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Cost and benefit of perioperative antimicrobial prophylaxis: methods for economic analysis.

Cost-benefit analysis of perioperative prophylaxis with antimicrobial agents involves efforts in two main areas: first, economic aspects of a decision whether or not to use prophylaxis are examined; and second, the financial benefit of a drug or regimen is compared with that of the currently used drug or regimen. Both cost and benefit have a number of components, both direct and indirect; methods are available for the analysis of some of these components. Systematic economic analysis permits evaluation of the relative importance and magnitude of the various elements of cost and benefit. Often the analysis shows that information about one or more elements is not worth collecting because it will have minor or no impact. Failure to clearly identify the viewpoints of persons interpreting the data hinders analysis; systematic economic analysis makes these differences in viewpoint clearer. Convincing economic data in favor of prophylaxis exist for some operative procedures; hospitals should insist that these regimens be implemented. Surgical wound infection is the only type of nosocomial infection for which a consistent drop in rate of occurrence has been seen during the past decade. This drop undoubtedly is related in part to the perioperative use of antimicrobial agents. Perhaps these results constitute the best cost-benefit assessment of all.

Anti-Infective Agents↗

[Medication prescription and transcription errors in a neonatal unit].

BACKGROUND: Medication errors occur because of pitfalls in one or more of the steps involved in the process of drug administration and should be considered as system errors. They should never be considered as human errors with assignment of responsibility. Rather, their causes should be analyzed to prevent repetition. The ultimate aim should be to improve working procedures to avoid these errors. PATIENTS AND METHODS: A total of 122 prescriptions were prospectively analyzed, along with their corresponding transcription to the nursing notes. Their legibility, dose, units, route of administration, and administration interval were evaluated. Units per kilogram of body weight and the use of generic names were also recorded. RESULTS: Prescription errors were detected in 35.2 % of the prescriptions reviewed. The most frequent errors were related to dosing (16.4 %). Analysis of the quality of the prescriptions revealed that 61.5 % of the drugs were prescribed by their generic name, but only 4.1 % specified the dose per kilogram of body weight. Errors were detected in 21.3 % of transcriptions, the most frequent being the absence of the administration route (7.4 %). The generic name was used in 57.4 % of the transcriptions. CONCLUSIONS: In the busy and complex environment of neonatal units, medication errors can be frequent. However, most of these errors are trivial and do not harm patients. Medication errors are indicators of the quality of the healthcare provided. Therefore, their detection and systematic analysis of their causes can contribute to their systematic prevention, thus improving the healthcare delivery process.

Humans↗

Auditory brainstem response in the identification of cochlear synaptopathy in aged rodents: a systematic review with meta-analysis.

PURPOSE: This systematic review and meta-analysis evaluated the diagnostic performance of auditory brainstem response (ABR) for identifying age-related cochlear synaptopathies in rodents. METHOD: Following PRISMA guidelines, searches were conducted in PubMed/MEDLINE, Cochrane Library, Scopus, Embase, Web of Science, SciELO, LILACS, and gray literature. Studies evaluating CS in naturally aged rodents using short-latency auditory evoked potentials (AEPs) were included. Study selection, data extraction, risk-of-bias (JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies), and certainty of the evidence (GRADE® system) assessment were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model, with standardized mean differences and 95% confidence intervals. ABR wave I amplitudes were analyzed for click (80 and 90 dB SPL) and tone-burst stimuli stratified by frequency. RESULTS: Among 3,008 identified records, 12 studies were included in the review and five in the meta-analysis. All included studies used ABR measures to investigate CS, with wave I amplitude being the most frequently evaluated biomarker. Meta-analysis demonstrated a significant reduction in ABR wave I amplitude in aged rodents compared with young controls for both click- and tone-burst-evoked responses. Tone-burst ABR showed no significant differences among the evaluated frequencies. These findings should be interpreted with caution due to the limited number of studies and the methodological heterogeneity, which may have reduced statistical power and comparability. CONCLUSIONS: The evidence supports ABR wave I amplitude as a sensitive electrophysiological marker of age-related CS in rodents. Nevertheless, further studies with standardized protocols are needed to strengthen its diagnostic utility and improve comparability across studies.

