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Biomedical subjects

D M Sharp

Publications and source records attributed to D M Sharp.

14 recordsLinked to original sources
PubMed2005

Long-term outcome of cognitive behaviour therapy clinical trials in central Scotland.

OBJECTIVES: To establish the long-term outcome of participants in clinical trials of cognitive behaviour therapy (CBT) for anxiety disorders and psychosis, examining the effectiveness and cost-effectiveness associated with receiving CBT in comparison with alternative treatments. DESIGN: An attempt was made to contact and interview all of the participants in eight randomised, controlled, clinical trials of CBT for anxiety disorders and two randomised, controlled, clinical trials of CBT for schizophrenia conducted between 1985 and 2001. Case note reviews of healthcare resources used in the 2 years prior to entering the trials and the 2 years prior to follow-up interview were undertaken. SETTING: Mixed rural and urban settings in five localities in central Scotland. Anxiety disorder trials were conducted mainly in primary care and included three with generalised anxiety disorder, four with panic disorder and one with post-traumatic stress disorder (PTSD). The psychosis studies (one on relapse prevention and one with chronic disorder) were conducted in secondary care. PARTICIPANTS: Of the 1071 entrants to the 10 studies, 489 agreed to participate (46% of original entrants, 52% of those available to contact). INTERVENTIONS: Follow-up interviews took place between 1999 and 2003, 2-14 years after the original treatment. Interviews for Trials 1-8 were conducted by a research psychologist blind to original treatment condition. Interviews for Trials 9 and 10 were conducted by community psychiatric nurses also blind to treatment condition. Case note reviews were completed following the interview. MAIN OUTCOME MEASURES: For Trials 1-8 the main interview-based outcome measures were: Anxiety Disorders Interview Schedule-DSM-IV for diagnosis and co-morbidity, Clinical Global Severity (0-8) and the Hamilton Anxiety Rating Scale. The main patient-rated measures were: Brief Symptom Inventory, SF-36 II, Clinical Global Improvement (1-7), and the Positive and Negative Affect Scale. For Trials 9 and 10 the primary outcome measure was the interview-based Positive and Negative Syndrome Scale (PANSS). RESULTS: For the anxiety disorder studies (Trials 1-8), over half of the participants (52%) had at least one diagnosis at long-term follow-up, with significant levels of co-morbidity and health status scores comparable to the lowest 10% of the general population. Only 36% reported receiving no interim treatment for anxiety over the follow-up period with 19% receiving almost constant treatment. Patients with PTSD did particularly poorly. There was a 40% real increase in healthcare costs over the two time periods, mainly due to an increase in prescribing. A close relationship was found between poor mental and physical health for those with a chronic anxiety disorder. Treatment with CBT was associated with a better long-term outcome than non-CBT in terms of overall symptom severity but not with regard to diagnostic status. The positive effects of CBT found in the original trials were eroded over longer time periods. No evidence was found for an association between more intensive therapy and more enduring effects of CBT. Long-term outcome was found to be most strongly predicted by the complexity and severity of presenting problems at the time of referral, by completion of treatment irrespective of modality and by the amount of interim treatment during the follow-up period. The quality of the therapeutic alliance, measured in two of the studies, was not related to long-term outcome but was related to short-term outcome. The cost-effectiveness analysis showed no advantages of CBT over non-CBT. The cost of providing CBT in the original trials was only a very small proportion (6.4%) of the overall costs of healthcare for this population, which are high for both physical and mental health problems. In the psychosis studies (Trials 9 and 10), outcome was generally poor with only 10% achieving a 25% reduction in total PANSS scores from pretreatment to long-term follow-up, also cost-effectiveness analysis showed no advantages of CBT over non-CBT, although healthcare costs fell over the two time periods mainly owing to a reduction in inpatient costs. CONCLUSIONS: Psychological therapy services need to recognise that anxiety disorders tend to follow a chronic course and that good outcomes with CBT over the short term are no guarantee of good outcomes over the longer term. Clinicians who go beyond standard treatment protocols of about 10 sessions over a 6-month period are unlikely to bring about greater improvement. Poor outcomes over the long term are related to greater complexity and severity of presenting problems at the time of referral, failure to complete treatment irrespective of modality and the amount of interim treatment during the follow-up period. The relative gains of CBT are greater in anxiety disorders than in psychosis. Longitudinal research designs over extended periods of time (2-5 years), with large numbers of participants (500+), are required to investigate the relative importance of patient characteristics, therapeutic alliance and therapist expertise in determining the cost-effectiveness of CBT in the longer term.

