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PubMed2004

The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis.

BACKGROUND: A number of clinical trials have been undertaken to determine the efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals. However, the reported differences in patient populations, treatment duration, and study endpoints make comparisons difficult. An assessment of the efficacy of treatment with acamprosate was, therefore, undertaken using meta-analytical techniques. METHODS: All randomized, placebo-controlled trials (RCTs) that fulfilled predetermined criteria were identified using (1) a language unrestricted search of 10 electronic databases; (2) a manual search of relevant journals, symposia, and conference proceedings; (3) cross-referencing of all identified publications; (4) personal communications with investigators; and (5) scrutiny of Merck-Santé's internal reports of all European trials. Study quality was assessed, independently, by three blinded workers. Key outcome data were identified; some outcome variables were recalculated to ensure consistency across trials. The primary outcome measure was continuous abstinence at 6 months; abstinence rates were determined by estimating Relative Benefit (RB). RESULTS: A total of 19 published 1 unpublished RCTs were identified that fulfilled the selection criteria; 3 were excluded because the documentation available was insufficient to allow adequate assessment. The remaining 17 studies, which included 4087 individuals, 53% of whom received active drug, were of good quality and were otherwise reasonably comparable. There was no evidence of publication bias. Continuous abstinence rates at 6 months were significantly higher in the acamprosate-treated patients (acamprosate, 36.1%; placebo, 23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29-1.69]; p < 0.001). This effect was observed independently of the method used for assigning missing data. The effect sizes in abstinent rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively. At 12 months, the overall pooled difference in success rates between acamprosate and placebo was 13.3% (95% CI, 7.8-18.7%; number needed to treat, 7.5). Acamprosate also had a modest but significant beneficial effect on retention (6.01%; [95% CI, 2.90-8.82]; p = 0.0106). CONCLUSION: Acamprosate has a significant beneficial effect in enhancing abstinence in recently detoxified, alcohol-dependent individuals.

Acamprosate↗
PubMed1998

Validation of computerized Swedish dog and cat insurance data against veterinary practice records.

Large computerized medical databases offer great potential for epidemiological research. However, data-quality issues must be addressed. This study evaluated the agreement between veterinary practice records and computerized insurance data in a large Swedish claims database. For the year 1995, the company insured over 320,000 dogs and cats. A total of 470 hard-copy records were sampled from claims for health care (n = 236) and life insurance (n = 234). Computerized insurance data for these claims were accessed and records from the attending veterinary practices were collected. For health and life claims, respectively, 79.2 and 72.8% of practice records were retrieved. Variables compared between the computer and practice records were breed, sex, date of birth and diagnosis for the claim. The degree of agreement was categorized as agreement, minor disagreement, major disagreement or data missing. Multivariable logistic regression was used to examine factors associated with errors. The observed agreement for breed and sex was excellent. There was 28.9 and 33.8% minor disagreement for the date of birth for health and life claims, respectively. This was mainly because, prior to 1993, the date of birth was coded as the first of January when more complete information was unavailable. Major disagreement (different year of birth) was low for both health and life claims. For health and life claims, the observed agreement for diagnosis was 84.0 and 84.9%, minor disagreement was 6.4 and 4.3%, and major disagreement 5.9 and 9.4%, respectively. Although there was no difference based on size of the veterinary clinic involved, there was a tendency for better agreement between the practice record and the computerized insurance data for claims from clinics with computerized practice records (n = 40) than for clinics with manual practice records (n = 286). Rates of discrepancy were affected by the clerk who processed the claims. Records processed by two of the 21 clerks had significantly more disagreements. Given the nature of the data, it was only possible to calculate a measure of observed agreement. In general, the agreement between data in the insurance-company database and from the practice records was excellent for demographic data such as breed and sex and fair for diagnostic information and date of birth. In general, the data are adequate to support ongoing research with due considerations of certain limitations.

Animals↗
PubMed2005

Collection of population-based cancer staging information in Western Australia--a feasibility study.

