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Outcome of cardiopulmonary resuscitation in the neonatal intensive care unit.

This retrospective review of 83 infants undergoing CPR in the neonatal ICU of a teaching hospital found that 12 (14%) patients were discharged from the hospital and seven (8%) were alive at least 1 yr after discharge. Of these seven, five appeared neurologically intact. From another perspective, 41% (12/29) of the patients who survived at least 24 h after CPR were discharged alive. Factors significantly (p less than .05) associated with poor outcome included sepsis, oliguria 24 h before and/or after arrest, prematurity, and intraventricular hemorrhage. Variables significantly (p less than .05) related to good outcome were the need for intubation during resuscitation and the diagnosis of major congenital anomalies. Intraventricular hemorrhage was the single most powerful variable in the regression analysis. Outcome statistics from this study were strikingly similar to currently available adult data.

Cerebral Hemorrhage↗

Loss of interstitial cells of Cajal and gap junction protein connexin 43 at the vesicoureteral junction in children with vesicoureteral reflux.

PURPOSE: Symmetrical muscular contractions and unidirectional peristalsis are prerequisites for competent valve function at the ureterovesical junction. Interstitial cells of Cajal (ICCs) are pacemaker cells that create and coordinate peristaltic motility. We investigated ureteral endings immunohistochemically to elucidate the presence of c-kit positive ICCs as well as the occurrence of gap junction protein connexin 43 in children with vesicoureteral reflux (VUR) to identify a possible pathogenic factor of an insufficient antireflux mechanism. MATERIALS AND METHODS: Distal ureteral specimens were obtained from 27 children undergoing antireflux surgery. Routine histological paraffin embedded sections were immunostained detecting the c-kit proto-oncogene to study the presence of ICCs as well as connexin 43 positive cells to determine the gap junction density within the ureteral wall. Age matched nonrefluxing ureteral endings served as controls. All investigations were done using high power field magnification for semiquantitative analysis and statistically analyzed. RESULTS: ICCs were present in refluxing and nonrefluxing ureteral endings. Healthy individuals displayed significantly more ICCs than children with VUR. Connexin 43 immunoreactivity was significantly decreased in all refluxing ureteral specimens, whereas it was homogeneously distributed in normal controls. CONCLUSIONS: C-kit positive ICCs are found at the ureterovesical junction. Refluxing ureteral endings significantly lack these pacemaker cells, implying a malfunctioning valve mechanism permitting VUR. A substantial decrease in gap junctions in this region adversely affects intercellular signaling, aggravating coordinated peristalsis, which is essential for a competent anti-reflux mechanism.

Biomarkers↗

Investigation of protein refolding using a fractional factorial screen: a study of reagent effects and interactions.

A recurring obstacle for structural genomics is the expression of insoluble, aggregated proteins. In these cases, the use of alternative salvage strategies, like in vitro refolding, is hindered by the lack of a universal refolding method. To overcome this obstacle, fractional factorial screens have been introduced as a systematic and rapid method to identify refolding conditions. However, methodical analyses of the effectiveness of refolding reagents on large sets of proteins remain limited. In this study, we address this void by designing a fractional factorial screen to rapidly explore the effect of 14 different reagents on the refolding of 33 structurally and functionally diverse proteins. The refolding data was analyzed using statistical methods to determine the effect of each refolding additive. The screen has been miniaturized for automation resulting in reduced protein requirements and increased throughput. Our results show that the choice of pH and reducing agent had the largest impact on protein refolding. Bis-mercaptoacetamide cyclohexane (BMC) and tris (2-carboxyethylphosphine) (TCEP) were superior reductants when compared to others in the screen. BMC was particularly effective in refolding disulfide-containing proteins, while TCEP was better for nondisulfide-containing proteins. From the screen, we successfully identified a positive synergistic interaction between nondetergent sulfobetaine 201 (NDSB 201) and BMC on Cdc25A refolding. The soluble protein resulting from this interaction crystallized and yielded a 2.2 Angstroms structure. Our method, which combines a fractional factorial screen with statistical analysis of the data, provides a powerful approach for the identification of optimal refolding reagents in a general refolding screen.

