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In this paper, we rigorously study the problem of cost optimisation of hybrid (mixed) institutional incentives, which are a plan of actions involving the use of reward and punishment by an external decision-maker, for maximising the level (or guaranteeing at least a certain level) of cooperative behaviour in a well-mixed, finite population of self-regarding individuals who interact via cooperation dilemmas (Donation Game or Public Goods Game). We show that a mixed incentive scheme can offer a more cost-efficient approach for providing incentives while ensuring the same level or standard of cooperation in the long-run. We establish the asymptotic behaviour (namely neutral drift, strong selection, and infinite-population limits). We prove the existence of a phase transition, obtaining the critical threshold of the strength of selection at which the monotonicity of the cost function changes and providing an algorithm for finding the optimal value of the individual incentive cost. Our analytical results are illustrated with numerical investigations. Overall, our analysis provides novel theoretical insights into the design of cost-efficient institutional incentive mechanisms for promoting the evolution of cooperation in stochastic systems. [ABSTRACT FROM AUTHOR]

We study the problem of Brownian motion in a multiscale potential. The potential is assumed to have N + 1 scales (i.e. N small scales and one macroscale) and to depend periodically on all the small scales. We show that for nonseparable potentials, i.e. potentials in which the microscales and the macroscale are fully coupled, the homogenized equation is an overdamped Langevin equation with multiplicative noise driven by the free energy, for which the detailed balance condition still holds. This means, in particular, that homogenized dynamics is reversible and that the coarse-grained Fokker–Planck equation is still a Wasserstein gradient flow with respect to the coarse-grained free energy. The calculation of the effective diffusion tensor requires the solution of a system of N coupled Poisson equations. [ABSTRACT FROM AUTHOR]

Rising ocean temperature is a major driver of kelp forest decline worldwide and one that threatens to intensify over the coming decades. What is not particularly well understood are the mechanisms that drive loss and how they operate at differing life stages. This study aimed to establish an understanding of the effects of increasing temperature on the early developmental stages of the giant kelp, Macrocystis pyrifera. Sporulation was carried out across 10 temperature treatments from 9.5 to 26.2°C ± 0.2°C at approximately 2°C intervals. Spores were then incubated at these temperatures under a 20.3±1.7 μmol photons m-2 s-1, 16L:8D photoperiod for 5 days. Results indicate that spore release was positively correlated with increasing temperature, whereas an inverse trend was observed between temperature and the growth of germ-tube. The thermal threshold for spore and germling development was determined to be between 21.7°C and 23.8°C. Spore settlement was the most drastically effected developmental phase by increasing temperature. This study highlights the vulnerability of early life stages of M. pyrifera development to rising ocean temperature and has implications for modelling future distribution of this valuable ecosystem engineer in a changing ocean. [ABSTRACT FROM AUTHOR]

Background/Objectives: Medication review is an important component of the management of older hospital patients. Deprescribing (supervised withdrawal of inappropriate medicines) is one outcome of review. This study aimed to iteratively develop and test the usability of deprescribing guides, which support multidisciplinary clinicians to reduce inappropriate polypharmacy in older inpatients. Methods: Deprescribing guides for hospital clinicians were developed using a novel mixed-methods, ten-step process. Iterative development and usability testing were applied. This included content development through review of the literature; expert consensus through five rounds of feedback using a modified Delphi approach; and usability testing by 16 multidisciplinary hospital clinicians on hypothetical clinical scenarios involving observations, semi-structured interviews, and administration of the System Usability Scale. Results: This novel process was used to develop deprescribing guides that facilitate implementation of evidence on deprescribing in routine hospital care. The guides present evidence-based information in a format that aligns with workflows of multidisciplinary hospital clinicians. The guides were adapted for various clinical roles to navigate efficiently to suit differing workflow needs. Guides include unique communication support in the form of "preferred language". Clinicians can use the "preferred language" to apply the evidence to the individual patient and relay decisions between health providers and with patients/carers. The total System Usability Scale score was 80.6 ± 2.0 (mean ± standard error of the mean), indicating excellent usability. Guides have been developed using consistent format for nine medication classes that are common targets for deprescribing and are publicly available. Conclusion: This study demonstrates a novel approach to the development and implementation of evidence-based recommendations that support deprescribing in routine hospital care. [ABSTRACT FROM AUTHOR]

We are interested in exploring interacting particle systems that can be seen as microscopic models for a particular structure of coupled transport flux arising when different populations are jointly evolving. The scenarios we have in mind are inspired by the dynamics of pedestrian flows in open spaces and are intimately connected to cross-diffusion and thermo-diffusion problems holding a variational structure. The tools we use include a suitable structure of the relative entropy controlling TV-norms, the construction of Lyapunov functionals and particular closed-form solutions to nonlinear transport equations, a hydrodynamics limiting procedure due to Philipowski, as well as the construction of numerical approximates to both the continuum limit problem in 2D and to the original interacting particle systems. [ABSTRACT FROM AUTHOR]

