Impact of Genetic Variants on Postoperative Pain and Fentanyl Dose Requirement in Patients Undergoing Major Breast Surgery: A Candidate Gene Association Study.

BACKGROUND: Postoperative analgesia is crucial for the early and effective recovery of patients undergoing surgery. Although postoperative multimodal analgesia is widely practiced, opioids such as fentanyl are still one of the best analgesics. The analgesic response of fentanyl varies widely among individuals, probably due to genetic and nongenetic factors. Among genetic factors, single nucleotide polymorphisms (SNPs) may influence its analgesic response by altering the structure or function of genes involved in nociceptive, fentanyl pharmacodynamic, and pharmacokinetic pathways. Thus, it is necessary to comprehensively ascertain if the SNPs present in the aforementioned pathways are associated with interindividual differences in fentanyl requirement. In this study, we evaluated the association between 10 candidate SNPs in 9 genes and 24-hour postoperative fentanyl dose (primary outcome) and also with postoperative pain scores and time for first analgesia (secondary outcomes). METHODS: A total of 257 South Indian women, aged 18-70 years, with American Society of Anesthesiologists (ASA) physical status I-III, undergoing major breast surgery under general anesthesia, were included in the study. Patients were genotyped for candidate SNPs using real-time polymerase chain reaction. All patients received a standardized intravenous fentanyl infusion through a patient-controlled analgesic (PCA) pump, and the 24-hour postoperative fentanyl dose requirement was measured using PCA. RESULTS: The median 24-hour postoperative fentanyl requirement was higher in rs1799971 carriers (G/G versus A/A + A/G-620 µg [500-700] vs 460 µg [400-580]) with a geometric mean (GM) ratio of 1.91 (95% confidence interval [CI], 1.071-1.327). The median 24-hour pain scores were higher in rs4680 carriers (A/G + A/A versus G/G-34 [30-38] vs 31 [30-38]) with a GM ratio of 1.059 (95% CI, 1.018-1.101) and were lower in rs1045642 carriers (A/A + A/G versus G/G-34 [30-38] vs 30 [30-34]) with a GM ratio of 0.936 (95% CI, 0.889-0.987). The median time for first analgesic was lower in rs734784 carriers [C/C versus T/T + C/T-240 minutes (180-270) vs 240 minutes (210-270)] with a GM ratio of 0.902 (95% CI, 0.837-0.972). Five of 9 clinical factors, namely, history of diabetes, hypertension, hypothyroidism, anesthesia duration, and intraoperative fentanyl requirement were associated with different outcomes individually ( P < .05) and were used to adjust the respective associations. CONCLUSIONS: The SNP opioid receptor mu-1 ( OPRM1 ) (rs1799971) was associated with higher postoperative fentanyl requirement in South Indian patients undergoing major breast surgery. Twenty-four hour postoperative pain scores were higher in catechol-O-methyl transferase ( COMT ) (rs4680) carriers and lower in ATP binding cassette subfamily B member 1 ( ABCB1 ) (rs1045642) carriers, whereas time for first analgesic was lower in potassium channel subunit 1 ( KCNS1 ) (rs734784) carriers. However, these exploratory findings must be confirmed in a larger study.

Effectiveness of an Evidence-Based Practice Training Program for Nurse Educators: A Cluster-Randomized Controlled Trial.

BACKGROUND: Evidence-based practice (EBP) endeavors to integrate the best available evidence with clinical expertise and patient preference to enhance clinical outcomes. For nurses to effectively demonstrate EBP, the concepts of EBP should be systematically incorporated into the nursing curriculum, with nurse educators playing a pivotal role in execution. However, the effect of EBP training programs on nurse educators remains largely unexplored. AIM: To evaluate the effectiveness of an EBP training program on the knowledge, attitude, practice, and competency of nurse educators. METHODS: A pragmatic randomized controlled trial was conducted at a nursing education institution. Fifty-one nurse educators were cluster randomized into intervention and control groups. A 30-hour EBP training intervention was provided for nurse educators in the intervention group. The outcome variables were knowledge, attitude, practice, and competency regarding EBP. These outcomes were evaluated using the EBP knowledge and practice questionnaire, EBP attitude scale, and Fresno test. Data were collected at baseline, the end of 5 months, and the end of 10 months. RESULTS: Fifty-one eligible participants were enrolled in the study. The intervention and control group had three clusters each with 27 and 24 participants, respectively. Participants in both groups were comparable for variables such as age, years of experience, and educational background (p > .05). Between groups, outcome variables were compared using mixed linear multi-level modeling. Nurse educators who received the EBP training program demonstrated significant differences in knowledge (p < .05), attitude (p < .05), practice (p < .05), and competency scores (p < .05), than that of the control group, indicating the intervention effectiveness. LINKING EVIDENCE TO ACTION: EBP training programs are effective in improving the knowledge, attitude, practice, and competency of nurse educators.