Crystallography, X-Ray↗

Growth on stimulant medication; clarifying the confusion: a review.

AIMS: To get an overview of the studies of growth in height in children with attention deficit hyperactivity disorder (ADHD) treated with stimulant medication, to establish the consistencies and to try to resolve the discrepancies. METHODS: Twenty nine studies were reviewed following a Medline search: 22 related to children, six to late adolescents or adults, and one to children and adults. RESULTS: Children: Eleven studies gave results consistent with height attenuation on stimulant medication: eight were longitudinal, one was cross-sectional, and two showed growth rebound on ceasing medication. Studies with negative findings were inadequately powered (n = 3), lacked controls or statistical analysis (n = 3), measured height velocity without reference to treatment duration (n = 2), or used inappropriate growth parameters (n = 1), controls (n = 1), or normative data (n = 1). Late adolescents/adults treated with stimulant medication in childhood: Two studies associated childhood gastrointestinal side effects with attenuated late adolescent or adult height; all six cross-sectional studies had negative findings. The methodologies varied widely but there was some consistency in the degree of attenuation shown in studies with positive findings. The most sensitive methods analysed the changes in z-scores (standard deviation scores) or calculated the height deficits from paired measurements taken before and after an initial period of treatment with stimulant medication. The height deficit amounted to approximately 1 cm/year during the first 1-3 years of treatment. CONCLUSIONS: Further research is needed into the causal mechanisms, the rate of physical maturation, and the long term implications for final stature.

Attention Deficit Disorder with Hyperactivity↗

Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction.

Most gene expression profiling studies of mesothelioma have been based on relatively small sample numbers, limiting their statistical power. We did Affymetrix U133A microarray analysis on 99 pleural mesotheliomas, in which multivariate analysis showed advanced-stage, sarcomatous histology and P16/CDKN2A homozygous deletion to be significant independent adverse prognostic factors. Comparison of the expression profiles of epithelioid versus sarcomatous mesotheliomas identified many genes significantly overexpressed among the former, including previously unrecognized ones, such as uroplakins and kallikrein 11, both confirmed by immunohistochemistry. Examination of the gene expression correlates of survival showed that more aggressive mesotheliomas expressed higher levels of Aurora kinases A and B and functionally related genes involved in mitosis and cell cycle control. Independent confirmation of the negative effect of Aurora kinase B was obtained by immunohistochemistry in a separate patient cohort. A role for Aurora kinases in the aggressive behavior of mesotheliomas is of potential clinical interest because of the recent development of small-molecule inhibitors. We then used our data to develop microarray-based predictors of 1 year survival; these achieved a maximal accuracy of 68% in cross-validation. However, this was inferior to prognostic prediction based on standard clinicopathologic variables and P16/CDNK2A status (accuracy, 73%), and adding the microarray model to the latter did not improve overall accuracy. Finally, we evaluated three recently published microarray-based outcome prediction models, but their accuracies ranged from 63% to 67%, consistently lower than reported. Gene expression profiling of mesotheliomas is an important discovery tool, but its power in clinical prognostication has been overestimated.

Adult↗

[The influence of occlusion on sporting performance].

AIM: The purpose of the present study is to investigate the relationship between dental occlusion and physical performance using the Ergo-jump platform, and to highlight connections, if any. METHODS: For the purpose of this research, 30 patients suffering from cervico-facial pathology and 10 without temporomandibular joint dysfunction were selected from within the Dental Clinic of the University of Sassari. For the first group a resin plate was prepared to correct the malocclusion, while for the control group a bite was prepared that created it. Subjects carried out exercises with the Ergo-jump platform, a device that assesses physical capabilities and athletic performance. Patients were asked to do 2 exercises, a counter movement jump and a mechanical power test, with plate and without plate. RESULTS: The tests of the first group were as follows: flying times with the bite were 0.01 s longer; the average elevation in the counter movement jump test did not give statistically significant results; execution of the mechanical power test suggests an increase in average mechanical power with the plate. Execution of the same exercises in the other group showed greater flight times without the place; average elevation was not statistically significant; the execution of the mechanical power test showed a decrease in average mechanical power with the occlusion plate. CONCLUSION: Statistical analysis of individual results showed that patients do not always obtain a benefit during physical exercise using the bite. Research shows that the same pathology can cause different physical performance in different individuals; in fact, not all craniomandibular disturbances have repercussions on posture.

