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Liaison psychiatry in an HIV/AIDS unit.

OBJECTIVE: To provide an overview of the work of a liaison psychiatry service to an HIV/AIDS inpatient unit, and particularly to examine the identification of mood and related disorders by referring doctors. METHOD: The MICRO-CARES prospective clinical database system was used to obtain data on all patients referred to the HIV/AIDS consultation-liaison psychiatry service in an infectious diseases hospital in Melbourne. RESULTS: Three hundred and ninety-two inpatient referrals were made in the 2 years from 1993-1995: a referral rate of 16.7%. The most frequent reasons for referral were evaluation of coping problems (42%), assessment of possible depression (31%), and assessment of psychotropic medication (24.5%). The most common psychiatric diagnoses were mood disorders (36.5%), psychoactive substance use disorders (22.7%) and organic mental disorders (18.1%). Overall concordance of recognition of depression by the referring doctor and diagnosis of depression by the consultant psychiatrist was 79%; 20% false positive rate, 23% false negative rate. CONCLUSIONS: Psychiatric comorbidity is common in patients with HIV/AIDS. Reasons for referral vary from those seen in other inpatient settings. Previously noted problems such as the misdiagnosis of psychiatric disorder and the mislabelling of the syndrome recognised by psychiatrists as depression were noted here.

Acquired Immunodeficiency Syndrome

Consultation-liaison psychiatry in an obstetric service.

OBJECTIVE: The aim of this paper is to provide an overview of the work of a consultation-liaison (C-L) psychiatry service to an obstetric inpatient unit in a university affiliated teaching hospital, with the aid of a comprehensive clinical database. METHOD: The MICRO-CARES clinical database system was used for prospective recording of data on all obstetric inpatients referred to the C-L psychiatry service and the hospital clinical database was used to compare referred inpatients with all obstetric inpatients. RESULTS: Ninety patients were referred in 3 years, a referral rate of 1.2% of obstetric admissions. There was no bias in referral on age, but there were significantly more unmarried patients in the referred group (p < 0.001). Referred patients had a significantly prolonged length of stay: a mean of 9 days for referred patients, with 6 days for all obstetric patients (p < 0.001). The most frequent reasons for referral were: coping problems, depression, anxiety/fear and past history of major psychiatric illness. The most common DMS-III-R psychiatric diagnoses were: Personality Disorders (19%), Mood Disorders (17%), Schizophrenic Disorders (15%) and Adjustment Disorders (13%). At least one confirmed diagnosis was made in 77% of patients, but 42% of diagnoses remained differential. There were significantly more patients with diseases of the nervous system, endocrine and circulatory disorders in the referred group (p < 0.001). Recommendations of psychosocial interventions predominated over psychopharmacological interventions, and concordance with these was 97% and 98%, respectively. Issues in the relationship of obstetrics and psychiatric C-L services are discussed and future directions indicated. CONCLUSIONS: The referral rate was low compared with other specialty units. This is probably due to factors inherent in obstetric practice. A wide spectrum of psychiatric disorders was referred, including a higher than expected number of women with postpartum psychotic disorders, the majority of whom were managed successfully in the obstetric ward. There is a need for increased liaison with obstetric and community services and for collaborative research, with a particular emphasis on the prevention of psychiatric morbidity associated with pregnancy.

Adaptation, Psychological

Comparison of six microcomputer dietary analysis systems with the USDA Nutrient Data Base for Standard Reference.

We compared the general operating features and nutrient databases of six microcomputer dietary analysis systems. A 3-day food record with 73 food items was entered into each program; nutrient averages were compared with the US Department of Agriculture Nutrient Data Base for Standard Reference (USDA NDB), full version, release 9, for microcomputers. The six programs were found to vary widely in cost, number of foods and nutrients in the database, use of non-USDA data and imputation of data for missing values, number of print/export options, time to analyze the 3-day food record, and overall ease of use. Although all of the microcomputer dietary analysis systems were within 7% of the USDA NDB for energy, protein, total fat, and total carbohydrates, the proportion of other nutrients varying more than 15% from the USDA NDB varied considerably between programs. Variance among programs for 3-day food record nutrient values occurred because of differences in the number of food items included in the database (leading to varying degrees of substitution), the recency of the nutrient data (whether or not the most recent USDA releases had been incorporated), and the number of missing values (the degree to which non-USDA sources or estimated calculations were used to fill in the blanks from the USDA standard). Our results demonstrate that it is important for each dietitian to carefully choose a microcomputer dietary analysis system that is suitable to specific and predetermined needs.