Sudden death and its predictors in myocardial infarction survivors in an Indian population.

OBJECTIVE: This study was conducted to assess the incidence of sudden cardiac death (SCD) in post myocardial infarction patients and to determine the predictive value of various risk markers in identifying cardiac mortality and SCD. METHODS: Left ventricular function, arrhythmias on Holter and microvolt T wave alternans (MTWA) were assessed in patients with prior myocardial infarction and ejection fraction ≤ 40%. The primary outcome was a composite of cardiac death and resuscitated cardiac arrest during follow up. Secondary outcomes included total mortality and SCD. RESULTS: Fifty-eight patients were included in the study. Eight patients (15.5%) died during a mean follow-up of 22.3 ± 6.6 months. Seven of them (12.1%) had SCD. Among the various risk markers studied, left ventricular ejection fraction (LVEF) ≤ 30% (Hazard ratio 5.6, 95% CI 1.39 to 23) and non-sustained ventricular tachycardia (NSVT) in holter (5.7, 95% CI 1.14 to 29) were significantly associated with the primary outcome in multivariate analysis. Other measures, including QRS width, heart rate variability, heart rate turbulence and MTWA showed no association. CONCLUSIONS: Among patients with prior myocardial infarction and reduced left ventricular function, the rate of cardiac death was substantial, with most of these being sudden cardiac death. Both LVEF ≤30% and NSVT were associated with cardiac death whereas only LVEF predicted SCD. Other parameters did not appear useful for prediction of events in these patients. These findings have implications for decision making for the use of implantable cardioverter defibrillators for primary prevention in these patients.

A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition.

The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13-276 pmol·s-1·ml-1 per unit citrate synthase) than SC mice (17-394 pmol·s-1·ml-1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of NASH.NEW & NOTEWORTHY This study demonstrates in a first of kind longitudinal analysis, the evolution of nonalcoholic steatohepatitis (NASH) on a fast-food diet-induced model. Key findings include 1) hepatic lipid composition changes in a multiphasic fashion as NASH evolves; 2) insulin resistance precedes hepatic inflammation and fibrosis, answering a longstanding chicken-and-egg question regarding the relationship of insulin resistance to liver histology in NASH; and 3) mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent.

G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

A systematic review of community-based health insurance programs in South Asia.

BACKGROUND: Community-based health insurance (CBHI) has been evolving as an effective means of healthcare financing in many countries of South Asia. A systematic review in this context would give a comprehensive report of the performance of these schemes in terms of improving the health-seeking behaviour of the beneficiaries enrolled for the schemes. METHODS: Important databases like PubMed, Elsevier, SocINDEX (EBSCO), Cochrane Reviews, Medline and Scopus were reviewed along with relevant portals-Google Scholar, www.who.int/, www.worldbank.org and www.cochrane.org-and specific journals and discussion series with published literature in the areas of community health insurance and health microfinance. RESULTS: The review finally chronicles 20 CBHI schemes from published and unpublished literature from the countries comprising South Asia. These schemes have been reviewed in terms of their enrolment process, entry point and the extent to which they have contributed to the healthcare-seeking behaviour. CONCLUSION: The CBHI schemes can also serve as an alternative healthcare financing mechanism where fee-for-service and user fees have not made any impact. There have been very few studies that have tried to carry out an impact evaluation of the CBHI schemes on the target population, and more and more such studies can be a scope for further research. Copyright © 2016 John Wiley & Sons, Ltd.

DNA methylation analysis of phenotype specific stratified Indian population.