Adult↗

Considerations in design and use of scales in rehabilitative audiology.

Self-assessment questionnaires in rehabilitative audiology typically possess the measurement characteristics of scales based on forced-choice and rank-order. Data from these ordinal scales neither support arithmetic analysis nor arithmetic interpretation. However, powerful nonparametric statistics are available for application to data from ordinal level questionnaires. Thus, methodologic principles influence the way self-assessment scales are designed, constructed, and analyzed. They also influence the way clinicians interpret responses from individual patients. Within these constraints, well constructed questionnaires can provide information on a wide range of topics in rehabilitative audiology. Suggestions are given for generating interval level questionnaires that are more precise than existing, ordinal level scales.

Audiology↗

Effect of the temperature upon ultradian and circadian ERG amplitude rhythms during ontogeny of crayfish Procambarus clarkii.

The purpose of this work was to investigate whether the ultradian rhythms that are present prior the electroretinogram (ERG) amplitude circadian rhythm, and are superimposed upon it, during the different stages of development of the crayfish Procambarus clarkii are temperature sensitive, as well as the circadian rhythm. Temperature sensitivity was investigated using ERG amplitude recordings in free running conditions at high and low temperature from juvenile instars of different ages. All recordings were submitted to two types of statistical tests: X2 periodogram and power spectrum analysis. Cycles detected by both methods were selected from periodogram and Q10 was computed. Selected ultradian periods (ranging between 1.7 to 17.5 hrs.) seem to show temperature insensitivity that could imply temperature compensation, a property apparently shared with the emerging circadian period. These results support the endogenous nature of the ultradian ERG rhythms as well as their probably functional interaction with the circadian rhythm.

Activity Cycles↗

137Cs in freshwater fish in Finland since 1986--a statistical analysis with multivariate linear regression models.

The accident at the Chernobyl nuclear power plant in 1986 significantly elevated the 137Cs levels of fish in Finnish lakes. About 6200 fish samples from 390 lakes comprising 20 species have been analysed for 137Cs since 1986. The sizes of the lakes varied from a few hectares to about 1000 km2. Activity concentrations of 137Cs in fish still varied widely in 2003, from 16 to 6400 Bq/kg fresh weight. This paper presents the results of statistical analyses with multivariate linear regression models carried out on the empirical data collected since 1986. The statistical analysis resulted in separate models for two time periods describing temporal changes of 137Cs in fish. The explanatory variables were fish species with various feeding habits, the size class of the lake, municipal division, drainage area, time since the deposition and deposition level of the municipality. The calculated values for 137Cs in fish did not differ statistically significantly from the observed values in the validation data. The explanatory variables explained 58% (the first time period) and 72% (the second time period) of the total variability of 137Cs in fish.

Animal Feed↗

Corneal changes in schoolchildren.

Videokeratography (TMS-1) data from the right eyes of 788 children between the ages of 6 and 14 years, examined in 1994 as part of the Orinda Longitudinal Study of Myopia, were analyzed using the Fast Fourier Transform (FFT) to quantify corneal power, toricity, and toricity axis. Cross-sectional analysis showed no statistically significant age trend for these parameters. Conversely, longitudinal analysis of data for 387 of these children, first measured in 1991, showed a statistically significant decrease in corneal power. Corneal toricity did not change significantly over this 3-year period, although there was a minute but statistically significant clockwise axis shift. From this we conclude that in the elementary and junior high school years-during which period axial length is known to increase-corneal flattening continues, but corneal toricity is stable.

Adolescent↗

Intraoperative frozen section analysis in revision total joint arthroplasty.