Animals↗

Influence of Concave Versus Convex Emergence Profiles on Midfacial Mucosal Stability-A Systematic Review With Meta-Analysis.

OBJECTIVES: To systematically evaluate the influence of concave versus convex emergence profiles on midfacial mucosal stability in partially edentulous patients restored with implant-supported single restorations. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted and registered in PROSPERO (CRD420251139042). An electronic search in MEDLINE (PubMed) and Embase was performed up to May 7, 2026. Eligible studies included RCTs comparing concave (test group) and convex (control group) transmucosal prosthetic designs and reporting midfacial mucosal level changes (mm). Data extraction and risk of bias assessment (RoB 2) were performed independently. A random-effects meta-analysis was conducted using weighted mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic and sensitivity analyses were performed to evaluate the robustness of the findings. RESULTS: Four RCTs including 144 implants with a 12-month follow-up were included. Of these, 128 implants contributed to the quantitative synthesis, with 66 implants allocated to the concave/modified emergence profile group and 62 implants allocated to the convex/non-concave emergence profile group. The pooled analysis demonstrated a mean difference of -0.31 mm (95% CI -0.63 to 0.02; p = 0.064), indicating a trend toward greater midfacial mucosal recession with convex emergence profiles compared with concave designs. Between-study heterogeneity was low to moderate (I2 = 28%), suggesting consistent findings across studies. Sensitivity analyses confirmed the direction of the effect, with pooled estimates ranging from -0.12 to -0.43 mm. Exclusion of one study resulted in a statistically significant difference favoring concave emergence profiles (-0.43 mm; 95% CI -0.70 to -0.16; p = 0.002). CONCLUSIONS: Convex emergence profiles are associated with a tendency toward increased midfacial mucosal recession. Concave profiles are preferable to support peri-implant soft-tissue stability. CLINICAL RELEVANCE: Emergence profile design should be considered an integral component of prosthetic and surgical planning. The use of concave transmucosal contours during provisionalization and definitive restoration may contribute to improved peri-implant soft tissue stability and enhanced esthetic outcomes.

Humans↗

Multiple transrectal ultrasound-guided biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion.

A total of 251 men with suspected prostate cancer were examined by transrectal ultrasound (TRUS) in order to evaluate the usefulness of TRUS and core biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion (SVI). Biopsies targeting hypoechoic lesions were taken in combination with systematic biopsies obtained from six standardized locations. Bilateral seminal vesicle biopsies were obtained from 168 of the men. A total of 26 patients underwent surgery and a comparison between the results of the histopathological evaluation of core biopsies and the prostatectomy specimen was performed. A total of 137 cancers were detected. In 34 patients (25%) the tumors were diagnosed by systematic biopsies alone. Tumor volume as estimated by TRUS underestimated the volume when compared to a planimetric technique. Correlation between the two methods was not found by regression analysis. Systematic biopsies did not improve grading compared to the grading of prostatectomy specimens. A total of 24 SVIs were detected. Valuable information was obtained for the diagnosis of prostate cancer by taking systematic biopsies.

Adult↗

Limiting dilution analysis for estimating the frequency of hematopoietic stem cells: uncertainty and significance.

The ability to predict accurately the number of hematopoietic stem cells (HSCs) in a graft is important for the success of HSC transplantation. Limiting dilution analysis (LDA) in vitro and in vivo is widely used to enumerate HSCs. However, there have been few attempts to standardize this approach. Particularly, the role of statistical and experimental errors in the performance and evaluation of LDA has received little attention. Since these errors directly affect the interpretation, validity, and significance of the LDA results, we have here performed a systematic analysis of the contribution of different types of errors.Long-term culture-initiating cells (LTC-IC) in the bone marrow of C57BL/6 (B6) mice were measured. Experiments were designed to exclude systematically different types of experimental errors. Computer simulations were performed to estimate the statistical error. Analysis of 137 LTC-IC assays showed 2.8 +/- 1.06 LTC-IC per 10(5) cells in the bone marrow of B6 mice. The major components of the uncertainty were derived from variations introduced by performing the experiments at different time points and by the statistical error. Surprisingly, operator errors and mouse-to-mouse error, including age and sex of the animals, contributed little to the overall uncertainty. As expected, the errors were found to decrease when increasing numbers of replica were analyzed. A computer program was developed to assist with the optimal design of the assay. The analysis presented here provides rational strategies for standardizing the experimental design and for gauging the accuracy of LDA-based HSC measurements.

