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Biomedical subjects

D Stangl

Publications and source records attributed to D Stangl.

At least 19 recordsLinked to original sources

Assessing the impact of managed-care on the distribution of length-of-stay using Bayesian hierarchical models.

Hierarchical models provide a useful framework for the complexities encountered in policy-relevant research in which the impact of social programs is being assessed. Such complexities include multi-site data, censored data and over-dispersion. In this paper, Bayesian inference through Markov Chain Monte Carlo methods is used for the analysis of a complex hierarchical log-normal model that shows the impact of a managed care strategy aimed at limiting length of hospital stays. Parameters in this model allow for variability in baseline length-of-stay as well as the program effect across hospitals. The authors demonstrate elicitation and sensitivity analysis with respect to prior distributions. All calculations for the posterior and predictive distributions were obtained using the software BUGS.

Bayes Theorem↗

Perceived parental burden and service use for child and adolescent psychiatric disorders.

OBJECTIVES: Pediatric chronic physical illness and adult psychiatric disorders are substantial sources of burden for family care-takers, but little attention has been paid to parental burden resulting from children's or adolescents' psychiatric disorders. This paper describes the predictors of perceived parental burden and its impact on the use of specialty mental health and school services. METHODS: A representative general population sample of 1015 9-, 11-, and 13-year-olds and their parents completed structured psychiatric diagnostic interviews and the Child and Adolescent Burden Assessment. RESULTS: Weighted estimates indicated that 10.7% of parents in the general population perceived burden resulting from their children's symptomatology. Significant predictors of perceived burden were levels of child symptomatology and impairment and parental mental health problems. Children's depressive and anxiety disorders were associated with less burden than other diagnoses. The effects of child disorder severity on specialty mental health service use appeared to be mediated by the level of burden induced. CONCLUSIONS: Substantial levels of parental burden resulted from child psychiatric disorders and were a major reason for specialist mental health service use.

Adolescent↗

Bayesian inference in two-phase prevalence studies.

This paper discusses Bayesian methods for the assessment of the prevalence of a disorder based on data from a two-phase design with a short screening instrument administered at the first phase followed by an in-depth diagnostic instrument given at the second phase. In calculating the posterior distributions of the quantities of interest, for example, the prevalence, sensitivity and specificity, and predictive distributions, we used the Gibbs sampler. We illustrate our approach by assessing the prevalence of depression in adolescents with use of data attained from a two-phase design.

Adolescent↗

Children's mental health service use across service sectors.

This DataWatch explores the roles of human service sectors (mental health, education, health, child welfare, and juvenile justice) in providing mental health services for children. The data are from the first wave of the Great Smoky Mountains Study of Youth, a population-based study of psychopathology and mental health service use among children. The results show somewhat higher rates of mental health service use than has been reported previously, while continuing to show a substantial amount of unmet need, even among children with both a psychiatric diagnosis and functional impairment. The findings point to a significant role for the education sector, suggesting that schools may function as the de facto mental health system for children and adolescents.

Adolescent↗

Hospital stressors experienced by elderly medical inpatients: developing a Hospital Stress Index.

OBJECTIVE: To develop a long and short version of an index to measure experiences during hospitalization perceived by elderly patients as stressful. SAMPLES AND METHODS: Consecutive patients aged sixty or over admitted to a university teaching hospital were assessed for hospital-related stressors during two separate studies. In the first study, seventy-six patients were asked an open-ended question exploring what they found most stressful about being in the hospital. Responses were grouped into major categories, and questions were developed to address concerns in each category; the resulting forty items were called the Hospital Stress Index (HSI). The HSI was then administered to a separate group of ninety-two patients; data were also collected on functional disability (impaired ADLs), dysfunctional attitudes (DAS), and depressive symptoms (CES-D). RESULTS: Spontaneously reported hospital stressors were grouped into seven categories: 1) adverse effects of diagnostic or therapeutic procedures/treatments, 2) forced life-style changes, 3) relationships with staff, 4) individual psychiatric issues, 5) understanding diagnosis/prognosis, 6) family issues, and 7) the physical environment. The largest category of stressors concerned relationships with doctors and nurses. High HSI scores were significantly more common among Whites than Blacks and among patients with high CES-D, high DAS, or impaired ADLs scores. A number of potentially modifiable hospital-related stressors and individual patient issues were identified. Finally, an abbreviated fifteen-item HSI was developed to maximize patient discriminability, highlight individual differences, and enhance the detection of modifiable stressors. CONCLUSIONS: Hospital-reported stressors may contribute to the emotional distress that elderly inpatients experience. We have developed an index to identify such stressors.

