Quantifying the gap between policy and practice in cardiovascular risk reduction: a review of evidence from recent cardiovascular and diabetes audits in the UK

As part of CHD NSF implementation, a pilot project is being undertaken under the auspices of the National Screening Committee to test the practical implications and outcomes of implementing a systematic programme of cardiovascular risk reduction in primary care, initially identifying those at high risk due to pre-existing cardiovascular disease or diabetes. To assist in assessing the magnitude of the challenge faced by the pilot programmes, the UK National Screening Committee (NSC) commissioned a review of current practice based on recent cardiovascular and diabetes audits in the UK. This report details the findings of the review, providing 6 key recommendations for future cardiovascular audits.

The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model.

OBJECTIVES: To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths. DESIGN: Decision modelling using Markov chains compared costs and effects over 5 years. SETTING: The analysis was from the perspective of the National Health Service (NHS) in England and Wales. PARTICIPANTS: The model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment. DATA SOURCES: We modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources. MAIN OUTCOME MEASURES: We measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided. RESULTS: Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20,000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100,000 patients compared to psychosocial support alone over the course of 5 years. CONCLUSIONS: Nalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits. TRIAL REGISTRATION NUMBERS: This cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941).

Reduction of alcohol consumption by brief alcohol intervention in primary care: systematic review and meta-analysis.

BACKGROUND: Numerous trials of the efficacy of brief alcohol intervention have been conducted in various settings among individuals with a wide range of alcohol disorders. Nevertheless, the efficacy of the intervention is likely to be influenced by the context. We evaluated the evidence of efficacy of brief alcohol interventions aimed at reducing long-term alcohol use and related harm in individuals attending primary care facilities but not seeking help for alcohol-related problems. METHODS: We selected randomized trials reporting at least 1 outcome related to alcohol consumption conducted in outpatients who were actively attending primary care centers or seeing providers. Data sources were the Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of retrieved references and previous reviews. Study selection and data abstraction were performed independently and in duplicate. We assessed the validity of the studies and performed a meta-analysis of studies reporting alcohol consumption at 6 or 12 months of follow-up. RESULTS: We examined 19 trials that included 5639 individuals. Seventeen trials reported a measure of alcohol consumption, of which 8 reported a significant effect of intervention. The adjusted intention-to-treat analysis showed a mean pooled difference of -38 g of ethanol (approximately 4 drinks) per week (95% confidence interval, -51 to -24 g/wk) in favor of the brief alcohol intervention group. Evidence of other outcome measures was inconclusive. CONCLUSION: Focusing on patients in primary care, our systematic review and meta-analysis indicated that brief alcohol intervention is effective in reducing alcohol consumption at 6 and 12 months.

Molecular detection of human astrovirus in an urban sewage treatment plant in Rio de Janeiro, Brazil

The objective of this study was to evaluate the prevalence and dissemination of human astroviruses (HAstV) in the environment by analyzing urban sewage samples from a wastewater treatment plant in the city of Rio de Janeiro, Brazil. A one-year study was performed with a total of 48 raw and treated sewage composite samples, which were collected biweekly from an activated sludge plant. Virus particles were concentrated by the adsorption-elution method using negatively charged membranes associated to a Centriprep Concentrator® 50 (Nihon Millipore). HAstV were detected in 16.7% of the samples in raw and treated sewage by using both qualitative and quantitative reverse transcriptase-polymerase chain reactions (RT-PCR and qPCR, respectively). Positive untreated sewage sample exhibited mean values of 1.1 x 10(4) gEq/mL. The qPCR sensitivity was 18 gEq/reaction. Through utilization of qPCR, a HAstV recovery efficiency of 4.2% and 4.3% was demonstrated for raw and treated sewage samples, respectively. The presence of HAstV in both the raw and treated sewage samples demonstrated the dissemination of these viruses in the environment as well as viral permanence after sewage treatment. There was a reduction in the total and faecal coliform levels, indicating efficiency of the wastewater treatment plant.

