Mechanisms Underlying the Association of Chronic Obstructive Pulmonary Disease With Heart Failure.

OBJECTIVES: The purposes of this study were to determine why chronic obstructive pulmonary disease (COPD) is associated with heart failure (HF). Specific objectives included whether COPD is associated with myocardial fibrosis, whether myocardial fibrosis is associated with hospitalization for HF and death in COPD, and whether COPD and smoking are associated with myocardial inflammation. BACKGROUND: COPD is associated with HF independent of shared risk factors. The underlying pathophysiological mechanism is unknown. METHODS: A prospective, multicenter, longitudinal cohort study of 572 patients undergoing cardiac magnetic resonance (CMR), including 450 patients with COPD and 122 age- and sex-matched patients with a median: 726 days (interquartile range: 492 to 1,160 days) follow-up. Multivariate analysis was used to examine the relationship between COPD and myocardial fibrosis, measured using cardiac magnetic resonance (CMR). Cox regression analysis was used to examine the relationship between myocardial fibrosis and outcomes; the primary endpoint was composite of hospitalizations for HF or all-cause mortality; secondary endpoints included hospitalizations for HF and all-cause mortality. Fifteen patients with COPD, 15 current smokers, and 15 healthy volunteers underwent evaluation for myocardial inflammation, including ultrasmall superparamagnetic particles of iron oxide CMR. RESULTS: COPD was independently associated with myocardial fibrosis (p < 0.001). Myocardial fibrosis was independently associated with the primary outcome (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.08 to 1.20; p < 0.001), hospitalization for HF (HR: 1.25 [95% CI: 1.14 to 1.36]); p < 0.001), and all-cause mortality. Myocardial fibrosis was associated with outcome measurements more strongly than any other variable. Acute and stable COPD were associated with myocardial inflammation. CONCLUSIONS: The associations between COPD, myocardial inflammation and myocardial fibrosis, and the independent prognostic value of myocardial fibrosis elucidate a potential pathophysiological link between COPD and HF.

A large population-based study of the mental health and wellbeing of children and young people in the North of England.

BACKGROUND: There has been a recent reported rise in prevalence of mental health problems among children in the United Kingdom, alongside increased referrals into specialist services. There is a need for up-to-date information regarding changing trends of young people's mental health to allow for improved understanding and service planning. OBJECTIVES: This article aims to provide an overview of the current mental health and well-being of years 8, 9 and 11 secondary school-aged pupils from two large regions in the North of England. METHOD: This was a cohort cross-sectional study. Measures including the Strengths and Difficulties questionnaire, the EQ-5D-Y, social media use questions, and a mental health service use questionnaire were completed by participants. RESULTS: In total, 6328 questionnaires were returned from 21 secondary schools. One in 10 participating pupils scored 'very high' for total mental health difficulties. Significant differences on well-being scores were found between both gender and year groups. CONCLUSION: In recent years, the proportion of children facing mental health problems has increased. In particular, high levels of female pupils and year 11 pupils report facing difficulties. It is important to develop targeted, accessible interventions, and to continue to collect up-to-date measures for this population.

Sensitivity and attachment interventions in early childhood: A systematic review and meta-analysis.

A systematic review and meta-analysis of randomized controlled trials (RCT) was conducted to determine whether early interventions are effective in improving attachment security and parental sensitivity. Electronic databases were searched 2002-2015 onwards, All RCTs delivered to mothers, fathers or carers, before their child's mean age was 36 months, via 1:1 support, group work or guided self-help were included. The search was restricted to English Language publications. Study Selection, data extraction and quality appraisal were independently undertaken by two authors. With regard to analysis, where appropriate, dichotomous data were pooled using the Mantel- Haenszel odds ratio method and for continuous data descriptive statistics were collected in order to calculate standardized mean differences and effect sizes. Four studies met inclusion criteria and were divided into two groups: North American & Canadian and South African based studies. Combining data from both groups indicates that early interventions improve attachment security and improves rates of disorganized attachment. One study provided extractable data on the outcome of parental sensitivity which shows that early interventions were effective in improving maternal sensitivity at 6 and 12 months. Study results generally support the findings of a previous review (Bakermans-Kranenburg et al., 2003) which found that early interventions improved attachment security and maternal sensitivity.

Randomized trial of laparoscopic-assisted resection of colorectal carcinoma: 3-year results of the UK MRC CLASICC Trial Group.