BACKGROUND: Routine data from cancer registries often lack information on stage of cancer, limiting their use. This study aimed to determine whether or not it is feasible to add cancer staging data to the routine data collections of a population-based Western Australian Cancer Registry (WACR). METHODS: For each of the five most common cancer types (prostate, colorectal, melanoma, breast and lung cancers), 60 cases were selected for staging. For the 15 next most common cancer types, 20 cases were selected. Four sources for collecting staging data were used in the following order: the WACR, the hospital based cancer registries (HBCRs), hospital medical records, and letters to treating doctors. If the case was unable to be fully staged, due to lack of information on regional lymph node invasion or distant metastases, we made the following assumptions. Cases which had data available for tumour (T) and regional lymph nodes (N), but no assessment of distant metastasis (MX) were assumed to have no distant metastases (M0). Cases which had data for T and M, but no assessment of regional nodal involvement (NX) were assumed to have no regional nodal involvement (N0). RESULTS: The main focus of this project was the process of collecting staging data, and not the outcomes. For ovary, cervix and uterus cancers the existence of a HBCR increased the stageable proportion of cases so that staging data for these cancers could be incorporated into the WACR immediately. Breast and colorectal cancer could also be staged with adequate completeness if it were assumed that MX = M0. Similarly, melanoma and prostate cancer could be staged adequately if it were assumed that NX = N0 and MX = M0. Some cases of stomach, lung, pancreas, thyroid, testis and kidney cancers could be staged, but additional clinical input--on pathology request forms, for example--would be required to achieve useable levels of completeness. For the remaining cancer types either staging is widely regarded as not relevant, and no generally-accepted system exists, or an acceptable level of completeness is not achievable. CONCLUSION: Adding stage to routinely collected information in a cancer registry is possible for many cancer types, particularly if the assumptions regarding missing data are found to be acceptable or if the guidelines for MX = M0 assumptions are clarified. These findings should be generalizable to most cancer registries in developed countries, if hospital-based cancer registries or other specialized databases are accessible.

Journal Article↗
PubMed2000

The General Practice Assessment Survey (GPAS): tests of data quality and measurement properties.

OBJECTIVES: The aim of this study was to describe the psychometric properties of the General Practice Assessment Survey (GPAS) and its acceptability to patients in the UK. GPAS comprises seven multiple item scales and two single item scales addressing nine key areas of primary care activity (access, technical care, communication, inter-personal care, trust, knowledge of patient, nursing care, receptionists and continuity of care). A further four single items relate to patients' perceptions of the GP's role in referral and co-ordination of care, their willingness to recommend their GP and their overall satisfaction with care received. METHODS: Two hundred consecutive patients attending routine consulting sessions at 55 inner London practices were invited to complete the GPAS questionnaire. The acceptability, reliability and validity of GPAS was assessed using standard psychometric techniques. RESULTS: Out of 11 000 patients, 7247 (66%) completed a questionnaire in a GP surgery. Fifty-five out of a separate sample of 77 patients attending one practice completed a second questionnaire mailed to them 1 week following their attendance. GPAS was acceptable to patients as evidenced by low proportions of missing data for all items, and a full range of possible scores for all but one of the nine scales. Reliability of the instrument was good. Multiple item scales had excellent internal consistency, high item-total correlations, and test-retest reliability. Scaling assumptions were confirmed, with six of the seven scales achieving 100% scaling success (convergent and discriminant validity). Construct validity was evident, although this requires further evaluation against external measures. CONCLUSIONS: GPAS is a useful instrument for assessing several important dimensions of primary care. It is acceptable, reliable and valid, and has the potential for versatility in mode of administration. It will be a useful instrument for practices, primary care groups and primary care researchers evaluating key areas of primary care activity. Further work is required to evaluate its performance in non-inner-city settings and to evaluate further its validity against external criteria.

Adolescent↗
PubMed2002

The national fetal death file.

