Estimation of age-specific rates of reactivation and immune boosting of the varicella zoster virus

Studies into the impact of vaccination against the varicella zoster virus (VZV) have increasingly focused on herpes zoster (HZ), which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting) or by a reactivation attempt of the virus (endogenous boosting). Here we use transmission models to estimate age-specific rates of reactivation and immune boosting, exogenous as well as endogenous, using zoster incidence data from the Netherlands (2002–2011, n = 7026). The boosting and reactivation rates are estimated with splines, enabling these quantities to be optimally informed by the data. The analyses show that models with high levels of exogenous boosting and estimated or zero endogenous boosting, constant rate of loss of immunity, and reactivation rate increasing with age (to more than 5% per year in the elderly) give the best fit to the data. Estimates of the rates of immune boosting and reactivation are strongly correlated. This has important implications as these parameters determine the fraction of the population with waned immunity. We conclude that independent evidence on rates of immune boosting and reactivation in persons with waned immunity are needed to robustly predict the impact of varicella vaccination on the incidence of HZ.PIENTER2 serological stud

The value of reasons for encounter in early detection of colorectal cancer

BACKGROUND: Symptoms with a high predictive power for colorectal cancer (CRC) do not exist. OBJECTIVE: To explore the predictive value of patients' reason for encounter (RFE) in the two years prior to the diagnosis of CRC. METHODS: A retrospective nested case-control study using prospectively collected data from electronic records in general practice over 20 years. Matching was done based on age (within two years), gender and practice. The positive likelihood ratios (LR+) and odds ratios (OR) were calculated for RFE between cases and controls in the two years before the index date. RESULTS: We identified 184 CRC cases and matched 366 controls. Six RFEs had significant LR + and ORs for CRC, which may have high predictive power. These RFEs are part of four chapters in the International Classification of Primary Care (ICPC) that include tiredness (significant at 3-6 months prior to the diagnosis; LR+ 2.6 and OR 3.07; and from 0 to 3 months prior to the diagnosis; LR+ 2.0 and OR 2.36), anaemia (significant at three months before diagnosis; LR+ 9.8 and OR 16.54), abdominal pain, rectal bleeding and constipation (significant at 3-6 months before diagnosis; LR+ 3.0 and OR 3.33; 3 months prior to the diagnosis LR+ 8.0 and OR 18.10) and weight loss (significant at three months before diagnosis; LR+ 14.9 and OR 14.53). CONCLUSION: Data capture and organization in ICPC permits study of the predictive value of RFE for CRC in primary care

Herd immunity to Newcastle disease virus in poultry by vaccination

Newcastle disease is an economically important disease of poultry for which vaccination is applied as a preventive measure in many countries. Nevertheless, outbreaks have been reported in vaccinated populations. This suggests that either the vaccination coverage level is too low or that vaccination does not provide perfect immunity, allowing the virus to spread in partially vaccinated populations. Here we study the requirements of an epidemiologically effective vaccination program against Newcastle disease in poultry, based on data from experimental transmission studies. The transmission studies indicate that vaccinated birds with low or undetectable antibody titres may be protected against disease and mortality but that infection and transmission may still occur. In fact, our quantitative analyses show that Newcastle disease virus is highly transmissible in poultry with low antibody titres. As a consequence, herd immunity can only be achieved if a high proportion of birds (>85%) have a high antibody titre (log2 haemagglutination inhibition titre ≥3) after vaccination. We discuss the implications for the control of Newcastle disease in poultry by vaccination

