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Biomedical subjects

J Connelly

Publications and source records attributed to J Connelly.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of postmenopausal hormone replacement therapy on dental outcomes: systematic review of the literature and pharmacoeconomic analysis.

A systematic review and economic analysis of clinical trials evaluating the effect of hormone replacement therapy (HRT) on dental outcomes in postmenopausal women were conducted. Twenty published studies involving more than 13,735 postmenopausal women were summarized and analyzed. In prospective studies, the effect of HRT on osteoporosis (OP) has been well documented. The effect of OP on mandibular bone density has also been examined in some observational studies. Few studies, however, have examined the effect of HRT directly on mandibular bone density or on dental outcomes. From these studies, the effect of HRT on costs of dental treatment and prophylaxis was estimated directly and indirectly. It was determined that HRT use was associated with reduction in adverse dental outcomes and the associated costs of dental care. Annualized excess cost in a cohort of 1,000 untreated women averaged $100,000. From this analysis, it is clear that postmenopausal women with OP who do not receive HRT have a greater incidence of adverse dental outcomes and higher dental care costs than those who do.

Aged↗
PubMed2000

Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

BACKGROUND: Intravascular ultrasound (IVUS) is the generic name for any ultrasound technology used in vivo within the blood vessels. More specifically, intracoronary ultrasound enables imaging of the coronary arteries from within the lumen. This review concentrates on the role of intracoronary ultrasound as an adjunct to interventional cardiology. OBJECTIVES: (1) To identify the literature on IVUS for guiding coronary interventions, and to synthesise evidence about outcomes compared with outcomes when IVUS guidance has not been used. (2) To use this evidence, together with other information about costs and outcomes, to model the cost effectiveness of IVUS guidance. (3) To synthesise the evidence on the reproducibility of measurements of cross-sectional area made using IVUS. METHODS DATA SOURCES: (1) Electronic searches of MEDLINE, EMBASE, Science Citation Index, Index to Scientific and Technical Proceedings, Engineering Compendex, Engineering Page One, Cochrane Library, Inside (British Library), 1990-98. (2) Contacting experts and centres of expertise, 1990-99. (3) Internet search, 1990-99. METHODS STUDY SELECTION: Studies of IVUS-guided coronary interventions performed on humans were included in the review. Non-English language studies were also included when they covered IVUS-guided stenting or angioplasty. Control evidence regarding outcomes without IVUS guidance was sought only from randomised controlled trials (RCTs). Studies investigating the reproducibility of measurements of cross-sectional area were included only if the results were expressed in terms of the mean and standard deviation of paired differences. METHODS DATA EXTRACTION: Checklists that covered study details, patient characteristics and results were completed independently by three reviewers. Consensus was reached on any disagreements. Local data were gathered on the costs of IVUS-guided stenting. METHODS DATA SYNTHESIS: Overall event rates were calculated by pooling patient results from the included studies. A decision-analytic model was used to combine information from the literature with cost estimates, in order to predict cost-effectiveness in terms of cost per restenosis event avoided by the use of IVUS guidance. The analysis was performed from the perspective of the healthcare provider. Sensitivity analysis was undertaken. A simple extrapolation was made to long-term outcome so that cost-utility (using quality-adjusted life years (QALYs)) could be estimated. The minimum detectable change in cross-sectional area was estimated from the reproducibility results. RESULTS: Only one study on IVUS-guided angioplasty satisfied the inclusion criteria, and there were no studies on IVUS-guided atherectomy or other IVUS-guided interventions that satisfied the inclusion criteria. Of the 15 articles on IVUS-guided stenting that satisfied the inclusion criteria, seven presented data on outcomes at 6 months post-intervention. The angiographic restenosis rate was 16 +/- 1%. This compared with 24 +/- 2% derived from five articles on stenting without IVUS guidance. Data for follow-up periods longer than 6 months were presented in only two studies. Data from a total of five studies were included in the decision-analytic model. The cost per restenosis event avoided was 1545 pound sterling. After extrapolation to long-term outcome, the calculated cost per QALY was 6438 pound sterling. The baseline QALY gain was only 0.03 years. Sensitivity analysis resulted in large differences between the best- and worst-case scenarios, for example, from a saving of 5000 pound sterling to a cost of 24,000 pound sterling restenosis event avoided. The smallest changes in cross-sectional area that could be measured were 1.6 mm2 by a single observer and 1.9 mm2 by different observers. CONCLUSIONS: Implications for healthcare: The evidence available is too weak for there to be any reliable implications for clinical practice. (ABSTRACT TRUNCATED)

Algorithms↗
PubMed1999

High-resolution magic angle spinning 1H NMR spectroscopic studies on intact rat renal cortex and medulla.

