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PubMedDate not supplied

M-mode echocardiographic ratio indices in normal dogs, cats, and horses: a novel quantitative method.

A novel method for quantitative echocardiographic interpretations is introduced based on the calculation of ratio indices in which each raw M-mode measurement is divided by the aortic root dimension (Ao). "Aorta-based" indices were calculated with the animal's measured aortic root dimension (Ao(m)) as the length standard. Conversely, "weight-based" indices employed an idealized estimate of aortic dimension (Ao(w)) with a weighted least squares linear regression against the cube root of body weight (Ao(w) = kW(1/3)). Use of these indices circumvented undesirable statistical characteristics inherent in linear regression of echocardiographic dimensions against body weight and, to a lesser extent, body surface area. Compared with the regressions, ratio indices resulted in substantial refinement of the predictive range for each M-mode measurement in dogs, particularly with decreasing body size. Weight-based indices outperformed aorta-based indices in this regard. To refine the predictive range, neither type of index was clearly advantageous in cats compared with the simple average method typically employed for that species. Several of the raw M-mode measurements, however, were correlated with body weight in cats and horses, indicating the need for an appropriate correction for body size in these species. The ratio index method was suitable for this purpose. Summary statistics derived from normal dogs (n = 53), cats (n = 32), and horses (n = 17) are presented for each index, including novel clinical indices calculated from area ratios. The latter were designed to represent body size-adjusted lett ventricular stroke area (ie, volume overload) and myocardial wall area (ie, hypertrophy).

Animals↗

PubMed1998

[Clinical studies on emergency medicine. An application oriented classification, its planning and realization].

Clinical studies are usually conceived of as controlled randomized trials, as retrospective patient statistics or as single case reports. However, such a classification is too narrow and overlooks many other forms of study designs. This review, therefore, offers a more encompassing and practical classification of clinical studies for the field of emergency medicine. Randomized controlled trials fulfill scientific criteria at the highest level (gold standard): comparison, repeatability, objective measurement. At the same time, randomized trials also have to comply with demanding ethical criteria and must be justifiable in the individual patient. Therefore, comparable uncertainty with regard to the superiority of the treatment options under investigation is a sine qua non. In addition to randomized trials, six other groups of clinical trials have the potential to solve scientific questions in emergency medicine: observational studies, decision analysis, meta analysis, public health care studies, case reports and descriptive summary statistics and studies on ethical problems. This variability in trial designs calls for a clinically oriented methodologist; the concept and institutionalization of theoretical surgery has been a response to this demand. All study types in this review are illustrated by examples in emergency medicine. Literature for advanced reading in particular trial methodologies can be found in the reference list. A checklist summarizes all elements for designing and conducting randomized trials in emergency medicine. All clinical trials striving for a high standard of quality--whether randomized or not--depend on the following prerequisites:professional organization, time effort, a supportive social environment and a scientific culture.

Clinical Trials as Topic↗

PubMed2006

The use of background signal in the transformation of cDNA-microarray measurements.

As the application field of microarrays grows, so does the need for appropriate statistical tools to analyse the signal intensity measurements. Normalisation procedures are required to make the signals from different channels and arrays comparable. One objective, which is also the focus of this report, is to remove the curvature seen on plots of the log ratio versus the mean log intensity values of two channels.A number of methods already exist that are based on the assumption of a shift between the measurements of the two channels. In this article, we explore the use of background measurements to estimate and correct for the shift. We compare our proposal with some well known methods by applying them to microarrays from two studies. These two studies investigate the effect of vegetable diets on the gene expression in colon and lung tissue of mice. Graphical illustrations and a robust summary statistic show that all transformations are an improvement to the raw data. Overall, the best results are obtained with our proposed transformation that takes the background measurements into account.

Algorithms↗

PubMed2000

First steps in analysing NHS waiting times: avoiding the 'stationary and closed population' fallacy.

