Lung function indices for predicting mortality in COPD

Chronic obstructive pulmonary disease (COPD) is characterised by high morbidity and mortality. It remains unknown which aspect of lung function carries the most prognostic information and if simple spirometry is sufficient. Survival was assessed in COPD outpatients whose data had been added prospectively to a clinical audit database from the point of first full lung function testing including spirometry, lung volumes, gas transfer and arterial blood gases. Variables univariately associated with survival were entered into a multivariate Cox proportional hazard model. 604 patients were included (mean±sd age 61.9±9.7 years; forced expiratory volume in 1 s 37±18.1% predicted; 62.9% males); 229 (37.9%) died during a median follow-up of 83 months. Median survival was 91.9 (95% CI 80.8–103) months with survival rates at 3 and 5 years 0.83 and 0.66, respectively. Carbon monoxide transfer factor % pred quartiles (best quartile (>51%): HR 0.33, 95% CI 0.172–0.639; and second quartile (51–37.3%): HR 0.52, 95% CI 0.322–0.825; versus lowest quartile (<27.9%)), age (HR 1.04, 95% CI 1.02–1.06) and arterial oxygen partial pressure (HR 0.85, 95% CI 0.77–0.94) were the only parameters independently associated with mortality. Measurement of gas transfer provides additional prognostic information compared to spirometry in patients under hospital follow-up and could be considered routinely

Back pain reporting in young girls appears to be puberty-related

BACKGROUND: There is a large increase in back pain reporting in the early teens. In no previous study has the prevalence of low back pain been investigated in relation to the onset of puberty. The objective of this study was to establish whether the onset of puberty is associated with back pain reporting in young girls. METHODS: A subsample of 254 girls aged 8–10 years and 165 girls aged 14–16 years from a cross-sectional survey of 481 children aged 8–10 years and 325 adolescents aged 14–16 years of both sexes. Main outcome measures were back pain defined as low back pain, mid back pain, and/or neck pain in the past month. Other variables of interest were Puberty (five different stages), age, body mass index, and smoking. Independent information on onset of puberty was obtained through a physical examination and on back pain through an individual structured interview. The association was studied between onset of puberty and the outcome variable (the one month period prevalence of back pain), controlling for overweight, and smoking. Odds ratios with 95% confidence intervals were used to describe bivariate associations, logistic regression with robust standard errors was used for multivariate analyses. RESULTS: There is a highly significant trend for increased back pain reporting with increasing level of puberty until maturity is reached. The biggest leap appears between the second level (beginning of puberty) and the third level (mid puberty) and the findings remain after controlling for the covariates. These results emanate from the low back, whereas pain in the mid back and neck do not seem to be linked with pubertal stage. CONCLUSION: In girls, the reporting of low back pain increases in frequency during puberty until maturity, regardless of age. Why some girls are susceptible to back pain in the early stage of puberty is unknown

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P &lt; 0.001), age, bisphosphonate use, and rodding (P &lt; 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

An evaluation of factors associated with completion and benefit from pulmonary rehabilitation in COPD

All rights reserved. Background: Pulmonary Rehabilitation (PR) is an important treatment for patients with chronic obstructive pulmonary disease (COPD) but it is not established whether any baseline parameter can predict response or compliance. Aim: To identify whether baseline measures can predict who will complete the programme and who will achieve a clinically significant benefit from a Minimum Clinical Important Difference (MCID) in terms of exercise capacity and health-related quality of life (HRQoL). Methods: Data were collected prospectively from patients with COPD at their baseline assessment for an outpatient PR programme in one of eight centres across London. ‘Completion’ was defined as attending at least 75% of the designated PR visits and return for the follow-up evaluation. The MCID for outcome measures was based on published data. Results: 787 outpatients with COPD (68.1±10.5 years old; 49.6% males) were included. Patients who completed PR (n=449, 57.1%) were significantly older with less severe airflow obstruction, lower anxiety and depression scores, less dyspnoea and better HRQoL. Only baseline CAT score (OR=0.925; 95% CI 0.879 to 0.974; p=0.003) was retained in multivariate analysis. Patients with the lowest baseline walking distance were most likely to achieve the MCID for exercise capacity. No baseline variable could independently predict achievement of an MCID in HRQoL. Conclusions: Patients with better HRQoL are more likely to complete PR while worse baseline exercise performance makes the achievement of a positive MCID in exercise capacity more likely. However, no baseline parameter could predict who would benefit the most in terms of HRQoL