Clinical and economic impact of non-adherence in COPD:A systematic review

BACKGROUND: Medication for Chronic Obstructive Pulmonary Disease (COPD) has shown to substantially reduce symptoms and slow progression of disease. However, non-adherence to medication is common and associated with worsened clinical and economic outcomes. OBJECTIVE: The objective of this study was to perform a systematic review of published literature to assess the impact of non-adherence to COPD medication on clinical and economic outcomes. METHODS: A search in PubMed and Web of Science databases was conducted of original studies published from database inception to 2012. Studies must report on the association between adherence to COPD medication and outcomes, published in English in peer-reviewed journals and full texts needed to be available. RESULTS: Twelve full articles were included in the review. Most studies were retrospective database studies. Seven studies reported on the association between adherence and clinical outcomes, two on mortality, three on costs, four on quality of life and one on work productivity. Results indicated a clear association between adherence and both clinical and economic outcomes. Evidence from studies revealed increased hospitalizations, mortality, quality of life and loss of productivity among non-adherent patients. CONCLUSION: This review revealed a clear association between non-adherence to COPD medication and worsened clinical and economic outcomes making non-adherent patients a priority for cost-effective interventions.</p

Personalized medication adherence management in asthma and COPD:a review of effective interventions and development of a practical adherence toolkit

BACKGROUND: Medication non-adherence management of patients with asthma/COPD remains challenging. Given the multitude of underlying causes, a personalized approach is required. The Test of Adherence to Inhalers (TAI) can identify reasons for non-adherence, but does not provide guidance on how to effectively act on results. OBJECTIVE: To develop a practical, evidence-based decision support toolkit for healthcare professionals managing adult patients with asthma and/or COPD, by matching TAI-identified adherence barriers to proven effective adherence enhancing interventions. METHODS: A literature review in PubMed and Embase was performed identifying interventions that enhanced medication adherence in adult patients with asthma and/or COPD. Randomised controlled trials (RCTs) published in English with full-texts available were included. Effective interventions were assessed by the Cochrane risk of bias tool, categorized, matched with specific TAI responses and developed into a practical TAI Toolkit. The Toolkit was assessed on content and usability (System Usability Scale, SUS) by a multidisciplinary group of healthcare professionals. RESULTS: Forty RCTs were included in the review. In total, seven effective interventions catergories were identified, informing the TAI Toolkit: reminders, educational interventions, motivational strategies, feedback on medication use, shared decision making, simplifying medication regimen and multiple component interventions. Healthcare professionals rated the TAI Toolkit with a mean SUS score of 71.4 (range: 57.5-80.0). CONCLUSION: Adherence can be improved using different interventions that the TAI Toolkit helps selecting. The TAI Toolkit was well received by healthcare professionals. Further research is required to test its validity, practicality and effectiveness in practice

Errata: Initial results of imaging melanoma metastasis in resected human lymph nodes using photoacoustic computed tomography

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769-2 Progression and Regression of Coronary Atherosclerosis Occur within the Same Patient During Placebo Treatment and During Lipid-Lowering Therapy with Pravastatin

REGRESS (Regression Growth Evaluation Statin Study) is a placebo controlled multicenter study to asses the effect of 2-yr treatment with Pravastatin (PRAV) on progression and regression of angiographically documented coronary atherosclerosis (CA) in patients with a serum cholesterol between 4–8mmol/l (155-310mg/dl). Analyses of the coronary arteriograms were performed by quantitative computer analysis. The primary endpoints of the study, change in Mean Segment Diameter and Minimum Obstruction Diameter (MOD) averaged per patient, showed significant retardation of mean progression of CA in the PRAY-group as compared to the placebo (PLAC)-group. However, these mean changes per treatment group are hardly informative about individual CA-behavior. Therefore we determined for all 641 patients included in the primary MOD-analysis: 1. a mean progression score (MPS)-cumulative value of all &gt;0.4mm progressing obstructions divided by the number of contributing obstructions-, and 2. a mean regression score (MRS)-cumulative value of all&gt;0.4mm regressing obstructions divided by the number of contributing obstructions. Obstructions changing ≤0.4mm were considered stable and do not contribute to the scores. Thus, each patient is characterized by a MPS and a MRS. An overview of the patient MPS and MRS is presented in the figure below.Conclusionsignificant progression and regression of CA within the same patient occurred in 41 (13%) PRAY-patients and in 27 (9%) PLAC-patients. Thus, although pravastatin slows mean progression of CA, progression and regression of CA within the same patient still occurs in a considerable number of patients during lipid lowering therapy