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PubMed2006

A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition.

Repetitive transcranial magnetic stimulation (rTMS) procedures are being widely applied in therapeutic and investigative studies. Numerous studies have investigated the effects of rTMS on cortical excitability and inhibition, yielding somewhat contradictory results. The purpose of this study was to comprehensively review this literature to guide the selection of methodology in therapeutic studies. We conducted a comprehensive review of all identified studies that investigated effects of low and/or high frequency rTMS on motor cortical excitability or inhibition. Low frequency rTMS appears to produce a transient reduction in cortical excitability as assessed by motor evoked potential (MEP) size and produces no substantial effect on cortical inhibition. High frequency rTMS appears to produce a persistent increase in MEP size and a reduction in cortical inhibition measured with paired pulse methods although few studies have investigated frequencies greater than 5Hz. A number of novel stimulation paradigms have significant potential for altering cortical excitability but require further investigation. Although commonly applied forms of rTMS have effects on cortical excitability, more substantial effects may be obtained through the use of novel stimulation paradigms or innovative approaches to the stimulation of areas connected to a potential target site. Further research is required, however, before these paradigms can be more widely adopted.

Dose-Response Relationship, Radiation↗

PubMed2006

Phonological and conceptual activation in speech comprehension.

We propose that speech comprehension involves the activation of token representations of the phonological forms of current lexical hypotheses, separately from the ongoing construction of a conceptual interpretation of the current utterance. In a series of cross-modal priming experiments, facilitation of lexical decision responses to visual target words (e.g., time) was found for targets that were semantic associates of auditory prime words (e.g., date) when the primes were isolated words, but not when the same primes appeared in sentence contexts. Identity priming (e.g., faster lexical decisions to visual date after spoken date than after an unrelated prime) appeared, however, both with isolated primes and with primes in prosodically neutral sentences. Associative priming in sentence contexts only emerged when sentence prosody involved contrastive accents, or when sentences were terminated immediately after the prime. Associative priming is therefore not an automatic consequence of speech processing. In no experiment was there associative priming from embedded words (e.g., sedate-time), but there was inhibitory identity priming (e.g., sedate-date) from embedded primes in sentence contexts. Speech comprehension therefore appears to involve separate distinct activation both of token phonological word representations and of conceptual word representations. Furthermore, both of these types of representation are distinct from the long-term memory representations of word form and meaning.

Decision Making↗

PubMed2026

Comprehensive molecular profiling of advanced NSCLC in Greek patients:A prospective HeCOG study.

BACKGROUND: We report for the first time the molecular landscape and outcome associations from the prospective CLIMEDIN trial in Greece. METHODS: Two hundred patients with newly diagnosed advanced NSCLC (March 2022-October 2023) were enrolled and randomized to standard-of-care education versus additional automated, adverse-event-targeted digital interventions. Within this study baseline testing (EGFR, ALK, PD-L1) was performed in all; 165 tumors underwent comprehensive NGS (Oncomine Comprehensive Assay v3). Primary endpoint was improvement in AEs/QoL; secondary endpoints included ORR, PFS and OS. Associations between genomic alterations and outcomes were explored. RESULTS: Median age was 68 years; 75% male; 52% current smokers; adenocarcinoma 68.5%. Most received chemo-immunotherapy (66%). At data cut-off (December 2025; reverse-Kaplan-Meier median follow-up 36.3 months), median PFS was 9.6 months and median OS was 15.2 months. Across 200 tumors, 495 pathogenic variants (PVs) were identified in 83 genes. Exploratory outcome analyses showed longer OS in EGFR-mutant disease (preserved under parsimonious multivariable adjustment) and a formal KRAS × smoking interaction for OS (interaction P = 0.011). CONCLUSIONS: In this cohort, the molecular profile mirrors other Caucasian series, with clinically relevant enrichment patterns for EGFR and KRAS. ECOG performance status and first line treatment were the dominant prognostic factors in this cohort. A novel KRAS and smoking interaction for overall survival warrants prospective validation.

