The impact of public transport on the health of work commuters: a systematic review.

Although the public transport (PT) commute can form a substantial part of the working day, there is a significant gap in our understanding of how it influences health of those who engage in it. The purpose of this systematic review was to therefore generate evidence from 1972 about the extent to which the PT commute (involving train, bus, subway, tram, or metro) impacts on the mental health, physical health and well-being of the working people. We identified 47 studies in English worldwide involving an empirical quantitative focus which met the inclusion criteria. Of these, 23 studies involved over 500 participants. Although initial multi-modal comparisons showed impact on sickness rate, self-rated health complaints, perceived stress level and reduction in sleep, a more homogeneous analysis of rail commuters showed elevation in salivary cortisol, perceived stress, and affective reactions to crowding. Findings also revealed a bias towards use of endogenous self-report measures. On this basis, we argue that it would be of benefit to test theoretical models to account for more objective measures of job and commuting stress. Recommendations were made for flexible working agendas.

Change in diagnostic confidence brought about by using in utero MRI for fetal structural brain pathology: analysis of the MERIDIAN cohort.

AIM: To measure possible change in diagnostic confidence by performing in utero magnetic resonance imaging (iuMRI) studies on fetuses with brain abnormalities recognised on ultrasonography (US). MATERIALS AND METHODS: The analyses are based on the primary cohort from the prospective MERIDIAN study, which consisted of 570 fetuses with brain abnormalities detected on US, with iuMRI performed within 2 weeks of US and complete outcome reference data. The cohort was recruited between July 2011 and August 2014, and written informed consent was obtained for all participants. They all had indicators of diagnostic confidence measured on US by fetal medicine experts and iuMRI by the reporting radiologists. Three assessments were carried out using the conventional uncorrected (C2-C1%) method, the conventional (C2-C1%) with the Omary correction, and the score-based weighted average method. RESULTS: All three assessments showed statistically significant (p<0·0001) positive effects indicating that iuMRI was potentially beneficial when included in the diagnostic pathway for prenatal structural brain anomalies (in terms of diagnostic confidence). CONCLUSION: These results strongly support the routine clinical use of iuMRI as an adjunct to US when assessing fetuses with structural brain abnormalities.

'Fish out of water': a cross-sectional study on the interaction between social and neighbourhood effects on weight management behaviours.

OBJECTIVE: To analyse whether an individual's neighbourhood influences the uptake of weight management strategies and whether there is an interaction between individual socio-economic status and neighbourhood deprivation. METHODOLOGY: Data were collected from the Yorkshire Health Study (2010-2012) for 27 806 individuals on the use of the following weight management strategies: 'slimming clubs', 'healthy eating', 'increasing exercise' and 'controlling portion size'. A multi-level logistic regression was fit to analyse the use of these strategies, controlling for age, sex, body mass index, education, neighbourhood deprivation and neighbourhood population turnover (a proxy for neighbourhood social capital). A cross-level interaction term was included for education and neighbourhood deprivation. Lower Super Output Area was used as the geographical scale for the areal unit of analysis. RESULTS: Significant neighbourhood effects were observed for use of 'slimming clubs', 'healthy eating' and 'increasing exercise' as weight management strategies, independent of individual- and area-level covariates. A significant interaction between education and neighbourhood deprivation was observed across all strategies, suggesting that as an area becomes more deprived, individuals of the lowest education are more likely not to use any strategy compared with those of the highest education. CONCLUSIONS: Neighbourhoods modify/amplify individual disadvantage and social inequalities, with individuals of low education disproportionally affected by deprivation. It is important to include neighbourhood-based explanations in the development of community-based policy interventions to help tackle obesity.

Perceptions and experiences of using automated bolus advisors amongst people with type 1 diabetes: a longitudinal qualitative investigation.

