Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: A prospective study

Objective: Plasma total homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes. Research design and methods: tHcy levels were measured once, in plasma obtained in 1997–1999 from patients (n = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC “Year 6” (1998–2000) and “Year 12” (2004–2006), using B-mode ultra-sonography. Results: After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p < 0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p < 0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors. Conclusions: In a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997–1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.

Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK Clinical Practice Research Datalink

INTRODUCTION: Recent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients.

METHODS: A cohort of newly diagnosed breast cancer patients (1998 to 2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis).

RESULTS: After breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy.

CONCLUSIONS: Overall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.

Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection

Background: Differentiation between septic and aseptic loosening of joint replacements is essential for successful revision surgery, but reliable markers for the diagnosis of low-grade infection are lacking. The present study was performed to assess intra-articular and systemic levels of antimicrobial peptides and proinflammatory cytokines as diagnostic markers for periprosthetic joint infection. Methods: Fifteen consecutive patients with staphylococcal periprosthetic joint infections and twenty control patients with aseptic loosening of total hip and knee replacements were included in this prospective, single-center, controlled clinical trial. Expression of the antimicrobial peptides human β-defensin-2 (HBD-2), human β-defensin-3 (HBD-3), and cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in serum and joint aspirates with use of cytometric bead arrays. C-reactive protein in serum, microbiology, and histopathology of periprosthetic tissue served as the “gold standard” for the diagnosis of infection. Results: The antimicrobial peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from patients with periprosthetic joint infection compared with patients with aseptic loosening, and the area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 0.745 and 0.875, respectively. Additionally, significant local increases in the proinflammatory cytokines interleukin (IL)-1β, IL-4, IL-6, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were observed to be associated with infection. Logistic regression analysis indicated that the combination of an antimicrobial peptide with another synovial fluid biomarker improved diagnostic accuracy; the AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3 and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial peptides and cytokines in serum that showed a significant systemic increase in association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC value of <0.75). Conclusions: The present study showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection, and analysis of the levels in synovial fluid was more accurate than analysis of serum.

Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment

Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor alpha (TNF-alpha) antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).

Design Patients with IBD were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IL23R and IL12B variants. Skin lesions were examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-interleukin (IL)-12/IL-23 p40 antibody ustekinumab.

Results Among 434 anti-TNF-treated patients with IBD, 21 (4.8%) developed psoriasiform skin lesions. Multiple logistic regression revealed smoking (p=0.007; OR 4.24, 95% CI 1.55 to 13.60) and an increased body mass index (p=0.029; OR 1.12, 95% CI 1.01 to 1.24) as main predictors for these lesions. Nine patients with Crohn's disease and with severe psoriasiform lesions and/or anti-TNF antibody-induced alopecia were successfully treated with the anti-p40-IL-12/IL-23 antibody ustekinumab (response rate 100%). Skin lesions were histologically characterised by infiltrates of IL-17A/IL-22-secreting T helper 17 (Th17) cells and interferon (IFN)-gamma-secreting Th1 cells and IFN-alpha-expressing cells. IL-17A expression was significantly stronger in patients requiring ustekinumab than in patients responding to topical therapy (p=0.001). IL23R genotyping suggests disease-modifying effects of rs11209026 (p.Arg381Gln) and rs7530511 (p.Leu310Pro) in patients requiring ustekinumab.

Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL23 antibody therapy is a highly effective therapy for these lesions.

Are family physician visits and continuity of care associated with acute care use at end-of-life? A population-based cohort study of homecare cancer patients

Background: Previous end-of-life cancer research has shown an association between increased family physician continuity of care and reduced use of acute care services; however, it did not focus on a homecare population or control for homecare nursing.

Aim: Among end-of-life homecare cancer patients, to investigate the association of family physician continuity with location of death and hospital and emergency department visits in the last 2 weeks of life while controlling for nursing hours.

Design: Retrospective population-based cohort study.

Setting/participants: Cancer patients with ≥1 family physician visit in 2006 from Ontario, Canada. Family physician continuity of care was assessed using two measures: Modified Usual Provider of Care score and visits/week. Its association with location of death and hospital and emergency department visits in the last 2 weeks of life was examined using logistic regression.