Background The overall survival (OS) analysis of the ICON7 trial demonstrated that frontline ovarian cancer patients with a high risk of progression (stage III suboptimally debulked, and stage III or IV with unresectable disease) benefited from the addition of bevacizumab to standard chemotherapy compared with standard chemotherapy alone. The objective of the present study was to investigate the cost-effectiveness, from a Canadian publicly funded perspective, of adding bevacizumab to frontline treatment of ovarian cancer at high risk of progression. Methods An area-under-the-curve, Markov-structured model was used to estimate the cost-effectiveness of the treatments. Long-term progression-free survival (PFS) and OS were extracted from the ICON7 trial (subgroup at high risk of relapse) and extrapolated by parametric time-to-event functions over a time horizon of 10 years. Canadian PFS health state utility values were obtained from the EQ-5D (EuroQoL Group, Rotterdam, Netherlands) questionnaires in the ICON7 high-risk patient population. Canadian post-progression utility values were consistent with those for other gynecologic cancers. Cost inputs were informed by public sources. An annual 5% efficacy and cost discount rate was applied. A probabilistic sensitivity analysis and one-way sensitivity analyses were conducted. Results Ovarian cancer patients at high risk of progression receiving bevacizumab plus standard chemotherapy experienced a mean incremental quality-adjusted life year (QALY) gain of 0.374 years. At an additional cost of $35,901.54, the incremental cost-effectiveness ratio (ICER) for the addition of bevacizumab to standard chemotherapy, relative to standard chemotherapy alone, was $95,942 per QALY. Conclusions No formal health technology assessment willingness-to-pay threshold exists in Canada. However, at a threshold of $100,000 per QALY, bevacizumab in addition to chemotherapy is a cost-effective alternative for ovarian cancer patients who are at high risk of progression (stage III suboptimally debulked, and stage III or IV with unresectable disease). Using the $100,000 per QALY threshold in a probabilistic sensitivity analysis, it was determined that, compared with standard chemotherapy, the addition of bevacizumab to chemotherapy is cost-effective in 56% of tested scenarios. [ABSTRACT FROM AUTHOR]

Background: The recently developed Context Assessment for Community Health (COACH) tool aims to measure aspects of the local healthcare context perceived to influence knowledge translation in low- and middleincome countries. The tool measures eight dimensions (organizational resources, community engagement, monitoring services for action, sources of knowledge, commitment to work, work culture, leadership, and informal payment) through 49 items. Objective: The study aimed to explore the understanding and stability of the COACH tool among health providers in Vietnam. Designs: To investigate the response process, think-aloud interviews were undertaken with five community health workers, six nurses and midwives, and five physicians. Identified problems were classified according to Conrad and Blair’s taxonomy and grouped according to an estimation of the magnitude of the problem’s effect on the response data. Further, the stability of the tool was examined using a testretest survey among 77 respondents. The reliability was analyzed for items (intraclass correlation coefficient (ICC) and percent agreement) and dimensions (ICC and BlandAltman plots). Results: In general, the think-aloud interviews revealed that the COACH tool was perceived as clear, well organized, and easy to answer. Most items were understood as intended. However, seven prominent problems in the items were identified and the content of three dimensions was perceived to be of a sensitive nature. In the testretest survey, two-thirds of the items and seven of eight dimensions were found to have an ICC agreement ranging from moderate to substantial (0.50.7), demonstrating that the instrument has an acceptable level of stability. Conclusions: This study provides evidence that the Vietnamese translation of the COACH tool is generally perceived to be clear and easy to understand and has acceptable stability. There is, however, a need to rephrase and add generic examples to clarify some items and to further review items with low ICC. [ABSTRACT FROM AUTHOR]

Background: In northern Vietnam the Neonatal health - Knowledge Into Practice (NeoKIP, Current Controlled Trials ISRCTN44599712) trial has evaluated facilitation as a knowledge translation intervention to improve neonatal survival. The results demonstrated that intervention sites, each having an assigned group including local stakeholders supported by a facilitator, lowered the neonatal mortality rate by 50% during the last intervention year compared with control sites. This process evaluation was conducted to identify and describe mechanisms of the NeoKIP intervention based on experiences of facilitators and intervention group members.Methods: Four focus group discussions (FGDs) were conducted with all facilitators at different occasions and 12 FGDs with 6 intervention groups at 2 occasions. Fifteen FGDs were audio recorded, transcribed verbatim, translated into English, and analysed using thematic analysis.Results: Four themes and 17 sub-themes emerged from the 3 FGDs with facilitators, and 5 themes and 18 sub-themes were identified from the 12 FGDs with the intervention groups mirroring the process of, and the barriers to, the intervention. Facilitators and intervention group members concurred that having groups representing various organisations was beneficial. Facilitators were considered important in assembling the groups. The facilitators functioned best if coming from the same geographical area as the groups and if they were able to come to terms with the chair of the groups. However, the facilitators' lack of health knowledge was regarded as a deficit for assisting the groups' assignments. FGD participants experienced the NeoKIP intervention to have impact on the knowledge and behaviour of both intervention group members and the general public, however, they found that the intervention was a slow and time-consuming process. Perceived facilitation barriers were lack of money, inadequate support, and the function of the intervention groups.Conclusions: This qualitative process evaluation contributes to explain the improved neonatal survival and why this occurred after a latent period in the NeoKIP project. The used knowledge translation intervention, where facilitators supported multi-stakeholder coalitions with the mandate to impact upon attitudes and behaviour in the communes, has low costs and potential for being scaled-up within existing healthcare systems. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of the study was to identify the most useful clinical criteria to measure effectiveness and adherence to antiretroviral treatment in a rural area of Cameroon. Patients and method: All patients under antiretroviral therapy followed for at least 3 months at the Tokombéré UPEC hospital were eligible. Therapeutic failure was defined according to clinical criteria including weight, Karnofsky''s index, or occurrence of WHO stage IV conditions. The criteria for drug adherence were based on patient statement (drugs taken over the last 4 days) and pharmacy-controlled drug delivery. Patient sociodemographic characteristics were collected via a questionnaire. Results: Fifty-six patients were included, most of whom were at AIDS stage on treatment initiation. The mean duration of antiretroviral therapy was 1year. 21, 10, and 19% of patients were in therapeutic failure according to “weight”, “Karnofsky''s index”, and “WHO stage IV”, respectively. Non-adherence was reported in 5% of patients according to the declarative method and 20% according to pharmacy controlled drug delivery. Weight modification during treatment was significantly correlated with the evolution of Karnofsky''s index (p =0.03). A significant correlation between therapeutic failure and non-observance was only found when using the weight criterion and the declarative method (p =0.004). Conclusion: The effectiveness and adherence to antiretroviral therapy can be evaluated by simple clinical criteria. Using these criteria can be recommended in rural areas until access to biological follow-up becomes available in developing countries. [Copyright &y& Elsevier]