BACKGROUND: DNA methylation and its perturbations are an established attribute to a wide spectrum of phenotypic variations and disease conditions. Indian traditional system practices personalized medicine through indigenous concept of distinctly descriptive physiological, psychological and anatomical features known as prakriti. Here we attempted to establish DNA methylation differences in these three prakriti phenotypes. METHODS: Following structured and objective measurement of 3416 subjects, whole blood DNA of 147 healthy male individuals belonging to defined prakriti (Vata, Pitta and Kapha) between the age group of 20-30years were subjected to methylated DNA immunoprecipitation (MeDIP) and microarray analysis. After data analysis, prakriti specific signatures were validated through bisulfite DNA sequencing. RESULTS: Differentially methylated regions in CpG islands and shores were significantly enriched in promoters/UTRs and gene body regions. Phenotypes characterized by higher metabolism (Pitta prakriti) in individuals showed distinct promoter (34) and gene body methylation (204), followed by Vata prakriti which correlates to motion showed DNA methylation in 52 promoters and 139 CpG islands and finally individuals with structural attributes (Kapha prakriti) with 23 and 19 promoters and CpG islands respectively. Bisulfite DNA sequencing of prakriti specific multiple CpG sites in promoters and 5'-UTR such as; LHX1 (Vata prakriti), SOX11 (Pitta prakriti) and CDH22 (Kapha prakriti) were validated. Kapha prakriti specific CDH22 5'-UTR CpG methylation was also found to be associated with higher body mass index (BMI). CONCLUSION: Differential DNA methylation signatures in three distinct prakriti phenotypes demonstrate the epigenetic basis of Indian traditional human classification which may have relevance to personalized medicine.

Leucine modulates dynamic phosphorylation events in insulin signaling pathway and enhances insulin-dependent glycogen synthesis in human skeletal muscle cells.

BACKGROUND: Branched-chain amino acids, especially leucine, are known to interact with insulin signaling pathway and glucose metabolism. However, the mechanism by which this is exerted, remain to be clearly defined. In order to examine the effect of leucine on muscle insulin signaling, a set of experiments was carried out to quantitate phosphorylation events along the insulin signaling pathway in human skeletal muscle cell cultures. Cells were exposed to insulin, leucine or both, and phosphorylation events of key insulin signaling molecules were tracked over time so as to monitor time-related responses that characterize the signaling events and could be missed by a single sampling strategy limited to pre/post stimulus events. RESULTS: Leucine is shown to increase the magnitude of insulin-dependent phosphorylation of protein kinase B (AKT) at Ser473 and glycogen synthase kinase (GSK3ß) at Ser21-9. Glycogen synthesis follows the same pattern of GSK3ß, with a significant increase at 100 µM leucine plus insulin stimulus. Moreover, data do not show any statistically significant increase of pGSK3ß and glycogen synthesis at higher leucine concentrations. Leucine is also shown to increase the magnitude of insulin-mediated extracellularly regulated kinase (ERK) phosphorylation; however, differently from AKT and GSK3ß, ERK shows a transient behavior, with an early peak response, followed by a return to the baseline condition. CONCLUSIONS: These experiments demonstrate a complementary effect of leucine on insulin signaling in a human skeletal muscle cell culture, promoting insulin-activated GSK3ß phosphorylation and glycogen synthesis.

The sphericity deviation score: a quantitative radiologic outcome measure of Legg-Calvé Perthes disease applicable at the stage of healing and at skeletal maturity.

AIM: This study aimed to determine if a new measure of sphericity of the femoral head, the Sphericity Deviation Score (SDS), could be estimated reliably at the stage of healing of Legg-Calvé-Perthes disease (LCPD) and to determine if the SDS at the healing stage reflects the outcome at skeletal maturity. METHODS: The SDS was measured with image analysis software on radiographs of 120 children with unilateral LCPD at healing of the disease and at skeletal maturity. The reproducibility of measurement was assessed. SDS values for hips in different Stulberg classes were calculated. On the basis of SDS values at healing of 82 children, a logistic regression model was developed to determine the probability of a good outcome at skeletal maturity. The validity of the model was tested on another 38 children. RESULTS: The SDS values at the stage of healing and at skeletal maturity were comparable. The SDS values were lowest for Stulberg Class I hips and highest for Class IV and V hips. The validated regression model showed a very high probability of a good outcome (Stulberg Class I or II) at skeletal maturity if the SDS at the stage of healing was below 10. CONCLUSIONS: A reliable estimate of the outcome of LCPD at skeletal maturity can be made by computing the SDS as soon as the disease heals.