Comparative study of two extraction methods for enteric virus recovery from sewage sludge by molecular methods

The aim of this study was to compare two nucleic acid extraction methods for the recovery of enteric viruses from activated sludge. Test samples were inoculated with human adenovirus (AdV), hepatitis A virus (HAV), poliovirus (PV) and rotavirus (RV) and were then processed by an adsorption-elution-precipitation method. Two extraction methods were used: an organic solvent-based method and a silica method. The organic-based method was able to recoup 20% of the AdV, 90% of the RV and 100% of both the PV and HAV from seeded samples. The silica method was able to recoup 1.8% of the AdV and 90% of the RV. These results indicate that the organic-based method is more suitable for detecting viruses in sewage sludge.

Comparing methods for dimensionality reduction when data are density functions

Functional Data Analysis (FDA) deals with samples where a whole function is observedfor each individual. A particular case of FDA is when the observed functions are densityfunctions, that are also an example of infinite dimensional compositional data. In thiswork we compare several methods for dimensionality reduction for this particular typeof data: functional principal components analysis (PCA) with or without a previousdata transformation and multidimensional scaling (MDS) for diferent inter-densitiesdistances, one of them taking into account the compositional nature of density functions. The difeerent methods are applied to both artificial and real data (householdsincome distributions)

Gap junction reduction in cardiomyocytes following transforming growth factor-β treatment and Trypanosoma cruzi infection

Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-β (TGF-β). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-β T. cruzi, or SB-431542, an inhibitor of TGF-β receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-β signalling had been shown previously to be highly activated. We demonstrated that TGF-β treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-β secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-β levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease.

Réduction de volume pulmonaire dans l'emphysème sévère: importance d'une prise en charge multidisciplinaire [Lung volume reduction (LVR) in severe emphysema: a multidisciplinary approach].

Most cases of emphysema are managed conservatively. However, in severe symptomatic emphysema associated with hyperinflation, lung volume reduction (LVR) may be proposed to improve dyspnea, exercice capacity, pulmonary functions, walk distance and to decrease long-term mortality. LVR may be achieved either surgically (LVRS) or endoscopically (EVLR by valves or coils) according to specific clinical criteria. Currently, the optimal approach is discussed in a multidisciplinary setting. The latter permits a personalized evaluation the patient's clinical status and allows the best possible therapeutic intervention to be proposed to the patient.

Full label space reduction in MPLS networks: asymmetric merged tunneling

Traffic Engineering objective is to optimize network resource utilization. Although several works have been published about minimizing network resource utilization in MPLS networks, few of them have been focused in LSR label space reduction. This letter studies Asymmetric Merged Tunneling (AMT) as a new method for reducing the label space in MPLS network. The proposed method may be regarded as a combination of label merging (proposed in the MPLS architecture) and asymmetric tunneling (proposed recently in our previous works). Finally, simulation results are performed by comparing AMT with both ancestors. They show a great improvement in the label space reduction factor

Label Space Reduction in MPLS Networks: How Much Can A Single Stacked Label Do?

Most network operators have considered reducing LSR label spaces (number of labels used) as a way of simplifying management of underlaying virtual private networks (VPNs) and therefore reducing operational expenditure (OPEX). The IETF outlined the label merging feature in MPLS-allowing the configuration of multipoint-to-point connections (MP2P)-as a means of reducing label space in LSRs. We found two main drawbacks in this label space reduction a)it should be separately applied to a set of LSPs with the same egress LSR-which decreases the options for better reductions, and b)LSRs close to the edge of the network experience a greater label space reduction than those close to the core. The later implies that MP2P connections reduce the number of labels asymmetrically

Emerging pharmacotherapies for alcohol dependence: a systematic review focusing on reduction in consumption.