Anti-Anxiety Agents↗
PubMed2001

Identification of selective inhibitors of cyclin dependent kinase 4.

A new structural type of kinase inhibitor, containing a benzocarbazole nucleus, has been identified. Members of the series are selective for inhibition of the cyclin dependent kinase family of enzymes. Although the cdks are highly homologous, representatives of the series showed intra-cdk selectivities, especially for cdk4. SAR studies elucidated the important features of the molecules for inhibition.

Carbazoles↗
PubMed2000

Reducing therapist contact in cognitive behaviour therapy for panic disorder and agoraphobia in primary care: global measures of outcome in a randomised controlled trial.

BACKGROUND: Panic disorder, with and without agoraphobia, is a prevalent condition presenting in general practice. Psychological treatments are effective but are limited by restricted availability. Interest has grown in methods by which the efficiency and thus availability of psychological treatments can be improved, with particular emphasis on reduced therapist contact formats. AIM: To evaluate the relative efficacy in a primary care setting of a cognitive behaviour therapy (CBT) delivered at three levels of therapist contact: standard contact, minimum contact, and bibliotherapy. METHOD: A total of 104 patients were randomly allocated to receive standard therapist contact, minimum therapist contact or bibliotherapy, with 91 patients completing treatment. All patients received an identical treatment manual and were seen by the same psychologist therapist. Outcome was reported in terms of brief global ratings of severity of illness, change in symptoms, and levels of social disruption. These brief measures were chosen to be suitable for use in general practice and were used at treatment entry and endpoint. RESULTS: The standard therapist contact group had the strongest and most comprehensive treatment response, showing significant differences from the bibliotherapy group on all, and the minimum therapist contact group on some, endpoint measures. Some reduction in efficacy was therefore found for the reduced therapist contact groups. CONCLUSION: The standard therapist contact group showed the greatest treatment efficacy in the present study. As it was of notably shorter duration than many other current formulations of CBT, it represents a useful and efficient treatment for panic disorder and agoraphobia in primary care.

Adolescent↗
PubMed1999

Analysis of site-specific phosphorylation of the retinoblastoma protein during cell cycle progression.

Differential phosphorylation of the retinoblastoma protein plays a pivotal role in cell cycle regulation. The retinoblastoma protein is specifically phosphorylated during the cell cycle by cyclin-dependent kinase complexes which intersect with many cellular signaling networks. Since the loss of the retinoblastoma signaling pathways occurs in a wide variety of human tumors, understanding the significance of site-specific phosphorylation can clarify the role of selected cyclin-dependent kinase complexes during cell cycle progression. Here we describe the phosphospecificity and cellular characterization of a panel of polyclonal antibodies that recognize unique phosphorylation sites within the retinoblastoma protein. These reagents were used to validate authentic cellular retinoblastoma phosphorylation sites at amino acids 780, 795, and 807/811 correlating with the G1-S transition.

Animals↗
PubMed1997

Treatment-outcome research in panic disorder: dilemmas in reconciling the demands of pharmacological and psychological methodologies.