A prospective study of the sensitivity, specificity, and predictive values for frozen sections against cultures obtained at the time of revision total joint replacement was done. One hundred twenty-one revision total joint replacements were done in 92 men and 29 women. A positive frozen section with more than 10 polymorphonuclear leukocytes per high power field was compared with the intraoperative cultures. Twenty-one patients who had revision surgery had greater than 10 polymorphonuclear leukocytes per high power field. Of these, 14 patients had positive cultures. The remaining 100 patients had less than 10 polymorphonuclear leukocytes per high power field, but seven had positive cultures. Statistical analysis of frozen sections for all total joint arthroplasties revealed a 67% sensitivity, 93% specificity, 67% positive predictive value, and 93% negative predictive value. Analysis of frozen sections for total hip arthroplasties revealed a 45% sensitivity, 92% specificity, 55% positive predictive value, and 88% negative predictive value. Analysis for total knee arthroplasties revealed 100% sensitivity, 96% specificity, 82% positive predictive value, and 100% negative predictive value. Comparisons of sensitivity, positive predictive value, and negative predictive value between total knee arthroplasty and total hip arthroplasty were significant. The results indicate that the use of intraoperative frozen section analysis with greater than 10 polymorphonuclear leukocytes per high power field as an indication of infection lacks the positive predictive value and sensitivity for accurate determination of prosthetic infection at the time of revision total hip arthroplasty. Frozen sections have an acceptable sensitivity and positive predictive value in total knee arthroplasty. The results of the current study show the limitation of using frozen sections as a diagnostic test for infection in revision total hip arthroplasty.

Adult↗

Comparative trials on hybrid walking systems for people with paraplegia: an analysis of study methodology.

A new orthosis (SEPRIX) which combines user friendliness with low energy cost of walking has been developed and will be subject to a clinical comparison with conventional hip-knee-ankle-foot orthoses. In designing such comparative trials it was considered it may be worthwhile to use previous clinical studies as practical examples. A literature search was conducted in order to select all comparative trials which have studied two walking systems (hip-knee-ankle-foot orthoses) for patients with a complete thoracic lesion. Study population, intervention, study design, outcome measurement and statistical analyses were examined. Statistical power was calculated where possible. Of 12 selected studies, 7 were simple A-B comparisons, 2 A-B comparisons with a replication, 2 cross-over trials and 1 nonrandomised parallel group design, the last of which was considered internally invalid due to severe confounding by indication. All A-B comparisons were considered internally invalid as well, since they have not taken into account that a comparison of two orthoses requires a control for aspecific effects (like test effects) which may cause a difference. Statistical power could only be examined in 4 studies and the highest statistical power achieved in one study was 47%. It is concluded that statistical power was too low to be able to detect differences. Even analysis through interval estimation showed that the estimation of the difference was too imprecise to be useful. Since the majority of the surveyed papers have reported small studies (of only 4-6 patients), it is assumed that lack of statistical power is a more general problem. Three possibilities are discussed in order to enhance statistical power in comparative trials, i.e. multicentre studies, statistical pooling of results and improving the efficiency of study design by means of interrupted time series designs.

Equipment Design↗

Assessment of underlying etiology and cardiac sympathetic innervation to identify patients at high risk of cardiac death.

