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Capturing error rates and reporting significant data.

Programs that embrace sound outcomes, process, and structure assessment complemented by systematic inquiry and improvement serve as protectors of quality during an era of dramatic cost reduction. Outcome data presented alongside process and structural methods enable a clear understanding of quality, balancing the scales between societal cost and individual health. The ability to change a system through the generation and use of powerful data reporting mechanisms takes on increased significance as we strive to improve the safety of US health care. The NQF's work is just the tip of the iceberg; health care organizations must accept the inevitable: Practice standardization and delineation of concrete, nationwide quality benchmarks are the future of US health care.

Benchmarking↗

Changing indications of open stone surgery.

OBJECTIVES: To compare the current role of open stone surgery at our institution to previously reported data. In 1989, the indications for open surgical treatment of urinary calculi at our institution were reviewed. In the intervening years, tremendous advances have been made in minimally invasive treatment of urinary calculi. METHODS: A retrospective evaluation of all patients undergoing procedures for the purpose of stone removal or fragmentation at Wake Forest University Baptist Medical Center between January 1, 1998 and May 31, 2001 was conducted. This was compared with data reported from our institution describing similar procedures in the first 19 months after introduction of the Dornier HM3 lithotriptor. RESULTS: Of 986 procedures performed for the purpose of stone removal or fragmentation between January 1, 1998 and May 31, 2001, 0.7% were open surgical procedures. Of these procedures, 85.8% were performed for anatomic indications. Patients referred from other institutions for evaluation after endoscopic treatment failure comprised the remaining 14.2% of this group. In the previously reported data, 893 procedures were performed for the treatment of urinary calculi, of which 4.1% were open operations. Of these patients, 48.6% underwent an open surgical procedure after unsuccessful endoscopic treatment of urinary calculi, and 48.7% of these patients underwent open surgery for anatomic indications. CONCLUSIONS: Open surgical stone removal remains a viable treatment option for select patients. Technologic advances and improved surgical skills have greatly reduced the number of patients requiring open surgery. This approach is mainly used for patients with complex calculous disease associated with anatomic abnormalities.

Adult↗

Pain assessment and management in cognitively impaired nursing home residents: association of certified nursing assistant pain report, Minimum Data Set pain report, and analgesic medication use.

OBJECTIVES: The primary purpose of this preliminary study was to investigate the associations between certified nursing assistant (CNA) report of pain, Minimum Data Set (MDS) report of pain, and analgesic medication use in cognitively impaired nursing home residents. DESIGN: Correlational study. SETTING: Three nursing homes in the greater Birmingham, Alabama area. PARTICIPANTS: Fifty-seven cognitively impaired nursing home residents with a mean Mini-Mental State Examination (MMSE) score of 11.1. MEASUREMENTS: Pain was assessed using a three-item proxy pain questionnaire (PPQ), developed by the researchers and administered to the residents' primary CNA. MDS and analgesic medication data corresponding with the time of PPQ data collection were gathered from medical records. Cognitive status was measured with the MMSE. RESULTS: The PPQ elicited substantially higher estimates of pain prevalence than the MDS (48% versus 20%), and the PPQ and the MDS were not well correlated (pain frequency: r=.19, P=.18; pain intensity: r=.22, P=.11). The PPQ was also more strongly associated with analgesic medication use than the MDS. Cognitive status was significantly associated with pain report on the PPQ but not on the MDS. Test-retest reliability coefficients for the three items of the PPQ were excellent, ranging from.84 to.87 (P </=.01). CONCLUSIONS: The CNA-generated PPQ was a more sensitive measure of pain than the MDS for this sample. Although the MDS represents an important step toward systematic and standardized assessment of pain, more emphasis should be placed on multimodal assessment, including CNAs' perceptions and observations about pain experienced by cognitively impaired nursing home residents.

Aged↗

Systematic analysis of bicistronic reporter assay data.