The most comprehensive source of US data on fetal deaths of 20 gestational weeks or greater is available through the National Vital Statistics System (NVSS). The NVSS is a collaborative effort between the independent reporting areas (the individual States and the territories), and the federal government or its agent, the Centers for Disease Control, and Prevention's National Center for Health Statistics (NCHS). The federal government has no authority to register vital events. The registration of births, deaths, fetal deaths, marriages, and divorces is solely a state responsibility. However, NCHS is mandated by law to produce national data based on vital events. To promote the uniformity necessary to create a national file from this decentralized system, NCHS attempts to influence state systems via the development of certain standards, primarily, The Model State Vital Statistics Act and Regulations (The Model Law), and the Standard Certificates and Reports. The Model Law definitions for live birth, fetal death and induced termination of pregnancy are based on international standards set by The World Health Organization. All states have definitions of fetal death consistent with the Model Law. The Model Law also recommends reporting requirements for fetal death, but state requirements vary. This variation results in differences in reporting of fetal deaths among areas. Other limitations to the national fetal death file include: the under-reporting of fetal deaths incidence, higher than acceptable levels of missing data for some items, and the accuracy of the data reported. Also of concern is the potential misclassification of fetal deaths and short-lived live births. These limitations are amenable to improvement. The upcoming revision of the US Standard Report of Fetal Death addresses these issues and offers an opportunity to strengthen the quality of fetal death data. The development of worksheets, detailed specifications and instruction manuals, and a reformatted cause of death section should importantly enhance the quality of national fetal death file and ultimately reduce the incidence of these tragic events.

Cause of Death↗
PubMed2002

Use of the short form health survey (SF-36) in patients with amyotrophic lateral sclerosis: tests of data quality, score reliability, response rate and scaling assumptions.

OBJECTIVES: To evaluate response rate, data quality, score reliability and scaling assumptions of the 36 item Short Form Health Survey (SF-36) in a large scale pan European survey of amyotrophic lateral sclerosis (ALS) patients. DESIGN: A questionnaire based survey of patients diagnosed with ALS across 15 European countries. SAMPLE PATIENTS: presenting at neurological clinics for treatment of their condition were asked to partake in the survey. RESULTS: 948 patients have been recruited into the survey, from whom responses have been gained in 754 (79.5%). Scores on the eight dimensions of the SF-36 were found to manifest high internal consistency reliability. Items were, in most instances, found to be most highly correlated with their own (corrected) scale score than with other scale scores. However, on two dimensions (role-physical and role-emotional) there was high levels of missing data, together with substantial floor and ceiling effects. The two factor model (of underlying constructs of physical and emotional health) for the SF-36 suggested by the developers was not supported in this patient group. CONCLUSION The SF-36 appears to provide reliable information for this patient group, and for the most part there are high levels of item completeness and good spread of scores. This is not, however, true for the role functioning dimensions. Furthermore, the underlying two factor model for the SF-36 was not supported. The implications for measuring health status in this patient group are discussed.

Aged↗
PubMed2007

Knowledge-based interpolation of curves: application to femoropopliteal arterial centerline restoration.

We present a novel algorithm, Partial Vector Space Projection (PVSP), for estimation of missing data given a database of similar datasets, and demonstrate its use in restoring the centerlines through simulated occlusions of femoropopliteal arteries, derived from CT angiography data. The algorithm performs Principal Component Analysis (PCA) on a database of centerlines to obtain a set of orthonormal basis functions defined in a scaled and oriented frame of reference, and assumes that any curve not in the database can be represented as a linear combination of these basis functions. Using a database of centerlines derived from 30 normal femoropopliteal arteries, we evaluated the algorithm, and compared it to a correlation-based linear Minimum Mean Squared Error (MMSE) method, by deleting portions of a centerline for several occlusion lengths (OL: 10 mm, 25 mm, 50 mm, 75 mm, 100 mm, 125 mm, 150 mm, 175 mm and 200 mm). For each simulated occlusion, we projected the partially known dataset on the set of basis functions derived from the remaining 29 curves to restore the missing segment. We calculated the maximum point-wise distance (Maximum Departure or MD) between the actual and estimated centerline as the error metric. Mean (standard deviation) of MD increased from 0.18 (0.14) to 4.35 (2.23) as OL increased. The results were fairly accurate even for large occlusion lengths and are clinically useful. The results were consistently better than those using the MMSE method. Multivariate regression analysis found that OL and the root-mean-square error in the 2 cm proximal and distal to the occlusion accounted for most of the error.