High-resolution magic angle spinning 1H NMR (MAS-NMR) spectroscopy was used to investigate the biochemical composition of normal renal cortex and renal papilla samples from rats, and results were compared with those from conventional 1H NMR analysis of protein-free tissue extracts. 1H MAS NMR spectra of samples obtained from inner and outer cortex were found to be broadly similar in terms of metabolite profile, and intra- and inter-animal variability was small. However, the MAS NMR spectra from renal papilla samples were qualitatively and quantitatively different from those obtained from cortex. High levels of free amino acids and several organic acids were detected in the cortex, together with choline, glucose, and trimethylamine-N-oxide. The dominant metabolite resonances observed in papillary tissue were from glycerophosphocholine (GPC), betaine, myo-inositol, and sorbitol. On increasing the magic angle spinning rate from 4,200 to 12,000 Hz, the lipid MAS 1H NMR signal profile remained largely unchanged in papillary tissue, whereas "new" resonances from triglycerides appeared in the spectra of cortical tissue, this effect being reversible on returning the spinning rate to 4,200 Hz. Further investigation into the behavior of the lipid components under different spinning rates suggested that the lipids in the cortex were present in more motionally constrained environments than those in the papilla. 1H MAS NMR spectra of tissues are of value both in interrogation of the biochemical composition of whole tissue, and in obtaining information on the mobility and compartmentalization of certain metabolites.

Animals↗
PubMed1999

Being in the present moment: developing the capacity for mindfulness in medicine.

Medical practice is beset by interruptions, contests for the attention of the physician, and urgent demands that diminish the attentiveness required for the humanistic care of patients. This essay discusses skills for "being in the present moment" that can help doctors to overcome distractedness. Because of some striking similarities between the experience of reading poetry and the attentiveness required of medicine, the author uses 19th- and 20th-century American poetry to illustrate the state of mindfulness and "being in the moment," and suggests the helpfulness of poetry in developing these skills in physicians. Applying these skills in everyday practice rewards the physician with renewed energy, a fresh perspective, and increased strength while preventing the stress and harm caused by a distracted or inattentive practice.

Delivery of Health Care↗
PubMed1999

Rethinking public health: new training for new times.

The new public health agenda will require major changes in the way health authorities, local authorities, Trusts and Primary Care Groups organise and manage their activities. The requirement is for inter-agency co-ordination and inter-professional and inter-sectoral working to a shared agenda, yet the human and resources development planning to achieve these goals has not been done. This paper summarises the key training issues and argues for a collaborative, decentralised and quality assured approach to multidisciplinary public health management education and training. Only with such a joined up human resources plan can Our Healthier Nation succeed where The Health of the Nation signally failed.

Health Planning↗
PubMed1999

Management of major trauma: changes required for improvement.

AIMS: To describe the views of key healthcare professionals on the changes they considered to be important in the reduction of major trauma mortality between 1988 and 1995 in Leeds. METHODS: Qualitative unstructured interviews with a purposive sample of 10 healthcare professionals deemed to be key personnel by an experienced consultant who had provided acute trauma care throughout the relevant period. Each interview was tape recorded and transcribed; each transcript was analysed for important themes by two independent researchers who then discussed their results to resolve any differences in interpretation. RESULTS: Three categories of change became evident: "policy", "infrastructure", and "philosophy of care". Each of these categories seemed to be equally important. Policy changes identified as important were the Royal College of Surgeons of England's report into trauma care (1988), the setting of standards for paramedic training, and the national audit of major trauma outcomes. Important infrastructure changes identified were training in advanced trauma life support, decreased ambulance response times, reorganisation towards "consultant led" hospital services, and an emphasis on quality monitoring. Changes in philosophy of care were increases in levels of teamwork, commitment, communication, and confidence. Together these facilitated an overall restructuring and refocusing of care. CONCLUSIONS: No individual change is seen as dominant for improved care, but rather a strategic mixture of facilitating national and regional policy guidance, organisational restructuring, and congruent professional attitudes were integral components leading to the observed changes. Improving outcomes in other areas is likely to involve an integrated series of changes which must be managed as a total system.

