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Biomedical subjects

Michael King

Publications and source records attributed to Michael King.

At least 19 recordsLinked to original sources

Acceptability of an advance care planning interview schedule: a focus group study.

There is growing recognition that patients should have greater opportunity to plan their future care, a process known as advance care planning. The aims of this phase I qualitative focus group study were (1) to explore the acceptability of an interview schedule, designed to encourage conversations regarding future care; and (2) to explore the suitability of such discussions and inquire about their possible timing, nature and impact. Purposive sampling was used to achieve a balanced sample of 22 palliative care and oncology patients, relatives and user group members. The results showed that, although some patients welcome the opportunity to discuss end-of-life care, others may not feel ready or able to do so. The timing of a discussion is likely to influence its acceptability and effect. A discussion might best be initiated after recurrence of disease. The person initiating discussion should be skilled in responding to the cues of the patient, and should enable the patient to close the topic down at the end of the discussion, in order to avoid dwelling too much on the end of life. Advance care planning should take place over a number of meetings, and be conducted by an appropriately trained professional with sufficient time to talk through the issues raised, and with the knowledge and skills to answer questions, tailor the discussion to the individual, and avoid destroying hope. Advance decisions to refuse treatment should not be the focus of the discussion, but one component of a broader conversation about end-of-life issues. If patients make an advance decision to refuse certain treatments, they should be given the opportunity to change their minds in the future.

Adult↗

Harmful alcohol use in Goa, India, and its associations with violence: a study in primary care.

AIMS: To determine (i) the prevalence and characteristics of harmful alcohol consumption in general practice attendees; (ii) social and psychological associations with harmful drinking and (iii) recognition of harmful drinking by GPs. METHODS: A cross-sectional study of ten general practices in Goa, India. A total of 1567 general practice attendees were recruited. RESULTS: A total of 338 men (41%) and 597 women (81%) reported that they never consumed alcohol. One hundred and twenty-eight people or 8.2% scored >or=8 on the AUDIT [123 (15%) men and five (0.7%) women] and were classified as harmful or dependent drinkers. The population attributable fraction of harmful drinking in the perpetration of any physical violence by men over 12 months was 0.36. The population attributable fraction of moderate drinking (vs abstention) in the perpetration of any physical violence by women over 12 months was 0.27. Doctors identified almost 60% of problem drinkers but misidentified approximately 5% of moderate drinkers as problem drinkers. CONCLUSIONS: The male pattern of drinking in Goa is one of the high rates of abstention coupled with relatively high rates of harmful and dependent drinking in those who consume alcohol. Most women are abstainers. These data provide the first evidence in India on (i) the role of the GP in identification of harmful alcohol use and (ii) the contribution of harmful drinking to the perpetration of physical violence from the perspective of the alcohol user.

Adult↗

The 5-HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: the PREDICT-gene study.

Previous reports and meta-analyses have yielded inconclusive results as to whether the s/s genotype at the 5-HTTLPR serotonin transporter polymorphism confers increased risk for depression. We tested the association between s/s genotype and depression in a large cohort (n = 737) of Spanish primary care consecutive attendees participating in a European study on predictors for depression in primary care (PREDICT study). Participants were administered the Composite International Diagnostic Interview (CIDI) depression subscale allowing diagnoses using ICD-10 criteria for depressive episodes. Participants were genotyped to establish 5HTTLPR genotype. Both univariable and multivariable associations between the s/s genotype and depression were tested twice using two different depressive outcomes (ICD-10 depressive episode and ICD-10 severe depressive episode). We found an association between the s/s genotype and both depressive outcomes that was independent of age, sex, family history of psychological problems among first degree relatives and presence of comorbid generalized anxiety disorder. When comparing s/s homozygous versus the rest, the adjusted odds ratio for any ICD-10 depressive episode and for severe ICD-10 depressive episode were 1.50 (95% CI: 1.0-2.2; P = 0.045) and 1.79 (95% CI: 1.1-2.8; P = 0.016), respectively. The association was significantly stronger with increasing severity of depression (chi2 for linear association=6.1; P = 0.013) suggesting a dose-dependent relationship. Our results are consistent with previous reports suggesting a small but independent effect by the s/s 5-HTTLPR genotype increasing the risk for depression.

Adult↗

Codeine and 6-acetylcodeine analgesia in mice.

