Zero-inflated negative binomial mixed model: an application to two microbial organisms important in oesophagitis.

Altered microbial communities are thought to play an important role in eosinophilic oesophagitis, an allergic inflammatory condition of the oesophagus. Identification of the majority of organisms present in human-associated microbial communities is feasible with the advent of high throughput sequencing technology. However, these data consist of non-negative, highly skewed sequence counts with a large proportion of zeros. In addition, hierarchical study designs are often performed with repeated measurements or multiple samples collected from the same subject, thus requiring approaches to account for within-subject variation, yet only a small number of microbiota studies have applied hierarchical regression models. In this paper, we describe and illustrate the use of a hierarchical regression-based approach to evaluate multiple factors for a small number of organisms individually. More specifically, the zero-inflated negative binomial mixed model with random effects in both the count and zero-inflated parts is applied to evaluate associations with disease state while adjusting for potential confounders for two organisms of interest from a study of human microbiota sequence data in oesophagitis.

Factors associated with the technical performance of colonoscopy: An EPAGE Study.

BACKGROUND: Variations in colonoscopy practice exist, which may be related to healthcare quality. AIMS: To determine factors associated with three performance indicators of colonoscopy: complete colonoscopy, adenomatous polyp diagnosis, and duration. PATIENTS: Consecutive patients referred for colonoscopy from 21 centres in 11 countries. METHODS: This prospective observational study used multiple variable regression analyses to identify determinants of the quality indicators. RESULTS: Six thousand and four patients were included in the study. Patients from private, open-access centres (odds ratio: 3.17, 95% confidence interval: 1.87-5.38) were more likely to have a complete colonoscopy than patients from public, gatekeeper centres. Patients from centres where over 50% of the endoscopists were of senior rank were roughly twice as likely to have an adenoma diagnosed, and longer average withdrawal duration (odds ratio: 1.08, 95% confidence interval: 1.07-1.09) was associated with more frequent adenoma diagnoses. Patients who had difficulty during colonoscopy had longer durations to caecum (time ratio: 2.87, 95% confidence interval: 2.72-3.01) and withdrawal durations (time ratio: 1.26, 95% confidence interval: 1.18-1.33) than patients who had no difficulties. CONCLUSIONS: Multiple factors have been identified as being associated with key quality indicators. The non-modifiable factors permit the identification of patients who may be at greater risk of not having quality colonoscopy, while changes to the modifiable factors may help improve the quality of colonoscopy.

Calcium and neuronal cytoskeletal proteins: alterations with aging.

Calcium plays a major role in regulating cellular function. Alterations in calcium systems may underlie some of the physiological changes associated with aging. Calcium activates calmodulin-dependent protein kinase, and this enzyme mediates some effects of calcium on cellular function. Calcium/calmodulin-dependent kinase II may play a significant role in specific cytoskeletal abnormalities of normal aging and selected neurodegenerative diseases.

Stereotactic proton beam therapy of skull base meningiomas.

PURPOSE: To review outcomes for patients with skull base meningiomas treated using the stereotactic proton beam at the National Accelerator Center (NAC), Republic of South Africa. METHODS AND MATERIALS: Since 1993, 27 patients with intracranial meningiomas have been treated stereotactically with protons at NAC. Of those, 23 were located on the skull base, were large or had complex shapes, and were treated with radical intent. Both stereotactic radiotherapy (SRT, 16 or more fractions) and hypofractionated stereotactic radiotherapy (HSRT, 3 fractions) were used. Eighteen patients underwent proton HSRT, while 5 patients were treated with SRT. The mean target volume for the HSRT group was 15.6 cm(3) (range 2.6-63 cm(3)). The mean ICRU reference dose was 20.3 cobalt Gray equivalent (CGyE), and the mean minimum planning target dose was 16.3 CGyE. The mean clinical and radiologic follow-up periods were 40 and 31 months respectively. The mean volume in the SRT group was 43.7 cm(3), with ICRU reference doses ranging from 54 CGyE in 27 fractions to 61.6 CGyE in 16 fractions. RESULTS: In the HSRT group, 16/18 (89%) of patients remained clinically stable or improved, while 2/18 (11%) deteriorated. Radiologic control was achieved in 88% of patients, while 2 patients had a marginal failure. Among the 5 SRT patients, 2 were clinically better, and 3 remained stable. All SRT patients achieved radiologic control. Three patients (13%), 2 of them in the HSRT group, suffered permanent neurologic deficits. Analyzing different dose/fractionation schedules, an alpha/beta value of 3.7 Gy for meningiomas is estimated. CONCLUSION: Proton irradiation is effective and safe in controlling large and complex-shaped skull base meningiomas.

