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A placebo-controlled comparison of zotepine versus chlorpromazine in patients with acute exacerbation of schizophrenia.

OBJECTIVE: The aim of this study was to evaluate the efficacy of zotepine in the treatment of acute episodes of schizophrenia. METHOD: Patients with acute exacerbation of schizophrenia (DSM-III-R criteria; n = 158) were allocated on a random, double-blind basis to receive zotepine (150 or 300 mg/day), chlorpromazine (300 or 600 mg/day) or placebo for 8 weeks. Symptoms were assessed on the BPRS, SANS and CGI scales at baseline and weeks 1, 2, 4, 6 and 8 and patients were assessed at these times for adverse effects. Analysis was by analysis of variance on the intent-to-treat population, with last observation carried forward. RESULTS: Mean BPRS scores improved statistically significantly more with zotepine than chlorpromazine (point estimate of difference -12.4, 95% CI -18.3 to -6.5) or placebo (point estimate of difference -12.7, 95% CI -18.6 to -6.8). Zotepine produced significantly fewer extrapyramidal symptoms (EPS) than chlorpromazine. CONCLUSION: Zotepine is an effective antipsychotic with low propensity for EPS.

Acute Disease↗

Chronic dieting and the belief that smoking controls body weight in a biracial, population-based adolescent sample.

OBJECTIVE: To evaluate the prevalence of weight concerns and smoking for body weight reasons as a function of race and gender. DESIGN: A questionnaire measuring a number of factors thought to be predictive of smoking was administered. SETTING: The Memphis (Tennessee) school system. PARTICIPANTS: Participants were 6961 seventh-grade students (mean age 13 years). This population consisted of 80.8% black children, 16.5% white children, and 2.7% of other ethnic origins. MAIN OUTCOME MEASURES: Weight concerns were assessed using items from a restraint scale. Students were questioned regarding their smoking status, beliefs that smoking controls body weight, and their own weight-control smoking behaviour. RESULTS: Dietary restraint interacted with race in that, whereas white girls scored the highest on dietary restraint, black boys scored higher on dietary restraint than white boys. Almost 40% of subjects at this school level believed that smoking controls their body weight. Of the regular smokers, 12% indicated they have smoked to control their weight, with white girls endorsing this belief significantly more than other respondents. CONCLUSIONS: The propensity to smoke for weight control reasons, previously described by other researchers among white females of college and high-school age, was also found among this sample of students of junior high school age.

Adolescent↗

Genetic influences on motion sickness susceptibility in adult women: a classical twin study.

BACKGROUND: Motion sickness is a common and potentially debilitating condition that characteristically occurs in situations of conflicting sensory input. While the precise stimuli that give rise to this trait are increasingly well characterized, the underlying determinants of individual susceptibility to motion sickness remain unclear. This study uses a classical twin design to assess the influence of genetic and environmental factors. METHODS: A postal survey was conducted in an age-matched sample of 3652 monozygotic (MZ) and dizygotic (DZ) adult female twins selected from the TwinsUK Registry. Study participants were asked to complete items from a validated questionnaire relating to their lifetime susceptibility to motion sickness. The relative contribution of genetic and environmental factors to motion sickness susceptibility was assessed using variance components analysis. RESULTS: The response rate to the questionnaire was 78%. Approximately 40% of respondents reported at least moderate susceptibility to motion sickness. The pattern of responses among twins indicated a significant genetic contribution with heritability for a motion sickness factor score estimated as 57% (95% CI: 51%, 63%). The heritability of recalled motion sickness was at its highest in childhood (70% [59%, 80%]) and declined through puberty and the early adult years. DISCUSSION AND CONCLUSIONS: The findings highlight the importance of genetic factors in determining an individual's underlying propensity to motion sickness and should stimulate the search for specific susceptibility genes.

Adult↗

[Fusion of opposite visual images by high, medium and low creative groups under response free and response restricted situations].

Two sets each of High, Medium, and Low Creative Groups (HCG, MCG and LCG), N=12 each, were selected on the basis of JARAT (RAT Revised In Japanese) scores from 364 male college students. One set was asked to entitle each of six pairs of superimposed slide photographs in order to assess mental fusion of visual images under Response Free Situation (RFS), and the other set under Response Restricted Situation (RRS). Under RFS, HCG showed significantly stronger propensity for fusing images that had opposite impression than the other groups. MCG and LCG responded to a few images more promptly, while HCG elaborated their responses more than the rest under both response conditions, and especially under RRS in which each group was encouraged to produce excellent ones. Thus, it was suggested that HCG might process opposites more flexibly and reversibly in both remote associative thinking and in homospatial imagery synthesizing.