Aged↗

PubMed2005

Comprehensive assessment of aquatic community responses to a new anionic surfactant, high-solubility alkyl sulfate.

High-solubility alkyl sulfate (HSAS) is a new anionic surfactant for use in consumer product applications that provides enhanced water solubility and improved water hardness tolerance. A comprehensive model stream ecosystem investigation was conducted to assess ecological and toxicological effects of HSAS on stream invertebrates. Model streams were dosed with HSAS for a period of 56 days following 56 days of colonization in a single-pass, flow-through system. Exposures were control and 9.1, 24.1, 64.0, 165.8, and 426.5 microg/L based on specific analytical detection methods. Benthic abundance on gravel substrates, drift, and insect emergence were assessed. Several taxonomically unrelated taxa were found sensitive to HSAS and formed the basis of toxicological conclusions. Abundance or biomass of a limpet (Ferrissea), a bivalve (Corbicula), flatworms (Turbellaria), and a mayfly (Stenonema) was reduced at concentrations ranging from 165.8 to 426.5 microg/L. Principal response curve analysis, a constrained form of principal components analysis, demonstrated consistency with univariate analyses and identified similar populations as being sensitive to HSAS. Comparison with historical studies from the same testing site, streams, and experimental design, but with structurally related alkyl sulfate and alkyl ethoxysulfate anionic surfactants, revealed several similar trends in response profiles at the population level for both tolerant and sensitive species. Based on the comprehensive nature of the study, strength of data trends, and demonstrated sensitivity of the aquatic communities contained in the experimental system, the no-observed-effect concentration for HSAS was concluded to be 64.0 microg/L. An application factor of 1 is justified for deriving a predicted no-effect concentration) for HSAS in aquatic systems.

Animals↗

PubMed2004

Multicenter randomized trial of a comprehensive hospital discharge and outpatient heart failure management program.

AIMS: Disease management programs can reduce hospitalizations in high-risk heart failure (HF) patients, but generalizability to the population hospitalized for HF remains to be proven. We aimed to assess the effectiveness of a discharge and outpatient management program in a non-selected cohort of patients hospitalized for HF. METHODS AND RESULTS: Patients admitted with decompensated HF were randomized to receive usual care (n=174) or an intervention (n=164) consisting of a comprehensive hospital discharge planning and close follow-up at a HF clinic. After a median of 509 days, there were fewer events (readmission or death) in the intervention as compared with the control group (156 vs. 250), which represents 47% (95%CI: 29-65; P<0.001) event reduction per observation year. At 1-year, time to first event, time to first all-cause and HF readmission, and time to death were increased in the intervention group (P<0.001). All-cause and HF readmission rates per observation year were significantly lower, quality of life improved and overall cost of care was reduced in the intervention group. CONCLUSIONS: This comprehensive hospital discharge and outpatient management program prolonged time to first event, reduced hospital readmissions, improved survival and quality of life of patients hospitalized for HF, while reducing cost of management.

Ambulatory Care↗

PubMedDate not supplied

Application of a comprehensive subtelomere array in clinical diagnosis of mental retardation.

In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere.

Adult↗

PubMed2026

Investing in Canada's nursing workforce: a comprehensive review to inform policy innovations and directions.