Algorithms↗
PubMed2005

Maternal perspectives on children's health-related quality of life during the first year after pediatric hematopoietic stem cell transplant.

OBJECTIVE: To assess the longitudinal health-related quality of life (HRQL) of children receiving hematopoietic stem cell transplantation (HSCT). METHODS: Mothers (N = 160) of HSCT recipients aged 5-20 at six US transplant centers completed the Child Health Ratings Inventories (CHRIs), the Disease Impairment Inventory (DSII)-HSCT module, and the Short Form (SF)-36 at baseline, 3, 6, and 12 months. RESULTS: HRQL domain scores at baseline varied by recipient age and program site. Longitudinal data over the first year post-HSCT revealed lowest functioning at baseline and 3 months, with largest improvement in functioning between the 3 and 6-months assessments and continued improvement from 6 to 12 months. Recipients of unrelated donor transplants had steepest declines in functioning at 3 months and great HSCT-specific issues at 3 and 6 months. Among children who survived the first year, functioning at 12 months was similar across transplant types and surpassed baseline scores. Children who did not survive the first year exhibited deterioration in HRQL in the months before death and trajectories were strikingly different than for survivors. CONCLUSIONS: This study offers the first glimpse of the 12-month trajectory of HRQL following pediatric HSCT from mothers' perspectives. This study also highlights the importance of and approaches to addressing missing data in longitudinal research.

Activities of Daily Living↗
PubMed1999

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.

Cardiovascular Diseases↗
PubMed2001

The effect of pretransplant interferon therapy on the outcome of unrelated donor hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in first chronic phase.

Various therapeutic options are available for patients with chronic myelogenous leukemia. Allogeneic stem cell transplantation, though often curative, is associated with high nonrelapse mortality and long-term morbidity, particularly when cells from unrelated donors are used. Many physicians and patients opt for a trial of interferon-alpha (IFN)-based therapy first, reserving transplantation for patients with inadequate response or intolerance to IFN. Data were analyzed on 740 patients receiving unrelated donor transplants for chronic myelogenous leukemia in first chronic phase provided by the International Bone Marrow Transplant Registry and the National Marrow Donor Program to see whether IFN pretreatment compromised transplantation outcome. A total of 489 (66%) had received IFN prior to transplantation; 251 (34%) had not. Disease characteristics in the 2 groups were similar at diagnosis but at the time of transplantation, hematologic parameters and weight were lower in IFN patients and the interval between diagnosis and transplantation was longer. After adjustment for baseline covariates, no effect of IFN exposure was found on overall survival, leukemia-free survival, nonrelapse mortality, engraftment, relapse, or acute or chronic graft-versus-host disease. Evaluation of effects based on duration of therapy and time off IFN prior to transplantation was limited by missing data and confounding with IFN intolerance and disease responsiveness. In conclusion, no evidence was found for an independent adverse effect of IFN pretreatment on the outcome of subsequent unrelated donor transplantation.

Acute Disease↗
PubMed2004

Decompression sickness in Miskito Indian lobster divers: review of 229 cases.

BACKGROUND: The Miskito Indian lobster divers of Central America employ very provocative diving profiles and experience severe neurological decompression sickness (DCS) and/or arterial gas embolism (AGE). Scientific data are scarce regarding the clinical patterns of injury, response to treatment, and functional outcomes for such cases. METHODS: A retrospective review of 229 cases of DCS and/or AGE was conducted at 2 hyperbaric units in Central America. RESULTS: The following deficits were recorded on presentation: any neurological deficit: 94%; motor: 79%; sensory: 60%; urinary: 48%; reflex: 45%; and loss of consciousness: 20%. The patterns of weakness (n = 182) were as follows: paraparesis: 27%; paraplegia: 26%; lower extremity monoparesis: 14%; lower extremity monoplegia: 6%; quadriparesis: 4%; hemiparesis: 4%; hemiplegia: 3%; and quadriplegia: 2%. Treatment was delayed by a mean and median of 5 and 2 d, respectively. The majority received hyperbaric oxygen and systemic steroids. Motor function on discharge (n = 182) was as follows: normal: 30%; paraparesis: 15%; lower extremity monoparesis: 15%; paraplegia: 3%; quadriparesis: 2%; hemiparesis: 2%; and missing data/other: 33%. Gait on discharge (n = 182) was as follows: normal: 19%; abnormal: 19%; required one crutch: 10%; required two crutches: 16%; not ambulatory: 5%; and missing data: 31%. DISCUSSION: The majority of severe injuries could be localized to the thoracolumbar spinal cord. One-fifth had bilateral cerebral dysfunction manifested by loss of consciousness. Despite long delays to treatment, divers responded to hyperbaric oxygen. At the time of discharge, almost a third had complete recovery of strength and the majority were ambulatory.