Adolescent↗

Preventive effect of Fluosol-DA for paraplegia encountered after surgical treatment of the thoracic aorta. Preliminary results in a dog model.

The effectiveness of Fluosol-DA (Green Cross Corporation, Osaka, Japan) on circulatory dynamics and neurologic outcome in dogs with ischemic spinal cord injury produced by aortic crossclamping was tested. The control group (receiving saline solution) had an elevated mean aortic proximal pressure (112.9 +/- 30.2 mm Hg versus 175.3 +/- 20.5 mm Hg, p greater than 0.05) and a drastic drop in mean distal aortic pressure (112.9 +/- 30.2 mm Hg versus 29.8 +/- 11.2 mm Hg, p less than 0.05). Although the same trend occurred in dogs treated prophylactically with Fluosol-DA, these changes were not statistically significant. However, there was a significant difference in mean distal aortic pressure during the ischemic phase between the two groups (58.9 +/- 16.0 mm Hg versus 29.8 +/- 11.2 mm Hg, p less than 0.05). Postoperatively all animals had mean arterial pressures within the normal range. All dogs in the control group were paraplegic (partial or complete); the treatment group had one dog with partial paraplegia. The difference between the mean neurologic scores of the two groups was of high statistical significance (3.7 +/- 0.5 versus 1.6 +/- 1.0, p less than 0.05). Our preliminary results show that prophylactic use of Fluosol-DA has favorable effects on hemodynamics and neurologic outcome in dogs with spinal cord ischemia produced by aortic crossclamping. The high propensity of the drug to carry oxygen and carbon dioxide and to provide nutritional support to the ischemic area with resultant improvement in local microcirculation and blood rheology are some speculative mechanisms advocated for these changes.

Animals↗

Gaps in structurally similar proteins: towards improvement of multiple sequence alignment.

An algorithm was developed to locally optimize gaps from the FSSP database. Over 2 million gaps were identified from all versus all FSSP structure comparisons, and datasets of non-identical gaps and flanking regions comprising between 90,000 and 135,000 sequence fragments were extracted for statistical analysis. Relative to background frequencies, gaps were enriched in residue types with small side chains and high turn propensity (D, G, N, P, S), and were depleted in residue types with hydrophobic side chains (C, F, I, L, V, W, Y). In contrast, regions flanking a gap exhibited opposite trends in amino acid frequencies, i.e., enrichment in hydrophobic residues and a high degree of secondary structure. Log-odds scores of residue type as a function of position in or around a gap were derived from the statistics. Three simple experiments demonstrated that these scores contained significant predictive information. First, regions where gaps were observed in single sequences taken from HOMSTRAD structure-based multiple sequence alignments generally scored higher than regions where gaps were not observed. Second, given the correct pairwise-aligned cores, the actual positions of gaps could be reproduced from sequence more accurately using the structurally-derived statistics than by using random pairwise alignments. Finally, revision of the Clustal-W residue-specific gap opening parameters with this new information improved the agreement of Clustal-W alignments with the structure-based alignments. At least three applications for these results are envisioned: improvement of gap penalties in pairwise (or multiple) sequence alignment, prediction of regions of single sequences likely (or unlikely) to contain indels, and more accurate placement of gaps in automated pairwise structure alignment.

Algorithms↗

The use of various properties of amino acids in color and monochrome dot-matrix analyses for protein homologies.

Software has been developed to allow the use of a number of parameters in the comparative representation of proteins in color and monochrome dot matrices. They include the parameters of partial specific volume, residue bulkiness, the mean area buried of side chains, seven additional hydropathy scales, mutability, polarity, secondary structure propensities, energy/residue, energy/atom, Rf values, the pKs at the N and C terminals, user-defined parameters and, if desired, randomly generated values. Many of these parameters can be combined in n space using an algorithm based on the Euclidian distance relationship in order to derive consensus values. The problem of scoring matched identities is addressed and the user may stipulate that they score 100 on a 0-100 scale or be determined from the Dayhoff MDM78 values with the rest of the matrix scaled appropriately. The PAMs matrix has been incorporated in such a way to allow the user to stipulate various PAM's values or estimated percentage difference between two peptide sequences, and converting to log odds values. In addition, the similarity ring developed by Swanson and the matrix proposed by Bacon and Anderson have been adapted for use in the program. Color indices have been utilized to give a 'third dimension' to the projections, allowing the user to judge the degree of similarity of different regions which are represented. The software also provides for the plotting of nucleotides in which case color is used to code individual nucleotides, purines versus pyrimidines, or similar colors are used to differentiate between A and T bases on the one hand, and G and C on the other.

