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R Hardy

Publications and source records attributed to R Hardy.

At least 37 records · Page 2Linked to original sources
PubMed2002

Does early growth influence timing of the menopause? Evidence from a British birth cohort.

BACKGROUND: Few adult environmental or behavioural factors have been consistently associated with age at menopause. The peak number of follicles attained in utero or lost before ovulation begins may be more important. This study investigates whether birthweight, childhood body size, having been breastfed and early socioeconomic circumstances are associated with age at menopause. METHODS: Menopausal status and risk factor information have been collected prospectively from 1572 British women followed up since their birth in 1946, so far until 53 years. Cox's regression models were used to investigate the relationships between early life factors and rate of menopause. RESULTS: Age at menopause varied by duration of breastfeeding, weight at age 2 years, childhood socioeconomic status, but not birthweight. In a multiple regression model, women of low weight at 2 years had an earlier menopause [hazard ratio (HR) = 0.75 for highest versus lowest quarter: 95% confidence interval (CI) 0.54-1.02] and those who had been breastfed had a later menopause (HR = 0.69 for vertical line 7 months versus never breastfed: 95% CI 0.51-0.92) than others. The influence of socioeconomic status was attenuated. CONCLUSIONS: Early life influences may influence ovarian ageing, highlighting the importance of investigating factors from across the life course.

Adult↗
PubMed2002

Mortality from infective endocarditis: clinical predictors of outcome.

OBJECTIVE: To identify clinical markers available within the first 48 hours of admission that are associated with poor outcome in infective endocarditis. DESIGNS: Retrospective cohort study. SETTING: Teaching hospital. PATIENTS: 208 of 220 patients with infective endocarditis. METHODS: Consecutive patients with infective endocarditis presenting between 1981 and 1999 to a tertiary centre were studied. Clinical, echocardiographic, and haematological data recorded within 48 hours of admission were obtained. Data were analysed using logistic regression models. MAIN OUTCOMES MEASURES: Mortality at discharge and at six months. RESULTS: Data were obtained for 93% of patients who were eligible for inclusion. 194 (93%) were positive for Duke criteria. Mean age was 52 (1.2) years, and 138 (66%) were men. 82 (39%) were transferred from other hospitals. 181 (87%) were blood culture positive, and 47 (23%) infections were Staphylococcus aureus. The infection was located on aortic (n = 85, 41%), mitral (n = 77, 37%), tricuspid (n = 18, 9%), and multiple valves (n = 20, 10%). 67 (32%) had prosthetic valve endocarditis. 48% of the cohort were managed with antibiotics alone. Mortality at discharge was 18% and at six months 27%. Duration of illness before admission, age, sex, valve infected, infecting organism, and left ventricular function were not predictors of adverse mortality. However, abnormal white cell count, serum albumin concentration, serum creatinine concentration, or cardiac rhythm, the presence of two major Duke criteria, or visible vegetation conferred a poor prognosis. CONCLUSIONS: Conventional prognostic factors in this study did not appear to predict outcome early during hospital admission. However, simple clinical indices, which are readily available, are reliable, cheap, and potentially powerful predictors of poor outcome.

Biomarkers↗
PubMed2001

Birth weight and cognitive function in the British 1946 birth cohort: longitudinal population based study.

OBJECTIVE: To examine the association between birth weight and cognitive function in the normal population. DESIGN: A longitudinal, population based, birth cohort study. PARTICIPANTS: 3900 males and females born in 1946. MAIN OUTCOME MEASURES: Cognitive function from childhood to middle life (measured at ages 8, 11, 15, 26, and 43 years). RESULTS: Birth weight was significantly and positively associated with cognitive ability at age 8 (with an estimated standard deviation score of 0.44 (95% confidence interval 0.28 to 0.59)) between the lowest and highest birthweight categories after sex, father's social class, mother's education, and birth order were controlled for. This association was evident across the normal birthweight range (>2.5 kg) and so was not accounted for exclusively by low birth weight. The association was also observed at ages 11, 15, and 26, and weakly at age 43, although these associations were dependent on the association at age 8. Birth weight was also associated with education, with those of higher birth weight more likely to have achieved higher qualifications, and this effect was accounted for partly by cognitive function at age 8. CONCLUSIONS: Birth weight was associated with cognitive ability at age 8 in the general population, and in the normal birthweight range. The effect at this age largely explains associations between birth weight and cognitive function at subsequent ages. Similarly, the association between birth weight and education was accounted for partly by earlier cognitive scores.