Results: Of 9467 patients identified, the Modified Usual Provider of Care score demonstrated a dose-response relationship with increasing continuity associated with decreased odds of hospital death and visiting the hospital and emergency department in the last 2 weeks of life. More family physician visits/week were associated with lower odds of an emergency department visit in the last 2 weeks of life and hospital death, except for patients with greater than 4 visits/week, where they had increased odds of hospitalizations and hospital deaths.

Conclusions: These results demonstrate an association between increased family physician continuity of care and decreased odds of several acute care outcomes in late life, controlling for homecare nursing and other covariates.©The Author(s) 2013 Reprints and permissions sagepub.co.uk/journalsPermissions.nav.

Family-based associations in measures of psychological distress and quality of life in a cardiac screening clinic for inheritable cardiac diseases: a cross-sectional study

BACKGROUND: Family-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic.

METHODS: Prospective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data.

RESULTS: There was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance.

CONCLUSIONS: High levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has implications for family screening and intervention programmes.

Cancer survivors with self-reported late effects: their health status, care needs and service utilisation

OBJECTIVE: Cancer survivors (CSs) are at risk of developing late effects (LEs) associated with the disease and its treatment. This paper compares the health status, care needs and use of health services by CSs with LEs and CSs without LEs.

METHODS: Cancer survivors (n = 613) were identified via the Northern Ireland Cancer Registry and invited to participate in a postal survey that was administered by their general practitioner. The survey assessed self-reported LEs, health status, health service use and unmet care needs. A total of 289 (47%) CSs responded to the survey, and 93% of respondents completed a LEs scale.

RESULTS: Forty-one per cent (111/269) of CSs reported LEs. Survivors without LEs and survivors with LEs were comparable in terms of age and gender. The LEs group reported a significantly greater number of co-morbidities, lower physical health and mental health scores, greater overall health service use and more unmet needs. Unadjusted logistic regression analysis found that cancer site, time since diagnosis and treatment were significantly associated with reporting of LEs. CSs who received combination therapies compared with CSs who received single treatments were over two and a half times more likely to report LEs (OR = 2.63, 95% CI = 1.32-5.25) after controlling for all other variables.

CONCLUSIONS: The CS population with LEs comprises a particularly vulnerable group of survivors who have multiple health care problems and needs and who require tailored care plans that take account of LEs and their impact on health-related quality of life.

Desire for fertility and associated factors among people living with HIV/AIDS (PLWHA) in selected antiretroviral therapy (ART) clinics of Horro Guduru Wollega Zone, North West Oromia, Ethiopia- A cross sectional study

Background: Most recently fertility issues in HIV positive men and women are becoming increasingly important. Because of ART access and its good life effect, it is expected that the need and desire to get married, to have children and to have sexual partners for PLWHA would change with the regard to reproductive health. In Ethiopia HIV positive individuals may or may not have desire to have children. And the extent of this desire and how it varies by individual, health and demographic characteristics is not well known.

Objective: the aim of the study was to assess desire for fertility and associated factors among PLWHA in selected ART clinics of Horro Guduru Wollega Zone, Oromia National Regional State, Ethiopia.

Methods: A cross-sectional, institutional-based study that employed quantitative and qualitative in-depth interviews was conducted. Three hundred twenty one study subjects were selected using systematic random sampling technique and the data was collected using interviewer administered structured questionnaire. Data entry and analysis were performed using EPI Info version 3.5.1 and SPSS version 16. P-value <0.05 was taken as statistically significant and logistic regression was used to control potential confounding factors.

Results: Seventy three (57.9%) of the males and seventy six (39%) of the females desired to have children, giving a total of 149(46.4%) of all study participants. PLWHA who desired children were younger (AOR:3.3, 95%CI: 1.3-8.9), married (AOR: 5.8, 95%CI: 2.7-12.8), had no children (AOR: 75, 95%CI: 20.1-273.3) and males (AOR; 1.9, 95%CI: 1.02-3.62) compared with their counter parts. The major reason for those people who did not desire children were having desired number of children 80 (46.5%) followed by fear of HIV transmission to child reported by 42 (24.4%) of them.

Conclusion: A considerable number of PLWHA wants to have a child currently or in the near future. Many variables like socio demography, partner related, number of alive children and HIV related disease condition were significantly associated with fertility desire.