Abstract: Objectives: The study''s objective was to evaluate with a standardized questionnaire the knowledge of healthcare workers (HCWs) regarding occupational vaccinations and their vaccination coverage. Population and Methods: This cross-sectional survey was conducted in the department of infectious diseases of a 1796 bed-teaching hospital in Dijon, France. Results: Fifty-seven (93%) out of 61 HCPs completed the questionnaire. Vaccination against HVB was the most frequently mentioned vaccination (79%), followed by BCG (66%), and combine vaccine against diphteria, tetanus, and polio (DTP) (66 %). Influenza was the most often quoted among recommended vaccinations (70%), followed by measles (61%), pertussis (39%), and varicella (14%). The number of correct answers was significantly correlated with age of participants, being a physician, and having had courses on vaccination. Almost all HCPs were up to date for mandatory vaccinations. In 2009 to 2010, vaccination rates against seasonal flu and H1N1 flu reached 88%. Only 52% of HCPs knew about their pertussis immunization and only a third of those born before 1980 had been tested for measles. Conclusions: HCPs knowledge of mandatory vaccinations is adequate but more limited for recommended vaccinations. Information on influenza vaccination has significantly improved its perception among HCPs resulting in a better adhesion to vaccination. [Copyright &y& Elsevier]

The preferences of the deer mouse (Peromyscus maniculatus (Wagner, 1845)), southern red-backed vole (Myodes gapperi (Vigors, 1830)), heather vole (Phenacomys intermedius Merriam, 1889), long-tailed vole (Microtus longicaudus (Merriam, 1888)), and meadow vole (Microtus pennsylvanicus (Ord, 1851)) for lodgepole pine (Pinus contorta Dougl. ex Loud.), white spruce (Picea glauca (Moench.) Voss), and subalpine fir (Abies lasiocarpa (Hook.) Nutt.) seeds were investigated using cafeteria-style feeding experiments. Seed selection by P. maniculatus and M. gapperi in the field was also studied. Peromyscus maniculatus, M. gapperi, M. longicaudus, and M. pennsylvanicus showed a distinct preference for lodgepole pine seeds and avoidance of subalpine fir seeds, and consumed the different species of seeds in similar relative proportions. Phenacomys intermedius behaved very differently from the other rodent species in that it did not show a preference among seed species, and consumed very few seeds in total. Findings from the field seed selection trials were consistent with laboratory results. We suggest that postdispersal seed predation by small mammals could limit the recruitment success of lodgepole pine and white spruce, but would not be a major problem in the regeneration of subalpine fir stands. This could provide an advantage for subalpine fir over neighbouring competitive species. [ABSTRACT FROM AUTHOR]

Background: IVX-0142 is a heparin-derived hypersulfated disaccharide devoid of anticoagulant activity while possessing anti-allergic and anti-inflammatory activity in preclinical studies. In a proof-of-concept study, the allergen inhalation challenge model was used to investigate the effect of IVX-0142 in mild atopic asthma. Methods: Nineteen subjects, not on controller medications, were randomized to an evaluator-blind, placebo-controlled, cross-over study. The effect of a single nebulized dose of IVX-0142 (80 mg) or placebo administered 30 min prior to allergen inhalation was evaluated on the allergic airway responses, airway responsiveness, and airway inflammation. Results: When compared with placebo, 14 and 13 subjects experienced a relatively smaller maximum fall in forced expiratory volume in 1 s (maxFEV1%) for the early airway response (EAR) and late airway response (LAR) with IVX-0142, respectively ( P < 0.01). The degree of attenuation in the EAR [maxFEV1% (mean ± SE) 26.5 ± 2.8% vs placebo 31.0 ± 2.8%, P = 0.059] and LAR (15.6 ± 2.9% vs placebo 19.0 ± 2.9%, P = 0.24) with IVX-0142, however, was small and did not reach statistical significance compared with placebo. Similarly, a trend in the attenuation of allergen-induced increase in the absolute sputum cell counts was also observed. No difference in the allergen-induced increase in airway hyper-responsiveness and exhaled nitric oxide was noticed. Conclusions: The majority of mild atopic asthmatics demonstrated a reduction in the EAR and LAR to IVX-0142. However, the treatment effect observed with a single prechallenge dose of IVX-0142 was small and heterogeneous. The potential anti-allergic and anti-inflammatory effects using multiple higher doses need to be evaluated. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance spectroscopic imaging (1H-MRSI) was used to study metabolic abnormalities inside the gray matter (GM) during or distant to white matter (WM) inflammatory processes reflected by T1 gadolinium-enhancing lesions in patients at the very early stage of multiple sclerosis (MS). The spectroscopic examination was performed in the axial plane using a home-designed acquisition-weighted, hamming shape, 2D-SE pulse sequence (TE = 135 ms; TR = 1,600 ms). Bilateral thalami and the medial occipital cortex were explored in 35 patients (15 with and 20 without T1-Gd enhancing lesions) with clinically isolated syndrome suggestive of MS and in 30 controls. The mean duration since the first presenting symptom was 9.1 (±6.7) months. The two groups of patients (with or without T1 Gd-enhancing lesions) did not differ in terms of time elapsed since the first clinical onset and T2 lesion load. The spatial contamination of surrounding WM tissues was obtained in each GM region by determining the tissue component in the ROI from GM and WM probability maps smoothed with the point spread function of the MRSI acquisition. Contribution of WM signal was important (60%) inside thalami while the region centered on the medial occipital cortex was well representative of GM metabolism (>70%). Comparisons of relative metabolite levels (ratios of each metabolite over the sum of all metabolites) between all patients and controls showed significant decrease in relative N-acetyl aspartate (NAA) levels, increase in relative choline-containing compounds (Cho) levels and no change in relative creatine/phosphocreatine levels inside the three ROIs. Decrease in relative NAA levels and increase in relative Cho levels were found in patients with inflammatory activity, while no metabolic alterations were present in patients without T1 Gd-enhancing lesions. These results suggest that abnormalities in GM metabolism observed in patients at the very early stage of MS are mainly related to neuronal dysfunction occurring during acute inflammatory processes. [ABSTRACT FROM AUTHOR]