Adolescent↗
PubMed2001

Counselling for depression in primary care.

BACKGROUND: There is wide clinician and patient support for counselling in primary care, particularly in the UK. This review examines the effectiveness and cost effectiveness of counselling for psychological and psychosocial problems in the primary care setting. OBJECTIVES: To assess the effects of counselling in primary care by reviewing cost and outcome data for patients with psychological and psychosocial problems considered suitable for counselling. SEARCH STRATEGY: The search strategy included electronic searching of databases (including the CCDAN Register of RCTs and CCTs) along with handsearching of a specialist journal. Published and unpublished sources (clinical trials, books, dissertations, agency reports etc.) were searched, and their reference lists scanned. Contact was made with subject experts and CCDAN members. SELECTION CRITERIA: Randomised and controlled patient preference trials comparing counselling in primary care with usual general practitioner care for patients with psychological and psychosocial problems considered suitable for counselling. Trials completed before the end of April 1998 were included in the review. DATA COLLECTION AND ANALYSIS: Trials were independently assessed by at least two reviewers for appropriateness of inclusion and methdological quality. MAIN RESULTS: Four trials, involving 678 participants, of whom 487 were followed up, were included. Data for psychological symptom levels (four trials) were pooled statistically. Patients receiving counselling had significantly better psychological symptom levels post intervention than patients receiving usual general practitioner care (standardised mean difference -0.30, 95% CI, (-0.49 to - 0.11). The effect remained statistically significant when the results from studies with less rigorous methodology were excluded in a sensitivity analysis. Patients who received counselling tended to be more satisfied with their treatment (three trials). Health service utilisation data were reported in all trials reviewed, but only one trial undertook a cost analysis. No clear cost advantage was associated with either counselling or usual general practice care. REVIEWER'S CONCLUSIONS: Patients who received counselling were more likely to have improved psychological symptom levels than those who did not receive counselling. Levels of satisfaction with counselling were high. There is limited information about the cost effectiveness of counselling, with one study reporting no clear cost advantage with either counselling or general practice care. The four trials included in this review were all pragmatic trials of counselling in primary care in the UK, which reflect the reality of clinical provision in this context. There were methdological weaknesses identified in the studies, which should be taken into account when considering the results. The evidence base will be extended by trials of counselling which are nearing completion.

Controlled Clinical Trials as Topic↗
PubMed2001

Antidepressants using active placebos.

BACKGROUND: Although there is a consensus that antidepressants are effective in depression, placebo effects are also thought to be substantial. Side effects of antidepressants may reveal the identity of medication to participants or investigators and thus may bias the results of conventional trials using inert placebos. Using an 'active' placebo which mimics some of the side effects of antidepressants may help to counteract this potential bias. OBJECTIVES: To investigate the efficacy of antidepressants when compared with 'active' placebos. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis review groups's search strategy was used to search MEDLINE (1966-2000), PsychLIT (1980-2000) and EMBASE (1974-2000) and this was last done in July 2000. Reference lists from relevant articles and textbooks were searched and 12 specialist journals were handsearched up to 1996. SELECTION CRITERIA: Randomised and quasi randomised controlled trials comparing antidepressants with active placebos in people with depression. DATA COLLECTION AND ANALYSIS: Since many different outcome measures were used a standard measure of effect was calculated for each trial. A subgroup analysis of inpatient and outpatient trials was conducted. Two reviewers independently assessed whether each trial met inclusion criteria. MAIN RESULTS: Nine studies involving 751 participants were included. Two of them produced effect sizes which showed a consistent and statistically significant difference in favour of the active drug. Combining all studies produced a pooled estimate of effect of 0.39 standard deviations (confidence interval, 0.24 to 0.54) in favour of the antidepressant measured by improvement in mood. There was high heterogeneity due to one strongly positive trial. Sensitivity analysis omitting this trial reduced the pooled effect to 0.17 (0.00 to 0.34). The pooled effect for inpatient and outpatient trials was highly sensitive to decisions about which combination of data was included but inpatient trials produced the lowest effects. REVIEWER'S CONCLUSIONS: The more conservative estimates from the present analysis found that differences between antidepressants and active placebos were small. This suggests that unblinding effects may inflate the efficacy of antidepressants in trials using inert placebos. Further research into unblinding is warranted.