Databases, Factual

Challenges of high throughput screening against cell surface receptors.

Excessive or inappropriate activation of cell surface receptors can mediate the development of disease. Receptors, therefore, are a focus for drug discovery activities. Empirical screening is important in the search for novel compounds acting as receptors. Technical developments and the application of molecular biology have facilitated access to receptors of interest and have provided efficient screening methods capable of very high throughput. Reliability in high throughput screening requires the use of appropriate methodology, good screen design and effective validation and quality control processes. Validation should aim to establish that the basic experimental design is sound. In developing software to handle high throughput screening data, a fundamental requirement is to provide performance monitoring and error trapping facilities. Additional requirements are automatic data capture from instruments, on-line data reduction and analysis and transfer of results to central databases. As data volumes increase through effective high throughput screening, conventional interrogation methods become less appropriate and are being augmented by newer computing techniques referred to as knowledge mapping or database mining. Targeting cell surface receptors has been very successful as an approach to drug discovery. If the challenges of high throughput empirical screening are addressed effectively, cell surface receptors will provide new opportunities for improved therapy in the coming years.

Animals

Does the normal contralateral wrist provide the best reference for X-ray film measurements of the pathologic wrist?

This study compares in normal subjects the variability of wrist x-ray film measurements between the right and left sides with the variability of the distribution of those measurements within the population. Additional purposes were to evaluate possible differences of these measurements according to sex, age, side, and hand dominance. The variability when comparing both sides was found to be statistically less for the carpal height, radiolunate, scapholunate, and capitolunate angles than within the whole group of subjects, and for those measurements, there was a high correlation (r > .88) between the right and left sides. In addition, the carpal height and the carporadial ratios were lower and the capitolunate angle was higher in women than in men. There was also a significant decrease of the scapholunate angle in older individuals. The clinical implication of these findings is that in unilateral wrist diseases, the normal wrist should be used to provide the reference values of the carpal height and of the carpal angles on profile x-ray films. However, for the radial inclination and palmar tilt of the distal radius and for the ulnar variance, the normal side does not provide a better reference than normal values obtained from databases.

Adult

Structure prediction and modelling.

Protein structure prediction from sequence remains a major goal in molecular biology. The methods described in this review concentrate on deriving structural information through the detection of similarities between a test sequence and a database of known structures. Such methods are often referred to as knowledge-based strategies reflecting the use of a structural database in the analyses. The past year has seen considerable advances in both the development of automated procedures and their application to protein sequences of outstanding biological interest.

Algorithms

Continuous quality improvement can improve glycemic control for HMO patients with diabetes.

OBJECTIVE: To evaluate the impact of a continuous quality improvement (CQI) intervention on glycemic control of patients with diabetes mellitus attending a primary care clinic. METHODS: A CQI process designed by the Minnesota Department of Health to improve diabetes care was implemented at a volunteer clinic, with another similar clinic not using the CQI process assessed for comparison. Adults with diabetes were identified at both clinics using diagnostic and pharmacy databases. Glycosylated hemoglobin (HbA1c) values (reference range, 4.3%-6.1%) and out-patient utilization and charges were compared for all patients with diabetes at each clinic for the 12 months before and 18 months after initiation of the CQI intervention. RESULTS: The mean HbA1c value at the intervention clinic fell from 8.9% at baseline to 8.4% at 12 months and to 7.9% at 18 months. The mean HbA1c value at the comparison clinic was 8.9% at baseline, 8.9% at 12 months, and 8.8% at 18 months (difference between clinics, t = 4.13, P < .001). Differences after the intervention in the proportion of patients at the comparison clinic (n = 121) vs the intervention clinic (n = 122) with HbA1c values of 8% or less (40% vs 51%), between 8% and 10% (33% vs 37%), and 10% or greater (27% vs 12%) were unlikely due to chance (chi 2 = 9.7, 2 df, P = .008). The intervention was not associated with increased utilization of outpatient visits or outpatient charges. CONCLUSIONS: Involvement of nurses, physicians, and managers in a CQI process can improve patients' glycemic control in some health maintenance organization primary care settings, without increasing utilization or charges. Health maintenance organizations should consider CQI as one possible method to improve diabetes outcomes.