Background Inhibition of DNA polymerase γ by nucleoside reverse transcriptase inhibitors (NRTIs) can cause mitochondrial dysfunction and cellular toxicity. Hyperlactataemia, which is a consequence of a shift in the metabolism of pyruvate, is an indicator of nucleoside-related mitochondrial toxicity. Methods We evaluated exercise and oxidative capacities as well as circulatory and ventilatory responses to exercise in 24 HIV-infected patients on NRTIs presenting hyperlactataemia [mean (±standard deviation) fasted lactate=3.5±1.1 mmol/L]; 27 NRTI-treated patients with normal baseline lactate concentrations were used as controls (mean fasted lactate=1.6±0.3 mmol/L). Results In the patients with hyperlactataemia, the average peak work capacity (1.7±0.6 W/kg) and peak oxygen consumption (VO2) (21±4 mL/kg/min) were significantly lower ( P<0.01) than in control subjects (work, 2.1±0.4 W/kg; VO2, 25±4 mL/kg/min). The capacity to increase oxygen extraction during exercise was significantly diminished in the hyperlactataemia group, as shown by a low peak systemic arteriovenous oxygen difference (a-vO2) difference compared with controls (11±3 vs 14±3 mL/dL; P=0.008), and as indicated by a linear correlation between VO2 and systemic a-vO2 difference ( r2=0.76). During exercise, the increases in cardiac output relative to VO2 (mean Δ cardiac output (Q)/ΔVO2=8±3.6) and ventilation (mean Δ ventilation (VE)/ΔVO2=48.6±13.2) were significantly higher in hyperlactataemia patients compared with controls (mean cardiac output Δ(Q)/ΔVO2=6±2; mean ΔVE/ΔVO2=42±12.7; P=0.03). Conclusions The degree of exercise limitation in patients with nucleoside-related mitochondrial toxicity correlates directly with the severity of impaired muscle oxidative phosphorylation, as indicated by the capacity for muscle oxygen extraction. Exaggerated circulatory and ventilatory responses to exercise are direct consequences of the level of impaired muscle oxidative phosphorylation. [ABSTRACT FROM AUTHOR]

Background: Ciclesonide exhibits clinical efficacy at 160 μg (ex-actuator) once daily but the anti-inflammatory effects at this dose are not known. We wished to know whether 4 weeks therapy with ciclesonide pMDI 160 μg once daily in the morning exhibited significant anti-inflammatory effects. Methods: Seventeen patients with mild persistent asthma (FEV1 3.35 l) were recruited into a double-blind placebo-controlled randomized crossover study. Measurements were made after ciclesonide and placebo treatment as well as after run-in and washout periods, for adenosine monophosphate (AMP) bronchial challenge (primary variable), exhaled nitric oxide (NO) and induced sputum (in a subgroup). Results: The mean (SEM) AMP bronchial challenge PC20 following ciclesonide (140 (63) mg/ml) was significantly ( P < 0.001) increased compared with placebo (17 (8) mg/ml), run-in (13 (5) mg/ml) and washout (9 (3) mg/ml) periods. This amounted to an eightfold (CI: 5.3–12.0) for ciclesonide vs placebo. Likewise, there were significant improvements in exhaled NO levels and a significant reduction in induced sputum eosinophil cell counts. Conclusion: We have shown that inhaled ciclesonide given at 160 μg once daily in the morning exhibits significant anti-inflammatory effects that are in keeping with the previously described clinical effects. [ABSTRACT FROM AUTHOR]

To evaluate the effect of a single nasal allergen challenge on peripheral blood eosinophil/basophil (Eo/B) progenitor cells and induced sputum eosinophil counts in subjects with allergic rhinitis.Sixteen adults entered a sequential nasal control and allergen challenge study, outside the pollen season. Blind assessment of peripheral blood Eo/B progenitor colony forming units (CFU), induced sputum and nasal lavage cell counts was made before and 24 h after both challenges. Subjects recorded their rhinitis symptoms and nasal peak inspiratory flow, hourly at home, following both challenges.When comparing the values 24 h after the control vs. the allergen challenge, there were no significant differences in Eo/B progenitor CFU (control (mean, SD): 3.6 (1.0)/106 cells; allergen: 4.4 (1.1)/106 cells) or sputum eosinophils (control (median, inter-quartile range): 1.0 (0.3–1.7)%; allergen: 0.7 (0.0–1.3)%) despite a significant increase in the percentage (median (inter-quartile range) of eosinophils in nasal lavage (control: 0.6 (0.1–0.9)%; allergen; 1.9 (0.9–8.1)% and significant worsening of nasal peak inspiratory flow and rhinitis symptoms.Despite a significant increase in nasal symptoms and lavage eosinophil counts, a single nasal allergen challenge was not sufficient to elicit a measurable haemopoietic response in circulation, or an increase in sputum eosinophil counts. [ABSTRACT FROM AUTHOR]