Root Cause Analysis by a Combined Sparse Classification and Monte Carlo Approach

Classification methods with embedded feature selection capability are very appealing for the analysis of complex processes since they allow the analysis of root causes even when the number of input variables is high. In this work, we investigate the performance of three techniques for classification within a Monte Carlo strategy with the aim of root cause analysis. We consider the naive bayes classifier and the logistic regression model with two different implementations for controlling model complexity, namely, a LASSO-like implementation with a L1 norm regularization and a fully Bayesian implementation of the logistic model, the so called relevance vector machine. Several challenges can arise when estimating such models mainly linked to the characteristics of the data: a large number of input variables, high correlation among subsets of variables, the situation where the number of variables is higher than the number of available data points and the case of unbalanced datasets. Using an ecological and a semiconductor manufacturing dataset, we show advantages and drawbacks of each method, highlighting the superior performance in term of classification accuracy for the relevance vector machine with respect to the other classifiers. Moreover, we show how the combination of the proposed techniques and the Monte Carlo approach can be used to get more robust insights into the problem under analysis when faced with challenging modelling conditions.

Large panel-survey data demonstrated country-level and ethnic minority variation in consent for health record linkage

Objectives
To investigate individual, household and country variation in consent to health record linkage.

Study Design and Setting
Data from 50,994 individuals aged 16-74 years recruited to wave 1 of a large UK general purpose household survey (January 2009 – December 2010) were analysed using multi-level logistic regression models.

Results
Overall, 70.7% of respondents consented to record linkage. Younger age, marriage, tenure, car ownership and education were all significantly associated with consent, though there was little deviation from 70% in subgroups defined by these variables. There were small increases in consent rates in individuals with poor health when defined by self-reported long term limiting illness (adjusted OR 1.11; 95%CIs 1.06, 1.16), less so when defined by General Health Questionnaire score (adjusted OR=1.05; 95%CIs 1.00, 1.10), but the range in absolute consent rates between categories was generally less than 10%. Larger differences were observed for those of non-white ethnicity who were 38% less likely to consent (adjusted OR 0.62; 95%CIs 0.59, 0.66). Consent was higher in Scotland than England (adjusted OR 1.17; 95%CIs 1.06, 1.29) but lower in Northern Ireland (adjusted OR 0.56; 95%CIs 0.50, 0.63).

Conclusion
The modest overall level of systematic bias in consent to record linkage provides reassurance for record linkage potential in general purpose household surveys. However, the low consent rates amongst non-white ethnic minority survey respondents will further compound their low survey participation rates. The reason for the country-level variation requires further study.

Characterisation of the frequent exacerbator phenotype in COPD patients in a large UK primary care population

BACKGROUND: The 'frequent exacerbator' is recognised as an important phenotype in COPD. Current understanding about this phenotype comes from prospective longitudinal clinical trials in secondary/tertiary care with little information reported in primary care populations.

AIMS: To characterize the frequent-exacerbator phenotype and identify associated risk factors in a large UK primary care COPD population.

METHODS: Using a large database of primary care patients from 80 UK general practices, patients were categorised using GOLD 2014 criteria into high and low risk groups based on exacerbation history. A multivariate logistic regression model was used to investigate covariates associated with the frequent-exacerbator phenotype and risk of experiencing a severe exacerbation (leading to hospitalisation).

RESULTS: Of the total study population (n = 9219), 2612 (28%) fulfilled the criteria for high risk frequent-exacerbators. Independent risk factors (adjusted odds ratio [95% CI]) for ≥2 exacerbations were: most severely impaired modified Medical Research Council (mMRC) dyspnoea score (mMRC grade 4: 4.37 [2.64-7.23]), lower FEV1 percent predicted (FEV1 <30%: 2.42 [1.61-3.65]), co-morbid cardiovascular disease (1.42 [1.19-1.68]), depression (1.56 [1.22-1.99]) or osteoporosis (1.54 [1.19-2.01]), and female gender (1.20 [1.01-1.43]). Older patients (≥75 years), those with most severe lung impairment (FEV1 <30%), those with highest mMRC score and those with co-morbid osteoporosis were identified as most at risk of experiencing exacerbations requiring hospitalisation.

CONCLUSIONS: Although COPD exacerbations occur across all grades of disease severity, female patients with high dyspnoea scores, more severely impaired lung function and co-morbidities are at greatest risk. Elderly patients, with severely impaired lung function, high mMRC scores and osteoporosis are associated with experience of severe exacerbations requiring hospitalisation.

