Use of variability in national and regional data to estimate the prevalence of lymphangioleiomyomatosis.

BACKGROUND: Understanding the true prevalence of lymphangioleiomyomatosis (LAM) is important in estimating disease burden and targeting specific interventions. As with all rare diseases, obtaining reliable epidemiological data is difficult and requires innovative approaches. AIM: To determine the prevalence and incidence of LAM using data from patient organizations in seven countries, and to use the extent to which the prevalence of LAM varies regionally and nationally to determine whether prevalence estimates are related to health-care provision. METHODS: Numbers of women with LAM were obtained from patient groups and national databases from seven countries (n = 1001). Prevalence was calculated for regions within countries using female population figures from census data. Incidence estimates were calculated for the USA, UK and Switzerland. Regional variation in prevalence and changes in incidence over time were analysed using Poisson regression and linear regression. RESULTS: Prevalence of LAM in the seven countries ranged from 3.4 to 7.8/million women with significant variation, both between countries and between states in the USA. This variation did not relate to the number of pulmonary specialists in the region nor the percentage of population with health insurance, but suggests a large number of patients remain undiagnosed. The incidence of LAM from 2004 to 2008 ranged from 0.23 to 0.31/million women/per year in the USA, UK and Switzerland. CONCLUSION: Using this method, we have found that the prevalence of LAM is higher than that previously recorded and that many patients with LAM are undiagnosed.

Emerging clinical picture of lymphangioleiomyomatosis.

OBJECTIVE: To provide a comprehensive update of the clinical picture of lymphangioleiomyomatosis (LAM) using two large patient registries. METHODS: A cross sectional questionnaire survey which included questions on 14 LAM symptoms, pneumothorax, tuberous sclerosis complex (TSC), date of diagnosis, and pulmonary function tests (PFTs). RESULTS: The response rate was 70.5% (n = 328). The mean age at the time of the survey was 46.7 years. The mean age at diagnosis was 42.7 years for women diagnosed 1 year before the survey and 35.8 years for women diagnosed 10 years previously. The main symptoms were dyspnoea (74%), fatigue (72%), cough (47%) and chest pain (44%); younger patients (<40 years) were less likely to report dyspnoea (p = 0.02). Patients with TSC (n = 51) were less likely to report dyspnoea (p = 0.05) and 76.5% reported angiomyolipoma (p < 0.0001) compared with patients with sporadic LAM. Patients with pneumothorax (63.0%) were less likely to report dyspnoea or fatigue (p < or = 0.05) than patients without pneumothorax. PFT results showed that low forced expiratory volume in 1 second and carbon monoxide transfer factor were highly associated with dyspnoea (p < 0.0001), but not with fatigue or history of pneumothorax. CONCLUSION: Previously considered a condition of women of childbearing age, more older women (50% without pneumothorax) are now being diagnosed with LAM. LAM should be considered in women over 40 with unexplained dyspnoea. LAM patients with pneumothorax have less fatigue and less dyspnoea than those without pneumothorax. Fatigue has been overlooked as a symptom of LAM and appears across the spectrum of pulmonary function.

Psychological and physical sequelae of intimate partner violence among women with limitations in their activities of daily living.

OBJECTIVE: To compare the psychological and physical sequelae of physical/sexual intimate partner violence in women with and without activity limitations. METHODS: We analyzed data from the Canadian 1999 General Social Survey. We included women reporting intimate partner violence in the previous 5 years (n = 897). RESULTS: As a result of the violence, women with activity limitations were significantly more likely to feel ashamed/guilty (21.7 vs. 14.5%), depression/anxiety (31.5 vs. 19.8%), fearful (43.0 vs. 33.0%), lowered self-esteem (35.2 vs. 21.1%), increased caution/awareness (20.3 vs. 10.9%), and problems relating to men (16.4 vs. 5.4%). Significantly more women with activity limitations reported physical injury from violence (57.0 vs. 36.6%) and having to take time off from everyday activities (42.1 vs. 30.3%). Women with activity limitations had higher medication use for sleeping problems (OR = 3.17, 95% CI = 1.36, 5.73), anxiety (OR = 3.29, 95% CI = 1.75, 6.19) and depression (OR = 2.63, 95% CI = 1.41, 4.90). CONCLUSION: Results suggest an additive effect between intimate partner violence and activity limitations that adds disproportionately to the burden of health for women with activity limitations.