Prognostic values of SYNTAX score II in patients with coronary artery disease undergoing percutaneous coronary intervention - Cohort study.

BACKGROUND: The data on prognostic values of SYNTAX score II in patients undergoing percutaneous coronary intervention is limited. We report predictive utility of SYNTAX score II in relation to in hospital and 1 year mortality of the patients undergoing percutaneous coronary intervention. METHODS: This was a cohort study of patients who underwent percutaneous coronary intervention (PCI) at a single centre from January 2018 to December 2019. In hospital and 12-month events and mortality was analysed among 1000 patients. The patients were divided into 3 groups based on tertiles of Syntax II score (<22, 22-27.7 and >27.7). RESULT: The total mortality at 12 months was 60 (6%). Major adverse cardiac events (MACE) occurred in 87 (9%). The patients who died had higher SYNTAX score II score compared to those alive at 12 months 34 (38, 24) vs 24 (28.1, 20.9) P < 0.01. The same trend was seen in patients who had major adverse cardiac events (MACE) 28 (34, 24) vs 24 (28.6, 21) P < 0.01 Among the 3 groups of SYNTAX score II, in hospital mortality, all-cause mortality, cardiovascular death, myocardial infarction, unstable angina, revascularization and major adverse cardiac events (MACE) were higher in the third tertile (>27.7) compared the lower tertiles. CONCLUSION: The patients who had higher SYNTAX score II had more in hospital and 12 month mortality and major adverse cardiac events (MACE). SYNTAX II score is a better predictor of in-hospital, and 12 month cardiovascular and all cause mortality.

Vitamin B12 and homocysteine in patients with major depressive disorder.

Background: Alterations in the level of neurotransmitters are evident in patients with major depressive disorder (MDD). Vitamin B12 mediates the synthesis of neurotransmitters, and hence, vitamin B12 deficiency could be associated with depression. Aims and Objectives: To assess the levels of serum vitamin B12, homocysteine (Hcy), and haematological profiles in patients of MDD. Materials and Methods: Fifty-nine patients with MDD were recruited based on ICD-10 criteria. Severity of depression was assessed by HAM-D scale. Vitamin B12, Hcy levels, and haematological profiles were analysed. Results: Vitamin B12 was deficient or depleted in all patients with MDD. The median level of vitamin B12 in serum was 164.2 pg./ml and significantly lower in patients with severe MDD. The mean value of Hcy was 18.34 µmol/L, which was high compared to the normal reference range. The red cell distribution width (RDW-CV) varied significantly between the three groups of MDD patients. Patients consuming non-vegetarian food had a significantly higher median value of serum vitamin B12. Conclusion: Vitamin B12 deficiency is found in patients with MDD and varies inversely with severity of MDD. Hcy is found to be higher in patients with MDD. The manifestation of depressive symptoms precedes the more commonly known haematological manifestations of vitamin B12 deficiency in this study.

Normative data for aquagenic wrinkling of palms in children 1-15 years of age: A cross-sectional study.

BACKGROUND: Aquagenic wrinkling of palms (AWP) is emerging as a screening test for cystic fibrosis (CF). There is lack of normative data for the same in our population. OBJECTIVES: To generate normative data for AWP in children 1-15 years of age and to describe the factors associated with it. METHODS: Children aged 1-15 years were enrolled after obtaining informed consent and assent of the parent and child based on age. Information regarding age, gender, anthropometry, indications for visiting hospital and drug intake were noted down. Wrinkling test was done using distilled water maintained in room temperature. Sweat chloride analysis was done using Nano duct sweat analysis system for children having AWP within 3 min. The mean/median time to wrinkle was noted and presented as centile curves after smoothing. RESULTS: The mean (SD) and median (interquartile range [IQR]) aquagenic wrinkling time in children 1-15 years of age was 4.88 (1.066) and 5 (4-5.75) minutes respectively. The mean (SD) and median (IQR) time for AWP was 4.78 (1.076) and 5 (4-5) minutes respectively for boys and 4.98 (1.048) and 5 (4-6) minutes, respectively for girls. The time taken to wrinkle was observed to increase with age. Males have earlier AWP than females. There was no association between AWP and anthropometry or sweat chloride levels. CONCLUSION: We have estimated the normative data for AWP in children 1-15 years of age which can be used for CF screening in children with typical clinical features from resource limited settings.

