life-years (QALYs). Four treatment strategies were evaluated: GPAs as part of initial medical management (Strategy 1); GPAs in patients with planned percutaneous coronary interventions (PCIs; Strategy 2); GPAs as an adjunct to the PCI procedure (Strategy 3); and no GPAs (Strategy 4). Baseline event rates and costs were taken from a UK observational study of ACS patients and relative risk reductions from GPAs were taken from a meta analysis of trials. Long-term costs and QALYs were estimated using data from a UK longitudinal study. RESULTS: The most cost-effective use of GPAs is likely to be Strategy 1, with an incremental cost per QALY gained of between pound4605 to pound10,343. Focusing this use of GPAs only on the subgroup of patients at high risk appears to represent the most cost-effective use of NHS resources. CONCLUSIONS: Medical management of patients with NSTE-ACS using GPAs is the most cost-effective use of resources, particularly if targeted to higher risk subgroups.

Coronary Disease↗

Outcome in severe irritable bowel syndrome with and without accompanying depressive, panic and neurasthenic disorders.

BACKGROUND: Irritable bowel syndrome often leads to impaired functioning. AIMS: To assess the contribution of psychiatric disorders to impaired outcome in severe irritable bowel syndrome. METHOD: Patients with severe irritable bowel syndrome entering a psychological treatment trial (n=257) were interviewed using the Schedules for Clinical Assessment in Neuropsychiatry. Outcomes were number of days of restricted activity, role limitation (physical) score of the Short Form Health Survey and costs. RESULTS: At baseline, depressive disorder (29% of patients), panic (12%) and neurasthenia (35%) were associated with impairment; number of psychiatric disorders was associated in a dose-response fashion (P=0.005). At follow-up, depressive disorder and neurasthenia were associated with role limitation score. Improved depression was associated with improved role functioning. CONCLUSIONS: Depressive, panic and neurasthenic disorders contribute to poor outcomes in severe irritable bowel syndrome, and appropriate treatment should be available to these patients.

Activities of Daily Living↗

Handling missing data in patient-level cost-effectiveness analysis alongside randomised clinical trials.

BACKGROUND: Missing data are potentially an extensive problem in cost-effectiveness analyses conducted alongside randomised clinical trials, where prospective collection of both resource use and health outcome information is required. There are several possible reasons for the presence of incomplete records, and the validity of the analysis in the presence of data with missing values is dependent upon the mechanism generating the missing data phenomenon. In the past, the most commonly used methods for analysing datasets with incomplete observations were relatively ad hoc (e.g. case deletion, mean imputation) and suffered from potential limitations. Recently, several alternative and more sophisticated approaches (e.g. multiple imputation) have been proposed that attempt to correct the flaws of the simple imputation methods. OBJECTIVES: The objectives are to provide a concise and accessible description of the quantitative methods most commonly used in trial-based cost-effectiveness analysis for handling missing data, and also to demonstrate the potential impact of these alternative approaches on the cost-effectiveness results reported in two case studies. METHODS: Data from two recently conducted, trial-based economic evaluations are used to explore the sensitivity of the study results to the technique used to deal with incomplete observations. A statistical framework for representing the uncertainty in the alternative methods is outlined using an approach based on net benefits and cost-effectiveness acceptability curves. RESULTS: The case studies demonstrate the potential importance of the approach used to handle missing data. Although the analytical strategy did not appear to alter the results of one of the studies, the other case study showed that that the results of the cost-effectiveness analysis were sensitive to both the decision to impute and also the imputation strategy adopted. CONCLUSIONS: Analysts should be more explicit in reporting the analytical strategies applied in the presence of missing data. The use of a multiple imputation approach is recommended in the majority of cases, so as to adequately reflect the uncertainty in the study results due to the presence of missing data.

Bias↗

Reemergence of canine Echinococcus granulosus infection, Wales.

As a consequence of large-scale outdoor slaughter of sheep during the 2001 foot and mouth disease (FMD) outbreak in the United Kingdom and the possibility of increased risk for transmission of Echinococcus granulosus between sheep and dogs, a large survey of canine echinococcosis was undertaken in mid-Wales in 2002. An Echinococcus coproantigen-positive rate of 8.1% (94/1,164) was recorded on 22% of farms surveyed, which compares to a rate of 3.4% obtained in the same region in 1993. Positivity rates between FMD-affected properties and unaffected ones did not differ significantly. Significant risk factors for positive results in farm dogs were allowing dogs to roam free and the infrequent dosing (>4-month intervals) of dogs with praziquantel. When these data are compared to those of a previous pilot hydatid control program in the area (1983-1989), an increase in transmission to humans appears probable.

