Occlusion of a tracheostomy tube after misinsertion.
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Aged, 80 and over↗
Biomedical subjects
M Trivedi
Publications and source records attributed to M Trivedi.
A response to 'Angiotensin-converting enzyme inhibitor related angioedema and the anaesthetist', Rai M R, Amen F and Idrees F, Anaesthesia 2004; 59: 283-9.
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Angioedema↗
Strengthening clinical effectiveness trials: equipoise-stratified randomization.
As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy, research studies with broader aims will become increasingly important. Randomized trials may need to accommodate multiple treatment options. In completely randomized designs, patients are assigned at random to one of the options, requiring that patients and clinicians find each of the options acceptable. In "clinician's choice" designs, patients are randomized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician. The clinician's choice design permits some scope to patient and clinician preferences, but sacrifices the ability to make randomization-based comparisons of specific options. We describe a new approach, which we call the "equipoise stratified" design, that merges the advantages and avoids the disadvantages of the other two designs for clinical trials. The three designs are contrasted, using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example.
Antidepressive Agents↗
Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis.
Caspases are key mediators of apoptosis. Using a novel expression cloning strategy we recently developed to identify cDNAs encoding caspase substrates, we isolated the intermediate filament protein vimentin as a caspase substrate. Vimentin is preferentially cleaved by multiple caspases at distinct sites in vitro, including Asp85 by caspases-3 and -7 and Asp259 by caspase-6, to yield multiple proteolytic fragments. Vimentin is rapidly proteolyzed by multiple caspases into similar sized fragments during apoptosis induced by many stimuli. Caspase cleavage of vimentin disrupts its cytoplasmic network of intermediate filaments and coincides temporally with nuclear fragmentation. Moreover, caspase proteolysis of vimentin at Asp85 generates a pro-apoptotic amino-terminal fragment whose ability to induce apoptosis is dependent on caspases. Taken together, our findings suggest that caspase proteolysis of vimentin promotes apoptosis by dismantling intermediate filaments and by amplifying the cell death signal via a pro-apoptotic cleavage product.
Apoptosis↗
Intermediate outcome of medical patients after intensive care.
Medical patients suffer a high mortality after critical illness; however, the causes of mortality after intensive care management are unclear. This study's aims were to (a) explore what factors affect outcome after intensive care and (b) identify medical patients at particularly high risk of mortality. During one year, all patients admitted with a medical cause to the Critical Care Complex were enrolled. Diagnosis on admission was recorded, and whether the reason for admission was a new clinical problem or an exacerbation of existing chronic illness. All patients were followed for a minimum of one year. A total of 186 medical patients were included in the study. Fifty-four medical patients died on intensive care (28.4% mortality), a further 16 died on the general ward after intensive care unit discharge (hospital mortality 36.8%) and six following discharge home (1 year's mortality 40.9%). Of the 16 patients who died on the general ward, 12 had been admitted to the intensive care unit with a new, previously unrecognised problem rather than exacerbation of a chronic pre-existing problem. However, on the general ward, 'Do Not Resuscitate' orders were placed on seven of these 12 patients. It would appear that some of the high post intensive care hospital mortality might be due to changes in resuscitation status in patients expected to survive following intensive care unit discharge.
APACHE↗
Ornithine transcarbamylase deficiency unmasked because of gastrointestinal bleeding.
Ornithine transcarbamylase (OTC) is a mitochondrial-matrix enzyme that catalyzes conversion of ornithine and carbamyl phosphate to citrulline, the second step in the urea cycle. The urea cycle is the most important pathway to detoxification of ammonia in human beings. Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, inherited as an X-linked disorder that can cause fatal hyperammonemia in male newborns. Women with OTCD have a variable expression of their disease, the variability being determined by lyonization (random inactivation) of the X chromosome. We report a case of a 28-year-old woman who presented with hyperammonemic encephalopathy that was precipitated by a gastrointestinal bleed unmasking OTCD.
Adult↗
Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls.
The amplitude and time course of slow-wave activity (SWA) during NREM sleep were compared in 76 outpatients with depression and 55 healthy control subjects. Lower SWA amplitude was evident in the depressed group, especially among depressed men. For the most part, significant differences between patients and control subjects were restricted to the first NREM period and only in those 20-30 years of age. Significant age-related declines in SWA amplitude were evident in control subjects but not in depressed patients. In addition, sex differences in the depressed group were twice as large as those seen in control subjects. The time course of SWA amplitude, presumed to reflect homeostatic sleep regulation of SWA, was only abnormal in depressed men with lower accumulation and slower dissipation over NREM sleep. Depressed women showed no evidence of an abnormal SWA time course. Furthermore, no sex differences in the time course of SWA were evident in control subjects, and age-related changes in this aspect of regulation were not striking in any group. Thus, the amplitude of SWA showed strong age effects in healthy individuals but not in those with MDD whereas the time course showed very subtle age effects. It was suggested that men, but not women, with MDD show impaired SWA regulation that is evident from 20 to 40 years of age. These findings provide further support that the pathophysiology of depression differs for men and women and suggest that maturational effects on SWA in depression differ from those observed in healthy individuals.