Adult

Efficacy of bronchodilator therapy in bronchiolitis. A meta-analysis.

OBJECTIVE: To determine if bronchodilators are efficacious in treating bronchiolitis. DATA SOURCES: A search of bibliographic databases (MEDLINE, Excerpta Medica, and Reference Update) for bronchiolitis and albuterol or ipratropium bromide, or adrenergic agents or bronchodilator agents. Reference lists were also used. STUDY SELECTION: Randomized, placebo-controlled trials of bronchodilator treatment in bronchiolitis were selected by 2 investigators. Fifteen of 89 identified publications met the selection criteria. DATA EXTRACTION: Investigators independently abstracted data for 3 outcomes: clinical score, oxygen saturation, and hospitalization. Clinical score was measured as a dichotomous variable (score +/- improved) or continuous variable (average score). DATA SYNTHESIS: For primary analysis, data were pooled from 8 trials of children with first-time wheezing. The effect size for average score was -0.32 (95% confidence interval [CI], -0.54 to -0.11; P < .01), favoring treatment; the relative risk for score +/- improved was 0.76 (95% CI, 0.60 to 0.95; P = .02), favoring treatment. Bronchodilators had no effect on hospitalization (relative risk, 0.85; 95% CI, 0.47 to 1.53; P = .58), but co-interventions may have been administered prior to this outcome. The results for oxygen saturation were too varied to allow pooling of the results. Secondary analyses were performed on 4 outpatient trials of children with first-time wheezing, 7 trials in which only nebulized beta-agonists were used, and on all 15 trials identified. The results were similar, but the data varied more. CONCLUSION: Bronchodilators produce modest short-term improvement in clinical features of mild or moderately severe bronchiolitis.

Albuterol

Prevalence of the Predisposing Gene MBD4 for Uveal Melanoma.

IMPORTANCE: MBD4 monoallelic germline pathogenic and likely pathogenic variants have recently been identified as predisposing to uveal melanoma, a rare primary intraocular tumor, with an estimated 9.15-fold increased risk of developing the disease for pathogenic variant carriers. OBJECTIVE: To assess the risk of developing uveal melanoma for carriers of the MBD4 monoallelic germline pathogenic variant. DESIGN, SETTING, AND PARTICIPANTS: In a case series involving 896 individuals, including 319 who were previously evaluated, germline target-sequencing of MBD4 was offered to every new patient with uveal melanoma at Curie Institute from February 2021 to September 2025. Non-Finnish European participants from the Genome Aggregation Database were used as a reference population. EXPOSURE: Diagnosis of uveal melanoma genetic predisposition. MAIN OUTCOMES AND MEASURES: Prevalence of MBD4 variants. RESULTS: A total of 23 of 896 patients were identified as carrying an MBD4 germline pathogenic or likely pathogenic variant, corresponding to a relative risk of 31.44 (95% CI, 18.18-53.00) of developing uveal melanoma compared with the general population (2-sided Fisher exact test, P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: These findings confirm that MBD4 is an important predisposing gene to uveal melanoma in the French population. This reinforces a strategy of broad patient screening given the therapeutic implications and the consequences of genetic counseling.

Humans

Dose-response assessment for developmental toxicity. II. Comparison of generic benchmark dose estimates with no observed adverse effect levels.