Medication safety program reduces adverse drug events in a community hospital.

BACKGROUND: There is widespread interest in improving medication safety, particularly in the hospital setting. Numerous suggestions have been made as to how this should be done, but there is a paucity of data demonstrating the effectiveness of any of the interventions that have been proposed. OBJECTIVES: To assess the impact of a wide ranging, community hospital based patient safety program on patient harm as measured by the rate of adverse drug events. DESIGN: An audit of discharged hospital patients was conducted from January 2001 to December 2003. Baseline data were collected for the first 6 months and multiple drug protocols and other interventions were instituted on the nursing units and in the pharmacy department over the subsequent 9 months (transition period). These interventions were largely based on information about medication risks acquired from internal medication event reporting. Each month of the study adverse drug events (ADE) were sought from a random sample of inpatient charts. A trigger tool was used to detect clues to ADEs, the presence of which was confirmed or excluded by detailed manual chart review. The severity of these events was categorized using the classification system of the National Coordinating Council for Medication Error and Reporting and Prevention. MAIN OUTCOME MEASURES AND RESULTS: Median ADEs per 1000 doses of medication dispensed declined significantly from 2.04 to 0.65 (p<0.001). Median ADEs per 100 patient days declined significantly from 5.07 to 1.30 (p<0.001). The proportion of inpatients with one or more ADE in the baseline period was 31% and declined threefold (p<0.001). The severity of reported medication events also declined. The number of ADEs associated conclusively with patient harm was 1.67 per total doses delivered in the baseline period and declined eightfold (p<0.001). CONCLUSION: The implementation of a carefully planned series of low cost interventions focused on high risk medications, driven by information largely from internal event reporting, and designed to improve a hospital's medication safety leads to a significant decrease in patient harm.

1985 NASA-Rockwell Space Station Crew Safety Study: results from Mir.

In 1985, Rockwell International (now Boeing--North American) completed the Space Station Crew Safety Alternatives Study for NASA. This five-volume study identified a wide range of potential safety threats and hazards that the crew might encounter on the future International Space Station. These threats included fire, explosion, collision, decompression, contamination, and radiation, among many others. One volume focused on the human factors aspects of safety, featuring the Crew Safety-Human Factors Interaction Model. In this model, a stressor (such as one of the threats) can lead to degraded performance, which can contribute to human error, unless appropriate and effective countermeasures are available to the crew. In 1986, the Soviet Union launched the Mir Space Station, the "second generation" that followed the Salyut series of space stations. The Mir was designed for a five-year life on orbit. It remained in use for fourteen years. During the first ten years, it performed well, with few safety issues. However, during the last four years, the aging station--operating at more than two times beyond its design lifetime--encountered a variety of safety hazards and human factors issues. Despite these often serious problems, the Mir crews always found a way to save the station, and no crew member was seriously injured or killed. This paper evaluates the safety record on Mir, and compares it to the NASA-Rockwell study, that was contemporaneous with the construction and launch of Mir. This comparison and analysis can provide a foundation for future space crew safety and related human factors support.

Frog decline, frog malformations, and a comparison of frog and human health.

The decline in frog populations and the increase in the frequency of frog malformations are discussed. Topics considered for analysis include chytridiomycosis, retinoids, UV-B radiation, chemical contaminants, environmental threats, introduced invasive species and predation, unsustainable use, and enigmatic decline. Care must be taken to distinguish between hypotheses, laboratory experiments, and the findings in feral frog populations. Clearly, the causes of population decline and malformations are heterogeneous. The subject of frogs and humans is addressed under three subheadings: the importance of frogs to human societies, medical implications of frog studies, and a comparison of frog and human disease factors.

Enhancement of contrast echocardiography by image variability analysis.