UNLABELLED: Cardiac (123)I-labeled metaiodobenzylguanidine (MIBG) activity has significant incremental prognostic value, but the difference between the long-term prognostic value of MIBG imaging for ischemic cardiomyopathies and the long-term prognostic value of MIBG imaging for idiopathic cardiomyopathies is not clear. This study aimed to determine whether assessment of cardiac (123)I-MIBG activities in ischemic and idiopathic cardiomyopathies have equally prognostic values and whether the kinetics are different because of the underlying etiologies. METHODS: After quantitative (123)I-MIBG imaging, 76 ischemic and 56 idiopathic cardiomyopathy patients were prospectively followed up for 54 mo. In addition to conventional parameters, cardiac (123)I-MIBG activity was quantified as a heart-to-mediastinum ratio (H/M) for early and late images and the washout kinetics were calculated using tomographic imaging. The data were compared with those obtained from 16 healthy volunteers. RESULTS: During follow-up, 29 deaths from heart failure, 11 sudden cardiac deaths, 2 deaths from arrhythmia, and 5 deaths from acute myocardial infarction were documented. Multivariate discriminant analysis using the Cox proportional hazards model showed that, in comparison with other variables, late H/M was the most powerful independent predictor of a lethal clinical outcome in ischemic (Wald chi(2) = 18.6502; P = 0.0000) and idiopathic (Wald chi(2) = 5.3394; P = 0.0208) groups. When patients with left ventricular ejection fraction (LVEF) < 40% were considered, late H/M had the greatest statistical power in both groups. Kaplan-Meier analysis showed late H/M to have an identical threshold (1.82) for both groups for identifying patients at risk of cardiac death. Likewise, when analysis was restricted to patients with an LVEF < 40%, the upper cutoff value of late H/M was 1.50 (P = 0.0358; log rank = 4.41) for ischemic patients and 2.02 (P = 0.0050; log rank = 7.86) for idiopathic patients. For patients with an LVEF < 40% and a late H/M less than the identified threshold of late H/M, the annual rate of cardiac death was greatest, 18.2%/y for the ischemic group and 11.9%/y for the idiopathic group. CONCLUSION: Cardiac (123)I-MIBG activity has the most powerful independent long-term prognostic value for both ischemic cardiomyopathy patients and idiopathic cardiomyopathy patients, indicating that both disease processes have common pathophysiologic and prognostic implications of impaired cardiac sympathetic innervation. Although combined testing of cardiac function and (123)I-MIBG activity is most likely to identify patients at increased risk of cardiac death, the underlying etiology of cardiac dysfunction may affect the threshold of (123)I-MIBG activity for the differentiation of high-risk patients.

3-Iodobenzylguanidine↗

Modifications of sleep EEG induced by chronic vagus nerve stimulation in patients affected by refractory epilepsy.

OBJECTIVE: The aim of this study was to evaluate the impact of chronic vagus nerve stimulation (VNS) on sleep/wake background EEG and interictal epileptiform activity (IEA) of patients with medically refractory epilepsy. METHODS: From a broader sample of 10 patients subjected to baseline and treatment polysomnographies, spectral analysis and IEA count have been performed on 6 subjects' recordings, comparing the results by means of statistical analysis. RESULTS: An overall increase in EEG total power after VNS has been observed, more marked in NREM sleep; collapsing EEG power spectra into 5 frequency bands, we have found a statistically significant increase in delta and theta in NREM sleep, and of alpha in wakefulness and REM sleep. The incidence of IEA is diminished, although not significantly; only the duration of discharges is significantly diminished. CONCLUSIONS AND SIGNIFICANCE: Long-term VNS produces an enhancement in sleep EEG power of medically refractory epileptic patients. These results may be related to a better structured composition of EEG, and it is possible that chronic VNS may have a major role in enhancing the brain's ability to generate an electrical activity.

Adult↗

Meta-analysis.

Systematic reviews use explicit and reproducible criteria to assemble, appraise, and combine articles with a minimum of bias. Meta-analysis is a form of systematic review that uses statistical techniques to derive quantitative estimates of the magnitude of treatment effects and their associated precision. Valid meta-analyses address focused questions, use appropriate criteria to select articles, assess the quality and combinability of articles, provide graphic and numeric summaries, consider potential biases, and can be generalized to a meaningful target population. The rate difference, or absolute risk reduction, is the preferred measure of clinical effect size; the reciprocal tells the number needed to treat for one additional favorable outcome. The benefits of meta-analysis over individual trials include greater precision, increased statistical power, and the ability to identify and explore diversity among studies. Threats to validity include heterogeneity, citation bias, publication bias, language bias, and variations in study quality. Because meta-analysis defines rational treatment expectations at a population level, it is an adjunct to, not a substitute for, clinical judgment in the care of individual patients.

Humans↗

Methodological issues in case-control studies: validity and power of various design/analysis strategies.

Computer stimulations have been used to estimate the efficiency, as measured by the statistical power, of various combinations of design and analysis strategies for case-control studies. Conditions under which the various forms of analysis yield consistent relative risk estimators are derived for the general model. The results indicate that the loss of efficiency resulting from the use of a less than optimum design or analysis strategy in many real life situations is small. Practical considerations are of more importance than theoretical statistical ones in deciding upon appropriate strategies. It is concluded that matching is rarely, if ever, justified in most case-control studies of chronic diseases.

Adult↗