Predictive models for fentanyl dose requirement and postoperative pain using clinical and genetic factors in patients undergoing major breast surgery.

ABSTRACT: Fentanyl exhibits interindividual variability in its dose requirement due to various nongenetic and genetic factors such as single nucleotide polymorphisms (SNPs). This study aims to develop and cross-validate robust predictive models for postoperative fentanyl analgesic requirement and other related outcomes in patients undergoing major breast surgery. Data regarding genotypes of 10 candidate SNPs, cold pain test (CPT) scores, pupillary response to fentanyl (PRF), and other common clinical characteristics were recorded from 257 patients undergoing major breast surgery. Predictive models for 24-hour fentanyl requirement, 24-hour pain scores, and time for first analgesic (TFA) in the postoperative period were developed using 4 different algorithms: generalised linear regression model, linear support vector machine learning (SVM-Linear), random forest (RF), and Bayesian regularised neural network. The variant genotype of OPRM1 (rs1799971) and higher CPT scores were associated with higher 24-hour postoperative fentanyl consumption, whereas higher PRF and history of hypertension were associated with lower fentanyl requirement. The variant allele of COMT (rs4680) and higher CPT scores were associated with 24-hour postoperative pain scores. The variant genotype of CTSG (rs2070697), higher intraoperative fentanyl use, and higher CPT scores were associated with significantly lower TFA. The predictive models for 24-hour postoperative fentanyl requirement, pain scores, and TFA had R-squared values of 0.313 (SVM-Linear), 0.434 (SVM-Linear), and 0.532 (RF), respectively. We have developed and cross-validated predictive models for 24-hour postoperative fentanyl requirement, 24-hour postoperative pain scores, and TFA with satisfactory performance characteristics and incorporated them in a novel web application.

Efficacy of mHealth Interventions for Improving Maternal and Neonatal Outcomes Among Pregnant Women With Hypertensive Disorders: Protocol for a Systematic Review.

BACKGROUND: Hypertension is one of the most prevalent medical conditions that arise during pregnancy, resulting in maternal and neonatal complications. Mobile health (mHealth) has emerged as an innovative intervention for delivering maternal and child health care services. The evidence on the effectiveness of mHealth interventions in improving the health outcomes of pregnant women with hypertensive disorders is lacking. Therefore, there is a need for evidence synthesis using systematic review methods to address this evidence gap. OBJECTIVE: This review aims to determine the efficacy of mHealth interventions in improving maternal and neonatal outcomes among pregnant women with hypertensive disorders. The review will answer the following research questions: (1) What are the types of mHealth interventions used in pregnant women with hypertensive disorders? (2) Are the various mHealth interventions effective in improving maternal and neonatal health outcomes, health behaviors, and their knowledge of the disease? and (3) Are mHealth interventions effective in supporting health care providers to make health care decisions for pregnant women with hypertensive disorders? METHODS: This review will include randomized controlled trials, nonrandomized controlled trials, and cohort studies focusing on mHealth interventions for pregnant women with hypertensive disorders. Studies reporting health care providers use of mHealth interventions in caring for pregnant women with hypertensive disorders will be included. The search strategy will be tailored to each database using database-specific search terms. The search will be conducted in PubMed-MEDLINE, ProQuest, CINAHL, Scopus, Web of Science, and CENTRAL. Other literature sources, such as trial registries and bibliographies of relevant studies, will be additionally searched. Studies published in English from January 2000 to January 2023 will be included. A total of 2 review authors will independently perform the data extraction and the quality appraisal. For quality appraisal of randomized controlled trials, the Cochrane Risk of Bias 2 tool will be used. The Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-1) tool will be used for nonrandomized controlled trials, and the Critical Appraisal Skills Programme checklist for cohort studies will be used. Any disagreements between the 2 reviewers will be resolved through discussion and a third reviewer if required. A meta-analysis will be performed based on the availability of the data. RESULTS: As per the protocol, the study methodology was followed, and 2 independent reviewers conducted the search in 6 databases and clinical registries. Currently, the review is in the full-text screening stage. The review will publish the results in the first quarter of 2024. CONCLUSIONS: The evidence synthesized from this systematic review will help guide future research, support health care decisions, and inform policy makers on the effectiveness of mHealth interventions in improving the maternal and neonatal outcomes of pregnant women with hypertensive disorders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51792.

Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis.

BACKGROUND: The increasing incidence of breast cancer necessitates the need to explore alternate screening strategies that circumvent the setbacks of conventional techniques especially among population that report earlier age at diagnosis. Serum autoantibodies is one such potential area of interest. However, their ubiquitous presence across cancer types limits its applicability to any one specific type of cancer. This review was therefore carried out to explore and consolidate available evidence on autoantibodies for early detection of breast cancer and to identify those that demonstrated a higher sensitivity. METHODS: A diagnostic test accuracy (DTA) review was carried out to ascertain serum autoantibodies that could be used for early detection of breast cancer among women. All relevant articles that investigated the role of autoantibodies in early detection of breast cancer were included for the review. MEDLINE, Scopus, ProQuest, Ovid SP, and Cochrane Library were searched extensively for eligible studies. Quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. RevMan 5.3 was used for exploratory and MetaDTA 2019 for hierarchical analyses. The review helped identify the most frequently investigated autoantibodies and a meta-analysis further consolidated the findings. RESULTS: A total of 53 articles were included for the final analysis that reported over a 100 autoantibodies that were studied for early detection of breast cancer in women. P53, MUC1, HER2, HSP60, P16, Cyclin B1, and c-Myc were the most frequently investigated autoantibodies. Of these P53, MUC1, HER2, and HSP60 exhibited higher summary sensitivity measures. While the individual pooled sensitivity estimates ranged between 10 and 56%, the panel sensitivity values reported across studies were higher with an estimated range of 60-87%. CONCLUSION: Findings from the review indicate a higher sensitivity for an autoantibody panel in comparison to individual assays. A panel comprising of P53, MUC1, HER2, and HSP60 autoantibodies has the potential to be investigated as an early detection biomarker for breast cancer.

Physical interventions to interrupt or reduce the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a global threat. Antiviral drugs and vaccinations may be insufficient to prevent their spread. OBJECTIVES: To review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. SEARCH STRATEGY: We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3), which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to October 2010), OLDMEDLINE (1950 to 1965), EMBASE (1990 to October 2010), CINAHL (1982 to October 2010), LILACS (2008 to October 2010), Indian MEDLARS (2008 to October 2010) and IMSEAR (2008 to October 2010). SELECTION CRITERIA: In this update, two review authors independently applied the inclusion criteria to all identified and retrieved articles and extracted data. We scanned 3775 titles, excluded 3560 and retrieved full papers of 215 studies, to include 66 papers of 67 studies. We included physical interventions (screening at entry ports, isolation, quarantine, social distancing, barriers, personal protection, hand hygiene) to prevent respiratory virus transmission. We included randomised controlled trials (RCTs), cohorts, case-controls, before-after and time series studies. DATA COLLECTION AND ANALYSIS: We used a standardised form to assess trial eligibility. We assessed RCTs by randomisation method, allocation generation, concealment, blinding and follow up. We assessed non-RCTs for potential confounders and classified them as low, medium and high risk of bias. MAIN RESULTS: We included 67 studies including randomised controlled trials and observational studies with a mixed risk of bias. A total number of participants is not included as the total would be made up of a heterogenous set of observations (participant people, observations on participants and countries (object of some studies)). The risk of bias for five RCTs and most cluster-RCTs was high. Observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis. The highest quality cluster-RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Benefit from reduced transmission from children to household members is broadly supported also in other study designs where the potential for confounding is greater. Nine case-control studies suggested implementing transmission barriers, isolation and hygienic measures are effective at containing respiratory virus epidemics. Surgical masks or N95 respirators were the most consistent and comprehensive supportive measures. N95 respirators were non-inferior to simple surgical masks but more expensive, uncomfortable and irritating to skin. Adding virucidals or antiseptics to normal handwashing to decrease respiratory disease transmission remains uncertain. Global measures, such as screening at entry ports, led to a non-significant marginal delay in spread. There was limited evidence that social distancing was effective, especially if related to the risk of exposure. AUTHORS' CONCLUSIONS: Simple and low-cost interventions would be useful for reducing transmission of epidemic respiratory viruses. Routine long-term implementation of some measures assessed might be difficult without the threat of an epidemic.

