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Biomedical subjects

T Sivakumaran

Publications and source records attributed to T Sivakumaran.

16 recordsLinked to original sources
PubMed2002

How does the threshold score to enter a major depression trial influence the size of the available patient population for study?

BACKGROUND: This paper describes the relationship between entry criteria and eligible population for inclusion in Major Depression (MD) clinical trials. Inclusion criteria for a MD study typically require patients to pass a threshold score on a depression rating scale, most commonly the HAM-D or MADRS. A Score To Enter (STE) of > or = 17 on the HAM-D 17-item scale is a typical value, although higher values (i.e. > or = 22 or even > or = 25 points) are often used. It is commonly supposed that patients with higher baseline scores form a more sensitive sample for discriminating active drug from placebo. METHOD: We present data from a sample of depressed hospital outpatients and describe their general characteristics. We then introduce a model, based upon this sample, which predicts the impact of STE on eligible trial population. RESULTS AND CONCLUSION: A small increase in STE has a marked effect on eligible population: an increase in HAM-D (17 item) STE from 17 to 21 and 25 reduces the eligible population by 42 and 76%, respectively. These predictions are reasonably robust when our model is validated with known clinical trial data. CLINICAL RELEVANCE: Our findings have major implications for planning and managing Major Depression trials as higher STEs substantially restrict the proportion of patient eligible for study.

Adolescent↗
PubMed2002

Defining remission by cut off score on the MADRS: selecting the optimal value.

BACKGROUND: Remission from major depression may be conceptualised in terms of a cut-off score on an appropriate rating scale. Candidate values proposed hitherto have not been directly validated. METHOD: The relationship between The Clinical Global Impression Scale for Severity (CGI-S) and the Montgomery-Asberg Depression Rating Scale (MADRS) was explored in 684 major depressed patients (1114 observations). The value on the MADRS which had greatest concordance with remission, as defined by the CGI-S, was computed using two models. Concordance between clinician and patient judgements of global illness were also compared. RESULTS AND CONCLUSION: The two models yielded optimal definitions of remission of <9 and <10 on the MADRS. Either value offers a workable operationalisation of remission and there is little to choose between them. CLINICAL RELEVANCE: The data confirm that MADRS <10 should provide the clinician with a valid, and reasonably objectifiable, target for remission

Adult↗
PubMed2000

Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. Hertfordshire Neuroscience Research Group.

Several case reports have engendered concern about the safety of coadministering lithium and selective serotonin reuptake inhibitor (SSRI) antidepressants and there are theoretical reasons to suppose that lithium and serotonergic antidepressants may be associated with dangerous interactions. Systematic reports regarding combination therapy with lithium and SSRI antidepressants were assimilated for the purpose of this review. Although there are many publications, few are directly informative as to safety and tolerability. A total of 503 patients are considered in systematic reports and, among these, no serious or life-threatening adverse events can be identified. Such data as there are demonstrate little potential for toxic interactions between lithium and SSRIs, although new, non-serious, adverse events do frequently arise. The evidence for the efficacy of addition of lithium to SSRIs in treatment refractory depression is only provisional.

Antimanic Agents↗
PubMed1998

A protocol for the pharmacologic treatment of major depression. A field test of a potential prototype.

BACKGROUND: Much attention is being given to developing clinical practice guidelines for management of mental health disorders. The aim of this study was to field test a prototype protocol for the pharmacologic treatment of Major Depression. METHOD: The protocol consisted of four, six week, treatment phases with critical choices in therapy defined by scores on the MADRS (Montgomery Asberg Depression Rating Scale). Observational data as collected on the behaviour of the protocol in terms of relevance, acceptability, ease of use and effectiveness. RESULTS: Effectiveness of the protocol was good for those patients who were retained within it, with three quarters of them attaining remission. However more than half of all patients dropped out-non attendance and adverse events being the most common reasons for this. CONCLUSION: The protocol for the treatment of Major Depression appeared relevant, easy to use and potentially effective. LIMITATION: Problems with non-adherence by both doctors and patients posed major challenges to the protocol's design. Such difficulties demonstrate the need to field test any proposed design as preconceptions about a protocol's performance may be misplaced. CLINICAL RELEVANCE: The protocol tested represents progress towards the goal of developing optimal strategies for the use of pharmacotherapeutic agents in the treatment of depression.

Adolescent↗
PubMed1997

A preliminary study to examine the adequacy of long-term treatment of depression and the extent of recovery in general practice.

About 1% of patients in general practice take antidepressants for long periods. Many receive repeat prescriptions, without review. It might be assumed that these patients are well and are on adequate maintenance treatment. Our findings refute this assumption; of 78 patients on long-term repeats, only a third were in remission and a fifth had Beck Depression Inventory scores suggesting persisting syndromal major depression. Subtherapeutic dosing of classic tricyclics was the norm rather than the exception. Patients on long term antidepressant treatment need regular review and adequate treatment to ensure remission is maintained.