AIMS: We explored people's reasons for, and experiences of, using bolus advisors to determine insulin doses; and, their likes/dislikes of this technology. SUBJECTS AND METHODS: 42 people with type 1 diabetes who had received instruction in use of bolus advisors during a structured education course were interviewed post-course and 6 months later. Data were analysed thematically. RESULTS: Participants who considered themselves to have poor mathematical skills highlighted a gratitude for, and heavy reliance on, advisors. Others liked and chose to use advisors because they saved time and effort calculating doses and/or had a data storage facility. Follow-up interviews highlighted that, by virtue of no longer calculating their doses, participants could become deskilled and increasingly dependent on advisors. Some forgot what their mealtime ratios were; others reported a misperception that, because they were pre-programmed during courses, these parameters never needed changing. Use of data storage facilities could hinder effective review of blood glucose data and some participants reported an adverse impact on glycaemic control. DISCUSSION: While participants liked and perceived benefits to using advisors, there may be unintended consequences to giving people access to this technology. To promote effective use, on-going input and education from trained health professionals may be necessary.

HIV/hepatitis C virus coinfection management: changing guidelines and changing paradigms.

OBJECTIVES: The aim of the study was to consider the impact of new direct-acting antiviral (DAA) regimens on hepatitis C virus (HCV) treatment in HIV/HCV coinfection. METHODS: Current coinfection guidelines were reviewed and the impact of recent DAA publications evaluating HIV-coinfected individuals was considered. RESULTS: Current coinfection guidelines recommend HIV antiretroviral therapy initiation prior to HCV antiviral therapy. New all-oral, combination antiviral therapy composed of one or more DAAs with or without ribavirin will change this paradigm. As these regimens are better tolerated, it will be possible to offer nearly all HCV-infected patients antiviral therapy, including those with HIV infection. All-oral regimens may impact the incidence of HCV infection by providing a treatment option that can be safely and broadly utilized in high-risk populations with the benefits of curing individual patients and addressing broader public health concerns related to HCV. CONCLUSIONS: HCV infection treatment should no longer be a secondary consideration restricted to the minority of HIV/HCV-coinfected patients.

A quantitative approach to histopathological dissection of elastin-related disorders using multiphoton microscopy.

BACKGROUND: Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin. OBJECTIVES: To quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilizing autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders. METHODS: Cross-sections of skin samples from elastin-related disorders were analysed by MPM and correlated to histopathology. In situ visualization of elastic fibres by MPM was conducted by en face imaging of ex vivo skin samples through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions. RESULTS: Based on the MPM-detected elastin-specific autofluorescence, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in vivo. CONCLUSIONS: MPM has the potential for noninvasive in vivo visualization of elastic fibres in the dermis with near histological resolution. DEMI allows objective assessment of elastic fibres to support diagnosis and monitoring of disease progress or therapy of elastin-related skin disorders.

Re-treatment with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have relapsed or not responded to a first course of pegylated interferon-based therapy.

BACKGROUND: Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported. AIM: To assess the effectiveness of the retreatment of patients who have previously failed an initial course of pegIFN-based therapy with pegIFNalpha-2a and ribavirin. METHODS: A post-hoc analysis of a multicentre open-label study was performed. Patients received pegIFNalpha-2a and ribavirin at a dose of 800 mg/day and later 1000 mg/day to 1200 mg/day for 24 to 48 weeks at the discretion of the investigator. Outcomes at week 12 (early virological response [EVR]) and week 24 (sustained virological response [SVR]) were analyzed. RESULTS: Eighty-seven patients who had relapsed after previous pegIFN-based therapy (n=28; 78% genotype 1) or were nonresponders (n=59; 71% genotype 1) were analyzed. Of the relapsers, 86% achieved an EVR and 68% achieved an SVR. In relapsers to pegIFN monotherapy (n=15) or pegIFN plus ribavirin (n=13), 60% and 77% achieved an SVR, respectively. Fibrosis and genotype did not affect the likelihood of SVR in relapsers although this may be the result of the relatively small number of patients. In previous nonresponders, an EVR was achieved in 53% but an SVR occurred in only 17%. In nonresponders to pegIFN monotherapy (n=9) and pegIFN plus ribavirin (n=50), 33% and 14% achieved an SVR, respectively. Genotype did not affect SVR in nonresponders. Only 10% with a METAVIR score of F3 or F4 on liver biopsy achieved an SVR. CONCLUSIONS: Relapse after previous pegIFN-based therapy is associated with a strong probability of treatment success whereas retreatment of those with previous nonresponse does not.