Attitude of Health Personnel↗
PubMed1998

Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for the detection of abnormal cervical lesions: systematic review and meta-analysis.

Objective: The primary objective of this project was to determine the diagnostic accuracy of a fluid-based, thin-layer system (ThinPrep) compared to conventional Papanicolaou smears for the detection of abnormal (cancerous and pre-cancerous) cervical lesions.Methods: Five comparative studies including 12 study sites, screening centers, and high-risk hospital centers and 10,377 patients were included in a systematic review and meta-analysis examining the cytological diagnoses of ThinPrep with conventional smears using odds ratios (ORs) and risk differences (RDs). All abnormal samples (squamous intraepithelial neoplasia [SIL] or more severe abnormalities) classified by an independent pathologist reviewer were analyzed. Sensitivity analyses using jackknife techniques examined the robustness of the results. Logistic regression models were fit to the data using study level information and the individual patient data to examine the effect of baseline covariates on the results.Results: ThinPrep results were significantly better than conventional smears. For all abnormal diagnoses, the OR = 1.95 (95% CI: 1.40-2.70, P <.0001). For each SIL diagnostic subgroup, the results also strongly favored ThinPrep: LGSIL (OR = 2.20, 95% CI: 1.50-3.22, P =.001) and HGSIL (OR = 1.33, 95% CI: 0.85-2.07, P =.091). Analyses with RDs were similar and also statistically significant. Sensitivity analyses showed the studies to be homogeneous (using Cochran's Q statistic = NS). Logistic regression models examining the meta-analysis results controlling for individual patient level and study level covariates increased the significance of the ThinPrep results.Conclusion: In a meta-analysis of the results of five comparative studies, the ThinPrep system showed significantly higher diagnostic accuracy for the detection of abnormal cervical lesions overall and by SIL diagnostic subgroups.

Journal Article↗
PubMed1998

Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins.

1H NMR spectroscopy of urine combined with pattern recognition (PR) methods of data analysis has been used to investigate the time-related biochemical changes induced in Sprague-Dawley rats by three model hepatotoxins: alpha-naphthyl isothiocyanate (ANIT), d-(+)-galactosamine (GalN), and butylated hydroxytoluene (BHT). The development of hepatic lesions was monitored by conventional plasma analysis and liver histopathology. Urine was collected continuously postdosing up to 144 h and analyzed by 600-MHz 1H NMR spectroscopy. NMR spectra of the urine samples showed a number of time-dependent perturbations of endogenous metabolite levels that were characteristic for each hepatotoxin. Biochemical changes common to all three hepatotoxins included a reduction in the urinary excretion of citrate and 2-oxoglutarate and an increased excretion of taurine and creatine. Increased urinary excretion of betaine, urocanic acid, tyrosine, threonine, and glutamate was characteristic of GalN toxicity. Both GalN and ANIT caused increased urinary excretion of bile acids, while glycosuria was evident in BHT- and ANIT-treated rats. Data reduction of the NMR spectra into 256 integrated regions was used to further analyze the data. Mean values of each integrated region were analyzed by principal components analysis (PCA). Each toxin gave a unique time-related metabolic trajectory that could be visualized in two-dimensional PCA maps and in which the maximum distance from the control point corresponded to the time of greatest cellular injury (confirmed by conventional toxicological tests). Thereafter, the metabolic trajectories changed direction and moved back toward the control region of the PR map during the postdose recovery phase. The combination of urinary metabolites which were significantly altered at various time points allowed for differentiation between biliary and parenchymal injury. This NMR-PR approach to the noninvasive detection of liver lesions will be of value in furthering the understanding of hepatotoxic mechanisms and assisting in the discovery of novel biomarkers of hepatotoxicity.