Cardiovascular reactivity to psychological stress in aerobically trained versus untrained mild hypertensives and normotensives.

Cardiovascular reactivity to video game and mental arithmetic stressors was compared among three groups of men: aerobically trained mild hypertensives, untrained mild hypertensives, and a comparison group of untrained normotensives. Relative to the untrained hypertensives, the trained hypertensives reacted to the video game with marginally smaller systolic blood pressure and diastolic blood pressure, but there were no significant differences between these groups in reactivity during the mental arithmetic task. Comparisons between each hypertensive group and the normotensive group showed that blood pressure (BP) reactivity of normotensives during the video game was generally similar to that of trained hypertensives but smaller than that of untrained hypertensives. These results indicate that aerobic training, which has been found to reduce resting BP in mild hypertensives, may also exert a favorable impact in reducing cardiovascular reactivity of hypertensives during some stressful situations.

Mottled cyan opacification of the posterior cornea in contact lens wearers.

PURPOSE: We studied patients who had mottled cyan-colored opacities of the cornea to better understand the cause and prognosis of this entity. METHODS: We reviewed examinations of patients who had a mottled cyan opacification of the cornea. Risk factors, including contact lens wear and exposure to heavy metals, were analyzed. Clinical findings, pachymetry specular microscopy, and progression of the abnormality were noted. RESULTS: Six patients who had a mottled cyan opacification at the level of Descemet's membrane were identified. These opacities were located in the peripheral and midperipheral cornea. All patients had bilateral findings, had visual acuities of 20/20 or better, and were asymptomatic. All patients had worn soft contact lenses bilaterally for periods ranging from seven to 14 years. CONCLUSION: All patients had the similar clinical appearance of a mottled cyan opacification at the level of Descemet's membrane in the peripheral cornea. Long-term contact lens wear appears to be associated; however, the exact cause is unclear.

Utility of a demographic equation in detecting impaired NART performance after TBI.

OBJECTIVES: This study applies a demographic regression equation devised by Crawford, Allan, Cochrane, and Parker (1990) to determine its utility in New Zealand, and to determine the proportion of persons with traumatic brain injury (TBI) with impaired performance on the National Adult Reading Test (NART). METHOD: The NART was administered to 80 community participants, 65 people with traumatic brain injury (TBI), and 27 orthopaedic controls. The Crawford et al. (1990) equation was applied to all three samples. RESULTS: The Crawford et al. (1990) equation was applicable in the New Zealand community sample. It was found that 30% of the TBI sample had impaired performance on the NART. Using corrected NART scores, a significantly larger proportion of the TBI sample was detected as intellectually impaired than in the control sample. CONCLUSION: Nearly one-third of the TBI sample evidenced impaired performance on the NART. Consequently, clinicians that use the NART in assessing people with TBI should use the demographic equation to check the accuracy of NART performances, and correct the NART scores if this is indicated.

A perinatal continuing education program: its effects on the knowledge and practices of health professionals.

OBJECTIVES: To determine whether there was an increase in knowledge when an interdisciplinary group of health care providers participated in the same comprehensive perinatal continuing education program and to determine whether care practices followed before the program differed from those followed 1 year after its completion. DESIGN: Administration of a 100-item comprehensive pretest and a similar posttest measuring knowledge before the continuing education program and 1 year after taking it, as well as an ex post facto audit of medical records of newborns who were sick and at risk. SETTING: Hospitals throughout the state of Oklahoma that provide perinatal care. Test data were derived from health care providers in 24 hospitals; data on care practices were obtained from 12 hospitals. INTERVENTION: A comprehensive program of perinatal continuing education. PARTICIPANTS: Physicians, nurses, and other providers of perinatal health care. MAIN OUTCOME MEASURES: Scores on a 100-item test measuring knowledge of perinatal care and newborn care practices taught in the educational program. RESULTS: Pretest and posttest scores demonstrated an increase in scores at the p < 0.001 level for each group of providers studied. There was a statistically significant increase in use of two care practices and a definite trend toward an increase in the use of three others. CONCLUSION: A continuing education program delivered to a multidisciplinary group of health care providers can increase knowledge and improve perinatal care to newborns who are sick and at risk.