Activities of Daily Living↗

Photoaffinity labeling of rat calcitonin gene-related peptide receptors and adenylate cyclase activation: identification of receptor subtypes.

Different biological effects of calcitonin gene-related peptide (CGRP) analogs have suggested receptor subtypes. Here we have investigated molecular forms of rat CGRP receptors, ligand binding, and activation of adenylate cyclase. A single class of [125I]alpha-human (h)CGRP binding sites was identified in rat cerebellum, liver, and spleen, with dissociation constants of 206 +/- 70 pM, 128 +/- 23 pM, and 229 +/- 64 pM (mean +/- SEM), respectively. Competition experiments showed the same rank order of displacement of [125I]alpha-hCGRP binding in all the tissues examined with rat alpha-CGRP approximately alpha-hCGRP approximately beta-hCGRP > alpha-hCGRP(8-37) > [acetamidomethyl-Cys2,7]alpha-hCGRP > human amylin > salmon calcitonin. Photoaffinity labeling of CGRP receptors using [125I][C gamma-(4-azidoanilino)Asp3]alpha-hCGRP revealed specifically labeled 71-kilodalton (kDa) binding proteins in the cerebellum, brainstem, and spinal cord, of 74 kDa and 68 kDa in the liver, and of 75-90 kDa in the spleen. Enzymatic N-deglycosylation converted the labeled binding proteins into a common 48-kDa form (44 kDa with the molecular mass of the photoligand subtracted). In the presence of 100 microM guanosine-5'-O-(3-thiotriphosphate), the dissociation constant of [125I]alpha-hCGRP binding remained unchanged in the cerebellum but was increased 3-fold in the liver and spleen, suggesting interaction with GTP-binding proteins. In accordance with these results, adenylate cyclase was stimulated by CGRP in the liver and spleen, but not in the cerebellum and brainstem. Furthermore, the linear analog [acetamidomethyl-Cys2,7]alpha-hCGRP enhanced cAMP formation in the liver but not in the spleen. In conclusion, rat CGRP receptors with tissue-specific N-glycosylation but indistinguishable protein molecular mass have been identified in the cerebellum, brainstem, spinal cord, liver, and spleen. Activation of adenylate cyclase by CGRP in the liver and spleen, but not in the central nervous system, and by the linear analog [acetamidomethyl-Cys2,7]alpha-hCGRP in the liver alone provide evidence for CGRP receptor subtypes.

Adenylyl Cyclases↗

Comparison of a calcitonin gene-related peptide receptor in a human neuroblastoma cell line (SK-N-MC) and a calcitonin receptor in a human breast carcinoma cell line (T47D).

A specific CGRP-binding protein of M(r) 60,000 has been identified in the human neuroblastoma cell line SK-N-MC. After N-deglycosylation a M(r) of 48,000 was found. The M(r) were indistinguishable from those determined in the human cerebellum. Receptor binding of CGRP is coupled to cyclic AMP formation. The latter is antagonized by hCGRP-I8-37. CT and DAPamide interact only minimally with the CGRP receptor, whereas CGRP and DAPamide are full agonists in T47D cells. The CT receptor on human breast cancer cell line T47D is clearly different from the human CGRP receptor.

Amino Acid Sequence↗

Characterization and photoaffinity labeling of a calcitonin gene-related peptide receptor solubilized from human cerebellum.

