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Biomedical subjects

David Baldwin

Publications and source records attributed to David Baldwin.

At least 19 recordsLinked to original sources
PubMed2006

Generalised anxiety disorder.

Generalised anxiety disorder is a persistent and common disorder, in which the patient has unfocused worry and anxiety that is not connected to recent stressful events, although it can be aggravated by certain situations. This disorder is twice as common in women than it is in men. Generalised anxiety disorder is characterised by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. These symptoms are recognised as part of the anxiety syndrome rather than independent complaints. The symptoms overlap greatly with those of other common mental disorders and we could regard the disorder as part of a spectrum of mood and related disorders rather than an independent disorder. Generalised anxiety disorder has a relapsing course, and intervention rarely results in complete resolution of symptoms, but in the short term and medium term, effective treatments include psychological therapies, such as cognitive behavioural therapy; self-help approaches based on cognitive behavioural therapy principles; and pharmacological treatments, mainly selective serotonin reuptake inhibitors.

Anti-Anxiety Agents↗
PubMed2006

Measuring the success of transbronchial needle aspiration in everyday clinical practice.

BACKGROUND: Trans-bronchial needle aspiration (TBNA) is a simple, safe technique that can be performed without additional resources in any centre with a bronchoscopy service. It provides rapid diagnostic information in malignant and benign conditions and staging information in non-small cell lung cancer (NSCLC) and may avoid the delays, risks, in-patient stay and financial implications associated with surgical exploration of the mediastinum. Despite this, centres have been slow to adopt the technique. This may be due to the lack of clarity about the clinical success of TBNA in everyday clinical practice and the absence of a single valid measurement of clinical utility for TBNA against which to audit. METHODS: We undertook a retrospective analysis of all TBNA carried out at Nottingham City Hospital since the service began. "Success" was carefully and strictly defined. The influences of various factors on the likelihood of a successful outcome were analysed. RESULTS: Fifty percent (71/142) of patients undergoing TBNA received an exact histological diagnosis whilst in 72% (97/134) of patients in whom a final diagnosis was made, TBNA results correctly predicted malignant versus benign conditions. We defined the former, more stringent, outcome measure as "success--exact". This outcome was not significantly affected by patient age or gender, lesion size or position, experience of the bronchoscopist or number of aspiration attempts. Final diagnosis strongly influenced "success--exact" with NSCLC 6.5 times and small cell lung cancer 28.5 times more likely to yield a diagnostic sample than benign conditions. CONCLUSIONS: TBNA should be used as a standard first line invasive investigation for diagnosis of mediastinal lymphadenopathy or submucosal endobronchial disease. The stringent outcome defined in this study as "success--exact" is simple for clinicians and patients to understand and would be a useful definition to standardise audit and future research.

Age Factors↗
PubMed2006

Treatment of posttraumatic stress disorder with venlafaxine extended release: a 6-month randomized controlled trial.

CONTEXT: No large-scale posttraumatic stress disorder drug trials have been conducted to evaluate treatment effects beyond 12 weeks outside of those with selective serotonin reuptake inhibitors. OBJECTIVE: To evaluate the efficacy of venlafaxine extended release (ER), a serotonin norepinephrine reuptake inhibitor, in posttraumatic stress disorder. DESIGN: 6-month, double-blind, placebo-controlled trial. SETTING: International study at 56 sites. Patients Adult outpatients (N = 329) with a primary diagnosis of posttraumatic stress disorder as defined in the DSM-IV, symptoms for 6 months or longer, and a 17-item Clinician-Administered Posttraumatic Stress Disorder Scale score of 60 or higher. Intervention Patients randomly assigned to receive flexible doses of venlafaxine ER (37.5-300 mg/d) or placebo for 24 weeks. MAIN OUTCOME MEASURES: Primary measure was the change from baseline in the Clinician-Administered Posttraumatic Stress Disorder Scale score. Secondary measures included remission, defined as a Clinician-Administered Posttraumatic Stress Disorder Scale score of 20 or lower, and changes in symptom cluster scores, frequency of remission, and time to remission. Measures of stress vulnerability, resilience, depression, quality of life, functioning, and global illness severity were also taken. RESULTS: Mean changes from baseline in Clinician-Administered Posttraumatic Stress Disorder Scale total scores at end point were -51.7 for venlafaxine ER and -43.9 for placebo (P = .006). Improvement was significantly greater for the venlafaxine ER group than for the placebo group in cluster scores for reexperiencing (P = .008) and avoidance/numbing (P = .006), but not for hyperarousal. Remission rates were 50.9% for venlafaxine ER and 37.5% for placebo (P = .01). The venlafaxine ER group also showed significantly greater improvement at end point than the placebo group (P<.05) on all other reported outcome measures. The mean maximum daily dose of venlafaxine ER was 221.5 mg/d. Withdrawal rates were similar between groups with no significant difference in dropouts attributable to adverse events. CONCLUSION: In this study, venlafaxine ER was effective and well tolerated in short-term and continuation treatment of patients with posttraumatic stress disorder.