Panic disorder with or without agoraphobia has been the subject of sustained treatment-outcome research. Studies have been conducted by both pharmacologically- and psychologically-oriented researchers each employing their own methodologies. Problems arise in attempting to reconcile the demands of these two treatment-outcome methodologies, whilst at the same time ensuring that research designs reflect the reality of wider clinical practice. In the following discussion a series of studies comparing pharmacological and psychological treatments for panic disorder and agoraphobia are reviewed. The review highlights areas where the competing demands of research design and clinical applicability lead to dilemmas for the researcher. Attempts to overcome such dilemmas are described and alternative solutions discussed.

Anti-Anxiety Agents↗
PubMed1997

Global measures of outcome in a controlled comparison of pharmacological and psychological treatment of panic disorder and agoraphobia in primary care.

BACKGROUND: Panic disorder, with and without agoraphobia, is a prevalent condition which presents primarily in general practice. Previous clinical outcome studies have been conducted mainly in specialist university departments or hospital settings, and have tended to employ complex rating scales that are not well suited for use as outcome measures in primary care. AIM: To evaluate the outcome, in a primary care setting, of fluvoxamine versus cognitive behaviour therapy, each used alone and in combination in a double-blind placebo-controlled framework, balanced for therapist contact. METHOD: A total of 149 patients satisfying DSMIII-R criteria for panic disorder were randomly allocated to receive one of the following: fluvoxamine, placebo, fluvoxamine plus cognitive behaviour therapy, placebo plus cognitive behaviour therapy, and cognitive behaviour therapy alone. These five treatment groups represent the minimum number acceptable for such a comparison to be made. All patients received an identical schedule of contact over 13 weeks. Measures of symptom severity, general health and social disruption were taken at entry point and end point; measures of change in symptoms were taken at end point only. Outcome was reported in terms of brief global ratings of severity of illness and change in symptoms, and of ratings of general health and social disruption that are suitable for use in general practice. RESULTS: All active treatment groups showed statistically significant advantages over placebo over a range of outcome ratings. The groups employing cognitive behaviour therapy showed the most robust and consistent response. CONCLUSION: The brief global measures reported here proved adequate to the task of assessing treatment outcome. Results indicate that treatments including cognitive behaviour therapy can be effective in the treatment of panic disorder and agoraphobia in primary care.

Adolescent↗
PubMed1994

Controlled comparison of the characteristics of patients with panic disorder.

BACKGROUND: Increased general practice attendance rates have been associated with the diagnosis of mental illness but panic disorder has not been specifically investigated in this respect. In addition, studies have failed adequately to assess type and frequency of secondary care referral and patterns of psychotropic prescription in patients with panic disorder in relation to matched controls. AIM: This study set out to compare subjects with panic disorder with age and sex matched controls on measures of general practice consultation rate; psychotropic and non-psychotropic drug use; referral to secondary care, laboratory and radiological tests and hospital admissions; history of illness and complaints; and psychiatric comorbidity. METHOD: The study was carried out in nine practices in the Forth Valley area. One hundred patients with panic disorder, previously diagnosed using DSM III-R criteria, were identified and matched by age and sex with controls. Data were collected by review of general practice case notes. RESULTS: Subjects with panic disorder had significantly higher rates of general practice consultation over the 10 year period prior to DSM III-R diagnosis of panic disorder than controls. Subjects with panic disorder had also been prescribed a significantly greater number of psychotropic and non-psychotropic medications over this period, had had more secondary care investigations and had higher rates of mainly minor illness and related complaints than controls. High comorbidity of panic disorder with depression which had been diagnosed over the 10 year period prior to DSM III-R diagnosis of panic disorder was found. CONCLUSION: The results of this study describe a population of subjects with panic disorder who are long-term heavy users of primary care services. The results also suggest an association between panic disorder and both minor illness and psychiatric comorbidity over the 10 year period prior to DSM III-R diagnosis of panic disorder.

Adult↗
PubMed1992

Linkage analysis in X-linked congenital stationary night blindness.