1. Acetylation of morphine at the 6-position changes its pharmacology. To see if similar changes are seen with codeine, we examined the analgesic actions of codeine and 6-acetylcodeine. 2. Like codeine, 6-acetylcodeine is an effective analgesic systemically, supraspinally and spinally, with a potency approximately a third that of codeine. 3. The sensitivity of 6-acetylcodeine analgesia to the mu-selective antagonists beta-FNA and naloxonazine confirmed its classification as a mu opioid. However, it differed from the other mu analgesics in other paradigms. 4. Antisense mapping revealed the sensitivity of 6-acetylcodeine to probes targeting exons 1 and 2 of the mu opioid receptor gene (Oprm), a profile distinct from either codeine or morphine. Although heroin analgesia also is sensitive to antisense targeting exons 1 and 2, heroin analgesia also is sensitive to the antagonist 3-O-methylnaltrexone, while 6-acetylcodeine analgesia is not. 5. Thus, 6-acetylcodeine is an effective mu opioid analgesic with a distinct pharmacological profile.

Analgesia↗

The health of people classified as lesbian, gay and bisexual attending family practitioners in London: a controlled study.

BACKGROUND: The morbidity of gay, lesbian or bisexual people attending family practice has not been previously assessed. We compared health measures of family practice attendees classified as lesbian, gay and bisexual. METHODS: We conducted a cross-sectional, controlled study conducted in 13 London family practices and compared the responses of 26 lesbian and 85 bisexual classified women, with that of 934 heterosexual classified women and 38 gay and 23 bisexual classified men with that of 373 heterosexual classified men. Our outcomes of interest were: General health questionnaire; CAGE questionnaire; short form12; smoking status; sexual experiences during childhood; number of sexual partners and sexual function and satisfaction. RESULTS: In comparison to people classified as heterosexuals: men classified as gay reported higher levels of psychological symptoms (OR 2.48, CI 1.05-5.90); women classified as bisexual were more likely to misuse alcohol (OR 2.73, 1.70-4.40); women classified as bisexual (OR 2.53, 1.60-4.00) and lesbian (OR 3.13, 1.41-6.97) and men classified as bisexual (OR 2.48, 1,04, 5.86) were more likely to be smokers and women classified as bisexual (OR 3.27, 1.97-5.43) and men classified as gay (OR 4.86, 2.28-10.34) were much more likely to report childhood sexual experiences in childhood. Psychological distress was associated with reporting sexual experiences in childhood in men classified as gay and bisexual and women classified as heterosexual. Men classified as bisexual (OR 5.00, 1.73-14.51) and women classified as bisexual (OR 2.88, 1.24- 6.56) were more likely than heterosexuals to report more than one sexual partner in the preceding four weeks. Lesbian, gay and bisexual classified people encountered no more sexual function problems than heterosexuals but men classified as bisexual (OR 2.74, 1.12-6.70) were more dissatisfied with their sex lives. CONCLUSION: Bisexual and lesbian classified people attending London general practices were more likely to be smokers and gay classified men were at increased risk of psychological distress in comparison to heterosexual classified people. Increased awareness of the sexuality of people seen in primary care can provide opportunities for health promotion.

Adult↗

The REACT study: randomised evaluation of assertive community treatment in north London.

OBJECTIVE: To compare outcomes of care from assertive community treatment teams with care by community mental health teams for people with serious mental illnesses. DESIGN: Non-blind randomised controlled trial. SETTING: Two inner London boroughs. PARTICIPANTS: 251 men and women under the care of adult secondary mental health services with recent high use of inpatient care and difficulties engaging with community services. INTERVENTIONS: Treatment from assertive community treatment team (127 participants) or continuation of care from community mental health team (124 participants). MAIN OUTCOME MEASURES: Primary outcome was inpatient bed use 18 months after randomisation. Secondary outcomes included symptoms, social function, client satisfaction, and engagement with services. RESULTS: No significant differences were found in inpatient bed use (median difference 1, 95% confidence interval -16 to 38) or in clinical or social outcomes for the two treatment groups. Clients who received care from the assertive community treatment team seemed better engaged (adapted homeless engagement acceptance schedule: difference in means 1.1, 1.0 to 1.9), and those who agreed to be interviewed were more satisfied with services (adapted client satisfaction questionnaire: difference in means 7.14, 0.9 to 13.4). CONCLUSIONS: Community mental health teams are able to support people with serious mental illnesses as effectively as assertive community treatment teams, but assertive community treatment may be better at engaging clients and may lead to greater satisfaction with services.