The process of exempt immediate relative immigration to the United States.

"To examine the chain migration issue [in the United States], this article develops and analyzes a new data base that links information on a sample of exempt immediate relative immigrants in Fiscal Year 1985 with information on the characteristics of their petitioners or sponsors. The analysis generally does not indicate that an explosive increase in future chain migration of exempt immediate relative immigrants is likely in the next ten years." Exempt immediate relative immigrants are defined as those who are exempt from numerical limitations because of their relationship with a U.S. citizen. Data are from the U.S. General Accounting Office.

Pulmonary diffusion and aerobic capacity: is there a relation? Does obesity matter?

AIM: We sought to determine whether pulmonary diffusing capacity for nitric oxide (DLNO), carbon monoxide (DLCO) and pulmonary capillary blood volume (Vc) at rest predict peak aerobic capacity (VO2peak), and if so, to discern which measure predicts better. METHODS: Thirty-five individuals with extreme obesity (body mass index or BMI = 50 +/- 8 kg m((-2)) and 26 fit, non-obese subjects (BMI = 23 +/- 2 kg m((-2)) participated. DLNO and DLCO at rest were first measured. Then, subjects performed a graded exercise test on a cycle ergometer to determine (VO2peak). Multivariate regression was used to assess relations in the data. RESULTS: Findings indicate that (i) pulmonary diffusion at rest predicts (VO2peak) in the fit and obese when measured with DLNO, but only in the fit when measured with DLCO; (ii) the observed relation between pulmonary diffusion at rest and (VO2peak) is different in the fit and obese; (iii) DLNO explains (VO2peak) better than DLCO or Vc. The findings imply the following reference equations for DLNO: (VO2peak) (mL kg(-1) min(-1)) = 6.81 + 0.27 x DLNO for fit individuals; (VO2peak) (mL kg(-1) min(-1)) = 6.81 + 0.06 x DLNO, for obese individuals (in both groups, adjusted R(2 )=( )0.92; RMSE = 5.58). CONCLUSION: Pulmonary diffusion at rest predicts (VO2peak), although a relation exists for obese subjects only when DLNO is used, and the magnitude of the relation depends on gender when either DLCO or Vc is used. We recommend DLNO as a measure of pulmonary diffusion, both for its ease of collection as well as its tighter relation with (VO2peak).

Ability of VKORC1 and CYP2C9 to predict therapeutic warfarin dose during the initial weeks of therapy.

BACKGROUND: CYP2C9 and VKORC1 genotypes predict therapeutic warfarin dose at initiation of therapy; however, the predictive ability of genetic information after a week or longer is unknown. Experts have hypothesized that genotype becomes irrelevant once international normalized ratio (INR) values are available because INR response reflects warfarin sensitivity. METHODS: We genotyped the participants in the Prevention of Recurrent Venous Thromboembolism (PREVENT) trial, who had idiopathic venous thromboemboli and began low-intensity warfarin (therapeutic INR 1.5-2.0) using a standard dosing protocol. To develop pharmacogenetic models, we quantified the effect of genotypes, clinical factors, previous doses and INR on therapeutic warfarin dose in the 223 PREVENT participants who were randomized to warfarin and achieved stable therapeutic INRs. RESULTS: A pharmacogenetic model using data from day 0 (before therapy initiation) explained 54% of the variability in therapeutic dose (R(2)). The R(2) increased to 68% at day 7, 75% at day 14, and 77% at day 21, because of increasing contributions from prior doses and INR response. Although CYP2C9 and VKORC1 genotypes were significant independent predictors of therapeutic dose at each weekly interval, the magnitude of their predictive ability diminished over time: partial R(2) of genotype was 43% at day 0, 12% at day 7, 4% at day 14, and 1% at day 21. CONCLUSION: Over the first weeks of warfarin therapy, INR and prior dose become increasingly predictive of therapeutic dose, and genotype becomes less relevant. However, at day 7, genotype remains clinically relevant, accounting for 12% of therapeutic dose variability.