BACKGROUND: Health systems worldwide face persistent health workers challenges including nursing shortages, workforce strain, and inequities. In Canada, these challenges have prompted renewed national and provincial reforms to strengthen recruitment, retention, leadership, and sustainability. This paper compares nursing workforce policy directions across Canada, and international jurisdictions to inform policy and planning. METHODS: A cross-country comparative analysis of policies building on a comprehensive national funded review that included an umbrella review of 69 systematic reviews, a comparative policy review of nursing workforce strategies in five jurisdictions, and validation through national horizon-scanning and policy dialogues (n >100). Evidence was analyzed across system, organizational, and individual levels. RESULTS: At the system level, international jurisdictions demonstrate comprehensive, legislated approaches integrating data, governance, and multi-year funding have advanced key nursing strategies. In Canada, the advances show the importance of strategies to have national and provincial/territorial alignment emphasizing leadership, flexibility, and inclusion as key levers. Organizational and individual-level reforms such as mentorship, leadership development, and wellness initiatives are expanding but remain variably evaluated. Experts identified national workforce data strategies and policy integration with embedded evaluation as key enablers to inform scalability and sustainability of implemented strategies. CONCLUSIONS: Canada's nursing workforce reforms are advancing toward coordinated, equity-driven, and evidence-informed strategies. Continued investment in evaluation, leadership, and national integrated data systems along with integrating nursing workforce planning within broader intersectoral planning will consolidate these gains and position Canada as an international leader in sustainable nursing workforce policy.

Canada↗

PubMed2005

Rectal toxicity profile after transperineal interstitial permanent prostate brachytherapy: use of a comprehensive toxicity scoring system and identification of rectal dosimetric toxicity predictors.

PURPOSE: To better understand rectal toxicity after prostate brachytherapy, we employed the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0), a comprehensive system with distinct and separately reported gastrointestinal adverse event items (unlike Radiation Therapy Oncology Group morbidity scoring), to evaluate item-specific postimplant rectal toxicities. METHODS AND MATERIALS: We analyzed 135 patients treated with brachytherapy +/- hormonal therapy, using CTCAE v3.0 to score acute/late rectal toxicities (median follow-up, 41 months). Dosimetric parameters were evaluated for ability to predict toxicities. RESULTS: Use of CTCAE yielded a novel rectal toxicity profile consisting of diarrhea, incontinence, urgency, proctitis, pain, spasms, and hemorrhage event rates. No item had a < 5% Grade 1-2 acute toxicity rate (except spasms). Rectal dosimetry predicted late toxicities: for diarrhea, 5% Grade 1 toxicity rate for %V25 (percent of rectal volume receiving 25% of prescribed prostate dose) < or = 25% vs. 60% for %V25 > 25% (p < 0.001); for maximum toxicity, 10% Grade 1 toxicity rate for %V10 < or = 40% vs. 44% for %V10 > 40% (p = 0.007). CONCLUSIONS: A comprehensive understanding of item-specific postimplant rectal toxicities was obtained using CTCAE. Rectal %V25 > 25% and %V10 > 40% predicted worse late diarrhea and maximum toxicity, respectively.

Aged↗

PubMed2005

Using a comprehensive examination to assess multiple competencies in surgical residents: does the oral examination still have a role?

BACKGROUND: While specialty-level evaluations evolve from traditional examinations to objective structured clinical examination-like assessments, a broader range of competencies are tested; consequently, examiners are forced to integrate results when making a determination of competency. The aim of this study was to describe how experts weigh relative performances on specific components of a comprehensive examination to make decisions of overall competency. STUDY DESIGN: The Patient Assessment and Management Examination is a standardized patient-based assessment of general surgery in which each 25-minute station encompasses four components: history and physical examination, investigation interpretation, diagnosis and treatment discussion with the patient, and a structured oral examination (SOE). A six-station Patient Assessment and Management Examination was administered to 21 senior surgery residents. Surgeons marked each station with global rating scales and, in addition, provided an end-of-station overall global assessment of performance. A "gold-standard" examination pass-or-fail decision was determined through videotape review of each candidate's performance across six stations by two blinded surgeons. Multiple linear regression analysis was used to determine which components were associated with the end-of-station overall global assessments. Multivariable logistic regression was used to determine which components were associated with the final "gold-standard" pass-or-fail assessment. RESULTS: The only component notably (p < 0.005) associated with end-of-station global assessment for all six stations was the SOE. Mean SOE score was the only notable independent variable associated with the gold-standard pass-or-fail decision (R(2) = 0.63, p < 0.001). CONCLUSIONS: Performance on the SOE section of a multicompetency examination is markedly associated with the final determination of competency. These results have implications for the design and implementation of comprehensive specialty-level assessments.