BACKGROUND: European Medicines Agency guidelines recognize two different treatment goals for alcohol dependence: abstinence and reduction in alcohol consumption. All currently approved agents are indicated for abstinence. This systematic review aimed to identify drugs in development for alcohol dependence treatment and to establish, based upon trial design, if any are seeking market authorization for reduction in consumption. METHODS: We searched PubMed and Embase (December 2001-November 2011) to identify agents in development for alcohol dependence treatment. Additional studies were identified by searching ClinicalTrials.gov and the R&D Insight and Clinical Trials Insight databases. Studies in which the primary focus was treatment of comorbidity, or n≤20, were excluded. Studies were then classified as 'abstinence' if they: described a detoxification/alcohol withdrawal period; enrolled patients who had undergone detoxification previously; or presented relapse/abstinence rates as the primary outcome. Studies in patients actively drinking at baseline were classified as 'reduction in consumption'. RESULTS: Of 602 abstracts identified, 45 full-text articles were eligible. Five monotherapies were in development for alcohol dependence treatment: topiramate, fluvoxamine, aripiprazole, flupenthixol and nalmefene. Nalmefene was the only agent whose sponsor was clearly seeking definitive approval for reduction in consumption. Development status was unclear for topiramate, fluvoxamine, aripiprazole and flupenthixol. Fifteen agents were examined in published exploratory investigator-initiated trials; the majority focused on abstinence. Ongoing (unpublished) trials tended to focus on reduction in consumption. CONCLUSIONS: While published studies generally focused on abstinence, ongoing trials focused on reduction in consumption, suggesting a change in emphasis in the approach to treating alcohol dependence.

Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report

BACKGROUND Mixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day. METHODS Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA. RESULTS The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05). CONCLUSION Our preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.

Reduction in morbidity and mortality from childhood diarrhoeal disease after species A rotavirus vaccine introduction in Latin America : a review

Countries in Latin America were among the first to implement routine vaccination against species A rotavirus (RVA). We evaluate data from Latin America on reductions in gastroenteritis and RVA disease burden following the introduction of RVA vaccine. Published literature was reviewed to identify case-control studies of vaccine effectiveness and population-based studies examining longitudinal trends of diarrhoeal disease reduction after RVA vaccine introduction in Latin American countries. RVA vaccine effectiveness and impact on gastroenteritis mortality and hospitalization rates and RVA hospitalization rates are described. Among middle-income Latin American countries with published data (Mexico, Brazil, El Salvador and Panama), RVA vaccine contributed to a gastroenteritis-associated mortality reduction of 22-41%, a gastroenteritis-associated hospitalization reduction of 17-51% and a RVA hospitalization reduction of 59-81% among children younger than five years of age. In Brazil and El Salvador, case-control studies demonstrated that a full RVA vaccination schedule was 76-85% effective against RVA hospitalization; a lower effectiveness of 46% was seen in Nicaragua, the only low-income country with available data. A growing body of literature offers convincing evidence of "real world" vaccine program successes in Latin American settings, which may be expanded as more countries in the region include RVA vaccine in their immunization programs.

Comparative evaluation under routine conditions of the nitrate reduction assay, the proportion assay and the MGIT 960 assay for drug susceptibility testing of clinical isolates of Mycobacterium tuberculosis

The performance of the nitrate reductase assay (NRA) was compared with the proportion method (PM) on Lowenstein-Jensen medium and the BACTEC MGIT960 assay under routine conditions using 160 clinical isolates of Mycobacterium tuberculosis with a high proportion of resistant strains. The mean time to obtain results was 8.8 days and the overall agreements between NRA and PM and NRA and M960 were 95% and 94%, respectively. NRA was easy to perform and represents a useful tool for the rapid screening of drug-resistant M. tuberculosis strains in low-resource countries.

The efficiency of concentration methods used to detect enteric viruses in anaerobically digested sludge

The presence of enteric viruses in biosolids can be underestimated due to the inefficient methods (mainly molecular methods) used to recover the viruses from these matrices. Therefore, the goal of this study was to evaluate the different methods used to recover adenoviruses (AdV), rotavirus species A (RVA), norovirus genogroup II (NoV GII) and the hepatitis A virus (HAV) from biosolid samples at a large urban wastewater treatment plant in Brazil after they had been treated by mesophilic anaerobic digestion. Quantitative polymerase chain reaction (PCR) was used for spiking experiments to compare the detection limits of feasible methods, such as beef extract elution and ultracentrifugation. Tests were performed to detect the inhibition levels and the bacteriophage PP7 was used as an internal control. The results showed that the inhibitors affected the efficiency of the PCR reaction and that beef extract elution is a suitable method for detecting enteric viruses, mainly AdV from biosolid samples. All of the viral groups were detected in the biosolid samples: AdV (90%), RVA, NoV GII (45%) and HAV (18%), indicating the viruses' resistance to the anaerobic treatment process. This is the first study in Brazil to detect the presence of RVA, AdV, NoV GII and HAV in anaerobically digested sludge, highlighting the importance of adequate waste management.