Animals↗

[Use of echocardiography in mitral regurgitation for the assessment of its mechanism and etiology for the morphological analysis of the mitral valve].

Echocardiographic assessment of mitral regurgitation allows the diagnosis of its mechanism and cause which are major determinants in the feasibility of mitral valve repair. This assessment is based on a systematic analysis of the different structures of the mitral valve apparatus: mitral annulus (enlargement, calcification), mitral valve morphology (thickening, calcification, floppy valve, vegetations, perforation), mitral valve motion (restriction, identification of the prolapsed leaflets and scallops in patients with mitral valve prolapse or flail leaflets), subvalvular apparatus (ruptured chordae, thickening), papillary muscles, and left ventricular wall. This analysis can diagnose the mechanism of mitral regurgitation according to the Carpentier classification, and can clarify its cause: degenerative lesions (prolapse or flail leaflet with or without ruptured chordae), rheumatic lesions (thickened valves with restricted motion), endocarditis (vegetations, perforation, ruptured chordae), ischemic mitral regurgitation (restricted valve motion with inferior or posterior left ventricular wall asynergy), or functional mitral regurgitation (annular dilatation, displacement of papillary muscles with restricted leaflet motion). Transthoracic echocardiography with harmonic imaging usually allows a comprehensive assessment of functional anatomy of mitral regurgitation. Transesophageal echocardiography is indicated if transthoracic echocardiography is inadequate. It is also indicated just before surgery and as an intraoperative procedure. Real time 3D echocardiography should probably complete the evaluation of mitral regurgitation in the near future.

Echocardiography↗

Clinical and quantitative coronary angiographic predictors of coronary restenosis: a comparative analysis from the balloon-to-stent era.

OBJECTIVES: We sought to assess whether coronary stents have modified the predictive value of demographic, clinical and quantitative coronary angiographic (QCA) predictors of coronary restenosis. BACKGROUND: A systematic analysis in a large cohort of registries and randomized trials of the percutaneous transluminal coronary angioplasty (PTCA) and stent era has never been performed. METHODS: A total of 9,120 treated lesions in 8,156 patients included in nine randomized trials and 10 registries, with baseline, post-procedural and six-month follow-up QCA analyses, were included in this study. Predictors of restenosis were identified with univariate and multivariate logistic regression analyses. Interaction terms were introduced in the regression equation to evaluate whether the predictors of restenosis were common to both eras or specific for either one of the revascularization techniques. RESULTS: The restenosis rate was 35% after PTCA and 19% after angioplasty with additional stenting. In the univariate analysis, favorable predictors were previous coronary artery bypass graft surgery (CABG), stent use, stent length and a large pre-procedural minimal lumen diameter (pre-MLD); unfavorable predictors were weight, body mass index, diabetes mellitus, multi-vessel disease, lesion length and a high residual post-procedural diameter stenosis (post-DS). Predictors specific for the PTCA population were a large post-procedural MLD (post-MLD) as favorable and a severe pre-procedural DS (pre-DS) as unfavorable. Favorable predictors specific for the stent population were a large post-MLD and a large pre-procedural reference diameter (pre-RD). In the multivariate analysis, the best model included the following favorable predictors: stent use, a large post-MLD, previous CABG and the interaction term between stent use and a large post-MLD; unfavorable predictors were lesion length and diabetes mellitus. CONCLUSIONS: There are no major differences in demographic and clinical predictors of coronary restenosis between PTCA and stent populations. In the modern (stent) era, a severe pre-DS is no longer an unfavorable predictor of restenosis. Still important, but more so in the stent population, is a large post-MLD (optimal result). Finally, a larger pre-RD became a favorable predictor with the advent of stenting.