In the context of HIV infection and antiretroviral therapy, adiponectin concentrations have been shown to be related to lipodystrophy, metabolic alterations and HIV-protease inhibitor (PI) use. The replacement of PI by nevirapine has improved the lipid profile of patients under antiretroviral therapy. The aim of the present study was to examine whether adiponectin concentration or insulin sensitivity level correlate with the modifications of lipid parameters after the switch of PI by nevirapine. The evolution of metabolic parameters before and after 6 months of substitution of nevirapine for protease inhibitors was evaluated in a cohort of 55 HIV-1 infected patients. Adiponectin concentration, insulin sensitivity, lipid profile, cholesterol ester transfer protein (CETP) mass concentration and triglyceride enrichment of HDL were determined before and after the replacement of PI by nevirapine. Insulin sensitivity was evaluated by the HOMA model assessment. Twenty-four weeks of treatment with nevirapine improved significantly the lipid profile with a significant reduction of apoB (from 0·98 to 0·92 g L−1; P = 0·005) and triglyceride (from 2·02 to 1·66 mmol L−1; P = 0·02). HDL cholesterol and apoA1 increased significantly (from 0·99 to 1·19 mmol L−1; P = 0·001 and from 1·40 to 1·57 g L−1; P < 0·001, respectively). The triglyceride enrichment of HDL significantly decreased after the replacement of PI by nevirapine (from 0·248 ± 0·092 to 0·213 ± 0·093; P = 0·003). At baseline, and after 24 weeks of nevirapine treatment, we observed significant correlations between adiponectin level and lipid parameters [(HDL-cholesterol ( r = 0·66, P = 0·001 and r = 0·69, P = 0·001); triglycerides ( r = −0·42, P = 0·002 and r  =−0·57, P = 0·001), and triglyceride enrichment of HDL ( r = −0·43, P = 0·005 and r = −0·53, P = 0·005)]. Twenty-four weeks of treatment with nevirapine did not significantly change adiponectin concentrations (from 984 to 1086 µg L−1, P = 0·22), CETP mass and insulin sensitivity. This study shows that even though a strong correlation was found between adiponectin and some metabolic parameters at baseline and after 24 weeks of treatment by nevirapine, the improvement of lipid profile observed after the replacement of PI by nevirapine was not in relation to the change of plasma adiponectin concentration. The significant decrease of triglyceride enrichment of HDL after the replacement of PI by nevirapine probably leads to a decreased catabolism of HDL lipoprotein, and consequently explains the increase of plasma HDL concentration observed in this study. Eur J Clin Invest 2004; 34 (8): 569–575 [ABSTRACT FROM AUTHOR]

There is a growing concern about an increased risk for cardiovascular disease in HIV infected patients receiving antiretroviral therapy (ART). This risk could be related to metabolic abnormalities associated with long-term use of antiretroviral drugs. In fact, well recognized cardiovascular risk factors such as hypertension, dyslipidaemia, diabetes mellitus and central fat deposition are increasingly seen in HIV patients on ART. These factors can also be associated with non reversible risk factors, such as male sex, age greater than 40 years and family history of premature coronary artery disease. In addition, cigarette smoking and sedentary lifestyle may predispose these patients to significant cardiovascular disease. A direct atherogenic effect of HIV infection itself or antiretroviral drugs is unlikely. Epidemiological studies have suggested an increased risk for coronary artery disease in HIV infected persons; nevertheless, only long term follow-up could confirm this statement. Despite these uncertainties, it seems reasonable to identify and manage cardiovascular risk factors in HIV infected patients. [Copyright &y& Elsevier]

Background Abnormalities in lipid levels and lipodystrophy (LD) have been commonly reported after commencement of highly active antiretroviral therapy (HAART). A major mechanism by which plasma low-density lipoprotein (LDL) cholesterol levels may be influenced is via the regulation of hepatic LDL receptor expression. The activity of LDL receptors is under hormonal control. Moreover, HIV infection and HAART are associated with important modifications of hormonal status. As the cause of these adverse reactions is unknown, the effects of HAART and lipodystrophy on LDL receptors were evaluated. Materials and methods Thirty-nine HIV treated patients (21 with a protease inhibitor (PI) containing regimen, 18 without PI use) and 22 control subjects were tested for insulin resistance (HOMA model assessment), lipid profile, serum concentration of dehydroepiandrosterone (DHEA) and LDL-R expression. LDL-R on mononuclear cells were quantified by flow cytrometry. Results Among the 39 HIV infected patients, 14 patients had a lipodystrophy (LD). Patients with LD had significantly higher levels of triglyceride (TG) and insulin resistance compared to patients without LD. There was no significant difference in LDL-R count between patients with or without PI use. In contrast, LDL-R count was significantly lower in patients with LD compared with those without (8504 ± 3901 vs. 13 200 ± 4532, P= 0.001). There was no difference in LDL-R count between patients without LD and control subjects. Patients with LD had lower levels of DHEA compared to patients without LD. In HIV-infected patients, we found a significant correlation between LDL-R expression and TG (r = -0·32; P= 0·04) and LDL cholesterol (r=-0·33; P= 0·04). In contrast, we did not observe a correlation between DHEA level and LDL-R count or LDL cholesterol level. Conclusions HIV-lipodystrophy is associated with a lower expression of LDL-R. This decreased expression of LDL-R seems... [ABSTRACT FROM AUTHOR]