Clinical Competence↗

PubMed2004

Comparison of a generic and a disease specific quality of life scale to assess a comprehensive spa therapy program for knee osteoarthritis.

OBJECTIVES: To compare the differences or correlation between the results obtained from a generic and a disease-specific instrument for the study group and to assess the short-term effects of spa therapy on quality of life of patients with knee osteoarthritis. PATIENTS AND METHODS: Fifty patients with knee osteoarthritis were randomly recruited. They underwent a comprehensive spa therapy program for 21 days. Forty-six patients completed the study. The results were evaluated with Medical Outcomes Study 36-Item Short Form-36 (SF-36) and Arthritis Impact Measurement Scale 2 (AIMS2). RESULTS: Statistically significant improvement was observed in all subscales of SF-36. All subscales of AIMS2 improved too, but only half of them were significant. Correlation between matching subscales of each test was also significant, except physical activity. CONCLUSION: Comprehensive spa therapy seems to increase the quality of life of patients with knee osteoarthritis for short term.

Aged↗

PubMed2006

Comprehensive rhinoplasty technique to correct the bilateral cleft lip nasal deformity using conchal composite grafts.

INTRODUCTION: Anatomical abnormalities and heterogeneous tissue deficiencies of the bilateral cleft lip nasal deformity challenges the cranio-maxillofacial plastic surgeon to create a functional, yet aesthetically pleasing nose. The authors propose a comprehensive rhinoplasty technique to correct the bilateral cleft lip nasal deformity using composite conchal grafts. PATIENTS: Five children with bilateral cleft lip nasal deformities had nasal reconstruction using conchal composite grafts, averaging 5 years in age at time of surgery. Patient follow-up averaged 21 months. METHODS: An open tip rhinoplasty was performed using a 'V' shaped columellar incision. The conchal composite graft was obtained from the lateral aspect of the ear and was used to reconstruct the lateral alar mucosal defects. Conchal cartilage was used as a columellar strut. The columellar skin was closed in a 'V-Y' fashion, giving greater columellar length. RESULTS: Visual inspection confirmed that the cleft lip nasal deformity was improved in all patients. There were no postoperative complications. All patients had complete composite graft take with minimal donor site morbidity and deformity. CONCLUSIONS: This comprehensive rhinoplasty technique improves the abnormalities found in bilateral cleft lip nasal deformity by using the successful aspects of other methods and introducing the composite conchal graft.

Cartilage↗

PubMed2006

False belief and language comprehension in Cantonese-speaking children.

The current research compared two accounts of the relation between language and false belief in children, namely that (a) language is generally related to false belief because both require secondary representation in a social-interactional context and that (b) specific language structures that explicitly code metarepresentation contribute uniquely to the language-false belief relation. In three studies, attempts were made to correlate Cantonese-speaking children's false belief with their general language comprehension and understanding of certain structures that explicitly express metarepresentational knowledge. Results showed that these structures failed to predict false belief after age, nonverbal intelligence, and general language comprehension were considered. In contrast, general language remained predictive of false belief after controlling for age, nonverbal intelligence, and language structures. The current findings are more consistent with a general language account than a language structure account.

Asian People↗

PubMed2003

Water issues in comprehensive municipal planning: a review of the Motala River Basin.