Two-year survival of ART restorations placed in elderly patients: A randomised controlled clinical trial

OBJECTIVES: Older dentate adults are a high caries risk group who could potentially benefit from the use of the atraumatic restorative treatment (ART). This study aimed to compare the survival of ART and a conventional restorative technique (CT) using rotary instruments and a resin-modified glass-ionomer for restoring carious lesions as part of a preventive and restorative programme for older adults after 2 years.

METHODS: In this randomised controlled clinical trial, 99 independently living adults (65-90 years) with carious lesions were randomly allocated to receive either ART or conventional restorations. The survival of restorations was assessed by an independent and blinded examiner 6 months, 1 year and 2 years after restoration placement.

RESULTS: Ninety-six (67.6%) and 121 (76.6%) restorations were assessed in the ART and CT groups, respectively, after 2 years. The cumulative restoration survival percentages after 2 years were 85.4% in the ART and 90.9% in the CT group. No statistically significant between group differences were detected (p=0.2050, logistic regression analysis).

CONCLUSIONS: In terms of restoration survival, ART was as effective as a conventional restorative approach to treat older adults after 2 years. This technique could be a useful tool to provide dental care for older adults particularly in the non-clinical setting. (Trial Registration number: ISRCTN 76299321).

CLINICAL SIGNIFICANCE: The results of this study show that ART presented survival rates similar to conventional restorations in older adults. ART appears to be a cost-effective way to provide dental care to elderly patients, particularly in out of surgery facilities, such as nursing homes.

Using Brain Data for Sentiment Analysis

We present the results of exploratory experiments using lexical valence extracted from brain using electroencephalography (EEG) for sentiment analysis. We selected 78 English words (36 for training and 42 for testing), presented as stimuli to 3 English native speakers. EEG signals were recorded from the subjects while they performed a mental imaging task for each word stimulus. Wavelet decomposition was employed to extract EEG features from the time-frequency domain. The extracted features were used as inputs to a sparse multinomial logistic regression (SMLR) classifier for valence classification, after univariate ANOVA feature selection. After mapping EEG signals to sentiment valences, we exploited the lexical polarity extracted from brain data for the prediction of the valence of 12 sentences taken from the SemEval-2007 shared task, and compared it against existing lexical resources.

Metastatic non-small cell lung cancer: a benchmark for quality end-of-life cancer care?

Objectives: To investigate the quality of end-of-life care for patients with metastatic non-small cell lung cancer (NSCLC). Design and participants: Retrospective cohort study of patients from first hospitalisation for metastatic disease until death, using hospital, emergency department and death registration data from Victoria, Australia, between 1 July 2003 and 30 June 2010. Main outcome measures: Emergency department and hospital use; aggressiveness of care including intensive care and chemotherapy in last 30 days; palliative and supportive care provision; and place of death. Results: Metastatic NSCLC patients underwent limited aggressive treatment such as intensive care (5%) and chemotherapy (< 1%) at the end of life; however, high numbers died in acute hospitals (42%) and 61% had a length of stay of greater than 14 days in the last month of life. Although 62% were referred to palliative care services, this occurred late in the illness. In a logistic regression model adjusted for year of metastasis, age, sex, metastatic site and survival, the odds ratio (OR) of dying in an acute hospital bed compared with death at home or in a hospice unit decreased with receipt of palliative care (OR, 0.25; 95% CI, 0.21–0.30) and multimodality supportive care (OR, 0.65; 95% CI, 0.56–0.75). Conclusion: Because early palliative care for patients with metastatic NSCLC is recommended, we propose that this group be considered a benchmark of quality end-of-life care. Future work is required to determine appropriate quality-of-care targets in this and other cancer patient cohorts, with particular focus on the timeliness of palliative care engagement.

Susceptibility to Invasive Meningococcal Disease: Polymorphism of Complement System Genes and Neisseria meningitidis Factor H Binding Protein

BACKGROUND: Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH) is associated with altered risk of invasive meningococcal disease (IMD). We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP) affected the risk association.

METHODS: We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.

RESULTS: Rs12085435 A in C8B was associated with odds ratio (OR) of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction). A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10-4). There was no bacterial load (CtrA cycle threshold) difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025).

DISCUSSION: The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become important.