Antidepressive Agents↗
PubMed2001

Cis-acting RNA elements at the 5' end of Sindbis virus genome RNA regulate minus- and plus-strand RNA synthesis.

Alphavirus genome replication is a multistep asymmetric process. Several lines of evidence suggest that the template preference of the RNA replicase is regulated by proteolytic cleavage of the viral nonstructural polyprotein. Cis-acting RNA elements in the viral genome also play crucial roles in regulating genome replication and subgenomic RNA transcription. In this report, a series of RNA templates were analyzed in vitro and in vivo to define functional elements in the 5' end of the genome. The 5' UTR was shown to contain distinct core promoter elements for both minus- and plus-strand synthesis. In addition, two conserved stem-loop structures within the nsP1 coding sequence enhanced RNA replication but were not required. Studies with chimeric templates and trans-competition experiments suggest that the 5' determinant for minus-strand initiation can differ among alphaviruses and binds to one or more limiting replicase components. The results provide compelling evidence that the 5' and 3' ends of alphavirus genome RNAs must interact to initiate replication and we propose one model for how this interaction might occur. In addition to providing new insight into the initiation of alphavirus genome replication, these results have implications for the development of improved alphavirus vector systems with reduced recombination potential.

3' Untranslated Regions↗
PubMed2001

Adolescents' sense of coherence, oral health status, and oral health-related behaviours.

OBJECTIVE: To investigate the relationship between sense of coherence (SOC) and oral health. It was hypothesised that subjects with better oral health status and better oral health-related behaviours have higher levels of SOC. METHODS: A cross-sectional study was conducted in Goiânia-GO, Middle-West Brazil, on a sample of 664 15-year-olds randomly selected from schools. Data were collected through questionnaires, the short version of Antonovsky's SOC Scale (13-item) and clinical dental examinations. Multiple logistic regression and polytomous ordered regression were used in the data analysis. Two sets of outcome variables were selected for the analyses: oral health status (dental caries, oral cleanliness, and periodontal disease), and oral health-related behaviours (frequency of sugar intake, toothbrushing frequency, and pattern of dental attendance). RESULTS: Adolescents' SOC was associated with their caries experience in anterior teeth (OR=0.81 for 10 units increase in SOC scale; 95% CI=0.66-0.98), but the relationship did not remain significant after controlling for other factors. Adolescents with higher SOC were less likely to visit the dentist mainly when in trouble, compared with those with lower SOC (OR=0.83, 95% CI=0.71-0.98), or equivalently more likely to visit for mainly check-ups. Other measures of oral health status and behaviours were not significantly associated with SOC. CONCLUSION: SOC was identified as a psychosocial determinant of adolescents' oral health-related behaviour, particularly affecting their pattern of dental attendance.

Adolescent↗
PubMed2001

Enhancing staff development with a structured preceptor program.

The unexpected expansion of a 14-bed medical intensive care unit exposed the need for a structured preceptor/orientation program. Staff feedback and a review of quality indicators further substantiated this finding and revealed a decrease in standards of practice and problems in staff development. A restructured preceptor/orientation program yielded improvements in communication and staff satisfaction. Preceptors and orientees now have a better understanding of their roles and expectations, and quality of care is improving in an environment that promotes personal and professional growth.