Adult↗
PubMed2006

Comparison of once-daily glargine insulin with twice-daily NPH/regular insulin for control of hyperglycemia in inpatients after cardiovascular surgery.

BACKGROUND: Traditionally hyperglycemia in surgical inpatients has been managed with six-hourly sliding-scale regular insulin. However, this approach is usually ineffective in preventing hyperglycemia since no basal insulin is provided. We compared glycemic control using NPH and regular insulin versus glargine insulin alone in patients after cardiovascular surgery on a general surgical ward. METHODS: Ninety-four hyperglycemic patients were randomized to subcutaneous insulin using twice-daily NPH/regular or once-daily glargine if they required at least 1 unit/h of intravenous insulin at the time of transfer from the ICU. NPH/regular was adjusted twice daily; glargine was adjusted once daily. Blood glucose was measured four times daily and targeted to 80-140 mg/dL. RESULTS: The mean blood glucose after NPH/regular (124 mg/dL) and glargine (131 mg/dL) was similar (P = 0.065). In the subgroup of patients with a history of diabetes, mean blood glucose was significantly lower after NPH/regular (133 mg/dL) versus glargine (154 mg/dL) (P = 0.016). Blood glucose less than 60 mg/dL was significantly less common after glargine (0.5%) as compared with NPH/regular (2%) (P = 0.036). CONCLUSIONS: Once-daily glargine insulin provides good glycemic control in hyperglycemic patients after cardiovascular surgery. Although twice-daily NPH/regular insulin provided better control than glargine insulin monotherapy, the simplicity and safety of glargine insulin make it an attractive option for the management of postoperative hyperglycemia. Patients with established diabetes will achieve better glucose control with NPH/regular insulin as compared with glargine but have a higher incidence of hypoglycemia.

Adult↗
PubMed2006

Cost-effectiveness and cost-utility of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine: randomised controlled trial.

BACKGROUND: The cost-effectiveness of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) has not been compared in a prospective study in primary care. AIMS: To determine the relative cost-effectiveness of TCAs, SSRIs and lofepramine in UK primary care. METHOD: An open-label, three-arm randomised trial with a preference arm. Practitioners referred 327 patients with incident depression. RESULTS: No significant differences were found in effectiveness or cost-effectiveness. The numbers of depression-free weeks over 12 months (on the Hospital Anxiety and Depression Scale) were 25.3 (95% CI 21.3-29.0) for TCAs, 28.3 (95% CI 24.3-32.2) for SSRIs and 24.6 (95% CI 20.6-28.9) for lofepramine. Mean health service costs per patient were pound 762 (95% CI 553-1059) for TCAs, pound 875 (95% CI 675-1355) for SSRIs and pound 867 (95% CI 634-1521) for lofepramine. Cost-effectiveness acceptability curves suggested SSRIs were most cost-effective (with a probability of up to 0.6). CONCLUSIONS: The findings support a policy of recommending SSRIs as first-choice antidepressants in primary care.

Adolescent↗
PubMed2005

Rosiglitazone therapy of posttransplant diabetes mellitus.