CPG 7909 adjuvant plus hepatitis B virus vaccination in HIV-infected adults achieves long-term seroprotection for up to 5 years.

BACKGROUND: Human immunodeficiency virus (HIV)-infected persons are hyporesponsive to hepatitis B virus (HBV) vaccination. CPG 7909 is an oligodeoxynucleotide containing immunostimulatory CpG motifs that activate human B and plasmacytoid dendritic cells via Toll-like receptor 9. We previously reported that addition of CPG 7909 to a commercial HBV vaccine enhanced the kinetics, magnitude, and longevity of the seroprotective response over 48 weeks. We now report data for the 5-year period following vaccination. METHODS: A randomized, double-blind, controlled trial was conducted to determine clinical safety and immunogenicity of HBV vaccine in adult HIV-infected subjects receiving effective antiretroviral therapy. HBV-susceptible subjects, one-half of whom had experienced previous vaccination failure, were vaccinated at 0, 1, and 2 months with a double adult dose of recombinant HBV vaccine, with or without 1 mg of CPG 7909 (19 subjects per arm). Titers of antibody to HBV surface antigen (anti-HBs) were measured at 6-month intervals for up to 60 months. RESULTS: The proportion of participants achieving and retaining seroprotection (surface antibody titers, > or =10 mIU/mL) was greater in CPG 7909 recipients (P < .05 at all time points). Geometric mean anti-HBs titers were higher in the CPG 7909 group than in the control group (without CPG 7909 adjuvant) at all measured time points. CONCLUSIONS: The immunostimulatory properties of CPG 7909 present an important strategy in achieving long-term protection in HIV-infected patients and other HBV vaccine-hyporesponsive populations.

Perceptions of the causes of childhood disability among Pakistani families living in the UK.

It has been well documented that South Asian families caring for a child with a disability experience discrimination and disadvantage in accessing health and social care services. This gives increasing cause for concern as the number of South Asian people with severe learning impairments in the UK continues to rise. Mainstream services are ill-equipped to provide individual services to parents who choose to define and address disability differently, and whose concerns and solutions may differ from the majority population, despite the fact that these parents possess many strengths and may present alternative ways of addressing their needs. This study aimed to provide a detailed account of the ways that Pakistani parents living in a northern city in the UK and caring for a child with a disability, account for and understand their child's disability. Sixteen in-depth interviews were carried out between October 2002 and July 2003, with Pakistani parents and one grandparent of children with a disability. All final transcripts were in English, and a thematic analysis was undertaken. Results include a detailed account of parents' understanding of the causes of their child's disability. All parents made reference to theological explanations as to why they had a child with a disability; however, most parents also gave biomedical or other explanations. The relationship between theological and biomedical explanations was explored along with the consequences of the different beliefs for individuals and families. Parents also spoke vividly about the impact of negative and stigmatizing beliefs about causes of disability which they felt were prevalent in the Pakistani community, and they used a biomedical discourse to refute these ideas. The authors suggest that knowledge of individual and family beliefs, and awareness of the impact of these beliefs, can provide a valuable conceptual lens for health and social care practitioners to use when working in family-centred, culturally congruent ways with parents.

Development and psychometric validation of the HIV Treatment Knowledge Scale.