Aged↗

Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis.

BACKGROUND: No systematic review has evaluated the existing evidence regarding the association between packed red blood cell (pRBC) transfusion and clinical worsening of necrotizing enterocolitis (NEC) in neonates. This systematic review and meta-analysis was conducted to address this knowledge gap. MATERIALS AND METHODS: We searched the Cochrane Library, EBSCO, Embase, Web of Science, Google Scholar, and PubMed for studies on pRBC transfusion and NEC published before May 10, 2025. Relevant articles were selected through title, abstract, and full-text screening. English-language case-control studies or cohort studies, or randomized controlled trials involving newborns with NEC that compared pRBC transfusion with no transfusion and reported changes in NEC clinical status were included. Review articles, systematic reviews, case reports, editorials, animal studies, duplicate publications, and studies with incomplete data were excluded. RESULTS: Five studies involving 971 neonates with NEC were included. The pooled analysis demonstrated a potential association between pRBC transfusion and clinical deterioration of NEC in neonates (odds ratio: 6.05, 95% confidence interval: 3.02-12.14). CONCLUSIONS: pRBC transfusion was associated with an exacerbation of NEC in neonates. However, these findings should be interpreted cautiously because of the small number of eligible studies included in this meta-analysis, and future large-scale, well-designed studies are needed to confirm the observed association.

Humans↗

Characterization of matriptase expression in normal human tissues.

Matriptase is a type II transmembrane serine protease that has been implicated in the progression of epithelium-derived tumors. The role of this protease in the biology of normal epithelial cells remains to be elucidated. Matriptase mRNA has been detected by Northern analysis in tissues rich in epithelial cells, and the protein is expressed in vivo in normal and cancerous breast, ovarian, and colon tissues. However, a systematic analysis of the distribution of matriptase protein and mRNA in normal human tissues rich in epithelium has not been reported. In this study we characterized the expression of the protease in a wide variety of normal human tissues using a tissue microarray and whole tissue specimens. Significant immunoreactivity and mRNA expression were detected in the epithelial components of most epithelium-containing tissues. Matriptase expression was found in all types of epithelium, including columnar, pseudostratified columnar, cuboidal, and squamous. Distinct spatial distributions of reactivity were observed in the microanatomy of certain tissues, however. This suggests that although matriptase is broadly expressed among many types of epithelial cells, its activity within a tissue may be regulated in part at the protein and mRNA levels during the differentiation of selected epithelia.

Epithelium↗

Conformational analysis of environmental agents: use of X-ray crystallographic data to determine molecular reactivity.

This paper explores the use of crystallographic techniques as an aid in understanding the molecular reactivities of a number of agents that are of concern to pharmacologists and toxicologists. The selected examples demonstrate the role of structural data in the determination of absolute configuration, configurational flexibility and active-site topology for a reactive species. For example, the role of absolute stereochemistry in understanding synthetic pyrethroid structure-activity relationships is shown from analysis of their crystal structures; conformational flexibility among DDT analogues, and the importance of conformational and electronic properties in phenylalkanoic acid herbicides are shown from systematic analysis of their crystal structures; and interpretation of active-site stereochemistry is made by study of computer modeling of enzyme inhibitors in the active sites of related protein crystal structures. Thus, the observed patterns in conformational flexibility and their resultant effects on substrate pharmacological profile can be interpreted in understanding the molecular level events that influence biological reactivity.

Crystallography↗

[A model for clinical study based on genome science--trials in disorders of the immune system and allergies].