Bicistronic reporter assay systems have become a mainstay of molecular biology. While the assays themselves encompass a broad range of diverse and unrelated experimental protocols, the numerical data garnered from these experiments often have similar statistical properties. In general, a primary dataset measures the paired expression of two internally controlled reporter genes. The expression ratio of these two genes is then normalized to an external control reporter. The end result is a 'ratio of ratios' that is inherently sensitive to propagation of the error contributed by each of the respective numerical components. The statistical analysis of this data therefore requires careful handling in order to control for the propagation of error and its potentially misleading effects. A careful survey of the literature found no consistent method for the statistical analysis of data generated from these important and informative assay systems. In this report, we present a detailed statistical framework for the systematic analysis of data obtained from bicistronic reporter assay systems. Specifically, a dual luciferase reporter assay was employed to measure the efficiency of four programmed -1 frameshift signals. These frameshift signals originate from the L-A virus, the SARS-associated Coronavirus and computationally identified frameshift signals from two Saccharomyces cerevisiae genes. Furthermore, these statistical methods were applied to prove that the effects of anisomycin on programmed -1 frameshifting are statistically significant. A set of Microsoft Excel spreadsheets, which can be used as templates for data generated by dual reporter assay systems, and an online tutorial are available at our website (http://dinmanlab.umd.edu/statistics). These spreadsheets could be easily adapted to any bicistronic reporter assay system.

Data Interpretation, Statistical↗

Frequency of congenital abnormalities and of anatomical variations among JAX rabbits.

The frequency of congenital abnormalities and anatomical variations as observed among JAX rabbits is reported. Data were drawn from 32,082 inbred and partially inbred rabbits and 3,208 hybrids from the colony of the Jackson Laboratory over an eight-year period. Data reported here include stillbirths, rabbits dying from natural causes, and those killed for specific experimental regimens. Frequency data are based on the number of abnormalities observed in each category as a function of the total number of animals necropsied. This is approximately 95% of the animals born during the eight-year period and gives the frequency of abnormalities within each category rather than the number of individuals with one or more abnormalities. Anatomical variations have been found in almost all organ systems of JAX rabbits. Their presence adds to our knowledge of the characteristics of these strains, a knowledge that is critical to the understanding of the results of experimental manipulation or for determination of the presence of new mutations. There is considerable between-strain variation. Where frequencies are relatively high, the conditions are either known or suspected to be of genetic origin. Most of the anomalies are not deleterious, or their frequency is so low as to cause no problems within the colony. Hybrid populations have substantially fewer anomalies than do the parental strains. Where frequency is relatively high, it tends to be intermediate between the parental strains.

Animals↗

Safety of the newer antiepileptic drug oxcarbazepine during pregnancy.

OBJECTIVE: Seizure control in pregnant women with epilepsy is vital, as maternal seizures may have deleterious consequences. The treatment of pregnant women with epilepsy is, however, complicated by the teratogenicity of older antiepileptic drugs (AEDs). In this review, the safety of the newer AED oxcarbazepine during pregnancy is assessed based on published pregnancy outcome data. Other relevant safety issues, such as oxcarbazepine pharmacokinetics during pregnancy and the compatibility of oxcarbazepine treatment with breastfeeding, are also discussed. METHODS: Literature searches of the following databases were performed: MEDLINE, EMBASE, eNova, NOWIMA (an internal Novartis Germany database), Derwent Drug File, SciSearch and BIOSIS. Identified publications were examined for original data reporting rates of foetal malformation following maternal exposure to oxcarbazepine as monotherapy or adjunctive therapy. RESULTS: Relevant publications reporting data from the worldwide Novartis safety database and pregnancy registries or study centres in six countries were identified. A total of 248 pregnancies involving maternal exposure to oxcarbazepine monotherapy and 61 involving adjunctive therapy were reported. There were six malformations among the monotherapy group, equating to a malformation rate of 2.4% (6/248). The malformation rate reported in the general population is 2-4%. There were four malformations associated with oxcarbazepine adjunctive therapy, equating to a malformation rate of 6.6% (4/61). CONCLUSIONS: This literature review suggests that, compared with newborns in the general population, the newborns of women receiving oxcarbazepine monotherapy during pregnancy do not appear to show an increased risk for malformations. However, the number of pregnancies involving maternal exposure to oxcarbazepine identified by this review is not sufficient to draw definitive conclusions. Additional information from large-scale pregnancy registries is required to confirm the safety profile of oxcarbazepine as monotherapy or adjunctive therapy during pregnancy.

Abnormalities, Drug-Induced↗

Modulation frequency and modulation level owing to vocal microtremor.