PURPOSE: The aim of the current study is to report the long-term outcomes after laparoscopic-assisted surgery compared with conventional open surgery within the context of the UK MRC CLASICC trial. Results from randomized trials have indicated that laparoscopic surgery for colon cancer is as effective as open surgery in the short term. Few data are available on rectal cancer, and long-term data on survival and recurrence are now required. METHODS: The United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer (UK MRC CLASICC; clinical trials number ISRCTN 74883561) trial study comparing conventional versus laparoscopic-assisted surgery in patients with cancer of the colon and rectum. The randomization ratio was 2:1 in favor of laparoscopic surgery. Long-term outcomes (3-year overall survival [OS], disease-free survival [DFS], local recurrence, and quality of life [QoL]) have now been determined on an intention-to-treat basis. RESULTS: Seven hundred ninety-four patients were recruited (526 laparoscopic and 268 open). Overall, there were no differences in the long-term outcomes. The differences in survival rates were OS of 1.8% (95% CI, -5.2% to 8.8%; P = .55), DFS of -1.4% (95% CI, -9.5% to 6.7%; P = .70), local recurrence of -0.8% (95% CI, -5.7% to 4.2%; P = .76), and QoL (P > .01 for all scales). Higher positivity of the circumferential resection margin was reported after laparoscopic anterior resection (AR), but it did not translate into an increased incidence of local recurrence. CONCLUSION: Successful laparoscopic-assisted surgery for colon cancer is as effective as open surgery in terms of oncological outcomes and preservation of QoL. Long-term outcomes for patients with rectal cancer were similar in those undergoing abdominoperineal resection and AR, and support the continued use of laparoscopic surgery in these patients.

Laparoscopically assisted vs open colectomy for colon cancer: a meta-analysis.

OBJECTIVE: To perform a meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic colectomy for cancer is oncologically safe. DATA SOURCES: The databases of the Barcelona, Clinical Outcomes of Surgical Therapy (COST), Colon Cancer Laparoscopic or Open Resection (COLOR), and Conventional vs Laparoscopic-Assisted Surgery in Patients With Colorectal Cancer (CLASICC) trials were the data sources for the study. STUDY SELECTION: Patients who had at least 3 years of complete follow-up data were selected. DATA EXTRACTION: Patients who had undergone curative surgery before March 1, 2000, were studied. Three-year disease-free survival and overall survival were the primary outcomes of this analysis. DATA SYNTHESIS: Of 1765 patients, 229 were excluded, leaving 796 patients in the laparoscopically assisted arm and 740 patients in the open arm for analysis. Three-year disease-free survival rates in the laparoscopically assisted and open arms were 75.8% and 75.3%, respectively (95% confidence interval [CI] of the difference, -5% to 4%). The associated common hazard ratio (laparoscopically assisted vs open surgery with adjustment for sex, age, and stage) was 0.99 (95% CI, 0.80-1.22; P = .92). The 3-year overall survival rate after laparoscopic surgery was 82.2% and after open surgery was 83.5% (95% CI of the difference, -3% to 5%). The associated hazard ratio was 1.07 (95% CI, 0.83-1.37; P = .61). Disease-free and overall survival rates for stages I, II, and III evaluated separately did not differ between the 2 treatments. CONCLUSION: Laparoscopically assisted colectomy for cancer is oncologically safe.

Hand aging: patients' opinions.

BACKGROUND: The purpose of this article is to identify factors that make hands look youthful or old and to assess whether altering any of these factors could influence the perceived age of the patient. METHODS: A questionnaire showing digital images of female hands of different ages was administered. Some images were altered digitally to remove veins, blemishes, or wrinkles. Makeup and jewelry were added to others. A total of 93 questionnaires were completed. Statistical analysis of results with chi-square test was performed. RESULTS: Wrinkles, veins, prominent joints, thin skin, deformity, and spots characterized old hands. Fullness, lack of veins, and lack of wrinkles characterized young hands. Images with veins removed looked younger than the originals, and this was statistically significant in all cases. Images with added makeup and jewelry were also felt to look younger, but this was not statistically significant. Alterations to images of very elderly hands did not make them look younger. CONCLUSIONS: The authors have established factors that characterize the age of hands and established that hands with less visible veins, in general, look younger. Previous articles have claimed that fat grafting reduces the visibility of veins.

Minimization--reducing predictability for multi-centre trials whilst retaining balance within centre.