The aim of this paper is to demonstrate the effect of excluding incomplete observations and competing events when calculating cross-sectional measures of NHS waiting times, and to obtain a more accurate estimate of the 'time-to-admission' of those listed on NHS waiting lists using life-table methods. The official 'times-since-enrollment' of all elective 'admissions' in England, 1 July to 31 December 1994 inclusive, were extracted from Hospital Episode Statistics. The official 'times-to-census' of all those on a waiting list in England at 30 September 1994 were obtained from aggregated KH07 data. The percentage waiting at least three months, at least six months etc., was calculated separately for each data set and compared with a period life-table derived from the combined data. The cumulative likelihood of elective admission is markedly overestimated across the whole range of waiting times. The experience of those still waiting, those removed from the list, those suspended or deferred and those put to the back of the queue is not taken into account in the calculation of official waiting times. The Department of Health currently presents the 'time-since-enrollment' of those admitted as though it indicates how long all patients can expect to wait for admission. The consequent bias in published summary statistics incorrectly quantifies the real experience of patients. It is recommended that calculation of waiting times from KH07 census counts and Hospital Episode Statistics be reconsidered in the light of what patients, clinicians, managers and politicians need to know about treatment delay.

Bias↗

PubMed2004

Systematic correlation of transcranial magnetic stimulation and magnetic resonance imaging in cervical spondylotic myelopathy.

STUDY DESIGN: A prospective study over a 3.5-year period involving transcranial magnetic stimulation and magnetic resonance imaging. OBJECTIVES: To assess the correlation of transcranial magnetic stimulation and magnetic resonance imaging in cervical spondylotic myelopathy qualitatively and statistically. SUMMARY OF BACKGROUND DATA: Cervical spondylotic myelopathy presents with different degrees of cord compression, which can be assessed by magnetic resonance imaging. There are no large studies correlating transcranial magnetic stimulation and magnetic resonance imaging findings in this condition. METHODS: A total of 141 patients with a clinical diagnosis of cervical spondylotic myelopathy were prospectively studied over a 3.5-year period. They were classified into Groups 1 to 4 based on severity of cervical cord changes on magnetic resonance imaging. All had transcranial magnetic stimulation and central motor conduction time measurements within 2 months of the magnetic resonance imaging study. RESULTS: Twenty-eight, 49, 28, and 36 patients were classified into Groups 1 to 4, respectively. Mean upper limb and lower limb central motor conduction times correlated with the severity of magnetic resonance cord compression. The absence of central motor conduction time abnormalities correlated reliably with the absence of cervical cord impingement as in Group 1. Statistically significant right left difference in central motor conduction time in the lower limbs was seen between Groups 1 (no cord changes) and Group 2 (mild cord impingement). Eight other patients with diagnoses other than cervical spondylotic myelopathy all showed central motor conduction time abnormalities. The sensitivity and specificity for transcranial magnetic stimulation for differentiating the presence from absence of magnetic resonance imaging cord abnormality were 100% and 84.8%, respectively. CONCLUSIONS: Transcranial magnetic stimulation showed excellent correlation with magnetic resonance imaging findings and can be considered as an effective technique for screening patients for cervical cord abnormalities before magnetic resonance imaging in the clinical setting. The findings in this study have relevant implications in the pathophysiology, management, and health costs of cervical spondylotic myelopathy.

Adult↗

PubMed2006

Information-based functional brain mapping.

The development of high-resolution neuroimaging and multielectrode electrophysiological recording provides neuroscientists with huge amounts of multivariate data. The complexity of the data creates a need for statistical summary, but the local averaging standardly applied to this end may obscure the effects of greatest neuroscientific interest. In neuroimaging, for example, brain mapping analysis has focused on the discovery of activation, i.e., of extended brain regions whose average activity changes across experimental conditions. Here we propose to ask a more general question of the data: Where in the brain does the activity pattern contain information about the experimental condition? To address this question, we propose scanning the imaged volume with a "searchlight," whose contents are analyzed multivariately at each location in the brain.

Adolescent↗

PubMed2001

Survival estimates for patients with homozygous sickle-cell disease in Jamaica: a clinic-based population study.