BACKGROUND: The new onset of posttransplant diabetes mellitus (PTDM) is a common problem after solid organ transplantation. Because insulin resistance plays a significant role in the development of PTDM, we treated 40 consecutive patients with PTDM after liver and kidney transplantation with the insulin sensitizer rosiglitazone (ROSI). METHODS: Thirty-three of 40 patients with PTDM were initially stabilized with twice-daily NPH and regular insulin. All patients subsequently began ROSI 4 mg per day. Patients were followed for a mean of 26 weeks and insulin was adjusted using home blood glucose data and hemoglobin A1C (HBA1C). RESULTS: During 12 months of study, 32/107 liver transplant patients (30%) and 8/205 kidney transplant patients (4%) patients developed PTDM. After 3-4 months of insulin and ROSI therapy, insulin was able to be discontinued in 30/33 (91%) patients with PTDM. In all, 12/40 (30%) patients maintained normal HBA1C levels (5.6+/-0.8%) with ROSI monotherapy, whereas 25/40 (63%) required ROSI and a sulfonylurea to meet this goal. Three of 40 (7.5%) had persistent insulin dependence. 25/40 (63%) continued on 4 mg/day of ROSI, and 15/40 (37%) required an increase to 8 mg/day. Mild edema developed in 13% of patients; significant weight gain did not occur. CONCLUSIONS: Rosiglitazone is the first highly effective oral agent for PTDM. The majority of patients with PTDM may be safely treated with ROSI +/- a sulfonylurea. After the expected 3-6 week delay in the onset of ROSI action, most patients with PTDM will no longer require long-term insulin therapy.

Adult↗
PubMed2005

Resolution of sexual dysfunction during double-blind treatment of major depression with reboxetine or paroxetine.

The selective noradrenaline re-uptake inhibitor reboxetine may have advantages over the selective serotonin re-uptake inhibitors fluoxetine and citalopram, in effects on sexual function and satisfaction. The effects of reboxetine and paroxetine on sexual function were compared by examining data from the UK centres in an international double-blind flexible-dose parallel-group multi-centre randomized controlled trial of acute treatment of patients with DSM-IV major depression. Patients were randomly assigned to receive reboxetine (4 mg b.d.) or paroxetine (20 mg mane) using a double-dummy technique to preserve the blind. The dosage could be increased at day 28 (to reboxetine 4 mg mane, 6 mg nocte; or paroxetine 20 mg b.d.). Antidepressant efficacy was assessed by the 21-item Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impression Scale for Severity (CGI-S) at all study visits, and the Clinical Global Impression of Improvement (CGI-I) at each visit after randomization. Sexual function and satisfaction was assessed by visual analogue scale (VAS) items of the Rush Sexual Inventory completed at baseline and days 28 and 56. There were no significant differences between groups in demographic or clinical features at baseline. There was a gradual reduction in severity of depressive symptoms (reboxetine, 14.3; paroxetine, 12.0: observed case analysis), with no significant differences between groups. There were significant differences (p 0.05), with advantages for reboxetine, at Week 4 and Week 8 on the VAS item assessing ability to become sexually excited, and non-significant trends with advantages for reboxetine, in frequency of sexual thoughts at Week 4 (p 0.05) and Week 8 (p 0.08); and in desire to initiate sexual activity at Week 4 (p 0.09). Exclusion of patients who had ever experienced sexual dysfunction with any medication prior to participation in this study (n 10) reduced the statistical significance of the findings, although there were still numerical advantages for reboxetine. Sexual function and satisfaction in depressed patients improves during double-blind acute treatment with reboxetine or paroxetine, but this improvement is greater and more rapid with reboxetine.

Adult↗
PubMed2005

Heparanase-1 gene expression and regulation by high glucose in renal epithelial cells: a potential role in the pathogenesis of proteinuria in diabetic patients.

The molecular mechanisms of heparan sulfate proteoglycan downregulation in the glomerular basement membrane (GBM) of the kidneys with diabetic nephropathy remain controversial. In the present study, we showed that the expression of heparanase-1 (HPR1), a heparan sulfate-degrading endoglycosidase, was upregulated in the renal epithelial cells in the kidney with diabetic nephropathy. Urinary HPR1 levels were elevated in patients with diabetic nephropathy. In vitro cell culture studies revealed that HPR1 promoter-driven luciferase reporter gene expression, HPR1 mRNA, and protein were upregulated in renal epithelial cells under high glucose conditions. Induction of HPR1 expression by high glucose led to decreased cell surface heparan sulfate expression. HPR1 inhibitors were able to restore cell surface heparan sulfate expression. Functional analysis revealed that renal epithelial cells grown under high glucose conditions resulted in an increase of basement membrane permeability to albumin. Our studies suggest that loss of heparan sulfate in the GBM with diabetic nephropathy is attributable to accelerated heparan sulfate degradation by increased HPR1 expression.

Autopsy↗
PubMed2005

Eliminating inpatient sliding-scale insulin: a reeducation project with medical house staff.