BACKGROUND: Although there have been recent advances in echocardiography, many studies remain suboptimal due to poor image quality and unclear blood-myocardium border. We developed a novel image processing technique, cardiac variability imaging (CVI), based on the variance of pixel intensity values during passage of ultrasound microbubble contrast into the left ventricle chamber, with the aim of enhancing endocardial border delineation and image quality. METHODS AND RESULTS: CVI analysis was performed on simulated data to test and verify the mechanism of image enhancement. Then CVI analysis was applied to echocardiographic images obtained in two different clinical studies, and still images were interpreted by expert reviewers. In the first study (N = 15), using contrast agent EchoGen, the number of observable wall segments in end-diastolic images, for example, was significantly increased by CVI (4.93) as compared to precontrast (3.28) and contrast images (3.36), P < 0.001 for both comparisons to CVI. In the second study (N = 8), using contrast agent Optison, interobserver variability of manually traced end-diastolic volumes was significantly decreased using CVI (22.3 ml) as compared to precontrast (63.4) and contrast images (49.0), P < 0.01 for both comparisons to CVI. CONCLUSION: CVI can substantially enhance endocardial border delineation and improve echocardiographic image quality and image interpretation.

A multivariable model for predicting the need for blood transfusion in patients undergoing first-time elective coronary bypass graft surgery.

BACKGROUND: The incidence of blood transfusion in coronary artery bypass graft (CABG) surgery remains high. Preoperative identification of those at high risk for requiring blood will allow for the cost-effective use of some blood conservation modalities. Multivariable analysis techniques were used in this study to develop a prediction rule for such a purpose. STUDY DESIGN AND METHODS: Data were prospectively collected for all patients undergoing elective first-time CABG surgery from January 1997 to September 1998 at a tertiary-care teaching hospital (n = 1007). The prediction rule was developed on the first two-thirds of the sample by using logistic regression methods to examine the relationship of patient demographics, comorbidities, and preoperative Hb with perioperative blood transfusion. The remaining one-third of the sample was used to validate the rule. RESULTS: The transfusion rate was 29.4 percent. The prediction rule included preoperative Hb (g/dL, OR 0.928, p<0.0001), weight (kg, OR 0.938, p<0.0001), age (years, OR 1.037, p<0.01), and sex (male/female, OR 0.493, p<0.01); receiver operating characteristic = 0.86. When externally validated, the rule had a sensitivity of 82.1 percent and a specificity of 63.6 percent (at a selected probability cutoff). CONCLUSION: A simple and valid prediction rule is developed for predicting the risk of blood transfusion in patients undergoing first-time elective CABG surgery.

The validity of performance assessments using simulation.

BACKGROUND: The authors wished to determine whether a simulator-based evaluation technique assessing clinical performance could demonstrate construct validity and determine the subjects' perception of realism of the evaluation process. METHODS: Research ethics board approval and informed consent were obtained. Subjects were 33 university-based anesthesiologists, 46 community-based anesthesiologists, 23 final-year anesthesiology residents, and 37 final-year medical students. The simulation involved patient evaluation, induction, and maintenance of anesthesia. Each problem was scored as follows: no response to the problem, score = 0; compensating intervention, score = 1; and corrective treatment, score = 2. Examples of problems included atelectasis, coronary ischemia, and hypothermia. After the simulation, participants rated the realism of their experience on a 10-point visual analog scale (VAS). RESULTS: After testing for internal consistency, a seven-item scenario remained. The mean proportion scoring correct answers (out of 7) for each group was as follows: university-based anesthesiologists = 0.53, community-based anesthesiologists = 0.38, residents = 0.54, and medical students = 0.15. The overall group differences were significant (P < 0.0001). The overall realism VAS score was 7.8. There was no relation between the simulator score and the realism VAS (R = -0.07, P = 0.41). CONCLUSIONS: The simulation-based evaluation method was able to discriminate between practice categories, demonstrating construct validity. Subjects rated the realism of the test scenario highly, suggesting that familiarity or comfort with the simulation environment had little or no effect on performance.

Asymmetry: molecular, biologic, embryopathic, and clinical perspectives.

This overview of asymmetry addresses the following topics: chiral molecules; asymmetric signaling molecules, including N-cadherin, Shh, Fgf8, lefty1, lefty2, nodal, Pitx2, activin betaB, activin receptor IIA, and cSnR; situs abnormalities; asymmetric cell division; laterality in humans and animals; behavioral asymmetry in humans and animals; asymmetric embryopathies, including Tessier-type "clefts"; hemiasymmetries such as hemihyperplasia, hemihypoplasia, and hemiatrophy; asymmetric vascular syndromes, including Klippel-Trenaunay and Sturge-Weber syndromes; plagiocephaly of the synostotic and deformational types; somatic mosaicism, including a discussion of McCune-Albright syndrome, fibrous dysplasia, GNAS1 mutations, and Proteus syndrome.