The appropriateness of colonoscopy: a multi-center, international, observational study.

OBJECTIVE: To examine the appropriateness and necessity of colonoscopy across Europe. DESIGN: Prospective observational study. SETTING: A total of 21 gastrointestinal centers from 11 countries. PARTICIPANTS: Consecutive patients referred for colonoscopy at each center. INTERVENTION: Appropriateness criteria developed by the European Panel on the Appropriateness of Gastrointestinal Endoscopy, using the RAND appropriateness method, were used to assess the appropriateness of colonoscopy. MAIN OUTCOME MEASURE: Appropriateness of colonoscopy. RESULTS: A total of 5213 of 6004 (86.8%) patients who underwent diagnostic colonoscopy and had an appropriateness rating were included in this study. According to the criteria, 20, 26, 27, or 27% of colonoscopies were judged to be necessary, appropriate, uncertain, or inappropriate, respectively. Older patients and those with a major illness were more likely to have an appropriate or necessary indication for colonoscopy as compared to healthy patients or patients who were 45-54 years old. As compared to screening patients, patients who underwent colonoscopy for iron-deficiency anemia [OR: 30.84, 95% CI: 19.79-48.06] or change in bowel habits [OR: 3.69, 95% CI: 2.74-4.96] were more likely to have an appropriate or necessary indication, whereas patients who underwent colonoscopy for abdominal pain [OR: 0.64, 95% CI: 0.49-0.83] or chronic diarrhea [OR: 0.54, 95% CI: 0.40-0.75] were less likely to have an appropriate or necessary indication. CONCLUSIONS: This study identified significant proportions of inappropriate colonoscopies. Prospective use of the criteria by physicians referring for or performing colonoscopies may improve appropriateness and quality of care, especially in younger patients and in patients with nonspecific symptoms.

Current sedation and monitoring practice for colonoscopy: an International Observational Study (EPAGE).

BACKGROUND AND STUDY AIMS: Sedation and monitoring practice during colonoscopy varies between centers and over time. Knowledge of current practice is needed to ensure quality of care and help focus future research. The objective of this study was to examine sedation and monitoring practice in endoscopy centers internationally. PATIENTS AND METHODS: This observational study included consecutive patients referred for colonoscopy at 21 centers in 11 countries. Endoscopists reported sedation and monitoring practice, using a standard questionnaire for each patient. RESULTS: 6004 patients were included in this study, of whom 53 % received conscious/moderate sedation during colonoscopy, 30 % received deep sedation, and 17 % received no sedation. Sedation agents most commonly used were midazolam (47 %) and opioids (33 %). Pulse oximetry was done during colonoscopy in 77 % of patients, blood pressure monitoring in 34 %, and electrocardiography in 24 %. Pulse oximetry was most commonly used for moderately sedated patients, while blood pressure monitoring and electrocardiography were used predominantly for deeply sedated patients. Sedation and monitoring use ranged from 0 % to 100 % between centers. Oxygen desaturation (

Gastroenterologists overestimate the appropriateness of colonoscopies they perform: an international observational study.

BACKGROUND AND STUDY AIM: Little is known about how gastroenterologists perceive the appropriateness of colonoscopies they perform. The objective of this study was to compare the appropriateness and necessity of colonoscopies as assessed by an expert panel and by the gastroenterologists performing the colonoscopies. METHODS: This observational study included 21 centers in 11 countries. Patients referred for colonoscopy were consecutively included. Appropriateness and necessity of colonoscopies were independently rated on a 9-point scale by the gastroenterologists performing them and by an expert panel using a validated method (RAND). The differences between the ratings from the two groups were examined. RESULTS: 6004 patients were included in the study. Comparisons of ratings were possible for 5381 (89.6 %) patients. The gastroenterologists' mean appropriateness rating was 7.2 +/- 1.7, and the panel's mean appropriateness rating was 5.4 +/- 2.3 ( P < 0.001). The percentages of indications rated inappropriate, uncertain, appropriate, and necessary were 4.1 %, 23.8 %, 14.2 %, and 58.0 % for the gastroenterologists and 27.2 %, 26.7 %, 25.0 %, and 21.1 % for the panel, respectively. Agreement between the two groups' ratings was poor (28.8 %, kappa = 0.11). Differences between the two groups' ratings decreased with increasing patient age, decreasing health status, and decreasing expertise level of the referring physician. However, the gastroenterologists produced consistently higher ratings. CONCLUSIONS: Compared with an expert panel, gastroenterologists tend to overestimate the appropriateness of colonoscopies they perform. Except for well-delineated reasons, participating gastroenterologists weighed patient characteristics differently from the panel when judging appropriateness. Ways to increase the prospective use of appropriateness criteria in order to improve appropriateness and reduce overuse of colonoscopies should be examined further.