Disorders of the immune system, such as allergies, have multi-factorial etiologies that include both genetic and environmental components. The recent advances in genome science have facilitated two strategies for studying the genetic basis of disease: (1) systematic analysis of gene expression profiles and (2) comprehensive analysis of gene variations, such as polymorphisms. Here, we describe a unique research institute, Genox Research Inc., that can relate the clinical profile of a patient to genotyping and molecular profiling. Systematic gene expression analyses using differential display have been performed to explore genes related to allergy, and revealed 93 differentially expressed candidate genes in T-cells. Also, a single nucleotide polymorphism(SNP) analysis project has been designed to mine disease-related and/or drug-response-related genes involved in allergic disorders using biochip technologies. As exemplified above, clinical studies based on these applications of genome science would be of considerable value in clarifying our understanding of multi-gene disorders.

Gene Expression Profiling↗

Protein sequence motifs.

Protein sequence motifs are signatures of protein families and can often be used as tools for the prediction of protein function. The generalization and modification of already known motifs are becoming major trends in the literature, even though new motifs are still being discovered at an approximately linear rate. The emphasis of motif analysis appears to be shifting from metabolic enzymes, in which motifs are associated with catalytic functions and thus often readily recognizable, to structural and regulatory proteins, which contain more divergent motifs. The consideration of structural information increasingly contributes to the identification of motifs and their sensitivity. Genome sequencing provides the basis for a systematic analysis of all motifs that are present in a particular organism. A systematically derived motif database is therefore feasible, allowing the classification of the majority of the newly appearing protein sequences into known families.

Amino Acid Sequence↗

Post-surgery radiation in early breast cancer: survival analysis of registry data.

BACKGROUND AND PURPOSE: Overviews of randomized trials have shown a small survival advantage with post-surgery radiation in early breast cancer. The present study attempts to extend this observation through a systematic analysis of population data. MATERIALS AND METHODS: This retrospective cohort study used the Surveillance, Epidemiology, and End Results (SEER) data on 83,776 women with breast cancer diagnosed between 1988 and 1997, stage T1-T2, node negative or node positive. The analysis was performed using the proportional hazard models. RESULTS: Radiation was associated with a reduced mortality after breast-conserving surgery in node negative patients (hazard ratio 0.757; 95% confidence interval 0.709-0.809; using total mastectomy without radiation as reference) and in node positive patients (hazard ratio 0.777; 0.717-0.842), and after total mastectomy in node positive patients (hazard ratio 0.885; 0.815-0.961). Radiation was associated with an increased hazard ratio of 1.271 (1.080-1.496) after total mastectomy in node negative patients. Without radiation, breast-conserving surgery in node negative patients was associated with an increased hazard ratio (1.167; 1.036-1.314); a similar increase was not observed in node positive patients (hazard ratio 1.011; 0.884-1.155). In all cases, the best survival rates were found with combined breast-conserving surgery and radiation. CONCLUSION: The available data indicate that post-surgery radiation provides a survival advantage irrespective of the type of surgery in node positive patients. Likewise, survival advantage was observed with post-surgery radiation and breast-conserving procedure in node negative patients.

Adult↗

Analysis of differential gene expression in human colorectal tumor tissues by RNA arbitrarily primed-PCR: a technical assessment.

RNA arbitrarily primed (RAP)-PCR is a powerful tool for studying differential gene expression in cancer cells. Systematic analysis of human tumor samples may provide a list of markers with potential application to the diagnosis, prognostic assessment, and treatment of the disease. Nevertheless, because of characteristics inherent to the samples and technique, artifactual results are likely. We have assessed the effects of several factors on RAP-PCR performance to determine the sensitivity and reproducibility of the technique, as well as the accuracy of its results, under different conditions in human cell lines and in a series of 129 paired human normal colonic mucosa-colorectal carcinoma samples. Our results show that RAP-PCR provides reliable fingerprints in a relatively wide spectrum of circumstances, including variations in RNA concentration and contamination by DNA. Densitometric analysis indicated that relative band-intensity variations more than 20% were reproducible in 95% of the cases. Serial analysis of paired normal-tumor cases yielded a number of bands that were recurrently either underexpressed or overexpressed in tumor relative to normal mucosa. These differentially expressed bands are prime targets of research because they represent candidate tumor-specific up- or down-regulated genes with a relevant role in carcinogenesis.