Vocal microtremor designates a normal slow modulation of the vocal cycle lengths of speakers who do not suffer from pathological tremor of the limbs and whose voices are not perceived as tremulous. Vocal microtremor is therefore distinct from pathological vocal tremor. The objective is to report data about the modulation frequency and modulation level owing to vocal microtremor. The modulation data have been obtained for vowels [a], [i], and [u] sustained by normophonic and mildly dysphonic male and female speakers. The results are the following. First, modulation frequencies and relative modulation levels do not differ significantly for male and female speakers, normophonic and mildly dysphonic speakers, as well as for vowel timbres [a], [i], and [u]. Second, the typical interquartile intervals of the modulation frequency and modulation level are equal to 2.0-4.7 Hz and 0.4%-1.3%, respectively. Third, dissimilarities between data reported by different studies are due to different cutoff frequencies below which spectral peaks are considered not to contribute to vocal microtremor.

Data Interpretation, Statistical↗

Decrease in the size of the myotonic dystrophy CTG repeat during transmission from parent to child: implications for genetic counselling and genetic anticipation.

Recently an unstable trinucleotide CTG repeat, located within the 3' untranslated region of a gene on 19q13.3 was discovered in kindreds with myotonic dystrophy (DM). The age-of-onset/severity of DM shows a good correlation with CTG repeat size, and pedigrees and data reported to date have shown a striking trend toward amplification of the size of the CTG repeat during transmission from parent to child. The amplification has been accepted as the biological explanation for anticipation in the clinical severity observed in many families with DM. In this paper we report on 3 families where CTG amplification decreased during transmission from parent to child. In one case there was a gene conversion event, while in the remaining 2 there was a simpler reduction in the size of the repeat length. The changes appear to have been accompanied by a reduction in clinical severity in the child when compared to the parent. These observations are discussed in terms of their clinical implications and the biases that may exist in much of the reported data.

Adolescent↗

Effects of systematic peripheral group deuteration on the low-frequency resonance Raman spectra of myoglobin derivatives.

Resonance Raman spectra are reported for a series of systematically deuterated analogues of myoglobin in its deoxy state as well as for its CO and O(2) adducts. Specifically, the myoglobin samples studied are those that have been reconstituted with deuterated protoheme analogues. These include the methine deuterated, protoheme-d4; analogue bearing C(2)H(3) groups at the 1, 3, 5, and 8 positions, protoheme-d12; the species bearing C(2)H(3) groups at the 1 and 3 positions only, 1,3-protoheme-d6; and the species bearing C(2)H(3) groups at the 5 and 8 positions only, 5,8-protoheme-d6. While the results are generally consistent with previously reported data for synthetic metalloporphyrin models and previous studies of labeled heme proteins, the high-quality low-frequency RR data reported here reveal several important aspects of these low-frequency modes. Of special interest is the fact that, using the two d6-protoheme analogues, it is shown that certain modes are apparently localized on particular pyrrole rings, while others are localized on different rings; i.e., several of these low-frequency modes are localized on one side of the heme.

Animals↗

Adenohypophyseal hormone levels in the cerebrospinal fluid of patients with pituitary disease.

Measurement of adenohypophyseal hormones in the cerebrospinal fluid (CSF) was recently proposed as an useful procedure to differentiate pituitary intra and extrasellar tumors. So far, data reported are conflicting. We measured the concentrations of GH, TSH, LH and PRL in CSF and plasma in 30 controls and in 37 patients with various pituitary diseases (18 intrasellar adenomas, 14 extrasellar adenomas and 5 empty sella syndromes). The concentrations of examined hormones in CSF were very low or undetectable in all control subjects. In most patients with pituitary tumors, adenohypophyseal hormones were found to be present in CSF, in great amounts. No significant differences were found between intra and extrasellar tumors. In agreement with recently reported data, no significant correlation was found between GH, TSH, FSH and LH levels in CSF and plasma, while a significant correlation (p less than 0.01) was obtained between CSF and plasma levels of PRL, either in all patients or in those with extrasellar tumors only. All patients bearing an empty sella had PRL detectable in CSF: in 2 cases PRL levels were very high. In conclusion our data do not confirm that measurement of adenohypophyseal hormones in CSF represents an useful screening to differentiate tumors with extrasellar extension. PRL data deserve interest in order to gain understanding of the hormone dynamics between CSF and vascular compartments.

Adenoma↗

Respiratory mechanics after 180 days space mission (EUROMIR'95).