Adult↗

Specific changes in hippocampal spatial codes predict spatial working memory performance.

This study examined the relationship between hippocampal place fields and spatial working memory. Place cells were recorded while rats solved a spatial working memory task in light and dark testing conditions. Rats made significantly more errors when tested in darkness, and although place fields changed in multiple ways in darkness, only changes in place field specificity predicted the degree of impaired spatial memory. This finding suggests that more spatially distinct place fields may contribute to hippocampal-dependent mnemonic functions.

Animals↗

Prediction of depression in European general practice attendees: the PREDICT study.

BACKGROUND: Prevention of depression must address multiple risk factors. Estimating overall risk across a range of putative risk factors is fundamental to prevention of depression. However, we lack reliable and valid methods of risk estimation. This protocol paper introduces PREDICT, an international research study to address this risk estimation. METHODS/DESIGN: This is a prospective study in which consecutive general practice attendees in six European countries are recruited and followed up after six and 12 months. Prevalence of depression is assessed at baseline and each follow-up point. Consecutive attendees between April 2003 and September 2004 who were aged 18 to 75 were asked to take part. The possibility of a depressive episode was assessed using the Depression Section of the Composite International Diagnostic Interview. A selection of presumed risk factors was based on our previous work and a systematic review of the literature. It was necessary to evaluate the test-retest reliability of a number of risk factor questions that were developed specifically, or adapted, for the PREDICT study. In a separate reliability study conducted between January and November 2003, consecutive general practice attendees in the six participating European countries completed the risk factor items on two occasions, two weeks apart. The overall response rate at entry to the study was 69%. We exceeded our expected recruitment rate, achieving a total of 10,048 people in all. Reliability coefficients were generally good to excellent. DISCUSSION: Response rate to follow-up in all countries was uniformly high, which suggests that prediction will be based on almost a full cohort. The results of our reliability analysis are encouraging and suggest that data collected during the course of PREDICT will have a satisfactory level of stability. The development of a multi-factor risk score for depression will lay the foundation for future research on risk reduction in primary care. Our data will also provide the necessary evidence base on which to develop and evaluate interventions to reduce the prevalence of depression.

Adolescent↗

Beta1 integrins modulate cell adhesion by regulating insulin-like growth factor-II levels in the microenvironment.

The interactions between cancer cells and the extracellular matrix (ECM) regulate cancer progression. The beta1C and beta1A integrins, two cytoplasmic variants of the beta1 integrin subfamily, are differentially expressed in prostate cancer. Using gene expression analysis, we show here that the beta1C variant, an inhibitor of cell proliferation, which is down-regulated in prostate cancer, up-regulates insulin-like growth factor-II (IGF-II) mRNA and protein levels. In contrast, beta1A does not affect IGF-II levels. We provide evidence that beta1C-mediated up-regulation of IGF-II levels increases adhesion to Laminin-1, a basement membrane protein down-regulated in prostate cancer, and that the beta1C cytoplasmic domain contains the structural motif sufficient to increase cell adhesion to Laminin-1. This autocrine mechanism that locally supports cell adhesion to Laminin-1 via IGF-II is selectively regulated by the beta1 cytoplasmic domain via activation of the growth factor receptor binding protein 2-associated binder-1/SH2-containing protein-tyrosine phosphatase 2/phosphatidylinositol 3-kinase pathway. Thus, the concurrent local loss of beta1C integrin, of its ligand Laminin-1, and of IGF-II in the tumor microenvironment may promote prostate cancer cell invasion and metastasis by reducing cancer cell adhesive properties. It is, therefore, conceivable that reexpression of beta1C will be sufficient to revert a neoplastic phenotype to a nonproliferative and highly adherent normal phenotype.

Adaptor Proteins, Signal Transducing↗

What same sex civil partnerships may mean for health.

A growing number of countries have introduced a form of marriage or civil partnership registration for same sex couples. Marriage confers health benefits on heterosexual men and women and similar benefits could arise from same sex civil unions. The authors argue that legal and social recognition of same sex relationships may reduce discrimination, increase the stability of same sex relationships, and lead to better physical and mental health for gay and lesbian people.

Adult↗

Estimating needs in life threatening illness: a feasibility study to assess the views of patients and doctors.