Evidence for the "midline" hypothesis in associated defects of laterality formation and multiple midline anomalies.

A male infant was liveborn at 38 weeks of gestation to a G4P1AB2, 22-year-old, mother. Polyhydramnios and multiple congenital anomalies were noted by ultrasonography; the infant died 5 min after birth. At autopsy, the infant had multiple defects of blastogenesis including midline anomalies with asplenia and abnormalities of laterality formation. The laterality defects were unusual in that they combined asplenia with hypoplastic, symmetrically unilobate lungs and bilateral hyparterial bronchi more consistent with polysplenia, abdominal situs inversus with midline stomach, symmetric liver, and left gallbladder. No intracardiac abnormalities were present, but there was azygous continuation of the inferior vena cava. Additional multiple midline defects included bronchoesophageal fistula, duodenal atresia, absence of posterior leaf of diaphragm; horseshoe adrenal gland; microcephaly; Dandy-Walker anomaly with agenesis of cerebellar vermis and occipital encephalocele; holoprosencephaly with orbital encephalocele, midline defect of the orbital plate of the skull, bilateral anophthalmia, double proboscis with bilateral choanal atresia, midline upper lip and palatal cleft; single-lobed thyroid; hypoplastic external genitalia with midline cleft of scrotum, long tapering fingers, and defects of the cranium at the sites of orbital and occipital encephaloceles. Defects of laterality frequently are associated with other complex midline anomalies, which both result from a disturbance of pattern formation during blastogenesis, i.e., the induction of the progenitor fields. The latter are the result of the establishment of upstream expression domains of growth and transcription factors and other morphogens. Many of these and other genetic systems, expressed asymmetrically around the midline, are responsible for laterality formation and are the result of upstream and subsequent downstream gene expression cascades through the expression of genes such as HOX genes; bFGF; transforming growth factor beta/activins/BMP4; WNT-1,8; and SHH.

Bayes factor of model selection validates FLMP.

The fuzzy logical model of perception (FLMP; Massaro, 1998) has been extremely successful at describing performance across a wide range of ecological domains as well as for a broad spectrum of individuals. An important issue is whether this descriptive ability is theoretically informative or whether it simply reflects the model's ability to describe a wider range of possible outcomes. Previous tests and contrasts of this model with others have been adjudicated on the basis of both a root mean square deviation (RMSD) for goodness-of-fit and an observed RMSD relative to a benchmark RMSD if the model was indeed correct. We extend the model evaluation by another technique called Bayes factor (Kass & Raftery, 1995; Myung & Pitt, 1997). The FLMP maintains its significant descriptive advantage with this new criterion. In a series of simulations, the RMSD also accurately recovers the correct model under actual experimental conditions. When additional variability was added to the results, the models continued to be recoverable. In addition to its descriptive accuracy, RMSD should not be ignored in model testing because it can be justified theoretically and provides a direct and meaningful index of goodness-of-fit. We also make the case for the necessity of free parameters in model testing. Finally, using Newton's law of universal gravitation as an analogy, we argue that it might not be valid to expect a model's fit to be invariant across the whole range of possible parameter values for the model. We advocate that model selection should be analogous to perceptual judgment, which is characterized by the optimal use of multiple sources of information (e.g., the FLMP). Conclusions about models should be based on several selection criteria.

Effects of gravitational and optical stimulation on the perception of target elevation.

To examine the combined effects of gravitational and optical stimulation on perceived target elevation, we independently altered gravitational-inertial force and both the orientation and the structure of a background visual array. While being exposed to 1.0, 1.5, or 2.0 Gz in the human centrifuge at NASA Ames Research Center, observers attempted to set a target to the apparent horizon. The target was viewed against the far wall of a box that was pitched at various angles. The box was brightly illuminated, had only its interior edges dimly illuminated, or was kept dark. Observers lowered their target settings as Gz was increased; this effect was weakened when the box was illuminated. Also, when the box was visible, settings were displaced in the same direction as that in which the box was pitched. We attribute our results to the combined influence of otolith-oculomotor mechanisms that underlie the elevator illusion and visual-oculomotor mechanisms (optostatic responses) that underlie the perceptual effects of viewing pitched visual arrays.