The prevalence of silent myocardial ischemia (SMI) and the factors associated with SMI were evaluated in patients infected with human immunodeficiency virus (HIV) who had been receiving highly active antiretroviral therapy (HAART) for ≥ 12 months and did not have known coronary artery disease or cardiac symptoms. Patients prospectively underwent exercise stress testing. The prevalence of SMI was 11% (11 of 99 patients). Patients who had SMI were significantly older than were patients who did not ( mean ± SD, 51 ± 8 years vs. 42 ± 9 years; P=0.001) and were more likely to have trunk obesity (54% of patients vs. 17%; ). A significant correlation was found between a positive exercise test result and obesity (correlation, .006), waist-to- hip ratio (.007), and glucose and cholesterol levels (.04; p=.03 ). In multivariate analysis, age, central fat accumulation, and cholesterol level were independent variables associated with the detection of SMI. Exer-cise testing might be recommended for patients with HIV who have central fat accumulation and hyper-cholesterolemia. [ABSTRACT FROM AUTHOR]

Presents research which examined optimal CO2-emission abatement paths for specified long-term constraints on atmospheric CO2 concentrations. Interplay of uncertainty in concentrations and inertia in energy systems producing CO2 emissions; Integrated assessment models; Costs of deferring abatement; Minimizing risk to environmental and economic systems. INSET: Box 1 DIAM: A model of the dynamics of inertia...

Background: The gap between what is known and what is practiced results in health service users not benefitting from advances in healthcare, and in unnecessary costs. A supportive context is considered a key element for successful implementation of evidence-based practices (EBP). There were no tools available for the systematic mapping of aspects of organizational context influencing the implementation of EBPs in low- and middle-income countries (LMICs). Thus, this project aimed to develop and psychometrically validate a tool for this purpose.Methods: The development of the Context Assessment for Community Health (COACH) tool was premised on the context dimension in the Promoting Action on Research Implementation in Health Services framework, and is a derivative product of the Alberta Context Tool. Its development was undertaken in Bangladesh, Vietnam, Uganda, South Africa and Nicaragua in six phases: (1) defining dimensions and draft tool development, (2) content validity amongst in-country expert panels, (3) content validity amongst international experts, (4) response process validity, (5) translation and (6) evaluation of psychometric properties amongst 690 health workers in the five countries.Results: The tool was validated for use amongst physicians, nurse/midwives and community health workers. The six phases of development resulted in a good fit between the theoretical dimensions of the COACH tool and its psychometric properties. The tool has 49 items measuring eight aspects of context: Resources, Community engagement, Commitment to work, Informal payment, Leadership, Work culture, Monitoring services for action and Sources of knowledge.Conclusions: Aspects of organizational context that were identified as influencing the implementation of EBPs in high-income settings were also found to be relevant in LMICs. However, there were additional aspects of context of relevance in LMICs specifically Resources, Community engagement, Commitment to work and Informal payment. Use of the COACH tool will allow for systematic description of the local healthcare context prior implementing healthcare interventions to allow for tailoring implementation strategies or as part of the evaluation of implementing healthcare interventions and thus allow for deeper insights into the process of implementing EBPs in LMICs. [ABSTRACT FROM AUTHOR]

Background: In Vietnam, four or more antenatal care (ANC4+) visits/services among pregnant women have not been officially reported in the health system. Moreover, the factors associated with the use of ANC4+ services have not been studied in previous studies. In this study, we conducted an exploratory analysis to identify the rate of utilization of ANC4+ services and factors associated with use of ANC4+ services among pregnant women in rural areas of Vietnam. Methods: The study was conducted in eight provinces in the South Central Coast region of Vietnam between August 2013 and May 2014. A total of 907 women, who delivered in the past 1 year, participated in the study. Multivariate logistic regression model was used to examine the association between all potential factors and utilization of ANC4+ services. Results: The rate of utilization of ANC4+ services by women in eight South Central Coast provinces was 53.9%. Factors negatively associated with using ANC4+ services were belonging to ethnic minority groups having lower education, doing informal works, having lower income, having lower knowledge on ANC4+ services, and receiving no financial support from the husband. In particular, financial support from the husband was considered important in improving the use of ANC4+ services by women in rural areas. Conclusion: The study asserted an inadequacy for ANC4+ utilization and can contribute to missed opportunities to achieve better maternal outcomes for women in rural areas of Vietnam. The necessity of introducing ANC4+ services in the national guidelines on maternal health care should be disseminated to health policy-makers. Strategies to increase ANC4+ utilization should focus on knowledge improvement and on poor, low-income, and ethnic minority women. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (FMRI) studies have established that patients with multiple sclerosis show stronger activation in the lateral prefrontal cortices (LPFC) than healthy control subjects during effortful cognitive tasks. The aim of the present study was to assess the impact of these activation changes on cognitive performances. In addition to 19 controls, who were tested at a single timepoint to define a standard pattern of fMRI activation during the performance of the Paced Auditory Serial Addition Task (PASAT), 13 patients with clinically isolated syndrome underwent a longitudinal fMRI examination while performing the PASAT at the beginning of the study (M0) and one year later (M12). Relative to the M0 scores, PASAT performances improved in eight patients (group A) and either decreased (n = 4) or remained unchanged (n = 1) (group B) in five patients at M12. Random effect analyses (SPM2; Wellcome Institute, London, England) were performed to compare intra-group time-related effects on brain activation (paired t-test between M0 and M12), and inter-group differences were also compared between the two groups of patients (analysis of covariance with PASAT performances as the covariate). Relative to group B, group A showed larger increase in activation between M0 and M12 in the right LPFC. In the whole group of patients, interaction analyses showed that the differences in the PASAT scores between M0 and M12 were correlated with the differences in activation observed in the right LPFC. This longitudinal study shows that in patients with early multiple sclerosis, the increased levels of activation in the right LPFC was associated with improved individual working memory and processing speed performances. [ABSTRACT FROM AUTHOR]