Minimization is often used to assign patients to treatment groups to ensure good balance in patient numbers within centre and other prognostic factors. Balance within centre is preferable since large imbalances between treatment arms may have logistical implications for centres, such as cost and resource implications. However, recent concern over high predictability of treatment allocation by centres when using minimization has caused this method to be questioned. We used data from current clinical trials to assess predictability and summarize subsequent within-centre imbalances with the aim of finding the most effective minimization method for reducing predictability whilst still retaining sufficient balance within centre, when randomization is to one of two treatments. We compared prediction rates and imbalances for deterministic minimization, and minimization incorporating various random elements, p (p=0.95,0.90,0.80,0.75,0.70). We also compared prediction rates and imbalance when centre was and was not included as a stratification factor. Incorporating a random element proved successful in reducing prediction rates whilst minimizing the inevitable increase in within-centre imbalance, whereas excluding centre as a stratification factor incurred major within-centre imbalance. We therefore suggest that minimization can still be used, and that centre can be included as a stratification factor, but a random element has to be incorporated into the minimization algorithm. Minimization incorporating a random element of 0.80 is the most efficient method to use based upon the simulations undertaken in this study of real clinical trial data using different probabilities of allocation.

Reliability of pressure ulcer classification and diagnosis.

AIM: To assess the inter-rater reliability of the PRESSURE Trial pressure ulcer diagnosis (>/=Grade 2) and skin classification for all grades between the clinical research nurse (CRN) team leader and CRNs working across different hospital sites; and CRNs and ward-based nurses. BACKGROUND: The United Kingdom National Health Service Health Technology Assessment Programme has funded a multi-centre, randomized controlled trial to compare the clinical and cost-effectiveness of alternating pressure mattress overlays and mattress replacements - PRESSURE Trial. Outcome skin assessments were recorded by qualified ward-based nurses daily, and expert CRNs twice weekly. METHOD: Paired assessments were undertaken and skin assessed on seven body sites. The per cent agreement between nurses in the diagnosis of a pressure ulcer was determined and the Kappa statistic and confidence intervals calculated. Per cent agreement between nurses in classifying skin for all grades was also determined. RESULTS: Assessments were undertaken by 378 pairs: 16 paired patient assessments (107 site comparisons) by the CRN team leader and CRNs, and 362 paired patient assessments (2396 site comparisons) between CRNs and ward-based nurses. There was 100% agreement between the CRN team leader and CRNs in the diagnosis of a pressure ulcer, and the Kappa statistics indicated 'very good' agreement. There were only two (1.9%) disagreements in classifying skin for all grades between these nurses. The agreement in the diagnosis of a pressure ulcer between CRNs and ward-based nurses varied by skin site, ranging from 93.6% to 100%, with the Kappa statistics indicating 'good' and 'very good' agreement. However, there were 508 (21.2%) disagreements in classifying skin for all grades. CONCLUSIONS: Overall agreement and Kappa statistics indicated 'very good' and 'good' agreement between expert nurses, and between expert nurses and qualified ward-based staff, respectively. However, the high prevalence of normal skin concealed clinically important disagreements in both the diagnosis of pressure ulcers and skin classification for all grades.

Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial.

BACKGROUND: Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale randomised trials to support its use. We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes. METHODS: Between July, 1996, and July, 2002, we undertook a multicentre, randomised clinical trial in 794 patients with colorectal cancer from 27 UK centres. Patients were allocated to receive laparoscopic-assisted (n=526) or open surgery (n=268). Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins, proportion of Dukes' C2 tumours, and in-hospital mortality. Analysis was by intention to treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN74883561. FINDINGS: Six patients (two [open], four [laparoscopic]) had no surgery, and 23 had missing surgical data (nine, 14). 253 and 484 patients actually received open and laparoscopic-assisted treatment, respectively. 143 (29%) patients underwent conversion from laparoscopic to open surgery. Proportion of Dukes' C2 tumours did not differ between treatments (18 [7%] patients, open vs 34 [6%], laparoscopic; difference -0.3%, 95% CI -3.9 to 3.4%, p=0.89), and neither did in-hospital mortality (13 [5%] vs 21 [4%]; -0.9%, -3.9 to 2.2%, p=0.57). Apart from patients undergoing laparoscopic anterior resection for rectal cancer, rates of positive resection margins were similar between treatment groups. Patients with converted treatment had raised complication rates. INTERPRETATION: Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes. However, impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use.