BACKGROUND: Information about life expectancy of patients with homozygous sickle-cell disease is needed for research and patient counselling. Our aim was to study two Jamaican populations, one clinic-based and one birth cohort and, by careful consideration of data quality and statistical analysis, to identify ways to increase the chances of obtaining valid and generalisable results. METHODS: We investigated the survival experience of 3301 patients with homozygous sickle-cell disease attending the Jamaican sickle-cell clinic between Jan 1, 1987, and Dec 31, 1996. We applied and assessed a simulation technique for incorporating early life mortality using a birth cohort, and analysed the precision of this technique. Kaplan-Meier survival estimates are produced. FINDINGS: 290 of the 3301 patients died. Median survival calculated with the excess mortality rate simulation data was 53 years (95% CI 49.3-57.0) for men and 58.5 (55.1-67.5) for women. INTERPRETATION: Our simulation technique, with realistic assumptions based on empirical evidence, offers a new estimate of median survival for patients with homozygous sickle-cell disease. We present the precision of these survival estimates, which introduces an important level of uncertainty. The inherent biases of clinically ascertained populations of patients, and the assumptions underlying analysis techniques are crucial features of survival studies in sickle-cell disease, and can modify summary statistics substantially.

Adolescent↗

PubMed2006

Exact coalescent for the Wright-Fisher model.

The Kingman coalescent, which has become the foundation for a wide range of theoretical as well as empirical studies, was derived as an approximation of the Wright-Fisher (WF) model. The approximation heavily relies on the assumption that population size is large and sample size is much smaller than the population size. Whether the sample size is too large compared to the population size is rarely questioned in practice when applying statistical methods based on the Kingman coalescent. Since WF model is the most widely used population genetics model for reproduction, it is desirable to develop a coalescent framework for the WF model, which can be used whenever there are concerns about the accuracy of the Kingman coalescent as an approximation. This paper described the exact coalescent theory for the WF model and develops a simulation algorithm, which is then used, together with an analytical approach, to study the properties of the exact coalescent as well as its differences to the Kingman coalescent. We show that the Kingman coalescent differs from the exact coalescent by: (1) shorter waiting time between successive coalescent events; (2) different probability of observing a topological relationship among sequences in a sample; and (3) slightly smaller tree length in the genealogy of a large sample. On the other hand, there is little difference in the age of the most recent common ancestor (MRCA) of the sample. The exact coalescent makes up the longer waiting time between successive coalescent events by having multiple coalescence at the same time. The most significant difference among various summary statistics of a coalescent examined is the sum of lengths of external branches, which can be more than 10% larger for exact coalescent than that for the Kingman coalescent. As a whole, the Kingman coalescent is a remarkably accurate approximation to the exact coalescent for sample and population sizes falling considerably outside the region that was originally anticipated.

Algorithms↗

PubMed1990

Self-reported work-sampling methods for evaluating pharmaceutical services.

The steps involved in designing a self-reported work-sampling study of pharmacy department operations are described. Traditional methods of work measurement include subjective evaluation, time-and-motion studies, and analysis of departmental statistics and are appropriate when the research question concerns repetitive work and when data about single activities at single points in time are sought. When institution-wide changes are being considered, a more global measurement approach is needed. Work sampling allows a manager to measure indirectly the amount of time spent by employees on work activities during a specified period. Many instantaneous observations are taken randomly or systematically to estimate the proportion of time spent on any activity. Data may be collected by trained observers or may be self-reported; self-reporting facilitates a large number of short-interval observations and allows for the reporting of cognitive activities. In designing a self-reported work-sampling study, the manager must (1) identify the study objective, (2) define the service area and staff to be studied, (3) inform all staff members to be involved, (4) define temporally relevant workload measures, (5) decide how many observations are needed, (6) decide for how long data will be collected, (7) choose between randomized and systematic sampling times, (8) define categories of work representative of staff activities, (9) design data collection forms and communicate procedures, and (10) conduct a pilot study. To interpret the results, an analysis of simple summary statistics may be more appropriate than a sophisticated statistical analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Data Interpretation, Statistical↗

PubMed2006

Using propensity scores to estimate the cost-effectiveness of medical therapies.