Background:  Dendritic cells are key contributors to initiation and maintenance of T-cell immunity to inhaled allergen. The purpose of this study was to enumerate the changes in peripheral blood myeloid (mDCs) and plasmacytoid dendritic cells (pDCs), the DCs expressing chemokine receptor 6 (CCR6) and chemokine receptor 7 (CCR7), following diluent and allergen inhalation in asthmatic subjects. Methods:  Peripheral blood was obtained from 16 allergic asthmatic subjects before and at 0.5, 1, 2, 3, 4, 6, 24, and 48 h after inhaled diluent and allergen challenges. Dendritic cells were enumerated using flow cytometry. Results:  Allergen inhalation significantly reduced mDCs at 6 h (21.3 ± 2.0 vs 15.0 ± 1.8/μl blood; P < 0.05) and 24 h (21.5 ± 3.4 vs 16.4 ± 2.4/μl blood; P < 0.05) after challenge. Circulating pDCs were significantly lower than baseline up to 24 h after both allergen and diluent challenges. There was a significant efflux of CCR6+ mDCs from peripheral blood at 6 h and CCR6+ pDCs at 4 h after allergen challenge, when compared with diluent. There was no difference in the number of circulating CCR7+ mDCs or pDCs after diluent or allergen challenges. Conclusions:  Peripheral blood mDCs and CCR6+ mDCs, but not pDCs, are reduced up to 24 h after allergen inhalation. Thus, allergen inhalation causes trafficking of immature CCR6+ DCs from blood into the airway, while that of the trafficking of the mature CCR7+ DCs from the airways into the regional lymph nodes probably occurs through the lymphatic system. [ABSTRACT FROM AUTHOR]

• Antibiotics were prescribed to may patients with coronavirus disease 2019 during the first wave of the pandemic. • Bacterial co-infection seems to be rare, especially in patients who do not require transfer to an intensive care unit. • This study investigated the role of antibiotic therapy and its impact on prognosis. • Patients with more severe infection were often prescribed antibiotic therapy, but this had no impact on prognosis. • Antibiotic therapy should not be widely prescribed. Debate continues regarding the usefulness and benefits of wide prescription of antibiotics in patients hospitalized with coronavirus disease 2019 (COVID-19). All patients hospitalized in the Infectious Diseases Department, Dijon University Hospital, Dijon, France between 27 February and 30 April 2020 with confirmed COVID-19 were included in this study. Clinical, biological and radiological data were collected, as well as treatment and outcome data. An unfavourable outcome was defined as death or transfer to the intensive care unit. Patient characteristics and outcomes were compared between patients who did and did not receive antibiotic therapy using propensity score matching. Among the 222 patients included, 174 (78%) received antibiotic therapy. The univariate analysis showed that patients who received antibiotic therapy were significantly older, frailer and had more severe presentation at admission compared with patients who did not receive antibiotic therapy. Unfavourable outcomes were more common in patients who received antibiotic therapy [hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.07–8.11; P = 0.04]. Multi-variate analysis and propensity score matching indicated that antibiotic therapy was not significantly associated with outcome (HR 1.612, 95% CI 0.562–4.629; P = 0.37). Antibiotics were frequently prescribed in this study and this was associated with more severe presentation at admission. However, antibiotic therapy was not associated with outcome, even after adjustment. In line with recent publications, such data support the need to streamline antibiotic therapy in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Following the implementation of strict, coordinated animal health measures in the 1950s, France was officially declared free of bovine tuberculosis (bovine TB, bTB) in 2001 [1]. • the social representation of tuberculosis is still widespread and infection with M. bovis is commonly inappropriately confused by patients and their entourage with M. tuberculosis infection. Via a letter hand-delivered to each worker, the OP informs the worker's general practitioner of the actions taken, and if necessary of screening test results. [Extracted from the article]