BACKGROUND: Provision of palliative care for patients with non-cancer conditions is hindered by the difficulty of predicting when people will die and fear of causing distress by raising end-of-life issues. OBJECTIVES: To compare patients' and professionals' (1) estimations of prognosis; (2) perceptions of the seriousness of the illness and needs for supportive care; and (3) acceptability of this sensitive research, in end-stage cancer and non-cancer diseases. DESIGN: Prospective cohort study. SETTING: A teaching hospital and a Marie Curie hospice in London. SUBJECTS: Twenty patients with advanced non-malignant disease (heart failure, chronic obstructive pulmonary disease and renal failure) and 20 patients with advanced cancer, and their physicians in charge. METHOD: A feasibility study using vignettes to aid patients and doctors estimate of prognoses. Main outcome measures were (1) patients' and physicians' estimates of health status, care needs and prognosis; and (2) patient survival. RESULTS: Patients were willing and able to estimate their own life expectancy and cancer patients correctly estimated that they had a poorer prognosis than non-cancer patients. Non-cancer patients perceived that they had similar needs for supportive care as cancer patients. Physicians made little distinction in palliative care needs between patients with and without cancer, but tended to make more pessimistic estimates of prognosis in non-cancer patients. CONCLUSIONS: Patients are able to judge their health status and life expectancy and do not object to questions about end-of-life care. Cancer and non-cancer patients have similar needs for supportive care. We need further evidence on the value of self-rated prognosis and how to provide palliative and supportive care for all patients who are near death.

Attitude of Health Personnel↗

Depression in Irish migrants living in London: case-control study.

BACKGROUND: There is evidence that Irish migrants in Britain have higher rates of depression and suicide than other minority ethnic groups. AIMS: To examine the association between poorly planned migration and depression in Irish-born people living in London. METHOD: A sample of 360 Irish-born people was recruited from 11 general practices into a case-control study. Participants were interviewed using standardised measures, including the Beck Depression Inventory (BDI). We calculated the odds ratio for any association between depression and eight questions on preparation for migration. RESULTS: Poorly planned migration was associated with subsequent depression in Irish-born people living in London (OR=1.20, 95% CI1.06-1.35). The odds of depression were increased by a factor of 20% for each additional negative answer to eight questions on preparation for migration. Positive post-migration influences such as adequate social support protected some against depression. CONCLUSIONS: Depression in Irish-born people living in London is associated with poorly planned migration. However, this effect can be modified by experiences following migration.

Adult↗

Measuring spiritual belief: development and standardization of a Beliefs and Values Scale.

BACKGROUND: Higher levels of religious involvement are modestly associated with better health, after taking account of other influences, such as age, sex and social support. However, little account is taken of spiritual beliefs that are not tied to personal or public religious practice. Our objective was to develop a standardized measure of spirituality for use in clinical research. METHOD: We characterized the core components of spirituality using narrative data from a purposive sample of people, some of whom were near the end of their lives. These data were developed into statements in a scale to measure strength of spiritual beliefs and its reliability, validity and factor structure were evaluated in order to reach a final version. RESULTS: Thirty-nine people took part in the qualitative study to define the nature of spirituality in their lives. These data were used to construct a 47-item instrument that was evaluated in 372 people recruited in medical and non-medical settings. Analysis of these statements led to a 24-item version that was evaluated in a further sample of 284 people recruited in similar settings. The final 20-item questionnaire performed with high test-retest and internal reliability and measures spirituality across a broad religious and non-religious perspective. CONCLUSIONS: A measure of spiritual belief that is not limited to religious thought, may contribute to research in psychiatry and medicine.

Adult↗

Assessment of S-nitrosothiols on diaminofluorescein gels.