Developmental toxicity risk assessment currently relies on the estimation of reference doses (RfDDTS) of reference concentrations (RfCDTS) based on the use of no observed adverse effect levels (NOAELS) divided by uncertainty factors (UFs). The benchmark dose (BMD) has been proposed as an alternative basis for reference value calculations. A large database of 246 developmental toxicity experiments representing 1825 endpoints related to dead implants or malformed fetuses has been compiled for use in evaluating alternative approaches to developmental toxicity risk assessment. Using this database we have compared two approaches for BMD estimation with each other and with corresponding statistically derived NOAELS. Comparisons have been based on proportion of affected litters (litters with one or more affected offspring, a quantal response variable) and on the proportion of affected offspring within each litter (a continuous response variable). A quantal Weibull model was used to calculate generic BMDs for the quantal response variable (QBMDs) and a continuous power model was used to calculate generic BMDs for the continuous response variable (CBMDs) at three levels of additional risk (10, 5, and 1%). CBMD05s (continuous benchmark doses for 5% risk) and CNOAELs (statistically derived NOAELs based on the continuous response variable) were similar, with over 98% of the data subsets having CBMD05 and CNOAEL values that differed by less than an order of magnitude. In contrast, QNOAELs tended to be greater than corresponding QBMD10s. The observed conservatism of the QBMD values relative to the corresponding CBMD values was attributed to two factors, lower maximum likelihood estimates for the quantal model and wider confidence intervals around the maximum likelihood estimates, compared to the continuous model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Polymorphic SSR (simple-sequence-repeat) markers for chromosome 20.

Chromosome 20-specific simple-sequence-repeat (SSR) markers were developed from a flow-sorted phage library (LL20NS01), subcloned in Bluescript, and screened with a tetranucleotide repeat, (AAAG)6, to identify potentially polymorphic loci. Of 100 clones sequenced, 39 were selected to construct primers. Of these 39, 22 were polymorphic. Reference to the CEPH linkage database (version 5) permitted genetic mapping of 16 of the new markers to specific regions of chromosome 20. Ten of the SSRs showed heterozygosity indices (above 70%) that would qualify them as potential index markers.

Base Sequence

Cricoid pressure.

PURPOSE: Although cricoid pressure (CP) is a superficially simple and appropriate mechanical method to protect the patient from regurgitation and gastric insufflation, in practice it is a complex manoeuvre which is difficult to perform optimally. The purpose of this review is to examine and evaluate studies on the application of (CP). It deals with anatomical and physiological considerations, techniques employed, safety and efficacy issues and the impact of CP on airway management with special mention of the laryngeal mask airway. SOURCE OF MATERIAL: Three medical databases (48 Hours, Medline, and Reference Manager Update) were searched for citations containing key words, subject headings and text entries on CP to October 1996. PRINCIPLE FINDINGS: There have been no studies proving that CP is beneficial, yet there is evidence that it is often ineffective and that it may increase the risk of failed intubation and regurgitation. After evaluation of all available data, potential guidelines are suggested for optimal use of CP in routine and complex situations. CONCLUSIONS: If CP is to remain standard practice during induction of anaesthesia, it must be shown to be safe and effective. Meanwhile, further understanding of its advantages and limitations, improved training in its use, and guidelines on optimal force and method of application should lead to better patient care.

Cricoid Cartilage

To what extent do congestive heart failure patients in sinus rhythm benefit from digoxin therapy? A systematic overview and meta-analysis.

PURPOSE: To reappraise the effectiveness of digoxin for the treatment of congestive heart failure (CHF) in patients with sinus rhythm in light of data from recently published randomized controlled trials and to quantitatively assess its usefulness. STUDY IDENTIFICATION: Computerized searches of the MEDLINE database were performed, and the reference list of each retrieved article was reviewed. STUDY SELECTION: Review of more than 360 citations and the reference lists of 19 review articles and 61 potentially relevant articles revealed seven double-blind randomized controlled trials that were included in this overview. DATA EXTRACTION: Study quality was assessed and descriptive information concerning the study populations, the specific interventions, and clinically relevant outcome measurements was extracted. RESULTS OF DATA SYNTHESIS: The common odds ratio for CHF deterioration while receiving digoxin versus placebo was 0.28, with a 95% confidence interval of 0.16 to 0.49. Predictors of digoxin benefit included presence of a third heart sound and the severity and duration of CHF. CONCLUSION: Data from seven trials of high methodologic quality suggest that, on average, one out of nine patients with CHF and sinus rhythm derive a clinically important benefit from digoxin (with a 95% confidence interval of 1/33 to 1/5).