Adult↗
Temporal characteristics of delta activity during NREM sleep in depressed outpatients and healthy adults: group and sex effects.
STUDY OBJECTIVES: The primary aim was to evaluate group and sex differences in delta activity across non-rapid eye movement (NREM) sleep in depressed patients and healthy controls. DESIGN: Repeated-measures ANOVA contrasted delta power, amplitude and incidence in the first three NREM periods (stages 2, 3, and 4) of sleep. The time course of delta activity was evaluated with exponential regressions. Age effects on delta were evaluated with linear regression analysis. SETTING: Two consecutive nights were spent in the laboratory, the first of which served as adaptation. PATIENTS OR PARTICIPANTS: Twenty-two (9 men, 13 women) symptomatic, but unmedicated, outpatients with major depressive disorder (MDD) and 23 healthy controls (15 men, 8 women) participated in the study. MEASUREMENTS AND RESULTS: Delta power and amplitude showed significant group by sex interactions. Men with MDD showed lower power and amplitude in NREM sleep compared to women with MDD, but did not differ significantly from controls. However, the time course of delta power and amplitude was significantly different in men with MDD, with lower accumulation and slower dissipation across NREM sleep than all other groups. Women with MDD showed no evidence of lower delta power and amplitude or an abnormal time course compared to control women or men. Age had a differential influence on delta activity between the groups, with little age-related change in delta activity in the depressed groups. CONCLUSIONS: It was concluded that slow-wave sleep deficiencies may be characteristic of men, but not women, with MDD. It was also concluded that the influence of age on delta activity varied as a function of both psychiatric status and sex.
Adolescent↗
Evaluation of newer treatment interventions for psychotic depression.
Psychotic depression is characterized by greater severity, higher rate of recurrence, greater incapacitation, more frequent hospitalization, and longer episodes than nonpsychotic depression. The use of combined tricyclic antidepressants (TCAs) and neuroleptic therapy, as well as electroconvulsive therapy, has proven effectiveness in the treatment of psychotic depression. Although it is limited, evidence for efficacy of selective serontonin reuptake inhibitors both alone and in combination with antipsychotics in psychotic depression suggests that these strategies may provide a desirable alternative to the traditional TCA- neuroleptic therapy. These treatments, in addition to the continual introduction of new psychotropic agents suggest that the prospect of future research in this area is promising.
Antidepressive Agents↗
Usefulness of a pediatric colonoscope for colonoscopy in adults.
BACKGROUND: There are few published data on how different types of colonoscopes affect success in reaching the cecum and patient comfort. We examined the feasibility of using a pediatric colonoscope for routine colonoscopy in adults and investigated whether there were subgroups of patients in whom use of this instrument was preferable. METHODS: One-hundred fifty adults undergoing outpatient colonoscopy were randomized to colonoscopy with a standard colonoscope (Olympus CF-100L) or with a pediatric colonoscope (Olympus PCF-100). All procedures were performed by a faculty endoscopist and timed by an independent observer. After examinations, the endoscopist graded procedure difficulty and patients were given a questionnaire that assessed their experience. RESULTS: The adult (n = 77) and pediatric (n = 73) colonoscope groups were comparable in all outcomes measured, including success in reaching the cecum (91% vs. 93%, p = 0.61), mean time to reach the cecum (11.4 vs. 9.7 min, p = 0.07), mean total procedure time (21.8 vs. 21.9 min, p = 0.95), mean meperidine dose (55 vs. 52 mg, p = 0.17); median midazolam dose (2.0 mg in both groups, p = 0.10), the endoscopists' perception of procedure difficulty, and patient comfort scales. Of the 7 patients in whom colonoscopy with the adult colonoscope was unsuccessful, the cecum was reached in 4 by switching to a pediatric colonoscope (all women, 3 of whom had prior hysterectomy). In the 5 patients in whom colonoscopy with the pediatric colonoscope was unsuccessful, the cecum was reached in 1 by switching to an adult colonoscope. Including the cases in which the cecum was reached by switching to the alternative colonoscope, the overall frequency of cecal intubation was 143 of 150 (95%). Subgroup analysis disclosed no difference between the 2 groups in outcomes when gender, presence of diverticulosis, and patient size were considered. Colonoscopy with the pediatric colonoscope was more successful than with the adult instrument in reaching the cecum in women with prior hysterectomy (11 of 12 [92%] vs. 15 of 21 [71%]); however, the numbers in each group were relatively small and the difference was not significant (p = 0.22). CONCLUSIONS: The pediatric colonoscope is suitable for routine colonoscopy in adults. It is also useful in patients in whom colonoscopy with the adult colonoscope is unsuccessful in reaching the cecum (particularly in women). Additional study is needed to see if the pediatric colonoscope is actually superior to the adult colonoscopy for routine colonoscopy in women with prior hysterectomy.