Physical interventions to interrupt or reduce the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a world-wide threat. Antiviral drugs and vaccinations may be insufficient to prevent catastrophe. OBJECTIVES: To systematically review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2); MEDLINE (1966 to May 2009); OLDMEDLINE (1950 to 1965); EMBASE (1990 to May 2009); and CINAHL (1982 to May 2009). SELECTION CRITERIA: We scanned 2958 titles, excluded 2790 and retrieved the full papers of 168 trials, to include 59 papers of 60 studies. We included any physical interventions (isolation, quarantine, social distancing, barriers, personal protection and hygiene) to prevent transmission of respiratory viruses. We included the following study designs: randomised controlled trials (RCTs), cohorts, case controls, cross-over, before-after, and time series studies. DATA COLLECTION AND ANALYSIS: We used a standardised form to assess trial eligibility. RCTs were assessed by: randomisation method; allocation generation; concealment; blinding; and follow up. Non-RCTs were assessed for the presence of potential confounders, and classified into low, medium, and high risks of bias. MAIN RESULTS: The risk of bias for the four RCTs, and most cluster RCTs, was high. The observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis.The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Additional benefit from reduced transmission from children to other household members is broadly supported in results of other study designs, where the potential for confounding is greater. Six case-control studies suggested that implementing barriers to transmission, isolation, and hygienic measures are effective at containing respiratory virus epidemics. We found limited evidence that N95 respirators were superior to simple surgical masks, but were more expensive, uncomfortable, and caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. There was limited evidence that social distancing was effective especially if related to the risk of exposure. AUTHORS' CONCLUSIONS: Many simple and probably low-cost interventions would be useful for reducing the transmission of epidemic respiratory viruses. Routine long-term implementation of some of the measures assessed might be difficult without the threat of a looming epidemic.

Effect of prophylactic trochanteric epiphyseodesis in older children with Perthes' disease.

To evaluate the effect of prophylactic epiphyseodesis of the greater trochanter in Perthes' disease, 62 children with unilateral Perthes' disease who underwent trochanteric epiphyseodesis combined with varus osteotomy of the femur during the active stage of the disease (mean age at surgery: 8.4 y) and 20 controls were followed up until skeletal maturity. On radiographs taken at skeletal maturity, the articulo-trochanteric distance, the center-trochanteric distance, the length of the abductor lever arm, the neck-shaft angle, the radius of the femoral head, and the Reimer's migration index of normal and affected hips were measured. The shape of the femoral head was assessed according to the criteria of Mose. The range of hip motion, the strength of hip abduction, and limb lengths were measured and the Trendelenburg sign was elicited. The mean values of articulo-trochanteric distance and center-trochanteric distance were greater and the frequency of a positive Trendelenburg sign was less in children who had undergone trochanteric epiphyseodesis than in children who had no surgery (P<0.01). Trochanteric epiphyseodesis achieved optimal trochanteric growth arrest in 60% of operated children; the procedure was not effective in 30%, and in 10% of children there was overcorrection. Logistic regression analysis showed that the size of the femoral head at healing and the age at surgery were variables that significantly influenced the effectiveness of trochanteric growth arrest. At skeletal maturity, the mean shortening of the affected limb in operated children was 0.44 cm (SD 0.68 cm), whereas that of non-operated children was 0.86 cm (SD 0.78 cm) (P<0.05). The range of motion of the hip was excellent and there were no significant differences in the range of motion among children with optimal correction, under-correction, and overcorrection. A probability curve plotted on the basis of a logistic regression model suggests that effective trochanteric arrest may be achieved in a high proportion of children operated at or before 8.5 years of age and in half the children operated between the age of 8.5 years and 10 years. On the basis of this study, we recommend prophylactic epiphyseodesis of the greater trochanter as a means of minimizing trochanteric overgrowth and resultant Trendelenburg gait in older child with Perthes' disease.