The present study reports data on respiratory function of lung and chest wall following the 180 days long European - Russian EuroMir '95 space mission. Data reported refer to two subjects studied before the mission, on day 9 and 175 in flight and on days 1, 10, 12, 27 and 120 after return. In-flight vital capacity (VC) and expiratory reserve volume (ERV) were similar to those in supine posture, namely approximately 5% and approximately 30% less than in sitting posture. On day 1 after return, VC was reduced by approximately 30% in both postures. This reflected a decrease in ERV (approximately 0.5 L) and in IC (inspiratory capacity, approximately 1.7 L) that could be attributed to a marked weakening of the respiratory muscles. Regain of normal preflight values barely occurred 120 days after return. Post-flight pressure-volume curves of the lung, chest wall and total respiratory system are equal to preflight ones. The pressure-volume curve of the lung in supine posture is displaced to the right relative to sitting posture and shows a lower compliance. As far as the lung in-flight condition resembles that occurring in supine posture, this implies a lower compliance, a greater amount of blood in the pulmonary microvascular bed, a more homogeneous lung perfusion and therefore a greater microvascular filtration rate towards lung interstitium.

Adult↗

Genetic basis of anxiety-like behaviour: a critical review.

The way genetic and/or environmental factors influence psychiatric disorders is an enduring question in the field of human psychiatric diseases. Anxiety-related disorders provide a relevant example of how such an interaction is involved in the aetiology of a psychiatric disease. In this paper we review the literature on that subject, reporting data derived from human and rodent studies. We present in a critical way the animal models used in the studies aimed at investigating the genetic basis of anxiety, including inbred mice, selected lines, multiple marker strains, or knockout mice and review data reporting environmental components influencing anxiety-related behaviours. We conclude that anxiety is a complex behaviour, underlined not only by genetic or environmental factors but also by multiple interactions between these two factors.

Animals↗

Metabolic flux analysis as a tool for the elucidation of the metabolism of neurotransmitter glutamate.

A flux analysis model for the metabolism of neurotransmitter glutamate is constructed, in order to study functional aspects of its metabolism. This work is based on the potassium [K(+)] evoked neurotransmitter glutamate released, as measured in a series of experiments of superfused rat or mouse brain preparations. These measurements are combined with data reported, concerning the metabolism of glutamate and its precursors, glutamine and glucose in rat cerebral cells in vivo. The proposed stoichiometry of the specific reaction network renders the model solvable. The classification procedure establishes that the measured fluxes are all balanceable and all non-measured fluxes can be calculated. The system is well posed with a condition number of 7.8536. The results emphasize the importance of phosphate activated glutaminase and aspartate aminotransferase in the metabolism of neurotransmitter glutamate. Reported data on the rate of the malate-aspartate shuttle, as well as the anaplerotic flux of the glial pyruvate carboxylase reaction are in agreement with the estimations calculated from the proposed model.

Animals↗

Some biochemical properties of melatonin and the characterization of a relevant metabolite arising from its interaction with H2O2.

Melatonin is an efficient protector against hydrogen peroxide(H2O2)-induced lipid peroxidation and acts in a concentration-dependent manner. Hydrogen peroxide is rather a water stable molecule which is able to cross the cell membrane much better than some important free radicals such as superoxide anion, and consequently its local production can lead to significant spread by diffusion. In this paper we report data regarding some biochemical properties of melatonin as well as the chemical characterization of the major product formed from the interaction between melatonin and H2O2 (N1-acetyl-N2-formyl-5-methoxykynuramine) that are consistent with previous data reported by other authors. The effect of melatonin on catalase, glutathione peroxidase and superoxide dismutase in in vitro and in vivo experiments is also reported.

Animals↗

The size and conformation of Artemia (brine-shrimp) ribosomal RNA free in solution.

The RNA was isolated from the large ribosomal subunits of the brine shrimp Artemia, and its conformation free in solution was studied by determining its sedimentation and diffusion coefficients. A comparison was made of the hydrodynamic radius of the ribosomal subunit and its isolated RNA in various buffers. The conformation of the rRNA free in solution is more extended than when it is incorporated in the ribosome. This is not only the case when the rRNA solution lacks bivalent and polyvalent cations, but even in the presence of Mg2+ and spermidine, which cause a tightening of RNA. Thus the ribosomal proteins should induce a further tightening of the rRNA during the assembly of the ribosome. In the discussion, the reported data on Escherichia coli rRNA species are presented in such a way that large discrepancies between various studied are revealed, and that they can be compared with the data reported here on the larger rRNA of an eukaryote.

Animals↗