Colorectal Neoplasms↗

Morphometric analysis of serotoninergic bipolar cells in the retina and its implications for retinal image processing.

The entire population of retinal serotoninergic bipolar cells in the turtle Pseudemys scripta elegans was labeled by immunocytochemical methods. This allowed a systematic analysis to be made of the morphological variabilities among a functionally homogeneous neuronal population. The analyzed morphological characteristics included: size of the Landolt club, size of the soma, lateral extension of the ramification within the outer plexiform layer, course of the axon across the inner nuclear layer, pattern of the axonal ramification within the inner plexiform layer, lateral extension of these ramifications, and density of the cells. Whereas characteristics 1-4 and 7 show a morphological variability strictly related to the location of the bipolar cell with respect to the visual streak, a fovealike structure, characteristics 5 and 6 show no such correlation. The size of the soma increases by a factor of 4 from the visual streak toward the periphery. The area covered by the ramification in the OPL increases from 330 micron 2 at the visual streak to 50,000 microns 2 at the dorsal and ventral edges of the retina. The coverage factor remains the same throughout the retina, as well as the area covered by the ramifications in the IPL, which is about 2,000 microns 2. At the visual streak and at 110 degrees ventral and 68 degrees dorsal of the visual streak, the bipolar axons cross the INL perpendicularly. In between the axons take an oblique course leading to an axon-induced shift between input and output of up to 250 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Economic evaluation in stroke research : a systematic review.

BACKGROUND AND PURPOSE: The purpose of this review is to provide insight into the quality of economic evaluation in the field of cerebrovascular diseases (CVD) on the basis of a systematic analysis. METHODS: A literature search was performed using several sources. Trial-based full economic evaluation studies, were included in this review. The quality of the studies was independently assessed by 2 reviewers using a checklist. RESULTS: Twenty-three articles were found to comply with our inclusion and exclusion criteria. Only a few studies mentioned the perspective of the study, and in these cases it was always the societal perspective. The majority of the studies were cost-minimization and cost-effectiveness analyses based on cohort studies. All studies included healthcare costs, and in some instances patient and family costs were considered. Costs were usually measured by tariffs. Clinical end points and mortality were used to measure effects. Cost and effect measurements were based on hospital records. CONCLUSIONS: Only a few full economic evaluations have been undertaken in the domain of CVD. In most of the studies, the technical execution and methodology were limited.

Costs and Cost Analysis↗

Molecular analysis of IgA deficiency. Evidence for impaired switching to IgA.

The most common form of primary immunodeficiency is IgA deficiency (IgAD). However, the molecular basis of this disease remains elusive. Therefore, to address this issue we made a systematic analysis of the molecular events leading to IgA production. B lymphocytes that produce IgA have undergone somatic rearrangement that joins the switch (S) mu to S alpha region with deletion of the intervening sequences. Examination of the resulting S mu/S alpha junctions in unstimulated PBMC from IgAD patients by nested primer PCR revealed a significant decrease in the number of the S mu/S alpha fragments. To obtain the antisense primers to generate the S mu/S alpha fragments, we sequenced the human S alpha 1 and the downstream region extending to the C alpha 1 locus. Similar to previously reported switch sequences, we also found the S alpha 1 to be predominantly composed of pentameric repeats GAGCT and GGGCT. The decrease in the number of S mu/S alpha fragments is consistent with a profound decrease in the C alpha membrane mRNA expression in unstimulated PBMC, as well as in the C alpha mRNA levels and IgA production in PWM-stimulated PBMC. Sequence analysis of the switch junctions from IgA-producing cell lines, control donors, and an IgAD patient showed direct joining in 8 of 9 cases examined. TGF-beta 1, previously shown to be the switch factor for human and mouse IgA, was also examined. No difference in the TGF-beta 1 mRNA levels in unstimulated PBMC between the control subjects and the IgAD patients were detected. Our findings indicate that the failure to switch to IgA-producing B lymphocytes, or an impaired survival of such cells, may be an important molecular mechanism in IgAD.

Animals↗