OBJECTIVE: We studied a systematic program to reeducate our medical house officers on how to manage inpatient hyperglycemia without the use of sliding-scale insulin (SSI). RESEARCH DESIGN AND METHODS: Patients admitted to the general medical service with diabetes or a blood glucose >140 mg/dl were included. HbA(1c) was measured in all patients, and therapy was modified if the HbA(1c) was >7.0%. For each 24 h on call, two house officers were responsible for all glucose management for their team's patients and rounded with a teaching endocrinologist twice daily for 2 weeks. Oral agent or insulin therapy was modified using blood glucoses and HbA(1c). All patients who required insulin therapy were treated with basal and bolus insulin, usually NPH and regular, adjusted twice daily. RESULTS: During 8 weeks, 88 patients were identified and 16 house officers were instructed. The mean duration of diabetes was 10.4 years. Mean HbA(1c) level was 8.7%, and 48% of patients had HbA(1c) >8%. All patients with HbA(1c) >7% had diabetes therapy intensified. Overall 80% had their diabetes therapy changed by discharge. Compared with 98 historical control subjects, significantly fewer study patients had episodes of hyperglycemia, and a subgroup followed for 12 months showed a decrease in HbA(1c) from 10.1 to 8%. CONCLUSIONS: Medical history, blood glucose, and HbA(1c) testing can effectively identify patients with inpatient hyperglycemia. Using direct ward-based teaching and a widely disseminated pocket set of guidelines, house officers can be taught to effectively and safely manage inpatient hyperglycemia without the use of SSI.

Adult↗
PubMed2004

Rosiglitazone treatment of diabetes mellitus after solid organ transplantation.

BACKGROUND: Diabetes mellitus is a common clinical problem after solid organ transplantation. Whether patients have preexisting diabetes or develop posttransplant diabetes, insulin therapy is usually required. Achieving excellent diabetic control is an important target in reducing the incidence of cardiovascular disease after transplantation. METHODS: The authors treated 18 patients with type 2 diabetes after transplantation with rosiglitazone. Eleven patients had preexisting type 2 diabetes and seven patients developed posttransplant diabetes. Rosiglitazone was added to insulin or glyburide to improve elevated hemoglobin Hb A1C levels in patients with preexisting diabetes or was used to try to avoid insulin therapy in posttransplant diabetics. Blood levels of cyclosporine, tacrolimus, creatinine, and HbA1C were followed for a mean of 381 days (range, 133-718 days). RESULTS: The addition of rosiglitazone did not cause any significant changes in serum creatinine, cyclosporine, or tacrolimus. There were no significant changes in cyclosporine or tacrolimus doses. Mean HbA1C improved from 8.1+/-1.5% to 6.9+/-1.3% (P =0.01) in the 18 patients and from 8.6+/-1.5% to 6.7+/-0.5% (P =0.035) in the 7 patients with posttransplant diabetes. All patients with posttransplant diabetes were well controlled without insulin therapy. CONCLUSIONS: Rosiglitazone is a safe and effective oral agent for the treatment of diabetes mellitus after solid organ transplantation. It is the first agent to allow successful oral therapy for patients with posttransplant diabetes, and is a well-tolerated alternative to insulin for these patients.

Adult↗
PubMed2004

Pioglitazone in the management of diabetes mellitus after transplantation.

Type 2 diabetes mellitus is a common problem in patients after solid organ transplantation. We studied the safety and efficacy of pioglitazone therapy in this setting. Ten patients with diabetes mellitus treated with insulin or glyburide after transplantation were studied after the addition of the thiazolidinedione pioglitazone. Serum creatinine, HBA1C, total daily insulin dose, tacrolimus dose, tacrolimus level and prednisone dose were followed for a mean of 242 days and compared to the corresponding values measured before the initiation of pioglitazone. The addition of pioglitazone caused no significant changes in serum creatinine or mean tacrolimus dose, and caused decreases in HBA1C (8.36%+/- 1.5% pre-pioglitazone, 7.08%+/- 1.5% post-pioglitazone, p = 0.018) and total daily insulin dose (125.1 +/- 28.1 units pre-pioglitazone, 80.6 +/- 22.8 units post-pioglitazone, p = 0.002). Our preliminary study suggests that pioglitazone is a safe and effective oral agent for the management of diabetes mellitus after transplantation.

Adult↗
PubMed2003

Failure to find DUP25 in patients with anxiety disorders, in control individuals, or in previously reported positive control cell lines.