Algorithms↗

Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer.

PURPOSE: To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy. RESULTS: The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months. CONCLUSION: In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT < or = 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.

Adult↗

Correlates of pathological gambling propensity in prison inmates.

The South Oaks Gambling Inventory was administered to 136 consecutively admitted inmates in a medium-security prison in Nevada. According to the criteria of the authors of this instrument, 22.79% of these inmates had some problem and 26% were probable pathological gamblers. Significant positive correlations with the F, depression, psychopathic deviate, psychasthenia, paranoia, schizophrenia, and Mac Andrew alcoholism scales of the Minnesota Multiphasic Personality Inventory (MMPI) were found. Gambling score was negatively correlated with the Raven's Standard Progressive Matrices measure of intelligence. Clinical implications are suggested.

Adult↗

UK ward design: patient dependency, nursing workload, staffing and quality-an observational study.

BACKGROUND: There are important relationships between ward design, patient welfare and staff activity in the literature but studies seem not to have tested all the variables. Whether ward designs influence nursing structures, processes and outcomes, therefore, has not been fully answered. While studies provide helpful guidance, nursing efficiency and effectiveness implications are speculative. OBJECTIVES: To improve nursing efficiency and effectiveness by capitalizing on the best ward design features. SETTING: A database consisting of 375 UK wards, constructed for other research and development purposes, was revisited and reconfigured for the present study. The database was updated between 2003 and 2004. PARTICIPANTS: Of 390 wards approached, 375 generated usable data. METHOD: Patient dependency, nursing activity, workload, nursing quality and staffing data in the original database were obtained using mainly non-participation observation methods. Later, wards were classified in eight ways and differences between ward types examined. RESULTS: Patient dependency did not stand out in any ward type but as the literature predicted, direct patient care was higher in Nightingale wards. Racetrack ward nursing activity was also close to idyllic. Bay wards, owing to their greater occupancy peaks and troughs, had a propensity to generate heavier workloads. Time-out and down-time were not excessive in any ward type, and it is likely that ward leadership may be compensating for some variables' negative effects. Racetrack wards were considerably less-well staffed and grade-mix dilute and consequently the cheapest. Quality scores were higher in Nightingale wards-nurses' greater observation capability was a significant factor. Wards' central-core configurations also influenced nursing efficiency and effectiveness. CONCLUSIONS: Racetrack wards have an edge over other ward designs. However, replicating Nightingale conditions by, for example, equalising occupancy, throughput and staffing and maximising nurses' substations, could engender similar outcomes elsewhere.

Dependency, Psychological↗

Intent-to-treat analysis for longitudinal clinical trials: coping with the challenge of missing values.

Drop-out is a common phenomenon in clinical trials of drug treatments involving longitudinal assessments for a fixed duration of follow-up. For these trials intent-to-treat (IT) analysis is usually preferred because time effects are seen in practice. The IT analysis mandates that all subjects randomized to a treatment arm should be included in the analysis. The purpose of the present paper is to acquaint both clinicians and statisticians with recent statistical methodological advances in handling drop-outs and their usage for IT analysis. We discuss a sensitivity analysis of 12-month outcome data to investigate the efficacy of drug therapy from a longitudinal double-blind placebo-controlled clinical trial in the maintenance therapy of geriatric major depressive illness. Outcome measures consist of monthly Hamilton depression scores. The sensitivity analysis includes endpoint analysis, last observation carried forward analysis, repeated measures models and imputation models. Imputation models are based on multiple imputations of missing responses deriving from an 'as-treated' model. The model used imputed doses from a plausible treatment scenario after drop-out and a 'propensity-adjusted' model where the imputations for the drop-outs were obtained from the adhering subjects with the same probability to remain on study (propensity) given the observed trajectory prior to withdrawal. Issues related to bias and efficiency of the estimates obtained by different analyses are discussed. We recommend a more widespread use of imputation models for the IT analysis.

Aged↗

Female alcoholics. IV. Admission problems and patterns.

In an age-matched sample of male and female inpatient alcoholics (n = 518) of the same ethnic background, subjects under 35 years of age described significantly more problem areas than older age groups. Elderly subjects over 55 were the least articulate group. The first-ever addiction treatment subjects reported the lowest mean number of years of problem drinking, the lowest mean Michigan Alcoholic Screening Test scores and the lowest mean daily alcohol intakes. They also displayed greater current social stability than the 2 readmission treatment categories. The general determinants of admission to this addiction unit centered around the experience of crises, social instability and psychological complaints. The most important specific determinants for the individual subject were the propensity to fight when drunk, followed by a positive parental history of excess alcohol intake. Criminal and occupational factors were infrequently encountered in female subjects, but widowhood was common in the older ones.