Humans↗
PubMed2001

Long-term affective disorder in people with mild learning disability.

BACKGROUND: Increased risk of affective disorder in learning disability has been reported, although the extent to which this is due to adverse social and material circumstances is uncertain and there have been potential limitations in the measurement of affective disorder. AIMS: To determine risk of affective disorder in those classified with mild learning disability in the British 1946 birth cohort and to investigate whether this risk was accounted for by disadvantage in childhood and adulthood. METHOD: Learning disability was defined as the equivalent of an IQ < or =69 at age 15 years. The Present State Examination at age 36 years and the Psychiatric Symptom Frequency Scale at age 43 years provided psychiatric outcome measures. RESULTS: Learning disability was associated with a fourfold increase in risk of affective disorder, not accounted for by social and material disadvantage or by medical disorder. CONCLUSIONS: Learning disability is strongly associated with risk of affective disorder, persisting well into midlife.

Adolescent↗
PubMed2000

Aberrant P-cadherin expression is a feature of clonal expansion in the gastrointestinal tract associated with repair and neoplasia.

The recognition of key roles for cadherins in the determination of epithelial cell phenotype, migration, differentiation, and tumour dissemination have stimulated much interest in this family of adhesion molecules. In the gastrointestinal tract, alteration of the expression of classical cadherins with aberrant P-cadherin up-regulation, associated with co-expression or loss of E-cadherin expression, is seen in neoplastic transformation of oral and oesophageal squamous mucosa and in lesions representing early neoplastic transformation of glandular mucosa, such as aberrant crypt foci and metaplastic and adenomatous polyps. This same phenotype is seen in enterocytes adjacent to foci of ulceration in the intestine in colitis, including inflammatory bowel disease, and in colitis-associated dysplasia. In coeliac disease, reversible E-cadherin down-regulation correlates with the degree of villous atrophy, but in contrast with colitis, aberrant P-cadherin expression is not a feature. Aberrant epithelial P-cadherin expression is thus associated with a proliferative phenotype related to ulceration and neoplastic transformation in the gastrointestinal tract, which may confer a survival advantage on these cells, but the relative functional roles of P-cadherin and E-cadherin and the molecular mechanisms underlyingP-cadherin/catenin interactions have yet to be elucidated.

Cadherins↗
PubMed2000

New automated chemiluminescent assay for erythropoietin.

Erythropoietin (EPO) is a polypeptide hormone produced by the kidney that regulates erythropoiesis by controlling the proliferation and differentiation of erythroid progenitors in bone marrow. Assays for EPO are used to monitor dosage and response to human recombinant erythropoietin also may have diagnostic utility in the differential diagnosis of anemia and polycythemia. We evaluated an automated, chemiluminescent immunoassay for EPO (DPC Immulite) in terms of precision, linearity, interference, and correlation with reference assays. The Immulite assay demonstrated acceptable correlation with the reference immunochemiluminometric method (slope = 1.087, y intercept = 0.567, R value = 0.990). Within-run CVs ranged from 2.3% to 5.0%, while between-run CVs ranged from 4.1% to 9.5%. Linearity extended beyond the manufacturer's stated claims, and recovery ranged from 96.8% to 100.9% across the concentrations tested. No significant interference was noted with hemoglobin, bilirubin, or triglyceride. Overall, this method compares favorably with the existing immunochemiluminometric reference method and offers clinical laboratories an alternative for the analysis of erythropoietin.

Antibodies, Monoclonal↗
PubMed2000

Selective serotonin reuptake inhibitors versus tricyclic and heterocyclic antidepressants: comparison of drug adherence.