The cost-effectiveness ratio is a popular statistic that is used by policy makers to decide which programs are cost-effective in the public health sector. Recently, the net monetary benefit has been proposed as an alternative statistical summary measure to overcome the limitations associated with the cost-effectiveness ratio. Research on using the net monetary benefit to assess the cost-effectiveness of therapies in non-randomized studies has yet to be done. Propensity scores are useful in estimating adjusted effectiveness of programs that have non-randomized or quasi-experimental designs. This article introduces the use of propensity score adjustment in cost-effectiveness analyses to estimate net monetary benefits for non-randomized studies. The uncertainty associated with the net monetary benefit estimate is evaluated using cost-effectiveness acceptability curves. Our method is illustrated by applying it to SEER-Medicare data for muscle invasive bladder cancer to determine the most cost-effective treatment protocol.

Aged↗

PubMed2001

Surface anatomy of the face in Down's syndrome: anthropometric proportion indices in the craniofacial regions.

The objective of the study was to identify the proportions closest to normal and those indicating mild-to-moderate and severe degrees of disproportion. Eight proportion indices were analyzed in five craniofacial regions of 125 Down's syndrome patients, based on a total of 985 data points. More than two thirds of the patients fell within the normal range, although more than one quarter were abnormal (disproportionate). All statistical summaries were based on z-scores (adjusting for age and sex differences), converted into descriptive anthropometric categories to yield a simplified frequency distribution for each proportion index. Normal proportions were harmonious in 55.9% of patients. Disproportions were mild to moderate in 66.4%, severe in 33.6%. The highest frequency of harmony was found in the head (70.2%), the lowest in the orbits (40.8%). The highest percentage of mild-moderate disproportion was found in the face (79.3%). The highest percentage of severe disproportions was recorded in the intercanthal index of the orbits (44.7%) and the smallest frequency in the face (20.7%). In the five craniofacial regions among the normal proportions, harmonies were more frequent than disharmonies. Among the disproportions, the percentage of mild-moderate ones was greater than those of severe degree.

Adolescent↗

PubMed2005

Child health-related quality of life and household food security.

OBJECTIVE: To examine the association of household food insecurity with child self- or proxy-reported health-related quality of life (HRQOL). DESIGN: Cross-sectional telephone survey from January 1, 2000, through June 30, 2000. PARTICIPANTS: Three hundred ninety-nine children who live in 36 counties of the Delta region of Arkansas, Louisiana, and Mississippi. MAIN OUTCOME MEASURES: Household food insecurity status was measured using the US Household Food Security Scale. Child HRQOL was measured by the Pediatric Quality of Life Inventory, QL version 4.0. Analysis Summary statistics, linear and logistic regressions, incorporating survey weights, performed with SUDAAN version 8. RESULTS: Household food insecurity was significantly associated with total child HRQOL (P<.05) and physical function (P<.05), adjusted for child age, ethnicity, gender, and family income. Children aged 3 through 8 years in food insecure households were reported by parents to have lower physical function (P = .001), while children aged 12 through 17 years reported lower psychosocial function (P = .007). Black males in food insecure households reported lower physical function (P<.05) and lower total HRQOL (P<.05). CONCLUSIONS: Children who live in food insecure households have poorer HRQOL. The effect on physical or psychosocial function may differ by age, ethnicity, and gender. Food security should be considered an important risk factor for child health.

Adolescent↗

PubMed2005

Is this patient having a stroke?