Background: Annually, 2.8 million neonatal deaths occur worldwide, despite the fact that three-quarters of them could be prevented if available evidence-based interventions were used. Facilitation of community groups has been recognized as a promising method to translate knowledge into practice. In northern Vietnam, the Neonatal Health - Knowledge Into Practice trial evaluated facilitation of community groups (2008-2011) and succeeded in reducing the neonatal mortality rate (adjusted odds ratio, 0.51; 95 % confidence interval 0.30-0.89). The aim of this paper is to report on the process (implementation and mechanism of impact) of this intervention.Methods: Process data were excerpted from diary information from meetings with facilitators and intervention groups, and from supervisor records of monthly meetings with facilitators. Data were analyzed using descriptive statistics. An evaluation including attributes and skills of facilitators (e.g., group management, communication, and commitment) was performed at the end of the intervention using a six-item instrument. Odds ratios were analyzed, adjusted for cluster randomization using general linear mixed models.Results: To ensure eight active facilitators over 3 years, 11 Women's Union representatives were recruited and trained. Of the 44 intervention groups, composed of health staff and commune stakeholders, 43 completed their activities until the end of the study. In total, 95 % (n = 1508) of the intended monthly meetings with an intervention group and a facilitator were conducted. The overall attendance of intervention group members was 86 %. The groups identified 32 unique problems and implemented 39 unique actions. The identified problems targeted health issues concerning both women and neonates. Actions implemented were mainly communication activities. Communes supported by a group with a facilitator who was rated high on attributes and skills (n = 27) had lower odds of neonatal mortality (odds ratio, 0.37; 95 % confidence interval, 0.19-0.73) than control communes (n = 46).Conclusions: This evaluation identified several factors that might have influenced the outcomes of the trial: continuity of intervention groups' work, adequate attributes and skills of facilitators, and targeting problems along a continuum of care. Such factors are important to consider in scaling-up efforts.Trial Registration: ISRCTN ISRCTN44599712 . [ABSTRACT FROM AUTHOR]

Background: In almost 30 years since economic reforms or 'renovation' (Doimoi) were launched, Vietnam has achieved remarkably good health results, in many cases matching those in much higher income countries. This study explores the contribution made by Universal Health Insurance (UHI) policies, focusing on the past 15 years. We conducted a mixed method study to describe and assess the policy process relating to health insurance, from agenda setting through implementation and evaluation. Design: The qualitative research methods implemented in this study were 30 in-depth interviews, 4 focus group discussions, expert consultancy, and 420 secondary data review. The data were analyzed by NVivo 7.0. Results: Health insurance in Vietnam was introduced in 1992 and has been elaborated over a 20-year time frame. These processes relate to moving from a contingent to a gradually expanded target population, expanding the scope of the benefit package, and reducing the financial contribution from the insured. The target groups expanded to include 66.8% of the population by 2012. We characterized the policy process relating to UHI as incremental with a learning-by-doing approach, with an emphasis on increasing coverage rather than ensuring a basic service package and financial protection. There was limited involvement of civil society organizations and users in all policy processes. Intertwined political economy factors influenced the policy processes. Conclusions: Incremental policy processes, characterized by a learning-by-doing approach, is appropriate for countries attempting to introduce new health institutions, such as health insurance in Vietnam. Vietnam should continue to mobilize resources in sustainable and viable ways to support the target groups. The country should also adopt a multi-pronged approach to achieving universal access to health services, beyond health insurance. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Informal consultations for advice in the infectious diseases department (IDD) induce a significant workload for physicians. Our aim was to retrospectively quantify and describe this activity in our institution. Method: The data was obtained from files documented and faxed by physicians from October 2009 to May 2012. One thousand nine hundred and seventy-two files were included. The file was faxed to the IDD specialist, analyzed, then a telephone conversation allowed making precisions, and the documented form was faxed back. Results: The requests for advice concerned 39% of female and 61% of male patients with a mean age of 64±21 years. Twenty-nine percent of requests came from surgical departments and 71% from medical departments (P <0.01). The departments most frequently concerned were cardiology (10%), gastro-enterology (10%) and cardiovascular surgery (9.7%). The most frequent infections were urogenital (19%), osteoarticular (14%), and cardiovascular (11%). Forty-nine percent were considered as nosocomial and 25.3% were bacteremic. The requests concerned diagnostic aid in 16.2% of cases and therapeutic issues in 95.6%. The IDD specialist made therapeutic recommendation in 96.5% of cases and gave diagnostic advice in 43.7%. Treatment modification was suggested in 38.5% of cases. Twenty-two percent of consultations required a second one. Conclusion: This study documented the importance of antibiotic changes among medical and surgical units, the increasing need of these units to be helped, and also the complexity of the medical cases, all requiring the advice of an ID specialist. Our fax-phone-fax procedure seems to prevent the bias associated with informal consultations by phone, which is the most commonly used in other institutions. [Copyright &y& Elsevier]

Background: In almost 30 years since economic reforms or ‘renovation’ (Doimoi) were launched, Vietnam has achieved remarkably good health results, in many cases matching those in much higher income countries. This study explores the contribution made by Universal Health Insurance (UHI) policies, focusing on the past 15 years. We conducted a mixed method study to describe and assess the policy process relating to health insurance, from agenda setting through implementation and evaluation. Design: The qualitative research methods implemented in this study were 30 in-depth interviews, 4 focus group discussions, expert consultancy, and 420 secondary data review. The data were analyzed by NVivo 7.0. Results: Health insurance in Vietnam was introduced in 1992 and has been elaborated over a 20-year time frame. These processes relate to moving from a contingent to a gradually expanded target population, expanding the scope of the benefit package, and reducing the financial contribution from the insured. The target groups expanded to include 66.8% of the population by 2012. We characterized the policy process relating to UHI as incremental with a learning-by-doing approach, with an emphasis on increasing coverage rather than ensuring a basic service package and financial protection. There was limited involvement of civil society organizations and users in all policy processes. Intertwined political economy factors influenced the policy processes. Conclusions: Incremental policy processes, characterized by a learning-by-doing approach, is appropriate for countries attempting to introduce new health institutions, such as health insurance in Vietnam. Vietnam should continue to mobilize resources in sustainable and viable ways to support the target groups. The country should also adopt a multi-pronged approach to achieving universal access to health services, beyond health insurance. [ABSTRACT FROM AUTHOR]