Adult↗

Is trauma centre care helpful for less severely injured patients?

BACKGROUND: Trauma centres have been shown to reduce the number of preventable deaths from serious injuries. This is due largely to the rapid response of surgeons and health care teams to resuscitate, evaluate, and operate if necessary. Less is known about the effectiveness of trauma centre care on those patients who have not incurred immediate life-threatening problems and may not be as critically injured. The purpose of this study was to review the use of physician and hospital resources for this patient population to determine whether trauma team and trauma centre care is helpful or even needed. METHODS: This was a retrospective study of consecutive trauma patients (n=1592) admitted from 1998 to 2002 to the trauma service of an urban level I trauma centre and recorded in the hospital trauma registry. Patients were triaged in a tiered response to more or less severely injured. All patients' care was directed by trauma surgeons. RESULTS: Of the 1592 patients, 398 (25%) received a full trauma team response (Class I), 1194 were less seriously injured (Class II). The ISS for the Class I patients was 19+/-18 and for Class II patients 10+/-10. Nineteen percent of Class II patients had an ISS>15. Overall mortality in Class II patients was 2% including 20 unexpected deaths. Four hundred and three Class II patients (34%) had multisystem injuries. Of the Class II patients 423 (35%) were sent to the ICU or OR from the ED, 106 of whom required an immediate operation and 345 required an operation prior to discharge. Complications developed in 129 patients (11%), the majority of which were pulmonary. CONCLUSIONS: A large proportion of those patients thought initially to be less severely injured required resources available in a trauma centre, including specialty care, intensive care, and operating room accessibility. Over one-third of these patients had multisystem injuries and almost 20% were considered major trauma, needing prioritisation of care and expertise ideally found in a trauma centre environment. Complications developed in a sizable number of patients. This patient population, because of its heterogeneity and propensity for critical illness, deserves the resources of a trauma centre.

Adult↗

Toward an objective characterization of an anhedonic phenotype: a signal-detection approach.

BACKGROUND: Difficulties in defining and characterizing phenotypes has hindered progress in psychiatric genetics and clinical neuroscience. Decreased approach-related behavior and anhedonia (lack of responsiveness to pleasure) are considered cardinal features of depression, but few studies have used laboratory-based measures to objectively characterize these constructs. METHODS: To assess hedonic capacity in relation to depressive, particularly anhedonic, symptoms, 62 participants completed a signal-detection task based on a differential reinforcement schedule. Anhedonia was operationalized as decreased reward responsiveness. RESULTS: Unequal frequency of reward between two correct responses produced a response bias (i.e., a systematic preference to identify the stimulus paired with the more frequent reward). Subjects with elevated depressive symptoms (Beck Depression Inventory scores >/= 16) failed to show a response bias. Impaired reward responsiveness predicted higher anhedonic symptoms 1 month later, after controlling for general negative affectivity. CONCLUSIONS: Impaired tendency to modulate behavior as a function of prior reinforcement might underline diminished hedonic capacity in depression. When applied to a clinical population, objective assessments of participants' propensity to modulate behavior as a function of reward might provide a powerful tool for improving the phenotypic definition of depression and thus offer a reliable behavioral screening approach for neuroscience studies of depression.

Adolescent↗

Effects of cost sharing on care seeking and health status: results from the Medical Outcomes Study.

OBJECTIVES: This study sought to determine the effect of cost sharing on medical care use for acute symptoms and on health status among chronically ill adults. METHODS: Data from the Medical Outcomes Study were used to compare (1) rates of physician care use for minor and serious symptoms and (2) 6- and 12-month follow-up physical and mental health status among individuals at different levels of cost sharing. RESULTS: In comparison with a no-copay group, the low- and high-copay groups were less likely to have sought care for minor symptoms, but only the high-copay group had a lower rate of seeking care for serious symptoms. Follow-up physical and mental health status scores were similar among the 3 copay groups. CONCLUSIONS: In a chronically ill population, cost sharing reduced the use of care for both minor and serious symptoms. Although no differences in self-reported health status were observed, health plans featuring cost sharing need careful monitoring for potential adverse health effects because of their propensity to reduce use of care that is considered necessary and appropriate.

Adult↗

High-concentration ethylene-vinyl alcohol copolymer and endovascular treatment of experimental aneurysms: feasibility of embolization without protection devices at the neck.