BACKGROUND: Selective serotonin reuptake inhibitors are thought to have better discontinuation rates (i.e. less people dropping out) than tricyclic and heterocyclic antidepressant drugs. It is important to quantify the drop-out rates of different antidepressant drugs in order to have a better understanding of the relative tolerability of these drugs. OBJECTIVES: To assess the comparative tolerability of selective serotonin reuptake inhibitors and tricyclic/heterocyclic antidepressant drugs. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (1997 to 1999), MEDLINE (1966 to 1999), EMBASE (1974 to 1999) We also searched specialist journals, the reference lists of relevant papers and previous systematic reviews, conference abstracts and government documents. Representatives of the pharmaceutical industry were contacted. SELECTION CRITERIA: Parallel group randomised controlled trials comparing selective serotonin reuptake inhibitors with tricyclic or heterocyclic antidepressants in people with depression. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and a third reviewer checked any cases of disagreement. MAIN RESULTS: We included 136 trials. The selective serotonin reuptake inhibitors showed less participants dropping out compared to the tricyclic/heterocyclic group (odds ratio 1.21, 95% confidence interval 1.12 to 1.30). A statistically significant difference was found in total drop-outs between the selective serotonin reuptake inhibitors and the old tricyclics as well as the newer tricyclics. When the selective serotonin reuptake inhibitors were compared to the heterocyclic antidepressants, there was a non significant difference favouring the selective serotonin reuptake inhibitors. The poor tolerability profile of the old tricyclics was explained by differences in drop-outs for side-effects, but not for inefficacy. REVIEWER'S CONCLUSIONS: Whilst selective serotonin reuptake inhibitors do appear to show an advantage over tricyclic drugs in terms of total drop-outs, this advantage is relatively modest. This has implications for pharmaco-economic models, some of which may have overestimated the difference of drop-out rates between selective serotonin reuptake inhibitors and tricyclic antdepressants. These results are based on short-term randomised controlled trials, and may not generalise into clinical practice.

Antidepressive Agents↗
PubMed2000

The influence of childhood weight and socioeconomic status on change in adult body mass index in a British national birth cohort.

OBJECTIVE: To investigate the effect of childhood weight and childhood socioeconomic status on the pattern of change in body mass index (BMI) between 20 and 43 years. METHODS: A British birth cohort study where the survey members have been followed up regularly since their birth in 1946, with the most recent of 19 follow-ups when the cohort were aged 43 years. BMI was available at 20, 26, 36 and 43 years of age and thus multilevel models for repeated outcome measures were used to model the patterns of change in BMI. RESULTS: The rate of increase in BMI with age was non-linear, with the rate of increase in mean BMI accelerating with increasing age at different rates for men and women. The mean BMI for men was higher than that for women at all ages. Childhood manual social class, defined in terms of father's occupation, and high relative weight at 14 years of age were associated with higher mean BMI across adult life, and these effects increased with age. The effects of childhood relative weight and social class were independent of educational attainment and adult social class. CONCLUSION: The study provides evidence of a long-term effect of childhood social and biological circumstances on BMI. The pathways underlying these relationships may be social or biological, but are not yet fully understood.

Adolescent↗
PubMed2000

Birthweight, childhood growth and risk of breast cancer in a British cohort.

We have examined the relationship between birthweight and risk of breast cancer, taking into account growth in childhood, using data on a total of 2221 women born in 1946 and followed up to 1997. Thirty-seven breast cancers occurred during follow-up. There was evidence of greater risk of breast cancer with greater birthweight (rate ratio = 1.76 (95% CI: 0.92, 3.35) for birthweight >/= 3.5 kg vs birthweight < 3.5 kg), which was more marked at pre-menopausal ages (RR = 2.31, 95% CI: 0.93, 5.74). The relation with birthweight was not substantially confounded by any of the measured adult risk factors. A significant interaction was observed between the effects of birthweight and height at age 7 years. Relative to those born lighter than 3.5 kg, women who were heavy at birth (>/= 3.5 kg) and short or average at 7 years (< 1.22 m) had a 21% increase in breast cancer rates (RR = 1.21; 95% CI = 0.49-2.99), while women who were heavy at birth (>/= 3.5 kg) but tall at 7 years (>/= 1.22 m) had a four-fold increase (RR = 4.01; 95% CI = 1.82-8.83). These results suggest that the effect of birthweight on breast cancer risk may be modulated by childhood growth.