Adult↗
Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group.
BACKGROUND: Patients with Sjögren syndrome (SS) experience slowly progressive infiltration of lacrimal and salivary glands by mononuclear cells. This leads to diminished secretions, with resultant symptoms of xerostomia and xerophthalmia. Although pilocarpine hydrochloride tablets are currently indicated for the treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes in patients with SS are unclear. OBJECTIVE: To assess the safety and efficacy of pilocarpine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes caused by SS in a multicenter, doubleblind, placebo-controlled trial. METHODS: After providing written informed consent, 373 patients with primary or secondary SS and clinically significant dry mouth and dry eyes were randomized to receive 2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12 weeks. Symptoms were assessed by questionnaires with visual analog scales or categorical checkboxes. Whole-mouth salivary flow rates were measured. RESULTS: A significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement compared with the placebo group (P< or =.01) in global assessments of dry mouth, dry eyes, and other symptoms of dryness (P< or =.05). Salivary flow was significantly increased 2- to 3-fold (P<.001) after administration of the first dose and was maintained throughout the 12-week study. The most common adverse effect was sweating, and no serious drug-related adverse experiences were reported. CONCLUSION: Administration of 5-mg pilocarpine tablets 4 times daily (20 mg/d) was well tolerated and produced significant improvement in symptoms of dry mouth and dry eyes and other xeroses in patients with SS.
Adult↗
Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression.
The reversible inhibitors of monoamine oxidase type A (RIMAs) are a newer group of antidepressants that have had much less impact on clinical psychopharmacology than another contemporary class of medications, the selective serotonin reuptake-inhibitors (SSRIs). The RIMAs agents are distinguished from the older monoamine oxidase inhibitors (MAOIs) by their selectivity and reversibility. As a result, dietary restrictions are not required during RIMA therapy, and hypertensive crises are quite rare. In this article, we describe a series of meta-analyses of studies of the two most widely researched RIMAs, moclobemide (MOC; Aurorex) and brofaromine (BRO). Our findings confirm that both BRO and MOC are as effective as the tricyclic antidepressants, and they are better tolerated. However, BRO is not being studied at present for reasons unrelated to efficacy or side effects. MOC, which is available throughout much of the world (but not the United States), is significantly more effective than placebo and, at the least, comparable to the SSRIs in both efficacy and tolerability. For MOC, higher dosages may enhance efficacy for more severe depressions. We also found evidence that supports clinical impressions that MOC is somewhat less effective, albeit better tolerated, than older MAOIs, such as phenelzine or tranylcypromine. Little evidence has yet emerged to suggest that the RIMAs share older MAOIs' utility for treatment of depressions characterized by prominent reverse neurovegetative features. Based on available evidence, the RIMAs appear to have a limited, but useful, role in the differential therapeutics of the depressive disorders.
Benzamides↗
Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression.
The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind, placebo-substitution, continuation treatment trial. After 16 weeks of acute, single-blind treatment with nefazodone, 131 patients responding to treatment and in stable remission were randomized in a 36-week double-blind trial to either nefazodone (n = 65) or placebo (n = 66). Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy. Relapse rates were significantly lower for patients randomized to continued nefazodone treatment than for patients switched to placebo. Kaplan-Meier estimates of relapse rates 9 months (36 weeks) after the end of acute treatment were 1.8% for nefazodone versus 18.3% for placebo (P = 0.009) by the Hamilton Depression Scale and 17.3% versus 32.8% (P = 0.028) by discontinuation for lack of efficacy. The mean modal dose of nefazodone was 412 mg/day at study endpoint. These results demonstrate the clinical effectiveness of up to 1 year's treatment (16 weeks acute and 36 weeks continuation) with nefazodone in depressed patients. Long-term efficacy of nefazodone was accompanied by a good safety profile without any weight gain and with minimal symptoms of withdrawal upon abrupt discontinuation of treatment.