Investigation of the co-occurrence of panic and phobic disorders with joint laxity led to the identification of various forms of interstitial duplications involving human chromosome 15q24-q26 (named "DUP25") in a Spanish population. DUP25 was observed in 68 of 70 (97%) patients assigned the diagnosis panic disorder/agoraphobia. DUP25 was also found in 14 of 189 (7%) control individuals. In the present study, we replicated the experimental conditions described by Gratacòs and colleagues in which fluorescence in situ hybridization was used to examine metaphase chromosomes of patients with panic disorder/social phobia and of control individuals from a southern region of the United Kingdom, the primary aim being to determine the prevalence of this chromosomal rearrangement in a geographically and ethnically distinct population. DUP25 was not observed in any of our 16 patients or 40 control samples or in three previously reported DUP25-positive control (Centre d'Etude du Polymorphisme Humain) cell lines, indicating a highly significant difference in the frequency of DUP25 between the study by Gratacòs and colleagues and the present investigation.

Adult↗
PubMed2003

Placebo-controlled studies in depression: necessary, ethical and feasible.

Placebo-controlled trials are used widely in the development of new pharmacological treatments. They have sometimes been challenged as being unethical, in clinical situations where patients can receive an existing effective and acceptable treatment. It has been argued that studies of potential antidepressants should employ only a comparator-controlled design, whereby new compounds have to be found at least as efficacious as existing treatments. By contrast, others have argued that sole use of comparator-controlled trials is itself unethical, as more patients will be exposed to potentially unhelpful treatments. This article reviews the rationale for conducting placebo-controlled treatment studies in depressed patients, examines the underlying ethical issues, and describes the provisions that should be applied when investigating the efficacy and tolerability of potentially valuable new antidepressant treatments. Placebo-controlled studies of new antidepressants are justified, both scientifically and ethically; restrictions on placebo-controlled investigations will hinder the arrival of more efficacious and better tolerated antidepressants.

Antidepressive Agents↗
PubMed2003

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders, Part II: Treatment of Mania.

Identical to the preceding guidelines of this series, these practice guidelines for the biological, mainly pharmacological treatment of acute bipolar mania were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was finally not only graded, but has also been commented by the experts of the task force to ensure practicability. Key words: bipolar disorder, mania, acute treatment, evidence-based guidelines, pharmacotherapy, antipsychotics, mood stabiliser, electroconvulsive therapy.

Algorithms↗
PubMed2002

Defective proboscis extension response (DPR), a member of the Ig superfamily required for the gustatory response to salt.

Gustatory stimuli, such as sugar, induce a behavioral response in Drosophila that involves extension of the proboscis and consumption of the sugar-containing solution. Addition of salt to the sugar solution inhibits this behavioral response. However, the mechanisms and gene products involved in the salt aversion response have not been described. Here, we report the identification of a locus, defective proboscis extension response (dpr), that is required for salt aversion. dpr was expressed in a subset of primary neurons in the gustatory organs and encoded a protein with two Ig-like domains, a single putative transmembrane domain, and a short region C terminal to the transmembrane segment. In addition, DPR defines a large previously unknown group of > or =20 highly related Ig-containing proteins.

Animals↗
PubMed2002

The economic consequences of social phobia.

Background. Social phobia has been under-recognised and under-treated in many countries. Little is known about its economic impact. This study aimed to identify the economic consequences of social phobia for individuals, health services and wider society. Methods. Secondary analysis of 1993-1994 Psychiatric Morbidity Survey data compared 63 people with social phobia and 8501 people without psychiatric morbidity. Results. People with social phobia were less likely to be in the highest socio-economic group and had lower employment rates and household income compared to those with no psychiatric morbidity. They also had higher levels of drug dependency and use of prescribed oral medications. Although there were no differences in total health care costs, costs of GP contacts were significantly higher. Individuals with a comorbid psychiatric disorder made higher use of some health services than those without a comorbidity. Limitations. Analyses were performed post hoc on data collected for other purposes. The defining questions for social phobia have not been studied much before. The number of identified subjects is small and thus raises the possibility of type II errors. Larger numbers may have revealed even more differences from the psychiatrically well population. Data on treatment patterns of the psychiatrically well population were limited because the surveys focused on subjects with psychiatric morbidity. Conclusions. The burden of social phobia on individuals, health services and the wider society could be reduced through improved rates of detection and appropriate treatment.

Adolescent↗