Adolescent↗
PubMed1996

Occupational asthma: measures of frequency from four countries.

Disease registers and surveillance schemes are not necessarily designed to measure incidence and prevalence, but their data can provide useful epidemiological insights. Their main functions are the detection and identification of hazards so that further cases can be prevented, and to provide a database for research to improve our understanding of the determinants and consequences of disease. Occupational asthma probably accounts for only a small proportion of adult asthma, of the order of 2-6% in the UK. On the other hand, asthma is very common and so thousands of people in the UK and in other western countries have asthma as a result of their work. The frequency of the disease in less developed countries is unknown but is potentially very large. Information on incidence is patchy but from Finland, where ascertainment is most complete, there are approximately 140 per million working people affected each year, and even there disease in the self-employed is probably missed. Data for the UK are limited to cases seen by specialist physicians and the best estimate is that the annual incidence of such cases is about 50 per million. Through internal comparisons and analysis it is possible to judge the extent to which variation in ascertainment and reporting have affected the frequency of reported disease, but so far it has not been possible to measure the underestimation due to persons with work-related symptoms not seeking medical attention or not being referred to a specialist.

Adolescent↗
PubMed1989

A robust orthogonal algorithm for system identification and time-series analysis.

We describe and illustrate methods for obtaining a parsimonious sinusoidal series representation or model of biological time-series data. The methods are also used to identify nonlinear systems with unknown structure. A key aspect is a rapid search for significant terms to include in the model for the system or the time-series. For example, the methods use fast and robust orthogonal searches for significant frequencies in the time-series, and differ from conventional Fourier series analysis in several important respects. In particular, the frequencies in our resulting sinusoidal series need not be commensurate, nor integral multiples of the fundamental frequency corresponding to the record length. Freed of these restrictions, the methods produce a more economical sinusoidal series representation (than a Fourier series), finding the most significant frequencies first, and automatically determine model order. The methods are also capable of higher resolution than a conventional Fourier series analysis. In addition, the methods can cope with unequally-spaced or missing data, and are applicable to time-series corrupted by noise. Finally, we compare one of our methods with a well-known technique for resolving sinusoidal signals in noise using published data for the test time-series.

Algorithms↗
PubMed1997

Evaluation of the expert system for respiratory therapy of newborns on archival data.

The aim of this study was to evaluate the artificial ventilation expert system for neonates (AVES-N) using archival data. The recommendations of the system were compared to the decisions made by the expert-physician in the same clinical situation (patient condition, respirator settings). In our retrospective study we used data of 320 newborns which were ventilated in the Neonatal Intensive Care Unit of the Vanderbilt University Hospital in Nashville (USA). Best agreement between the recommendations of the system and the decisions of the experts was found for positive end expiratory pressure (PEEP), inspired oxygen fraction (FiO2) and peak inspiratory pressure (PIP)--about 70%. Worse agreement was found for time related parameters: respiratory frequency (f) - 54%, time of inspiration (ti) - 46%, time of next blood gas analysis - 15%. The expert system advised lower FiO2 PEEP and f. The differences were smaller in a group of patients who survived than in a group of patients who died. The overall agreement of the AVES-N advice and real therapeutic actions leads to the clinical evaluation of the expert system. The differences can be attributed to a) different therapeutic strategies at 2 NICU's, b) missing data regarding complications in the data base which were not taken into account by the expert system.