Adult↗
PubMed1986

Studies of intestinal permeability in inflammatory diseases using polyethylene glycol 400.

It has been proposed that increased bowel permeability might play a role in the pathogenesis of inflammatory disease. Intestinal permeation was investigated by measuring the 6-hour urinary excretion of polyethylene glycol (PEG) 400 in 40 adult volunteer controls and in patients with inflammatory disease. Of the patients, 15 had Crohn's disease; 7, ulcerative colitis; 2, celiac disease; and 7, rheumatoid arthritis. No significant difference in total urinary excretion over a 6-hour period was found between controls and patients with ulcerative colitis. Patients with Crohn's disease, celiac disease, or with rheumatoid arthritis were found to have significantly decreased urinary excretion of PEG 400. The results of this study indicate that there is no identifiable increase in intestinal permeation as measured by PEG 400 excretion during periods of active inflammatory disease.

Adult↗
PubMed1986

The effect of temperature and pH on the stability of human pepsin in stored gastric juice. A method to prevent activity loss.

The mechanisms controlling pepsin secretion are controversial. A contributory factor may be storage-dependent effects. We have studied the effects of temperature, pH, and storage time on human gastric pepsin. Gastric juice samples taken from three healthy volunteers under both basal and post-pentagastrin-stimulated (6 micrograms/kg subcutaneously) conditions were separated into four aliquots. Each aliquot was titrated to pH 1, 4, or 6 or left at ambient pH. Aliquots were then stored at 4 degrees C or frozen at -70 degrees C and stored. On days 1, 3, 7, and 28 aliquots were removed and assayed by the kinetic albumin-bromphenol blue method. In a second experiment we determined the effects of different concentrations of glycerol on the preservation of peptic activity. From these experiments we conclude that pepsin is unstable when stored frozen at low pH but not when stored above pH 2. This pH-dependent stability may explain the variable conclusions other workers report on optimal methods of storing gastric juice. In addition, we have confirmed the suitability of glycerol as a preservative of peptic activity and recommend that gastric juice be stored frozen with 11.5% glycerol.

Cold Temperature↗
PubMed1982

Beclomethasone dipropionate enemas for treating inflammatory bowel disease without producing Cushing's syndrome or hypothalamic pituitary adrenal suppression.

Since beclomethasone dipropionate (BDP) is a very potent glucocorticoid and since small oral doses (1 mg) seem to be metabolised (possibly in the gut wall or liver) before they reach the systemic circulation, a study was conducted to find out whether patients with inflammatory bowel disease could be treated with enemas containing small doses of BDP without their acquiring Cushing's syndrome or hypothalamic pituitary adrenal (HPA) suppression. The BDP in the 100 ml enemas used was stable and present in a concentration likely to be therapeutic (0.5 mg/dl). Single overnight BDP enemas, unlike conventional betamethasone (5 mg) enemas, did not interfere with the HPA axis in 6 healthy volunteers. In the double-blind randomised part of the study 2-week courses of BDP or betamethasone enemas were assessed in 9 patients having exacerbations of distal inflammatory bowel disease. The clinical and sigmoidoscopic responses as well as adrenocortical function (judged by the 'Cosyntropin' test) were evaluated on the morning after the last day of a course of enemas. Both types of enemas had similar beneficial effects, but only BDP enemas did not interfere with HPA function. Over a prolonged period, a patient with distal ulcerative colitis had been completely dependent on regular treatment with betamethasone enemas to control his symptoms. Substitution with BDP enemas successfully controlled his bowel symptoms, whilst his cushingoid features and HPA suppression regressed.

Adult↗
PubMed1975

Relationship between cortisol and lecithin/sphingomyelin ratios in human amniotic fluid.

Amniotic fluid was obtained from 85 women during the last trimester of gastation and analyzed for cortisol by a radioimmunoassay procedure and for lecithin/sphingomyelin (L/S) ratios by a combined thin-layer chromatography densitometer scanning technique. A total of 114 samples were examined. Cortisol values ranged from 38 to 438 ng. per milliliter; L/S ratios ranged from 0.3 to 9.2. Comparison of cortisol levels with L/S ratios by multiple regression analysis gave an "r" value of 0.371. From less than 32 weeks' gestation to 41 or 42 weeks there was an increase in cortisol levels from 139 plus or minus 124 to 290 plus or minus 78 ng. per milliliter whereas the L/S ratios increased from 1.8 plus or minus 2.3 to 3.9 plus or minus 2.0. These data indicate that there is no good correlation between cortisol and L/S ratios in the samples of amniotic fluid analyzed.

Amniotic Fluid↗