The performance level for water management is rising in Sweden after the passing of a number of Governmental Bills (1997-2000) that establish national environmental quality objectives, and furthermore after the adoption of the Water Framework Directive of the European Union (2000). The presentation of water issues in municipal physical planning is important because the municipalities have a local planning monopoly. We investigate to what extent water resources are considered in one of the most important tools for the regulation of physical infrastructure, namely the Comprehensive Municipal Plans. Thirteen plans from municipalities within the Motala River Basin in southern Sweden were studied. To characterise the comprehensiveness of the plans we used twelve criteria, divided into five groups: description, preventive measures, goal-setting, implementation strategy and future-oriented considerations. Descriptions of water quality, water use, wastewater plants, and urban water and wastewater systems were the most frequent items. These topics could be found in all plans in the study, along with more or less elaborated river basin perspectives. Issues related to national environmental quality objectives were mentioned in only five of the plans, and considerations about water flows were even more rare. We found, that the emphasis on water issues is not correlated with the size of the municipal population but rather with the age of the plans. In the old plans from the early 1990s water management is less recognised than in the newly revised ones. After their adoption the national water quality objectives, and suggested measures to fulfil them, are being translated into regional and local levels, and this has happened in the new plans. However, it seems that water has not yet gained the same importance as land in municipal physical planning, and strategies for public participation in the planning process are lacking.

Conservation of Natural Resources↗

PubMed2005

Status and fuzzy comprehensive assessment of combined heavy metal and organo-chlorine pesticide pollution in the Taihu Lake region of China.

The status of combined heavy metal and organo-chlorine pesticide (OCPs; i.e. HCH and DDT) pollution was investigated and the soil environmental quality of the Taihu Lake watershed, one of the most developed regions in China, was evaluated using a fuzzy comprehensive assessment. Statistical analyses showed the presence of combined pollution in the soil. At many sampling sites, heavy metal concentrations were above corresponding background values, indicating the effects of extraneous pollutants. It has been over 20 years since China banned the use of OCPs, but they can still be found in soil samples of this region. HCH levels at all investigated sites were below the Chinese Environmental Quality Standard for Soils. Fuzzy comprehensive assessment showed that the overall soil quality in this region could be categorized as class I. Nevertheless, the high coefficients of variation for levels of DDT, Cd and Hg indicated the existence of some point-source pollution. Continuous monitoring and further studies of the region are recommended to prevent pollution of farmland from these sources.

Agriculture↗

PubMed2026

Comprehensive profiling of antibiotic resistance genes and functional clusters of orthologous groups annotation of gut microbiota in Indonesian Kedu chickens.

Antibiotic resistance is a growing global health concern, with poultry systems acting as important reservoirs of antibiotic resistance genes (ARGs). However, resistome and functional profiles of indigenous chickens raised under traditional systems remain underexplored. This study aimed to characterize the antibiotic resistome, virulence factor genes, and metabolic potential of gut microbiota in Indonesian Kedu chickens using a shotgun metagenomic approach. Digesta samples from five gastrointestinal segments of 21 healthy adult chickens were analyzed through high-throughput sequencing. ARGs were identified using the Comprehensive Antibiotic Resistance Database (CARD) and Antibiotic Resistance Genes Databases (ARDB), while virulence factors and functional genes were annotated using Virulence Factor Database (VFDB), Clusters of Orthologous Groups (COG), and Carbohydrate-Active EnZymes (CAZy) databases. Results revealed a diverse resistome dominated by multidrug resistance and efflux pump mechanisms, with prominent genes associated with fluoroquinolone, tetracycline, β-lactam, and glycopeptide resistance. The detection of clinically relevant ARGs suggests that genetic determinants associated with antimicrobial resistance are present in the gut microbiota of traditionally raised Kedu chickens, although metagenomic data alone cannot determine whether these genes are actively expressed or confer phenotypic resistance. Virulence factor analysis showed functions related to adherence, immune evasion, iron acquisition, quorum sensing, and efflux activity, reflecting strong microbial adaptability. Functional profiling demonstrated enrichment in translation, carbohydrate and amino acid metabolism, genome maintenance, and cell envelope biogenesis. Additionally, CAZyme analysis indicated a high capacity for complex polysaccharide degradation, supporting efficient utilization of fiber-rich traditional diets. In conclusion, this study provides a comprehensive metagenomic overview of antibiotic resistance and functional potential in Kedu chicken gut microbiota, emphasizing the importance of incorporating indigenous poultry into antimicrobial resistance surveillance within a One Health framework.