A photoelastic substrate technique for dynamic measurements of forces exerted by moving organisms.

The forces produced by small moving organisms have been quantitatively measured by having the organisms move on a polymeric substrate which transduces the applied stress into an optical birefringence signal (photoelastic effect). The optical signal can be rigorously interpreted to give static force measurements, and by calibrating the substrate empirically, dynamic measurements are obtained. The technique measures stresses, forces applied to an area, so it is not possible to determine ultimate sensitivity of the technique for measurements of forces without regard to area. The technique is especially useful when small forces are exerted over very small areas as, for example, may be the situation with moving tissue cells. The technique is noninvasive, requires minimal equipment, and is easily performed on microscopes adapted for polarized light measurements. Gelatin has the highest sensitivity and adaptability as a photoelastic substrate.

Spontaneous pneumothorax: is it under tension?

A diagnosis of tension pneumothorax is usually only considered within the context of trauma, incorrect chest drain insertion or positive pressure ventilation. Four patients are presented who developed spontaneous tension pneumothorax with no precipitating factors. In three of these instances, the diagnosis was only made radiologically and in every case the treating physician was unaware that a spontaneous tension pneumothorax could occur. Previously, emphasis has been placed on tracheal deviation in a tension pneumothorax. However, this is an inconsistent finding as one of the cases highlights. Patients may appear surprisingly clinically well until they decompensate. These cases are highlighted to raise awareness of this potentially life threatening condition.

The role of emergency surgery in malignant spinal extradural compression: assessment of functional outcome.

The role of emergency surgery for spinal cord or cauda equina compression secondary to extradural metastases is assessed in terms of functional outcome in 84 cases. The records of patients with proven malignant extradural spinal compression were reviewed retrospectively to determine the influence of emergency versus elective decompressive surgery on functional outcome. A greater proportion undergoing emergency surgery, rather than electively (within 24 h) on the next list showed functional improvement, with recovered mobility (61.5% vs 25%). Overall, 70% of patients were mobile postoperatively. The findings suggest that despite initial delays in referral, and even if the patient is incontinent and immobile, emergency spinal decompression is justified.

The effects of nonconcurrent and concurrent relaxation training on cardiovascular reactivity to a psychological stressor.

Eight patients in a cardiac rehabilitation program, after exposure to two psychological stressors approximately equivalent with respect to cardiovascular reactivity, were given nonconcurrent progressive muscle relaxation training and retested for reactivity. They were then provided with relaxation training concurrently with one of the stressors and exposed again to the two stressors. No significant effects for nonconcurrent progressive muscle relaxation training were detected. Concurrent training, in contrast, produced reductions in both systolic and diastolic blood pressure. Reductions resulting from training on the target stressor showed little tendency to generalize to the nontarget stressor; the discrimination was particularly well defined for systolic blood pressure. We conclude that muscle relaxation techniques are maximally effective in reducing reactivity to psychological stressors when relaxation training is provided concurrently with the stressor. Our findings further suggest that to inculcate the relaxation response reliably across different situations, specific training to enhance generalization may be needed.

A rectal monitor for use with afterloading intracavitary radioactive implants.

A battery-powered monitor that uses a miniature Geiger-Muller tube operating in the pulse-counting mode has been constructed. It is used with low-activity cesium-137 sources. The monitor gives a reading within about 1 second, has a standard deviation of 2% of the mean, and is safe, reliable, and stable.