Calcitonin gene-related peptide (CGRP) receptors were solubilized from human (h) cerebellum with use of the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS). Scatchard analysis of equilibrium binding data indicated that the soluble extract contained a single class of CGRP binding sites with apparent dissociation constants of 50 pM for the intact 125I-hCGRP-I(1-37) and 160 pM for the antagonist 125I-hCGRP-I(8-37). Unlabeled hCGRP-I and -II and hCGRP-I(8-37) displaced 125I-hCGRP-I from solubilized CGRP receptors with similar potencies (ID50 = 70-150 pM). Human CGRP-I(15-37), -(21-37), and -(28-37) were less potent (ID50 greater than or equal to 70 nM), suggesting that amino acid residues 8-14 may be important for maintaining high binding affinity. A novel photoreactive analogue of hCGRP-I, 125I-[C gamma-(4-azidoanilino)Asp3] hCGRP-I, was prepared by carbodiimide coupling of 4-azidoaniline to 125I-hCGRP-I. Photoaffinity labeling of soluble CGRP receptors with the photoreactive analogue and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed three specifically labeled binding proteins with apparent molecular weights (Mr) of 60,000, 54,000, and 17,000. Cross-linking of 125I-hCGRP-I and -II and 125I-hCGRP-I(8-37) to soluble CGRP binding sites using disuccinimidyl suberate revealed three specifically labeled binding proteins with the same Mr. The C-terminal fragment 125I-hCGRP-I(8-37), unlike the intact peptide, was, furthermore, cross-linked specifically to a 95,000 Mr protein. The CGRP receptor is N-glycosylated. Treatment with endoglycosidase F/N-glycosidase F converted the 60,000 and 54,000 to 46,000 and 41,000 Mr components.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗

Methodologic issues in maintenance therapy clinical trials.

In the early 1980s, the National Institute of Mental Health supported a multicenter, randomized, controlled, clinical trial on unipolar and bipolar disorder to evaluate the comparative efficacies of lithium carbonate, imipramine hydrochloride, a lithium-imipramine combination, and placebo in preventing the recurrence of affective disorders. The objective of this report is to present a reanalysis of the relative efficacies of these treatments in patients with unipolar disorder to focus attention on general issues related to the design and conduct of maintenance therapy trials. We show that the earlier conclusions of that study that imipramine and the combination therapy are more effective than lithium and placebo in preventing the recurrence of depression in unipolar patients can be accounted for by alternative explanations that are a consequence of the design of the study. Our findings have important implications for the design, conduct, and interpretation of results of maintenance therapy clinical trials in general.

Adult↗

Major depression and personality disorder.

The authors examined an interview and paper-and-pencil assessment of the DSM-III personality disorders (PDs) in depressed inpatients, and depressed relatives of psychiatric patients and never-ill controls who had a lifetime history of major depression. The rates of PDs according to the Structured Interview for DSM-III Personality Disorders (SIDP) were similar in the two groups, except for borderline PD which was more frequent in the inpatients. Of the individuals with a PD, the patients were more likely than the relatives to have two or more PDs, and the borderline and histrionic patients were more prototypic of these disorders than were the borderline and histrionic relatives. In contrast to the SIDP results, the rates of PDs according to the Personality Disorders Questionnaire (PDQ) were higher in the patient sample. These results thus extend the previously described high rates of PDs in depressed patients to a sample of individuals with a lifetime history of treated or untreated depression, and they suggest that interview assessments of personality may be less sensitive to the state effects of depression than are questionnaires.

Adult↗

Association between post-dexamethasone cortisol level and blood pressure in depressed inpatients.

We examined the clinical data for 230 depressed inpatients who had completed a dexamethasone suppression test (DST) to determine whether those with an elevated post-DST serum cortisol level exhibited any of the classic physiological stigmata of Cushing's syndrome. Hypertension was significantly more frequent among DST nonsuppressors (21.2%) than among normal suppressors (11.3%). Percent blood lymphocyte count was significantly lower among nonsuppressors. Confounders such as gender, age, body weight, and use of antihypertensives did not account for the findings. Implications for morbidity and mortality rates among patients with affective disorder are discussed.

Adult↗

An introduction to survival analysis: statistical methods for analysis of clinical trial data.

The randomized controlled clinical trial (RCT) is a prospective study using random assignment of subjects to treatment groups to compare the effect and value of a therapeutic intervention against a control. The RCT is the most definitive clinical research tool for evaluating the efficacy of a new therapy in human subjects. Often the outcome of interest in an RCT is the length of time until an event occurs after treatment or intervention. In this article we introduce statistical methods for evaluating differences in the patterns of time to response between two groups of subjects to determine whether one therapy is better than another. The collection of methods for analyzing such data, known as survival data, is called survival analysis. Using data from a hypothetical clinical trial for the prevention of the recurrence of depression, we illustrate two elementary methods for analyzing survival data. We also discuss generalizations of these methods to incorporate covariates and conclude with a general discussion of clinical trials of psychiatric therapies.