Antibiotic resistance genes↗

PubMed2026

Comprehensive Microbiome Analyses for Regenerative Endodontic Therapy.

INTRODUCTION: Comprehensive microbiome analyses include the study of all microbial taxa, including bacteria, archaea, viruses, and fungi, as well as their functional activities and antibiotic resistance gene expression. Regenerative endodontic therapy presents a clinical situation where the most effective antimicrobial approaches are needed in order to ensure clinical success. METHODS AND RESULTS: In this paper, different contemporary technologies for the identification of endodontic microorganisms, such as with next generation sequencing, and their functional characterization, such as with whole genome sequencing, are described. The role of transcriptomics, as well as resistome analysis, are also discussed. Furthermore, the manner in which all this work and knowledge could be incorporated into clinical endodontics in general, and regenerative endodontic therapy as a special treatment, is outlined. CONCLUSIONS: Comprehensive microbiome analysis can lead to the development of more effective and personalized antimicrobial treatment.

Endodontics↗

PubMed2006

Evidence-based scientific data documenting the treatment and cost-effectiveness of comprehensive pain programs for chronic nonmalignant pain.

UNLABELLED: Chronic pain is one of the most prevalent and costly problems in the United States today. Traditional medical treatments for it, though, have not been consistently efficacious or cost-effective. In contrast, more recent comprehensive pain programs (CPPs) have been shown to be both therapeutically efficacious and cost-effective. The present study reviews available evidence demonstrating the therapeutic efficacy and cost-effectiveness of CPPs, relative to conventional medical treatment. Searches of the chronic pain treatment literature during the past decade were conducted for this purpose, using MEDLINE and PSYCHLIT. Studies reporting treatment outcome results for patients with chronic pain were selected, and data on the major outcome variables of self-reported pain, function, healthcare utilization and cost, medication use, work factors, and insurance claims were evaluated. When available, conventional medical treatments were used as the benchmark against which CPPs were evaluated. This review clearly demonstrates that CPPs offer the most efficacious and cost-effective, evidence-based treatment for persons with chronic pain. Unfortunately, such programs are not being taken advantage of because of short-sighted cost-containment policies of third-party payers. PERSPECTIVE: A comprehensive review was conducted of all studies in the scientific literature reporting treatment outcomes for patients with chronic pain. This review clearly revealed that CPPs offer the most efficacious and cost-effective treatment for persons with chronic pain, relative to a host of widely used conventional medical treatment.

Chronic Disease↗

PubMed2006

Turning whine into wine: the fiscal impact of comprehensive documentation and billing for nonoperative pediatric surgical services.

PURPOSE: Some pediatric surgeons rarely document nonoperative services, believing that the reimbursement provided for such care is negligible. We evaluated the impact of comprehensive documentation and billing for nonoperative, pediatric surgical care. METHODS: All bills submitted for inpatient, nonoperative care for 1 year were reviewed. Total receipts for documented admissions, consultations, critical care, and daily care were determined. The Evaluation and Management code billed for each service was recorded, and the total and average payments attributable to each Evaluation and Management code were calculated. RESULTS: Fifty-six percent of services were covered by Medicaid and 26% by a commercial insurer. There were 607 billed admission history and physical exams for which reimbursement totaled 43,493 dollars. Critical care services were provided to 49 patients and yielded 8964 dollars in payments. Six hundred thirty-nine inpatient consultations were performed with a reimbursement of 42,830 dollars. Daily care services were billed 1044 times and produced 71,579 dollars in payments. Overall reimbursement for documented, nonoperative services was 166,866 dollars. This represented 16.2% of total, noncontracted income for the practice. CONCLUSION: Despite a payer mix heavily weighted toward Medicaid, comprehensive documentation and billing for nonoperative services increased total, noncontracted reimbursement by almost 20% over what it would have been had only operative services been billed. The yield from properly documented, nonoperative care can be substantial.

Child↗