CONTEXT: Patients suspected of having a stroke or transient ischemic attack require accurate assessment for appropriate acute treatment and use of secondary preventive interventions. OBJECTIVE: To update a 1994 systematic review of the accuracy and reliability of symptoms and findings on neurological examination for the evaluation of patients with suspected stroke or transient ischemic attack. DATA SOURCES: We identified potential articles dated between 1994 and 2005 by multiple search strategies of the MEDLINE database and review of article and textbook bibliographies along with private collections. STUDY SELECTION: Selected articles provided primary data or appropriate summary statistics of the accuracy and/or reliability of the history or physical examination for diagnosis or short-term prognosis of patients with neurological signs prompting a consideration of stroke. Articles addressing accuracy also needed to provide a final diagnosis following neuroimaging and all relevant laboratory tests. DATA EXTRACTION: The authors reviewed and abstracted data for estimating sensitivities, specificities, positive and negative likelihood ratios (LRs). Reliability assessment was based on reported kappa (kappa) statistics or intraclass correlation coefficients as appropriate. DATA SYNTHESIS: The prior probability of a stroke among patients with neurologically relevant symptoms is 10%. Based on studies using modern neuroimaging, the presence of acute facial paresis, arm drift, or abnormal speech increases the likelihood of stroke (LR of > or =1 finding = 5.5; 95% CI, 3.3-9.1), while the absence of all 3 decreases the odds (LR of 0 findings = 0.39; 95% CI, 0.25-0.61). The accurate determination of stroke subtype requires neuroimaging to distinguish ischemic from hemorrhagic stroke. Early mortality increases among those with any combination of impaired consciousness, hemiplegia, and conjugate gaze palsy (LR of > or =1 finding = 1.8; 95% CI, 1.2-2.8 and LR of 0 findings = 0.36; 95% CI, 0.13-1.0). Symptoms associated with high agreement for the diagnosis of stroke or transient ischemic attack vs no vascular event are a sudden change in speech, visual loss, diplopia, numbness or tingling, paralysis or weakness, and non-orthostatic dizziness (kappa = 0.60; 95% CI, 0.52-0.68). The reliabilities of individual neurological findings vary from slight to almost perfect, but can be improved with standardized scoring systems such as the National Institutes of Health Stroke Scale. Based on examination findings, stroke vascular distribution can be determined with moderate to good reliability (kappa = 0.54; 95% CI, 0.39-0.68). CONCLUSIONS: The history and clinical findings provide the basis for evaluating patients with possible stroke and choosing appropriate treatments. Focusing on 3 findings (acute facial paresis, arm drift, or abnormal speech) might improve diagnostic accuracy and reliability.

Emergency Medical Services↗

PubMed2025

Polygenic Contributions to Lithium Augmentation Outcomes in Unipolar Depression.

IMPORTANCE: Lithium augmentation is an effective treatment for patients with major depression after inadequate antidepressant response, but therapeutic outcomes vary considerably between individuals. Molecular studies may provide novel insights into treatment prediction and guide personalized therapy. OBJECTIVE: To investigate the association of polygenic risk scores (PRS) for schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) with clinical outcomes after lithium augmentation. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed prospectively assessed treatment outcomes in patients who underwent lithium augmentation. Disorder-specific PRS were calculated using well-powered genome-wide association study summary statistics. Participants were recruited from 13 psychiatric hospitals, primarily in the greater Berlin area, between 2008 and 2020. They were patients with MDD who showed inadequate response to at least 1 antidepressant, a baseline score of 12 or more on the 17-item Hamilton Depression Rating Scale (HAMD-17), adequate treatment duration (≥4 weeks), and no diagnostic or co-medication changes. Data analysis was conducted between June 2022 and November 2023. EXPOSURE: Polygenic risk scores for MDD, SCZ, or BIP. MAIN OUTCOMES AND MEASURES: Response was defined as a 50% or greater reduction in HAMD-17 score, remission as a HAMD-17 score of 7 or less. Cox proportional hazards models, adjusted for ancestry, demographic, and clinical covariates, were used to estimate hazard ratios (HRs) for favorable outcomes. RESULTS: Among 193 patients (mean [SD] age, 49.5 [13.4] years; 118 [61.1%] female and 75 [38.9%] male), higher BIP-PRS were associated with both response (HR, 1.29; 95% CI, 1.02-1.63; P = .03) and remission (HR, 1.52; 95% CI, 1.14-2.04; P = .004), explaining 2.51% and 4.53% of the variability in treatment outcomes, respectively. Individuals in the highest tertile of the BIP-PRS distribution had a 2.02-fold (95% CI, 1.15-3.53) higher likelihood of response and a 2.26-fold (95% CI, 1.17-4.36) higher chance of remission compared with those in the lowest tertile. Additionally, lower MDD-PRS was associated with better response to lithium augmentation (HR, 0.81; 95% CI, 0.66-1.00; P = .048; Nagelkerke R2 = 1.99%). No significant associations were observed between SCZ-PRS and response (HR, 1.00; 95% CI, 0.80-1.24; P = .97) or remission (HR, 1.12; 95% CI, 0.85-1.48; P = .42). CONCLUSIONS AND RELEVANCE: Individuals carrying a higher polygenic burden for BIP and lower polygenic risk for MDD are more likely to benefit from lithium augmentation. Our findings suggest that disease-related PRS may aid in developing treatment prediction models for lithium augmentation response in depression, potentially informing clinical decision-making.