X-linked congenital stationary night blindness (XL-CSNB) is a nonprogressive disorder of the retina, characterized by night blindness, reduced visual acuity, and myopia. Previous studies have localized the CSNB1 locus to the region between OTC and TIMP on the short arm of the X chromosome. We have carried out linkage studies in three XL-CSNB families that could not be classified as either complete or incomplete CSNB on the criteria suggested by Miyake et al. (1986. Arch. Ophthalmol. 104: 1013-1020). We used markers for the DXS538, DMD, OTC, MAOA, DXS426, and TIMP loci. Two-point analyses show that there is close linkage between CSNB and MAOA (theta max = 0.05, Zmax = 3.39), DXS426 (theta max = 0.06, Zmax = 2.42), and TIMP (theta max = 0.07, Zmax = 2.04). Two multiply informative crossovers are consistent with CSNB lying proximal to MAOA and distal to DXS426, respectively. Multipoint analysis supports this localization, giving the most likely order as DMD-17 cM-MAOA-7.5 cM-CSNB-7.5 cM-DXS426/TIMP-cen, and thus refines the localization of CSNB.

Female↗
PubMed1987

Retinal dysfunction in central serous retinopathy.

Patients with acute and chronic central serous retinopathy (CSR) were studied by psychophysical and photochemical means to establish the extent of visual depression and to investigate the basis of rod dysfunction in this disorder. In acute disease with serous detachment of the retina, the loss of sensitivity attains 3 log units and parallels the height of retinal elevation as does its recovery with resolution of the episode. Immediately after resolution, there is a residual 0.5 log unit threshold elevation. In chronic disease, marked loss of function exists over areas of abnormal retinal pigment epithelium in the absence of clinically detectable serous detachment. Although rhodopsin levels are low in both acute and chronic CSR, this relative lack of visual pigment does not totally account for the functional deficits in either situation.

Fluorescein Angiography↗
PubMed1979

Stimulation by cyclic GMP of sodium efflux in barnacle muscle fibres.

1. The ouabain-insensitive Na efflux in barnacle muscle fibres is promptly stimulated by injection of cyclic GMP. The minimal effective injected concentration is found to be about 10(-7) M. This effect of cyclic GMP could not be mimicked by injecting 5'-GMP. 2. External application of ouabain (10(-4) M) to fibres not pretreated with ouabain during the stimulatory response to cyclic GMP causes some inhibition of the Na efflux indicating that cyclic GMP does not cause appreciable inhibition of the Na:K pump. 3. The magnitude of the stimulatory response to injected cyclic GMP depends on the external Ca2+ concentration, as well as pHe but not on the Na+, K+ or Mg2+ concentration. It also depends on pHi, since acidification of HCO3-containing ASW leads to a greater enhancement of the response to cyclic GMP than is observed with acidified HERPES-ASW. 4. Stabilization of myoplasmic pCa by injecting 100 mM-EGTA before or after cyclic GMP fails to alter the magnitude of the response to the nucleotide. Enrichment of the fibre with Mg2+ at the time of injection of cyclic GMP leads to a reduced response. No change in response, however, is seen when the internal free Mg concentration is suddenly reduced by injecting 0.05 M-pyrophosphate with cyclic GMP. 5. Injection of cyclic GMP-dependent protein kinase stimulatory modulator before cyclic GMP fails to enhance the response to the nucleotide. The same is true of the phosphodiesterase inhibitor protein. However pre-injection of 10(-2) M-papaverine enhances the response to a subsequent injection of 10(-3) M-cyclic GMP. 6. Injection of pure protein kinase inhibitor (1.6 x 10(-4) M) before 10(-3) M-cyclic GMP reduces the response to the nucleotide. 7. The argument is put forward that injected cyclic GMP stimulates the ouabain-insensitive Na efflux mainly by activating cyclic AMP-protein kinase rather than cyclic GMP-proton kinase.

Animals↗
PubMed1967

Safety in the home.

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Accident Prevention↗