Animals↗

Pharmacological inhibition of phosphodiesterase 4 triggers ovulation in follicle-stimulating hormone-primed rats.

Phosphodiesterases (PDEs) are a family of enzymes that hydrolyze cyclic nucleotides to render them biologically inactive. As such, these enzymes are critical regulators of signal transduction pathways that use cyclic nucleotides as second messengers. PDE4 is one such member that has been identified in ovarian tissue and purported to have a role in the regulation of gonadotropin action. In the present study, selective PDE4 inhibitors enhanced intracellular signaling in a human LH receptor-expressing granulosa cell line. In vivo, PDE4 inhibition in FSH-primed rats resulted in ovulation, indicating that the PDE4 inhibitors can substitute for LH and human chorionic gonadotropin (hCG) in this process. Moreover, when coadministered with a subeffective dose of hCG, PDE4 inhibitors acted synergistically to enhance the ovulation response. Inhibitors of PDE3 or PDE5 had no ovulatory effect under similar conditions. Oocytes that were ovulated after PDE4 inhibition could be fertilized in vitro at a rate similar to that of oocytes from hCG-induced ovulation. Moreover, such oocytes were fully capable of being fertilized in vivo and developing into normal live pups. These results indicate that small molecule PDE4 inhibitors may be orally active alternatives to hCG as part of a fertility treatment regimen.

3',5'-Cyclic-AMP Phosphodiesterases↗

A systematic review of test performance in screening for oral cancer and precancer.

Nine databases were searched for studies on test performance in screening for oral cancer and precancer in primary care. Of 481 papers, full texts of 47 were scrutinised by two reviewers. Only prospective investigations of population screening involving examination of the oral mucosa, with gold standard verification (examination by an expert of subjects screened positive and at least a proportion of negatives), were selected. Seven papers describing eight studies were finally included (kappa=0.83). The weighted pooled value of sensitivity, from random effects meta-analysis, was 0.848 (95% CI 0.730, 0.919). The corresponding value for specificity was 0.965 (95% CI 0.930, 0.982). Main sources of clinical heterogeneity occurred between large house-to-house case finding programmes from SE Asia, utilising primary health workers, and smaller studies from England and Japan. Meta-analysis regression showed no difference (P=0.99) in the generally high level of discriminatory ability of the test between these two groups.

Area Under Curve↗

The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome.

BACKGROUND & AIMS: Psychotherapy and antidepressants are effective in patients with severe irritable bowel syndrome (IBS), but the cost-effectiveness of either treatment in routine practice has not been established. METHODS: Patients with severe IBS were randomly allocated to receive 8 sessions of individual psychotherapy, 20 mg daily of the specific serotonin reuptake inhibitor (SSRI) antidepressant, paroxetine, or routine care by a gastroenterologist and general practitioner. Primary outcome measures of abdominal pain, health-related quality of life, and health care costs were determined after 3 months of treatment and 1 year later. RESULTS: A total of 257 subjects (81% response rate) from 7 hospitals were recruited; 59 of 85 patients (69%) randomized to psychotherapy and 43 of 86 (50%) of the paroxetine group completed the full course of treatment. Both psychotherapy and paroxetine were superior to treatment as usual in improving the physical aspects of health-related quality of life (SF-36 physical component score improvement, 5.2 [SEM, 1.26], 5.8 [SEM, 1.0], and -0.3 [SEM, 1.17]; P < 0.001), but there was no difference in the psychological component. During the follow-up year, psychotherapy but not paroxetine was associated with a significant reduction in health care costs compared with treatment as usual (psychotherapy, $976 [SD, $984]; paroxetine, $1252 [SD, $1616]; and treatment as usual, $1663 [SD, $3177]). CONCLUSIONS: For patients with severe IBS, both psychotherapy and paroxetine improve health-related quality of life at no additional cost.

Absenteeism↗