Adolescent↗
PubMed2000

Smoking, body mass index, socioeconomic status and the menopausal transition in a British national cohort.

BACKGROUND: This study investigates whether cigarette smoking, body mass index (BMI) and socioeconomic status are independently associated with age at menopausal transition. METHODS: Menopausal status and risk factor information were collected prospectively from 1572 British women followed up since their birth in 1946, so far until 50 years. Cox's regression models were used to investigate the relationships of interest. RESULTS: Cigarette smokers started the perimenopause and reached the menopause earlier than ex-smokers and non-smokers. The relative risk for smokers compared with non-smokers was 1.31 (95% CI : 1.09-1.56) for perimenopause and 1.63 (95% CI : 1.17-2.27) for menopause. Body mass index was associated with the age at inception of the perimenopause only among smokers and ex-smokers, with underweight women having the earliest perimenopause. No association was observed between BMI and age at menopause. Smokers and underweight women were more likely than others to start hormone replacement therapy (HRT) before becoming postmenopausal. There was no effect of education or social class on age at inception of the perimenopause or age at menopause. Single women had an earlier perimenopause but the effect was confounded by parity. CONCLUSIONS: Smoking was independently related to an earlier menopausal transition, although the effect on inception of the perimenopause was particularly observed among underweight women. There was no independent effect of socioeconomic status. The popularity of HRT use in this cohort may have had an impact on the findings.

Adult↗
PubMed2000

The bulk of the phosphorylation of human respiratory syncytial virus phosphoprotein is not essential but modulates viral RNA transcription and replication.

The ability of variants of the human respiratory syncytial virus (HRSV) phosphoprotein (P protein) to support RNA transcription and replication has been studied by using HRSV-based subgenomic replicons. The serine residues normally phosphorylated in P during HRSV infection have been replaced by other residues. The results indicate that the bulk of phosphorylation of P (98%) is not essential for viral RNA transcription or replication but that phosphorylation can modulate these processes.

HN Protein↗
PubMed2000

Social and behavioural influences on the uptake of hormone replacement therapy among younger women.

OBJECTIVE: To describe the social and behavioural influences on the uptake of hormone replacement therapy before the age of 50. DESIGN: Nationally representative birth cohort study with detailed hormone replacement therapy histories and prospective data on health, social and behavioural factors collected throughout life. SETTING: England, Scotland and Wales. POPULATION: General population sample of 1,572 women followed to the age of 50 years. MAIN OUTCOME MEASURE: Age at first hormone replacement therapy use RESULTS: By the age of 50 years, 45% of women had tried hormone replacement therapy and one third were current users. Over two-fifths of users had tried more than one preparation and over one quarter had episodic use. For the vast majority, prescribing conformed to current guidelines. More educated women took hormone replacement therapy for long term prevention compared with their less educated peers. Hysterectomy increased the chances of taking hormone replacement therapy, particularly where an oophorectomy had also been performed, and was associated with longer and more continuous use. Results of a Cox's proportional hazards model showed that the age at which first hormone replacement therapy is used by women who have not had a hysterectomy was influenced by previous contact with health services for menstrual disorders, previous use of oral contraception and cigarettes, past reporting of health problems and low social class. The relation between smoking and low social class with early use of hormone replacement therapy may be due to their association with early menopause. CONCLUSIONS: The trend over the last two decades towards greater use of hormone replacement therapy has continued unabated for younger women. So far, hormone replacement therapy users in this generation have had less healthy lifestyles and social advantages than nonusers, in contrast to many older mainly American studies based on earlier generations. This may have long term implications for health and health care as the postwar baby boom generation ages.

Adult↗