S-Nitrosylation is the modification of a cysteine thiol on a protein or peptide by a nitric oxide (NO) group. Increasing evidence suggests that S-nitrosylation of critical cysteine residues regulates protein function and cell signaling. However, progress in the field has been hampered by a lack of accurate and easy methods for detecting S-nitrosylation and other labile NO-based modifications in samples. We have developed a rapid method for analyzing protein and peptide S-nitrosothiols on gels using the fluorescent probes 4,5-diaminofluorescein (DAF-2) and 3-amino,4-aminomethyl-2'7'-difluorescein (DAF-FM). Low micromolar levels of S-nitrosylated bovine serum albumin (BSA), but not control BSA, are detected on the gels. In addition, NO-based modifications of proteins and peptides on nonsulfur groups (e.g., carbon, oxygen, nitrogen) are detected on DAF gels. Analysis of intracellular proteins on DAF gels indicated that the NO donor compound S-nitrosoglutathione S-nitrosylates significantly more proteins in mitochondrial lysates than in cytoplasmic lysates. In summary, the use of DAF gels is an easy method to analyze in vitro protein and peptide S-nitrosylation. The assay is also the first gel-based method to identify not only S-nitrosothiols but also other labile NO-based modifications of proteins and peptides.

Fluorescein↗

Impact of participant and physician intervention preferences on randomized trials: a systematic review.

CONTEXT: Allocation on the basis of randomization rather than patient choice is the gold standard of unbiased estimates of efficacy in clinical medicine. However, randomly allocating patients to treatments that do not accord with their preferences may influence internal and external validity. OBJECTIVE: To determine whether preferences affect recruitment to trials (external validity) and outcomes in trials (internal validity). DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, AMED, and the Cochrane Library for articles published between 1966 and September 2004. We also hand-searched several major medical journals, searched reference lists of relevant articles, and contacted authors of published preference designs. The 2 themes in the first filter of the search strategy were preferences and possible determinants of preferences. STUDY SELECTION: Comprehensive cohorts and 2-stage trials that measured or recorded patient or physician preference, included allocation of participants to random and preference cohorts, and followed up all participants. We excluded trials with no recording of preference; of decision aids; with measurements of preferences for economic analyses; in which patients who refused randomization were followed up without reference to preferences; and of nonclinical populations. DATA EXTRACTION: Up to 4 reviewers independently evaluated the articles, and disagreements were resolved at project steering group meetings. We extracted data on study design, measurement of preference, recruitment, attrition, and summary data on the primary outcome(s) at baseline and each follow-up point. DATA SYNTHESIS: Of 10,023 citations identified, 170 articles met screening criteria and 32 (27 comprehensive cohorts and 5 two-stage trials) were determined to be eligible and were used in the final review. Although treatment preferences led to a substantial proportion of people refusing randomization, there was less evidence of bias in the characteristics of individuals agreeing to be randomized. Differences in outcome across the trials between randomized and preference groups were generally small, particularly in large trials and after accounting for baseline measures of outcome. Therefore, there was little evidence that preferences substantially interfere with the internal validity of randomized trials. CONCLUSIONS: Preferences influence whether people participate in randomized trials, but there is little evidence that they significantly affect validity.

Humans↗

Patient preferences in randomised controlled trials: conceptual framework and implications for research.

Patient preferences have recently been highlighted as a potential threat to the validity of randomised controlled trials (RCTs). Although there have been significant methodological and statistical developments in relation to these issues, comparatively little attention has been paid to the development of a conceptual model concerning preferences and their effects on decision-making. This article describes the development of such a model, which was undertaken in parallel with a systematic review of the empirical data concerning preference effects. The model describes the concept of preference in terms of theoretical concepts from the psychological and economics literature, and describes a preliminary model of the development and operation of preferences in the context of RCTs. The paper then examines the implications of the model for informed consent and recruitment procedures. Key issues for future research are also outlined.

Clinical Trials as Topic↗

Psychotic symptoms in the general population of England--a comparison of ethnic groups (The EMPIRIC study).

BACKGROUND: There is considerable evidence that incidence of schizophrenia and other psychoses varies across ethnic groups in the UK, with particularly high rates for people of African-Caribbean origin. AIMS: The aims of this shady were to estimate in a community-based sample of people from ethnic minorities: 1) the prevalence of psychotic symptoms; and 2) risk factors for reporting psychotic symptoms. METHOD: Face-to-face interviews were carried out with a probabilistic sample of 4281 adults from six ethnic groups living in the UK. Psychotic symptoms were measured using the psychosis screening questionnaire (PSQ). RESULTS: There was a twofold higher rate of reporting psychotic symptoms on the PSQ in Black Caribbean people compared with Whites. Adjustment for demographic factors had little effect on this association. CONCLUSION: Prevalence rates of psychotic symptoms were higher in people from ethnic minorities, but were not consistent with the much higher first contact rates for psychotic disorder reported previously, particularly in Black Caribbeans.

Adolescent↗