Humans↗

PubMed1996

Causes of early human population growth.

The archaeological record indicates large increases in human population coincident with the emergence of food production about 10,000 years ago. The cause of the growth is unclear. Extreme views attribute the change to increases in the birth rate or to decreases in the death rate. Many argue that sedentism led to improved ovarian function and higher fertility through higher caloric intakes or reduced activity levels. Similarly, shortened lactation periods may have reduced birth spacing and increased fertility. Others attribute the rise in population to decreases in mortality, arguing that the evidence from skeletal populations indicates improvements in health and the expectation of life at birth, though others use the same evidence to argue that mortality increased. An analysis presented here draws on findings that indicate substantial increases in the survival of young children as populations switch from nomadic to sedentary lives. Projections indicate that this improvement in child survival is so critical that it may be followed by substantially larger decreases in survival at later ages, yet result in higher population growth rates and reduced expectation of life at birth. Increases in the birth rate are not necessary for population growth, even when overall mortality increases. Large increases in overall mortality can be associated with large increases in population. Because positive population growth can occur while the expectation of life at birth declines, this analysis shows that this summary statistic is not an appropriate indicator of population fitness.

Archaeology↗

PubMed1997

Dental caries in nineteenth century upper Canada.

This study examines the presence of dental caries in a large sample of adult skeletons from the 19th century cemetery of St. Thomas' Anglican Church in Belleville, Ontario. The cemetery was used from 1821 to 1874. Caries prevalence and frequencies of diseased and missing teeth were calculated both by observing summary statistics of individual rates and by the total sample of teeth. Postmortem tooth loss is low in this sample and antemortem tooth loss is highest in first mandibular molars, all other molars and then premolars. Age at death, but not sex, was found to be significantly related to the overall Caries Rate while both age and sex were significantly associated with the Diseased-Missing Index. The increase in diseased and missing teeth in older individuals is expected while the sex difference is not explained by simple dietary factors. When compared to reports on British and American samples, caries and antemortem tooth loss in the St. Thomas' sample is most similar to a pre-1850 British group and higher than American samples. Although there is undoubtedly a complex of factors contributing to caries prevalence in this sample, more data are required from large historic samples, particularly from the American northeast and late 19th century Britain, to have a clearer understanding of the influence of diet, cultural, and environmental factors affecting caries rates in historic populations.

Adult↗

PubMed1998

A mixture model for sucking patterns of breast-fed infants.

Previous studies of sucking patterns have mainly been on bottle-fed babies and have assumed that the babies' sucks occur within bursts separated by gaps of predetermined minimum length which is fixed over the feed. This study considers babies that are breast-fed, a more complex and natural process than bottle-feeding, and develops a more sophisticated model for the pattern of bursts and gaps which allows the parameters of the process to vary over the feed. We consider data from four breast feeds of each of 32 babies. We develop a two-component mixture model based on an underlying Markov chain model for the switching between bursts and gaps. We use the model to provide summary statistics for each feed and give estimates of the normal range of each of the model's parameters.

Breast Feeding↗

PubMedDate not supplied

Suggestions for the presentation of quality of life data from clinical trials.

Quality of life (QOL) data is complex since it is both multidimensional and longitudinal. This complexity is compounded with its unbalanced nature through missing observations as a consequence of patient non-compliance with assessment schedules, and, for example, in cancer clinical trials data absence due to patient attrition often through death. QOL data poses difficulties for presentation and analysis and hence interpretation. This paper illustrates, using data from a randomized trial of the United Kingdom Medical Research Council Lung Cancer Working Party, a step-by-step approach to presentation of QOL data. This begins with a description of compliance and its relationship with patient attrition caused by death, to a final summary profile to indicate change over time. We recognize that no single summary statistic is likely to be able to encapsulate all the subtleties of QOL data. We stress the importance of examining data graphically before performing detailed analysis and also to facilitate interpretation in the final clinical report. Although a description of analytical methods is not the purpose of this paper, we draw attention to the need for imputing missing values and to the (multi-level) modelling approach to summarizing the data, both essential adjuncts to the less formal methods described here.

Authorship↗