Clinical Trials as Topic↗

The reliability of the family history method for psychiatric diagnoses.

We evaluated the test-retest interrater reliability of the Family History Research Diagnostic Criteria (FH-RDC) in 58 depressed patients who described 341 first-degree relatives. Reliability was examined as a function of the threshold to determine caseness. In general, diagnostic reliability was good-excellent for specific FH-RDC disorders, but not for the residual category of other psychiatric disorder. A higher diagnostic threshold was associated with greater reliability, especially for the diagnosis of depression. Patient variance accounted for a greater percentage of the disagreements between the interviewers than did rater variance.

Data Collection↗

Diagnosing personality disorder in depressed patients. A comparison of patient and informant interviews.

Personality disorder (PD) diagnosis were made in 66 depressed patients based on independent interviews of the patient and a close informant. The patients and informants markedly differed in their descriptions of the patients' normal personality. The kappa coefficient of agreement for the diagnosis of any PD was .13, and all kappa values for the individual PD diagnoses were below .35. Informants reported more pathologic conditions than the patients, such that PDs were diagnosed in 57.6% (38/66) of the patients, based on the informant interview, and in 36.4% (24/66), based on the patient interview. We also examined dimensional scores. In general, we found only modest correlations between the patient and informant dimensional scores and that the ratings based on the informant interviews were higher. These results varied by specific PD diagnoses. Consensus ratings, which were based on both sources of information, were sometimes more strongly associated with patient information and sometimes with informant information, and this, too, varied among the different PDs.

Adult↗

Prognostic validity of the familial subtypes of depression.

We examined the prognostic validity of Winokur's familial subtypes of depression in 184 in-patients with primary unipolar major depression. Patients with familial pure depressive disease had a more favorable hospital course and reported less symptoms during a 6-month follow-up evaluation than patients with depressive spectrum disease or sporadic depressive disease. Consistent with previous studies of the validity of the familial subtypes, the use of stringent thresholds to diagnose the patient's relatives increased the validity of classification.

Antidepressive Agents↗

The prognostic validity of DSM-III axis IV in depressed inpatients.

DSM-III suggests that axis IV should have prognostic value--that patients with higher scores will have a better outcome than patients with low ratings. The authors used axis IV to assign scores to 130 depressed inpatients and examined these scores in association with the patients' course during the index hospitalization and at 6-month prospective follow-up. Higher axis IV scores were associated with more depressive symptoms on hospital discharge, but they did not predict follow-up outcome. These results are consistent with other studies of the prognostic value of ratings of psychosocial stress and indicate that, at least for depression, there is little empirical support for DSM-III's suggestion that stress is a favorable prognostic sign.

Adolescent↗

An American validation study of the Newcastle Diagnostic Scale. II. Relationship with clinical, demographic, familial and psychosocial features.

We completed the Newcastle Diagnostic Scale on 152 unipolar depressed in-patients: its validity was supported by the findings that endogenous depressives were, in contrast to neurotic depressives, older, more severely depressed, with better social support, fewer life events, less personality disorder, and a lower morbid risk of alcoholism and antisocial personality in their first-degree relatives. The relationship between Newcastle scores and the morbid risk for alcoholism was non-linear, such that a cut-off score of 4, rather than 5, maximised the difference between the endogenous and neurotic groups with respect to familial alcoholism rates as well as other validating variables.

Cognition Disorders↗

Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria, V. The complete amino-acid sequence of the mesophilic L-lactate dehydrogenase from Bacillus megaterium.

The complete amino-acid sequence of L-lactate-dehydrogenase from the mesophilic Bacillus megaterium was determined. 92% of the 318 amino acids were established by sequence analysis of the N-terminus, of four CNBr fragments and of one fragment obtained by cleavage with BNPS-skatole. The primary structure was completed by sequencing overlapping fragments obtained by further cleavage of suitable CNBr fragments and BNPS fragments with either trypsin, endoproteinase Lys-C, o-iodosobenzoic acid or hydroxylamine. The C-terminal amino acids were determined by degradation with carboxypeptidase A. The sequence homology between lactate dehydrogenases from B. megaterium and those from other Bacilli is 59-61% and 35-37% to those from higher organisms. The high sequence homology among lactate dehydrogenases from Bacilli, adapted to different temperatures, allows comparative studies of the structural basis of protein thermostability.

Amino Acid Sequence↗