No Threshold Exists for Recommending Revision Surgery in Metal-on-Metal Hip Arthroplasty Patients With Adverse Reactions to Metal Debris: A Retrospective Cohort Study of 346 Revisions

Background Surgeons currently have difficulty when managing metal-on-metal hip arthroplasty (MoMHA) patients with adverse reactions to metal debris (ARMD). This stems from a lack of evidence, which is emphasized by the variability in the recommendations proposed by different worldwide regulatory authorities for considering MoMHA revision surgery. We investigated predictors of poor outcomes following MoMHA revision surgery performed for ARMD to help inform the revision threshold and type of reconstruction. Methods We retrospectively studied 346 MoMHA revisions for ARMD performed at 2 European centers. Preoperative (metal ions/imaging) and intraoperative (findings, components removed/implanted) factors were used to predict poor outcomes. Poor outcomes were postoperative complications (including re-revision), 90-day mortality, and poor Oxford Hip Score. Results Poor outcomes occurred in 38.5%. Shorter time (under 4 years) to revision surgery was the only preoperative predictor of poor outcomes (odds ratio [OR] = 2.12, confidence interval [CI] = 1.00-4.46). Prerevision metal ions and imaging did not influence outcomes. Single-component revisions (vs all-component revisions) increased the risk of poor outcomes (OR = 2.99, CI = 1.50-5.97). Intraoperative modifiable factors reducing the risk of poor outcomes included the posterior approach (OR = 0.22, CI = 0.10-0.49), revision head sizes ≥36 mm (vs <36 mm: OR = 0.37, CI = 0.18-0.77), ceramic-on-polyethylene revision bearings (OR vs ceramic-on-ceramic = 0.30, CI = 0.14-0.66), and metal-on-polyethylene revision bearings (OR vs ceramic-on-ceramic = 0.37, CI = 0.17-0.83). Conclusion No threshold exists for recommending revision in MoMHA patients with ARMD. However postrevision outcomes were surgeon modifiable. Optimal outcomes may be achieved if surgeons use the posterior approach, revise all MoMHA components, and use ≥36 mm ceramic-on-polyethylene or metal-on-polyethylene articulations

Does prenatal micronutrient supplementation improve children's mental development? A systematic review

<p>Abstract</p> <p>Background</p> <p>Although maternal nutrient status influences all aspects of fetal development including the brain, the impact of micronutrient supplementation on the baby's mental function is a topic of debate. This systematic review assesses the effect of single and multiple micronutrient supplementation during pregnancy on offspring mental development.</p> <p>Methods</p> <p>Eleven electronic literature databases were searched using key terms of various combinations and filter string terms. Reference lists of articles selected for review were scanned for citations fitting the same inclusion criteria. Each stage of the literature retrieval and review process was conducted independently by two reviewers. The CONSORT checklist was used to assess study quality.</p> <p>Results</p> <p>A total of 1316 articles were retrieved from the electronic database search, of which 18 met the inclusion criteria and were evaluated. The selected studies were randomized controlled trials published from 1983 to 2010, with high variance in sample size, intervention type, and outcome measures. The median CONSORT score was 15 (range 12 - 19). Due to inconsistent interventions and outcome measures among the studies, no conclusive evidence was found that enhancing the intrauterine environment through micronutrient supplementation was associated with child mental development in a number of dimensions. There was some evidence to support n-3 fatty acids or multi-micronutrients having some positive effect on mental development, but the evidence for single nutrients was much weaker.</p> <p>Conclusions</p> <p>The study of children's mental outcomes as a function of prenatal supplementation is still relatively new, but the results of this systematic review suggest that further work with multiple micronutrients and/or n-3 fatty acids should be conducted.</p

Using a realist approach to evaluate smoking cessation interventions targeting pregnant women and young people

Background This paper describes a study protocol designed to evaluate a programme of smoking cessation interventions targeting pregnant women and young people living in urban and rural locations in Northeast Scotland. The study design was developed on so-called 'realist' evaluation principles, which are concerned with the implementation of interventions as well as their outcomes. Methods/design A two-phased study was designed based on the Theory of Change (TOC) using mixed methods to assess both process and outcome factors. The study was designed with input from the relevant stakeholders. The mixed-methods approach consists of semi-structured interviews with planners, service providers, service users and non-users. These qualitative interviews will be analysed using a thematic framework approach. The quantitative element of the study will include the analysis of routinely collected data and specific project monitoring data, such as data on service engagement, service use, quit rates and changes in smoking status. Discussion The process of involving key stakeholders was conducted using logic modelling and TOC tools. Engaging stakeholders, including those responsible for funding, developing and delivering, and those intended to benefit from interventions aimed at them, in their evaluation design, are considered by many to increase the validity and rigour of the subsequent evidence generated. This study is intended to determine not only the components and processes, but also the possible effectiveness of this set of health interventions, and contribute to the evidence base about smoking cessation interventions aimed at priority groups in Scotland. It is also anticipated that this study will contribute to the ongoing debate about the role and challenges of 'realist' evaluation approaches in general, and the utility of logic modelling and TOC approaches in particular, for evaluation of complex health interventions