1-Naphthylisothiocyanate↗
PubMed1998

The psychological impact of screening for risk of coronary heart disease in primary care settings.

AIMS: A prospective study was conducted to identify the psychological impact of labelling middle-aged men as having above average risk for coronary heart disease. A second aim was to find out the psychological effect of participation in a subsequent clinical trial. METHODS: 5813 men attended nine special screening clinics in England and Scotland for baseline measurement of psychological symptoms and coronary disease risk factors. Each man was later informed of his risk status by letter as either above average risk (high-risk) or no special risk (low-risk). In three clinics some men also received an intermediate risk (moderate-risk) between high-risk and low-risk. Follow-up psychological measurements were made after labelling and 3 months later. RESULTS: Men who received either the high-risk label (n=838) or the low-risk label (n=3114) showed a decrease in reported psychological symptoms after labelling. Men receiving the unexpected intermediate risk (moderate-risk) label, which communicated specific test abnormalities, increased their psychological symptoms to 'case' levels on the General Health Questionnaire; relative risk (compared with low-risk) was 1.80 (95% confidence interval 1.19-2.71) after adjustment for confounding factors. Compliers with a subsequent clinical trial decreased their risk of becoming cases and, if ill at trial entry, increased their case remission rate. CONCLUSIONS: The ascription of an 'above average risk' label for coronary disease to middle-aged men does not adversely affect the psychological state of those who receive it if they have received preparation for risk labelling. However, communicating abnormal coronary disease test results without adequate preparation confers short-term psychological harm. Non-specific support from familiar general practice professionals received by participants in a clinical trial reduces the risk of psychological ill-health. All coronary disease screening programmes should include adequate pre-labelling preparation for all risk labels and abnormal results.

Aged↗
PubMed1996

The nature of 'transient' and 'partial' psychoses: findings from the Northwick Park 'Functional' Psychosis Study.

Three hundred and twenty-six consecutively admitted patients with definite or possible functional psychotic illnesses to which no diagnostic classification had been applied were followed up after 2.5 years. In 86 cases symptomatology had been inadequate for the patients to enter the functional psychosis study, and in 75 cases this was because the symptoms were partial or transient. These patients were compared at follow-up with those who fulfilled operational criteria for schizophrenic, affective or schizoaffective psychoses. Differences between the 'partial' cases and those fulfilling specific diagnostic criteria were few, but the transient cases fared significantly better. Although the transient illnesses were recurrent, at follow-up at 2.5 years they appeared to have a good outcome in terms of social variables and symptomatology.

Affective Disorders, Psychotic↗
PubMed1995

Measurement of TSH receptor blocking immunoglobulins using 3H-adenine incorporation into FRTL-5 and JPO9 cells: use in a child with neonatal hypothyroidism.

OBJECTIVE: The aim of this study was to develop an assay for the measurement of thyroid blocking antibodies (TBAb), based on the ability of patient serum to inhibit TSH stimulated 3H-cAMP production following incubation of FRTL-5 or JPO9 cells with 3H-adenine. The assay was then used to evaluate a child born with neonatal hypothyroidism. DESIGN: The levels of TBAb, TSAb (thyroid stimulating antibodies), TBII (TSH binding inhibitory antibodies), and the thyroid antibodies anti-thyroid peroxidase and thyroglobulin antibodies were measured in both mother and child over a 6-month post-natal period. PATIENT: The assay for TBAb was used to evaluate a child born with neonatal hypothyroidism whose mother had a history of hypothyroidism due to Hashimoto's thyroiditis. A 99mTc pertechnetate scan showed no evidence of functioning thyroid tissue. At 20 months of age an ultrasound verified a normally positioned thyroid. RESULTS: Initially, high levels of TBII and antithyroid antibodies were present in the serum of both mother and child. In both, the levels of TSAb were undetectable but there were significant levels of TBAb. The levels of TBAb decreased to control levels in the child within 2 months of birth but remained elevated in the mother's serum. CONCLUSIONS: This case of neonatal hypothyroidism associated with the passage of thyroid blocking antibodies demonstrates the utility of this new assay in the differential diagnosis of neonatal hypothyroidism.

Adenine↗