BACKGROUND AND PURPOSE: Coiling of intracranial aneurysms is both safe and effective but may be followed by recurrences. The purpose of this study was to assess the feasibility of endovascular treatment of aneurysms with high-concentration ethylene-vinyl alcohol copolymer (HCEVOH), without the use of protection devices at the neck. METHODS: Wide-necked bifurcation aneurysms with a high propensity for recurrences were constructed in 22 dogs. HCEVOH embolization was performed with a dedicated high-pressure microcatheter in 12 animals. Angiographic results at 3 and 12 weeks and pathologic results at 12 weeks were compared with those of a separate group of 10 animals treated with platinum coils. We used a qualitative scoring system to grade angiographic results, neointima formation, and recanalization at the neck. RESULTS: Intraaneurysmal HCEVOH injections could be performed without carotid emboli and without a protection device in 11 of 12 animals. Fragments detached upon traction of the microcatheters at the end of the procedure on two occasions. Immediate and late angiographic results were not significantly different between the two groups (P =.807), with a tendency for angiographic recurrences at 3 months (angiographic scores were significantly worse in both groups at 12 weeks as compared with T0 [P <.02]). A complete occlusion, including the neck, even at the cost of protrusion of material at the level of the branches, is necessary to decrease risks of recurrences. Neointima formation at the surface of the embolic agent was complete at the neck of aneurysms treated with HCEVOH. The neointimal score was significantly improved with HCEVOH as compared with coil embolization (P =.03). CONCLUSION: HCEVOH embolization of aneurysms without neck protection is feasible. It does not, however, eliminate recurrences in an experimental wide-necked aneurysm model.

Animals↗

Presence and severity of anorexia and bulimia among male and female Omani and non-Omani adolescents.

OBJECTIVE: The population of Oman is a heterogeneous mix of nationalities providing a natural setting for studying the cross-cultural differences in the presence and severity of eating disorders as well as an opportunity for evaluating the performance of measurement instruments for these disorders. METHOD: Disordered eating screening instruments (the Eating Attitude Test and the Bulimic Investigatory Test) were administered to Omani teenagers, non-Omani teenagers, and Omani adults. RESULTS: On the Eating Attitude Test, 33% of Omani teenagers (29.4% females and 36.4% males) and 9% of non-Omani teenagers (7.5% of males and 10.6% females) showed a propensity for anorexic-like behavior. On the Bulimic Investigatory Test, 12.3% of Omani teenagers showed a propensity for binge eating or bulimia (13.7% females and 10.9% males). Among the non-Omani teenagers, 18.4% showed a tendency toward bulimia, with females showing a slightly greater tendency than males. In contrast, barely 2% of Omani adults showed either a presence of or a severity of disorderly behavior with food. CONCLUSION: Omani teenagers scored significantly higher than other ethnic groups and Omani adults. This finding is discussed in the light of emerging evidence from many parts of the world suggesting that cultural transition, compounded by demographic constraints, plays a significant role in abnormal eating attitudes.

Adolescent↗

Calcaneal bone mineral density in older patients who have fallen.

BACKGROUND: Annually, 35-40% of those aged >65 years fall; up to 5% of such falls result in fracture. Fracture is determined both by propensity to fall and by bone fragility. AIM: To determine osteoporosis prevalence and predictors in patients who have fallen. DESIGN: Observational cross-sectional study. METHODS: We measured calcaneal BMD in 408 consecutive patients aged >50 years attending after falling. Fall number, fracture history, weight, height, and risk factors for falls and osteoporosis were recorded. T scores (SD above or below the mean for young adults) were derived in both sexes, and Z scores (SD above or below age-related normal score) in females. RESULTS: In females (n = 300, 74%), mean (SD) T score was -1.1(1.6), and mean Z score was 0(1.4); 127 (42%) had osteoporosis (T score < - 1.6). ROC curves confirmed significant relationships between osteoporosis and age, weight and height (all p < 0.0001). Incorporating fracture history, our model (fracture aged >50 years, age >83 years, weight <57 kg, height <153 cm as dichotomous variables) predicted osteoporosis with 91% sensitivity, 34% specificity. Of 108 male fallers, 36 (33%) had osteoporosis. Age, height and weight all predicted osteoporosis (p < 0.02). The resulting model (fracture aged >50 years, age > or =80 years, weight < or =68 kg, height < or =167 cm as dichotomous variables) predicted osteoporosis with 92% sensitivity, 30% specificity. DISCUSSION: Osteoporosis prevalence is not increased in female fallers compared to age-related norms; empirical use of osteoporosis treatment solely on the basis of falls thus appears inappropriate. In both sexes, the factors predicting osteoporosis were age, height and weight. Where BMD is not practical, possible or economical, our model may be a sensitive means of predicting fallers with osteoporosis.

Absorptiometry, Photon↗