Digoxin

Control of expression of the human glutathione S-transferase pi gene differs from its rat orthologue.

We have examined regulation of the glutathione S-transferase pi gene by transient expression assay, and find that a fragment from 8 to 99 bp upstream of the cap site promotes transcription, but there is no evidence for any enhancer activity in a further 6 kb of flanking sequence. Analysis of this sequence by reference to a primate sequence database and Southern blotting revealed that as much as 5 kb of this flanking DNA were composed of repetitive insertion elements including an Alu and a LINE 1 repeat. The promoter fragment has been sequenced (Cowell et al (1988) Biochem. J. 255, 79-83) and contains a consensus AP1 binding site; in some cases, these have been associated with transcriptional induction by phorbol esters and ras oncogenes. We measured the steady state levels of glutathione S-transferase pi mRNA in human cell lines which were known to express ras oncogenes and compared them to human cell lines which have not been identified with ras activation. There was no correlation between expression of activated ras and expression of glutathione S-transferase pi mRNA. Treatment of HeLa cells, HepG2 cells and a small cell lung carcinoma line, GLC 8, with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate failed to alter the steady state levels of endogenous glutathione S-transferase pi mRNA. The differences between these results and those of similar studies on rat glutathione S-transferase subunit 7, a structural orthologue of glutathione S-transferase pi, are discussed.

Animals

Is routine carotid ultrasound surveillance after carotid endarterectomy worthwhile?

BACKGROUND: Periodic ultrasound studies are routinely performed after carotid endarterectomy with the aim of detecting recurrent stenosis or progression of contralateral disease. The frequency with which these studies should be performed and their clinical utility is at present unclear. Our experience with ultrasound surveillance after carotid endarterectomy was reviewed. METHODS: We performed a retrospective analysis of our carotid registry as a follow-up on patients who had undergone primary endarterectomy between 1982 and 1995. The database was searched for events referable to the contralateral carotid artery including incidence of contralateral endarterectomy, progression of contralateral stenosis, and development of new neurologic symptoms. Data was analyzed by life-table methodology. RESULTS: A total of 562 patients underwent 660 endarterectomies during the study interval with a postoperative stroke rate of 3.6% and a mortality of 1.1%. Of these, 496 patients had data available on the contralateral artery. There were 384 patent, nonoperated contralateral arteries available for long-term clinical follow-up, of which 276 had serial Doppler examinations. At the time of initial presentation, 30% of patients (141 cases) had greater than 50% diameter stenosis in the contralateral artery including 45 occlusions. There were 67 contralateral endarterectomies performed within 6 months of the original surgery. An additional 15 endarterectomies were performed within 24 months of the original surgery and only 16 subsequent endarterectomies were performed up to the 8-year follow-up. Progression of contralateral stenosis from less than to greater than 50% occurred in 10.1% of the patient population. The rate of disease progression was 5.1% at 3 years, 17.8% at 5 years, and 30% at 7 years. Stroke-free survival in patients without progression was 94.7% at 3 years and 93.3% at 5 years. CONCLUSIONS: Significant contralateral disease occurs in about one third of patients, most of whom are candidates for early contralateral endarterectomy. In patients who present with minimal contralateral disease, the incidence of progression is low over time. Follow-up duplex examinations on a biennial schedule is sufficient to detect clinically significant disease progression in these patients.

Carotid Stenosis

Whole-genome sequencing of adenovirus 41 directly from wastewater using nested overlapping PCR and MinION.