Archives↗
PubMed1991

Treatment of migraine attacks with sumatriptan.

BACKGROUND: The headache in migraine attacks may be caused by dilatation of certain cranial arteries or arteriovenous anastomoses, by neurogenic dural plasma extravasation, or by both of these mechanisms. Sumatriptan, a novel selective agonist of 5-hydroxytryptamine-like receptors, blocks these phenomena. We investigated its efficacy in migraine. METHODS: We studied 639 patients with migraine attacks in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. We assessed the effect of subcutaneous injections of 6 or 8 mg of sumatriptan or placebo on the severity of headache and associated migrane symptoms 30, 60, and 120 minutes after treatment. Patients who were not free of pain after 60 minutes subsequently received placebo if they had initially received placebo or 8 mg of sumatriptan, and 6 mg of sumatriptan or placebo if they had initially received 6 mg of sumatriptan. RESULTS: After 60 minutes, the severity of headache was decreased in 72 percent (95 percent confidence interval, 68 to 76 percent) of the 422 patients given 6 mg of sumatriptan, 79 percent (95 percent confidence interval, 71 to 87 percent) of the 109 patients given 8 mg of sumatriptan, and 25 percent (95 percent confidence interval, 17 to 33 percent) of the 105 patients given placebo (data on 3 patients could not be evaluated). As compared with the placebo group, 47 percent (95 percent confidence interval, 38 to 57 percent) more patients who had received 6 mg of sumatriptan and 54 percent (95 percent confidence interval, 43 to 65 percent) more patients who had received 8 mg of sumatriptan had a decrease in the severity of headache (P less than 0.001 for both comparisons). After 120 minutes, 86 to 92 percent of the 511 patients treated with sumatriptan (202 assigned to 6 mg plus placebo, 203 to 6 mg plus 6 mg, and 106 to 8 mg plus placebo) had improvement in the severity of headache, as compared with only 37 percent of the 104 patients who received placebo once or twice (P less than 0.001 for all comparisons). Twenty-one patients were excluded from the analysis because of missing data (19) or protocol violations (2). The response rates did not differ significantly among the sumatriptan regimens. Adverse events were minor and transient in all groups. CONCLUSIONS: We conclude that a single 6-mg dose of sumatriptan given subcutaneously is a highly effective, rapid-acting, and well-tolerated treatment for migrane attacks. The administration of a second dose 60 minutes later to patients not responding well to an initial dose affords little additional benefit.

Adolescent↗
PubMed2006

Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder.

OBJECTIVE: The effect of lamotrigine maintenance therapy on body weight was assessed retrospectively in analyses of data from two double-blind, placebo- and lithium-controlled, 18-month studies in patients with bipolar I disorder (n = 227 for lamotrigine, 190 for placebo, 166 for lithium). METHODS: Endpoints included mean change in weight, the percentage of patients with > or = 7% change (increase, decrease, fluctuation) in weight, and the percentage of patients with weight-related adverse events during double-blind treatment. RESULTS: Mean weight remained stable during maintenance therapy with lamotrigine. In a mixed-model repeated-measures analysis, mean changes in weight (kg) at week 52 were -1.2 with lamotrigine, +0.2 with placebo, and +2.2 with lithium [estimated difference (95% CI) lamotrigine minus placebo = -1.3 (-3.6, 0.9), p = 0.237; lithium minus placebo = +2.0 (-0.3, 4.4), p = 0.094; lithium minus lamotrigine = +3.4 (1.4, 5.4), p < 0.001]. Analyses were truncated at week 52 because of the high incidence of missing data at later time points. The percentages of patients with a >/=7% weight gain, during randomized treatment, were 10.9%, 7.6% and 11.8% for the lamotrigine, placebo, and lithium groups, respectively. The percentages of patients with a > or = 7% weight loss, during randomized treatment, were 12.1%, 11.5%, and 5.1% for the lamotrigine, placebo, and lithium groups, respectively. The percentage of patients with a > or = 7% weight loss did not significantly differ between lamotrigine and placebo but was significantly higher with lamotrigine than lithium. The incidences of > or = 7% weight changes and of weight changes reported as adverse events were comparable between active treatments and placebo. CONCLUSION: Lamotrigine was associated with stable body weight during 1 year of treatment and was comparable to placebo in mean weight change, incidence of clinically significant weight change, and incidence of weight changes reported as adverse events in patients with bipolar disorder. Lithium was associated with weight gain, but the magnitude of lithium-associated weight gain was lower in the current analysis than in previous studies.