Effectiveness of an online curriculum for medical students on genetics, genetic testing and counseling

Background: It is increasingly important that physicians have a thorough understanding of the basic science of human genetics and the ethical, legal and social implications (ELSI) associated with genetic testing and counseling. Methods: The authors developed a series of web-based courses for medical students on these topics. The course modules are interactive, emphasize clinical case studies, and can easily be incorporated into existing medical school curricula. Results: Results of a &#x2018;real world&#x2019; effectiveness trial indicate that the courses have a statistically significant effect on knowledge, attitude, intended behavior and self-efficacy related to genetic testing (p&#60;0.001; N varies between 163 and 596 for each course). Conclusions: The results indicate that this curriculum is an effective tool for educating medical students on the ELSI associated with genetic testing and for promoting positive changes in students&#x0027; confidence, counseling attitudes and behaviors

Suicidality among adolescents engaging in nonsuicidal self-injury (NSSI) and firesetting: The role of psychosocial characteristics and reasons for living

Background: Co-occurrence of problem behaviors, particularly across internalizing and externalizing spectra, increases the risk of suicidality (i.e., suicidal ideation and attempt) among youth. Methods: We examined differences in psychosocial risk factors across levels of suicidality in a sample of 77 school-based adolescents engaging in both nonsuicidal self-injury (NSSI) and repeated firesetting. Participants completed questionnaires assessing engagement in problem behaviors, mental health difficulties, negative life events, poor coping, impulsivity, and suicidality. Results: Adolescents endorsing suicidal ideation reported greater psychological distress, physical and sexual abuse, and less problem solving/goal pursuit than those with no history of suicidality; adolescents who had attempted suicide reported more severe NSSI, higher rates of victimization and exposure to suicide, relative to those with suicidal ideation but no history of attempt. Additional analyses suggested the importance of coping beliefs in protecting against suicidality. Conclusions: Clinical implications and suggestions for future research relating to suicide prevention are discussed

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.Massachusetts Institute of Technology. Faculty Discretionary Research FundNational Institutes of Health (U.S.) (Award UL1 RR 025758)Harvard Catalyst (Grant

NS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus

The development of novel therapeutic agents is essential for combating the increasing number of cases of dengue fever in endemic countries and among a large number of travelers from non-endemic countries. The dengue virus has three structural proteins and seven non-structural (NS) proteins. NS3 is a multifunctional protein with an N-terminal protease domain (NS3pro) that is responsible for proteolytic processing of the viral polyprotein, and a C-terminal region that contains an RNA triphosphatase, RNA helicase and RNA-stimulated NTPase domain that are essential for RNA replication. The serine protease domain of NS3 plays a central role in the replicative cycle of dengue virus. This review discusses the recent structural and biological studies on the NS2B-NS3 protease-helicase and considers the prospects for the development of small molecules as antiviral drugs to target this fascinating, multifunctional protein

Evaluating indices of traditional ecological knowledge: a methodological contribution

BACKGROUND: New quantitative methods to collect and analyze data have produced novel findings in ethnobiology. A common application of quantitative methods in ethnobiology is to assess the traditional ecological knowledge of individuals. Few studies have addressed reliability of indices of traditional ecological knowledge constructed with different quantitative methods. METHODS: We assessed the associations among eight indices of traditional ecological knowledge from data collected from 650 native Amazonians. We computed Spearman correlations, Chronbach's alpha, and principal components factor analysis for the eight indices. RESULTS: We found that indices derived from different raw data were weakly correlated (rho<0.5), whereas indices derived from the same raw data were highly correlated (rho>0.5; p < 0.001). We also found a relatively high internal consistency across data from the eight indices (Chronbach's alpha = 0.78). Last, results from a principal components factor analysis of the eight indices suggest that the eight indices were positively related, although the association was low when considering only the first factor. CONCLUSION: A possible explanation for the relatively low correlation between indices derived from different raw data, but relatively high internal consistency of the eight indices is that the methods capture different aspects of an individual's traditional ecological knowledge. To develop a reliable measure of traditional ecological knowledge, researchers should collect raw data using a variety of methods and then generate an aggregated measure that contains data from the various components of traditional ecological knowledge. Failure to do this will hinder cross-cultural comparisons