Accurate treatment knowledge is required for patients to successfully manage complex medical conditions. Existing HIV knowledge scales focus on disease transmission and risk factors. This is the first study to develop and validate a scale to measure HIV treatment knowledge about complex treatment issues such as adherence, side-effects and drug resistance. A total of 346 participants were recruited into this cross-sectional study. Participants included HIV-positive patients (n=130), HIV-hepatitis C co-infected patients (n=22), hepatitis C patients, (n=78), community healthcare providers (n=35) and college students (n=81). Participants completed the proposed HIV Treatment Knowledge Scale and a validated measure of general knowledge about HIV transmission and risk factors. Two-week test-retest data were collected. Results demonstrated that the HIV Treatment Knowledge Scale was significantly correlated with general HIV knowledge across all samples. Among HIV-positive patients, the HIV Treatment Knowledge Scale was positively associated with time since HIV diagnosis. HAART-experienced patients had significantly higher treatment knowledge than HAART-naïve patients. HIV-positive patients scored significantly higher than hepatitis C patients and college students on HIV treatment knowledge. Test-retest reliability (r=0.83) and internal consistency (reliability coefficient=0.90) were both satisfactory. The HIV Treatment Knowledge Scale is a novel, easy-to-administer measure demonstrating high levels of validity and reliability. It has important applications as a clinical teaching tool with patients and healthcare workers and it could be used as an outcome indicator in HIV educational intervention studies.

Once-daily nevirapine dosing: a pharmacokinetics, efficacy and safety review.

In the context of attempts to simplify treatment regimens and enhance adherence, there is great interest in once-daily dosing regimens for the treatment of HIV-1 infection. Nevirapine has a long half-life and achieves high steady-state plasma concentrations relative to the concentration required to inhibit 50% viral replication in vitro (IC(50)) in patients. For this reason, it has been considered as a once-daily antiretroviral. Pharmacokinetic and efficacy data support the use of this dosing approach, but excess rash and lingering concerns over liver toxicity preclude use of once-daily dosed nevirapine at this time. Tolerance to high nevirapine concentrations may develop when dose escalation is used during initiation of therapy. It is theoretically possible that the benefits of once-daily dosing may be achieved without excess toxicity by switching to once-daily nevirapine following several months of twice-daily administration. This dosing strategy is currently under evaluation.

Evaluation of nevirapine-switch strategies for HIV treatment.

Despite the benefits of protease inhibitor (PI)-based HIV treatment, issues of tolerability, dosing frequency, pill count and long-term metabolic complications necessitate evaluation of alternate treatment strategies. The weight of evidence demonstrates that a switch from a PI-based regimen to one containing nevirapine can be accomplished safely while maintaining virological suppression. There is no immunological cost. There is probably an overall benefit in terms of the metabolic milieu.

The changing nature of work: workplace stress and strategies to deal with it.

Workplace stress is costing the developed and developing world roughly between 5-10% of Gross National Product per annum in sickness absence, premature retirement due to ill health and lost productive value in terms of services and products. In addition, it is costing the health services of countries an additional burden in terms of treatment and incapacity benefits. A three prong approach to stress management and prevention is provided, exploring primary interventions (risk assessment), secondary interventions (training and development) and tertiary interventions (stress counselling and support).

A randomized controlled psycho-education intervention trial: Improving psychological readiness for successful HIV medication adherence and reducing depression before initiating HAART.

The purpose of this study was to evaluate a novel psycho-educational intervention intended to increase patients' medication preparedness and treatment adherence skills before initiating highly active antiretroviral therapy (HAART). Sixty-three HIV-positive patients not currently on antiretroviral therapy participated in a randomized controlled trial of a standardized, four-session psycho-educational intervention (Supportive Therapy for Adherence to Antiretroviral Treatment; STAART). Session topics included learning techniques to increase medication adherence and learning effective strategies to cope with stress and depression. Patients completed psychological questionnaires assessing psychological readiness to initiate HAART and depressed mood. They completed both measures at study baseline and at four-weeks post-baseline. After controlling for baseline medication readiness scores, intervention patients (n = 30) reported significantly higher mean medication readiness following the STAART intervention (four-weeks post-baseline) (27.3+/-6.9) compared to controls (n = 33; 24.6+/-9.9; p < 0.05). Among depressed patients (n = 27), those receiving the intervention (n = 15) reported significantly lower mean depression scores at four-weeks post-baseline (22.5+/-12.9) compared to controls (n = 12; 27+/-9.9; p < 0.05). The STAART intervention enhanced HIV treatment readiness by better preparing patients prior to initiating HAART. It was also beneficial for reducing depressive symptoms in depressed, HIV-positive patients.