Adult↗
PubMed1998

Management-related risk factors for M. paratuberculosis infection in Michigan, USA, dairy herds.

A cross-sectional study was conducted from June through December 1996 to identify management-related risk factors for herd-level M. paratuberculosis infection. Data were collected from 121 participating herds. A two-part questionnaire was administered to gather data on current and previous management practices and herd productivity. A random sample of cows aged > or = 24 months was selected from each herd and tested for antibodies to M. paratuberculosis using the IDEXX Antibody ELISA (sensitivity 64%, specificity 96%). A positive herd was one in which > or = 2 animals tested positive for antibodies to M. paratuberculosis. A negative herd was one in which no animal tested positive. Herds in which only one animal tested positive were dropped from statistical analysis to reduce the risk of including false-positive herds in the statistical analyses. There were 80 herds with one or more positive animals and 41 herds with no positive animals in the sample (66% herd-level prevalence). Twenty-six herds (21%) were dropped from further analyses because they had only one positive cow. Twelve herds (10%) were dropped from analysis because of missing data. The resulting sample used for statistical modeling included 46 positive herds and 37 negative herds (55% herd-level prevalence). A multi-variable logistic-regression model was used to evaluate the results. The variable 'use of an exercise lot for lactating cows' was associated with a three-fold increase in odds of a herd being positive for M. paratuberculosis infection (O.R. = 3.01, C.I. = 1.03-8.80); 'cleaning of maternity pens after each use' was associated with a three-fold reduction in odds of a herd being positive for M. paratuberculosis infection (O.R. = 0.28, C.I. = 0.08-0.89); 'application of lime to pasture areas in 1993' resulted in a ten-fold decrease in odds of a herd being positive for M. paratuberculosis infection (O.R. = 0.10, C.I. = 0.02-0.56).

Analysis of Variance↗
PubMed2004

A nearest-neighboring-end algorithm for genetic mapping.

MOTIVATION: High-throughput methods are beginning to make possible the genotyping of thousands of loci in thousands of individuals, which could be useful for tightly associating phenotypes to candidate loci. Current mapping algorithms cannot handle so many data without building hierarchies of framework maps. RESULTS: A version of Kruskal's minimum spanning tree algorithm can solve any genetic mapping problem that can be stated as marker deletion from a set of linkage groups. These include backcross, recombinant inbred, haploid and double-cross recombinational populations, in addition to conventional deletion and radiation hybrid populations. The algorithm progressively joins linkage groups at increasing recombination fractions between terminal markers, and attempts to recognize and correct erroneous joins at peaks in recombination fraction. The algorithm is O (mn3) for m individuals and n markers, but the mean run time scales close to mn2. It is amenable to parallel processing and has recovered true map order in simulations of large backcross, recombinant inbred and deletion populations with up to 37,005 markers. Simulations were used to investigate map accuracy in response to population size, allelic dominance, segregation distortion, missing data and random typing errors. It produced accurate maps when marker distribution was sufficiently uniform, although segregation distortion could induce translocated marker orders. The algorithm was also used to map 1003 loci in the F7 ITMI population of bread wheat, Triticum aestivum L. emend Thell., where it shortened an existing standard map by 16%, but it failed to associate blocks of markers properly across gaps within linkage groups. This was because it depends upon the rankings of recombination fractions at individual markers, and is susceptible to sampling error, typing error and joint selection involving the terminal markers of nearly finished linkage groups. Therefore, the current form of the algorithm is useful mainly to improve local marker ordering in linkage groups obtained in other ways. AVAILABILITY: The source code and supplemental data are http://www.iubio.bio.indiana.edu/soft/molbio/qtl/flipper/ CONTACT: ccrane@purdue.edu.

Algorithms↗