Human adenovirus F41 (HAdV-F41) is one of the leading causes of children's acute gastroenteritis and was recently linked to an outbreak of severe acute hepatitis of unknown etiology among children during 2021 to 2022. While most evidence is based on clinical data, wastewater-based epidemiology offers a community-level approach to monitoring circulating strains and enhancing outbreak preparedness. In this study, we developed an overlapping amplicon-based whole-genome sequencing approach to directly detect HAdV-F41 from archived wastewater samples, using nested PCR with 13 primer sets. Archived wastewater samples were collected between 2021 and 2022 from three treatment plants in Seattle, USA. The viral load ranged from 1.2 &#xd7; 103 to 8.4 &#xd7; 103 genome copies per liter. The Oxford Nanopore platform was used for whole-genome sequencing. Complete or partial (>84%) HAdV-F41 genomes were recovered from wastewater samples, with mean coverage depths ranging from 10&#xb3; to 10&#x2075;. The consensus sequences showed more than 99% similarity to reference genomes in the NCBI database. The phylogenetic analysis revealed that 2 sequences clustered within lineage 2a and 11 within lineage 2b, reflecting that at least two sub-lineages were circulating in the community at that time. Our results demonstrate that the overlapping amplicon-based whole-genome sequencing approach using the Oxford Nanopore platform reliably recovers HAdV-F41 genomes from wastewater. This method offers high-resolution genomic surveillance of circulating, clinically relevant HAdV-F41, supporting wastewater-based epidemiology as a valuable tool for detecting emerging variants and strengthening the early warning system for future disease outbreaks.IMPORTANCEHuman adenovirus F41 is a primary cause of childhood gastroenteritis and has been linked to recent outbreaks of severe acute hepatitis in children, yet community-level genomic surveillance of this virus remains limited. This study shows that wastewater can be used to recover nearly complete HAdV-F41 genomes through a targeted overlapping-amplicon sequencing strategy on the Oxford Nanopore platform. By applying this method to archived wastewater samples, we detected the simultaneous circulation of multiple viral lineages in a large city. These findings extend wastewater-based epidemiology beyond SARS-CoV-2 and emphasize its importance for monitoring clinically significant enteric viruses. The method described here offers a scalable tool for tracking viral evolution in communities and enhancing early warning systems for future outbreaks.

Wastewater

Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses.

BACKGROUND: Patients with mechanical heart valve prostheses may experience valve thrombosis and subsequent systemic embolism for which they are treated with oral anticoagulant therapy. It is essential to know reliable estimates of the risks and benefits of this therapy in order to answer a number of clinical questions rationally. We sought to obtain more precise estimates of the risks and benefits by combining the data from individual studies by using meta-analysis. METHODS AND RESULTS: We searched for studies in which the incidences were reported of embolic or bleeding complications in patients with mechanical heart valve prostheses. They were collected from the Medline and Current Contents database and by cross-references between 1970 and 1992. Since most studies vary greatly in many respects, we used a number of inclusion criteria, thus selecting comparable studies of acceptable quality only. The influence of antithrombotic therapy, valve position, and valve type was analyzed by univariate and by multivariate analysis with Poisson regression techniques. Forty-six studies were found, including 13,088 patients studied for 53,647 patient-years. We found an incidence of major embolism in the absence of antithrombotic therapy of 4 per 100 patient-years. With antiplatelet therapy this risk was 2.2 per 100 patient-years, and with coumarin therapy it was reduced to 1 per 100 patient-years. This risk varied with the type and the site of the prosthesis. A prosthesis in mitral position increased the risk almost twice as compared with the aortic position. Tilting disc valves and bileaflet valves showed a lower incidence of major embolism than caged ball valves. An incidence of major bleeding was found in patients treated with coumarin derivatives of 1.4 per 100 patient-years. The incidence of bleeding became significantly higher with the addition of antiplatelet therapy, although this did not decrease the risk of thromboembolism any further. CONCLUSIONS: These data provide a reference for future studies and give adequate risk estimates for clinical decision making.

Anticoagulants