Fluarix, inactivated split-virus influenza vaccine.

Influenza is a potentially fatal respiratory infection resulting from several influenza virus strains. It causes annual epidemics of disease for which vaccination is the cornerstone of public health policy. The inadequacies of vaccine supply in the US during the 2004 influenza season revealed the deficiencies of current vaccine development and delivery. One outcome of this was the accelerated approval of an inactivated split-virus influenza vaccine, Fluarix. This paper reviews the immunogenicity and reactogenicity of this vaccine, and makes recommendations for the incorporation of Fluarix into the public health framework alongside other similar vaccines. Other directions to explore in an effort to secure future vaccine supply are considered.

Analytical and biological variables influencing quantitative hepatitis C virus (HCV) measurement in HIV-HCV coinfection.

The present review considers issues pertaining to the precision and variability of quantitative hepatitis C virus (HCV) measurement in general, outlines the characteristics of HCV RNA in HIV-HCV coinfection and evaluates those factors which may affect this measure. The clinical relevance of accurate HCV measurement in HIV-HCV coinfection is discussed.

Clinical outcomes of first antiretroviral regimen in HIV/hepatitis C virus co-infection.

OBJECTIVES: Despite the benefits of HAART, initiation of antiretroviral therapy in HIV-HCV co-infected patients is often delayed as a consequence of patient and physician concern pertaining to liver toxicity. It is unclear whether this is justified. METHODS: We retrospectively evaluated treatment duration and outcome in 186 patients initiating a first HAART regimen. RESULTS: Despite frequent HIV RNA suppression and CD4 T-cell increase following initiation of HAART, the median duration of therapy was only 8 months. Therapy was discontinued primarily for gastrointestinal intolerance (26%), poor adherence (19%), neurocognitive side effects (13%), and substance abuse (6%). Regimes were changed to reduce pill burden and/or frequency of dosing as well (11%). Only six (4%) subjects interrupted therapy as a result of clinically apparent liver toxicity. None were on low dose ritonavir-containing therapy. In those subjects remaining on HAART for at least 12 months, the median ALT level increased marginally from a baseline of 44 IU/mL to 56 IU/mL. The median AST was 44 IU/mL at baseline and at month 12. CONCLUSIONS: These results support our contention that regimen potency, durability, and extrahepatic side effect profile should remain the paramount considerations related to the selection of HAART regimen in HIV-HCV co-infection.

The relationship between job satisfaction and health: a meta-analysis.

BACKGROUND: A vast number of published studies have suggested a link between job satisfaction levels and health. The sizes of the relationships reported vary widely. Narrative overviews of this relationship have been published, but no systematic meta-analysis review has been conducted. METHODS: A systematic review and meta-analysis of 485 studies with a combined sample size of 267 995 individuals was conducted, evaluating the research evidence linking self-report measures of job satisfaction to measures of physical and mental wellbeing. RESULTS: The overall correlation combined across all health measures was r = 0.312 (0.370 after Schmidt-Hunter adjustment). Job satisfaction was most strongly associated with mental/psychological problems; strongest relationships were found for burnout (corrected r = 0.478), self-esteem(r = 0.429), depression (r = 0.428), and anxiety(r = 0.420). The correlation with subjective physical illness was more modest (r = 0.287). CONCLUSIONS: Correlations in excess of 0.3 are rare in this context. The relationships found suggest that job satisfaction level is an important factor influencing the health of workers. Organisations should include the development of stress management policies to identify and eradicate work practices that cause most job dissatisfaction as part of any exercise aimed at improving employee health. Occupational health clinicians should consider counselling employees diagnosed as having psychological problems to critically evaluate their work-and help them to explore ways of gaining greater satisfaction from this important aspect of their life.

CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study.

Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p<0.0001), most were reported to be of mild to moderate intensity regardless of group. In summary, CPG 7909 as an adjuvant to Engerix-B was well-tolerated and enhanced vaccine immunogenicity. CPG 7909 may allow the development of a two-dose prophylactic HBV vaccine.