Reduced occupancy of hedgehogs (Erinaceus europaeus) in rural England and Wales: the influence of habitat and an asymmetric intra-guild predator

Agricultural landscapes have become increasingly intensively managed resulting in population declines across a broad range of taxa, including insectivores such as the hedgehog (Erinaceus europaeus). Hedgehog declines have also been attributed to an increase in the abundance of badgers (Meles meles), an intra-guild predator. The status of hedgehogs across the rural landscape at large spatial scales is, however, unknown. In this study, we used footprint tracking tunnels to conduct the first national survey of rural hedgehog populations in England and Wales. Single and two-species occupancy modelling was used to quantify hedgehog occupancy in relation to habitat and predator covariates. Hedgehog occupancy was low (22% nationally), and significantly negatively related to badger sett density and positively related to the built environment. Hedgehogs were also absent from 71% of sites that had no badger setts, indicating that large areas of the rural landscape are not occupied by hedgehogs. Our results provide the first field based national survey of hedgehogs, providing a robust baseline for future monitoring. Furthermore, the combined effects of increasing badger abundance and intensive agriculture may have provided a perfect storm for hedgehogs in rural Britain, leading to worryingly low levels of occupancy over large spatial scales

Lump-Sum Bonus Satisfaction: Testing the Construct Validity of a New Pay Satisfaction Dimension

There are both practical and theoretical reasons to measure lump-sum bonus satisfaction. The practical need for such a measure stems from its increased use as a component in modern compensation practices. Based on the means of administering and allocating lump-sum bonuses, a theoretical case can be built suggesting that lump-sum bonus satisfaction constitutes a separate component of pay satisfaction fitting into the Pay Satisfaction Questionaire\u27s (PSQ) theoretical framework. We develop 4 questions that complement the PSQ, and use a series of techniques to test the convergent and discriminant validity of the measure. Empirical evidence shows that bonus-related items are more related to the lump-sum bonus satisfaction measure than other PSQ dimensions. We also demonstrate that the dimension of lump-sum bonus satisfaction has a substantive relationship with attitudinal variables beyond that provided by pay level variables and the PSQ. The development of this measure should foster greater accuracy when assessing pay satisfaction levels and the effects of lump-sum bonus pay policies

Immunostimulatory Motifs Enhance Antiviral siRNAs Targeting Highly Pathogenic Avian Influenza H5N1

Highly pathogenic avian influenza (HPAI) H5N1 virus is endemic in many regions around the world and remains a significant pandemic threat. To date H5N1 has claimed almost 300 human lives worldwide, with a mortality rate of 60% and has caused the death or culling of hundreds of millions of poultry since its initial outbreak in 1997. We have designed multi-functional RNA interference (RNAi)-based therapeutics targeting H5N1 that degrade viral mRNA via the RNAi pathway while at the same time augmenting the host antiviral response by inducing host type I interferon (IFN) production. Moreover, we have identified two factors critical for maximising the immunostimulatory properties of short interfering (si)RNAs in chicken cells (i) mode of synthesis and (ii) nucleoside sequence to augment the response to virus. The 5-bp nucleoside sequence 5′-UGUGU-3′ is a key determinant in inducing high levels of expression of IFN -α, -β, -λ and interleukin 1- β in chicken cells. Positioning of this 5′-UGUGU-3′ motif at the 5′- end of the sense strand of siRNAs, but not the 3′- end, resulted in a rapid and enhanced induction of type I IFN. An anti-H5N1 avian influenza siRNA directed against the PB1 gene (PB1-2257) tagged with 5′-UGUGU-3′ induced type I IFN earlier and to a greater extent compared to a non-tagged PB1-2257. Tested against H5N1 in vitro, the tagged PB1-2257 was more effective than non-tagged PB1-2257. These data demonstrate the ability of an immunostimulatory motif to improve the performance of an RNAi-based antiviral, a finding that may influence the design of future RNAi-based anti-influenza therapeutics

Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Collaboration.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. METHODS: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. RESULTS: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. CONCLUSIONS: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Aims Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods and results Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44–9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73–0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92–0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). Conclusion Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICD

A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. [Figure not available: see fulltext.]