Adult↗
Mental health care from the public perspective: the Texas Medication Algorithm Project.
Medication treatment algorithms have been suggested as a strategy to provide uniform care at predictable costs. The Texas Medication Algorithm Project is a 3-phase study designed to provide solid data on the usefulness of medication algorithms. In phase 1, medication algorithms for the treatment of schizophrenia, major depressive disorder, and bipolar disorder were developed. Phase 2 was a feasibility study of these algorithms, and phase 3, now underway, compares the costs and outcome in 3 groups, one using a combination of an algorithm and patient/family education, a second using treatment as usual in a clinic that uses an algorithm for a different disorder, and a third using treatment as usual in a nonalgorithm clinic.
Algorithms↗
The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder.
BACKGROUND: This article describes the development of consensus medication algorithms for the treatment of patients with major depressive disorder in the Texas public mental health system. To the best of our knowledge, the Texas Medication Algorithm Project (TMAP) is the first attempt to develop and prospectively evaluate consensus-based medication algorithms for the treatment of individuals with severe and persistent mental illnesses. The goals of the algorithm project are to increase the consistency of appropriate treatment of major depressive disorder and to improve clinical outcomes of patients with the disorder. METHOD: A consensus conference composed of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of major depressive disorder in the Texas mental health system. After a series of presentations and panel discussions, the consensus panel met and drafted the algorithms. RESULTS: The panel consensually agreed on algorithms developed for both nonpsychotic and psychotic depression. The algorithms consist of systematic strategies to define appropriate treatment interventions and tactics to assure optimal implementation of the strategies. Subsequent to the consensus process, the algorithms were further modified and expanded iteratively to facilitate implementation on a local basis. CONCLUSION: These algorithms serve as the initial foundation for the development and implementation of medication treatment algorithms for patients treated in public mental health systems. Specific issues related to adaptation, implementation, feasibility testing, and evaluation of outcomes with the pharmacotherapeutic algorithms will be described in future articles.
Algorithms↗
Treatment of depression--newer pharmacotherapies.
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Antidepressive Agents↗
2-Iminohomopiperidinium salts as selective inhibitors of inducible nitric oxide synthase (iNOS).
An attractive approach to the treatment of inflammatory conditions such as osteo- and rheumatoid arthritis, inflammatory bowel disease, and sepsis is through the selective inhibition of human inducible nitric oxide synthase (hiNOS) since localized excess nitric oxide (NO) release has been implicated in the pathology of these diseases. A series of monosubstituted iminohomopiperidinium salts possessing lipophilic functionality at ring positions 3, 5, 6, and 7 has been synthesized, and series members have demonstrated the ability to inhibit the hiNOS isoform with an IC50 as low as 160 nM (7). Compounds were found that selectively inhibit hiNOS over the human endothelial constitutive enzyme (heNOS) with a heNOS/hiNOS IC50 ratio in excess of 100 and as high as 314 (9). Potencies for inhibition of hiNOS and the human neuronal constitutive enzyme (hnNOS) are comparable. Substitution in the 3 and 7 positions provides compounds that exhibit the greatest degree of selectivity for hiNOS and hnNOS over heNOS. Submicromolar potencies for 6 and 7 in a mouse RAW cell assay demonstrated the ability of these compounds to inhibit iNOS in a cellular environment. These latter compounds were also found to be orally bioavailable and efficacious due to their ability to inhibit the increase in plasma nitrite/nitrate levels in a rat LPS model.
Administration, Oral↗
Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms.
A series of analogues of 2-iminopiperidine have been prepared and shown to be potent inhibitors of the human nitric oxide synthase (NOS) isoforms. Methyl substitutions on the 4-position (3) or 4- and 6-positions (8) afforded the most potent analogues. These compounds exhibited IC50 values of 0.1 and 0.08 microM, respectively, for hiNOS inhibition. Substitution with cyclohexylmethyl at the 6-position (13) afforded an inhibitor that showed the best selectivity for hiNOS versus heNOS (heNOS IC50/hiNOS IC50 = 64). Following oral administration, inhibitors were found to decrease serum nitrite/nitrate levels in an in vivo rat endotoxin assay. This series of 2-iminopiperidines were prepared via the described synthetic methodologies. The effect of ring substitutions on potency and selectivity for this class of cyclic amidines as NOS inhibitors is described.
Animals↗