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Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.
Social Media Statement: Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
The Vulnerable fosa Cryptoprocta ferox is the largest native carnivore in Madagascar, fulfilling a unique ecological niche in the island's remaining forests. Negative interactions with humans threaten the long-term viability of most remaining fosa populations across Madagascar. Threats to the fosa include habitat loss and persecution by humans resulting from perceived predation on domestic animals. We used GPS collars to record space use and activity patterns of five fosas in Ankarafantsika National Park, Madagascar, during the dry seasons of 2016 and 2017. The results, with up to 2,110 recorded locations per individual, indicated fosas’ home ranges and movements were not limited to the forest, and all collared individuals used networks of habitat patches and corridors to navigate deforested areas. The fosas studied in Ankarafantsika National Park had significantly larger home ranges than those reported in previous studies in other protected areas. They were rarely found within village boundaries and appeared to avoid areas of human habitation, suggesting that during the study period livestock was not a significant component of the fosas’ diet in this Park. Our results suggest that fosas have some flexibility that enables them to adapt to living near deforested and human-dominated areas by altering their space-use patterns, but they are compensating by increasing their home range size.
Investigations of drinking behavior across military deployment cycles are scarce, and few prospective studies have examined risk factors for post-deployment alcohol misuse.
Prevalence of alcohol misuse was estimated among 4645 US Army soldiers who participated in a longitudinal survey. Assessment occurred 1–2 months before soldiers deployed to Afghanistan in 2012 (T0), upon their return to the USA (T1), 3 months later (T2), and 9 months later (T3). Weights-adjusted logistic regression was used to evaluate associations of hypothesized risk factors with post-deployment incidence and persistence of heavy drinking (HD) (consuming 5 + alcoholic drinks at least 1–2×/week) and alcohol or substance use disorder (AUD/SUD).
Prevalence of past-month HD at T0, T2, and T3 was 23.3% (s.e. = 0.7%), 26.1% (s.e. = 0.8%), and 22.3% (s.e. = 0.7%); corresponding estimates for any binge drinking (BD) were 52.5% (s.e. = 1.0%), 52.5% (s.e. = 1.0%), and 41.3% (s.e. = 0.9%). Greater personal life stress during deployment (e.g., relationship, family, or financial problems) – but not combat stress – was associated with new onset of HD at T2 [per standard score increase: adjusted odds ratio (AOR) = 1.20, 95% CI 1.06–1.35, p = 0.003]; incidence of AUD/SUD at T2 (AOR = 1.54, 95% CI 1.25–1.89, p < 0.0005); and persistence of AUD/SUD at T2 and T3 (AOR = 1.30, 95% CI 1.08–1.56, p = 0.005). Any BD pre-deployment was associated with post-deployment onset of HD (AOR = 3.21, 95% CI 2.57–4.02, p < 0.0005) and AUD/SUD (AOR = 1.85, 95% CI 1.27–2.70, p = 0.001).
Alcohol misuse is common during the months preceding and following deployment. Timely intervention aimed at alleviating/managing personal stressors or curbing risky drinking might reduce risk of alcohol-related problems post-deployment.
Performing patient care while wearing high-level personal protective equipment presents risks to healthcare providers. Our failure mode effects analysis identified 81 overall risks associated with providing hygienic care and linen change to a patient with continuous watery stool. Implementation of checklists and scheduled pauses could potentially mitigate 76.5% of all risks.
Tomato product consumption and estimated lycopene intake are hypothesised to reduce the risk of prostate cancer. To define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations, men scheduled to undergo prostatectomy (n 33) were randomised either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato soup (2–2¾ cups prepared/d), tomato sauce (142–198 g/d or 5–7 ounces/d) or vegetable juice (325–488 ml/d or 11–16·5 fluid ounces/d) intervention providing 25–35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured by HPLC. Tomato soup, sauce and juice consumption significantly increased plasma lycopene concentration from 0·68 (sem 0·1) to 1·13 (sem 0·09) μmol/l (66 %), 0·48 (sem 0·09) to 0·82 (sem 0·12) μmol/l (71 %) and 0·49 (sem 0·12) to 0·78 (sem 0·1) μmol/l (59 %), respectively, while the controls consuming the lycopene-restricted diet showed a decline in plasma lycopene concentration from 0·55 (sem 0·60) to 0·42 (sem 0·07) μmol/l ( − 24 %). The end-of-study prostate lycopene concentration was 0·16 (sem 0·02) nmol/g in the controls, but was 3·5-, 3·6- and 2·2-fold higher in tomato soup (P= 0·001), sauce (P= 0·001) and juice (P= 0·165) consumers, respectively. Prostate lycopene concentration was moderately correlated with post-intervention plasma lycopene concentrations (r 0·60, P =0·001), indicating that additional factors have an impact on tissue concentrations. While the primary geometric lycopene isomer in tomato products was all-trans (80–90 %), plasma and prostate isomers were 47 and 80 % cis, respectively, demonstrating a shift towards cis accumulation. Consumption of typical servings of processed tomato products results in differing plasma and prostate lycopene concentrations. Factors including meal composition and genetics deserve further evaluation to determine their impacts on lycopene absorption and biodistribution.
Despite many advances in recent years for patients with critical paediatric and congenital cardiac disease, significant variation in outcomes remains across hospitals. Collaborative quality improvement has enhanced the quality and value of health care across specialties, partly by determining the reasons for variation and targeting strategies to reduce it. Developing an infrastructure for collaborative quality improvement in paediatric cardiac critical care holds promise for developing benchmarks of quality, to reduce preventable mortality and morbidity, optimise the long-term health of patients with critical congenital cardiovascular disease, and reduce unnecessary resource utilisation in the cardiac intensive care unit environment. The Pediatric Cardiac Critical Care Consortium (PC4) has been modelled after successful collaborative quality improvement initiatives, and is positioned to provide the data platform necessary to realise these objectives. We describe the development of PC4 including the philosophical, organisational, and infrastructural components that will facilitate collaborative quality improvement in paediatric cardiac critical care.
To describe the epidemiology and healthcare costs of Clostridium difficile infection (CDI) identified in the outpatient setting.
Population-based, retrospective cohort study.
Kaiser Permanente Colorado and Kaiser Permanente Northwest members between June 1, 2005, and September 30, 2008.
We identified persons with incident CDI and classified CDI by whether it was identified in the outpatient or inpatient healthcare setting. We collected information about baseline variables and follow-up healthcare utilization, costs, and outcomes among patients with CDI. We compared characteristics of patients with CDI identified in the outpatient versus inpatient setting.
We identified 3,067 incident CDIs; 56% were identified in the outpatient setting. Few strong, independent predictors of diagnostic setting were identified, although a previous stay in a nonacute healthcare institution (odds ratio [OR], 1.45 [95% confidence interval (CI), 1.13-1.86]) was statistically associated with outpatient-identified CDI, as was age from 50 to 59 years (OR, 1.64 [95% CI, 1.18-2.29]), 60 to 69 years (OR, 1.37 [95% CI, 1.03-1.82]), and 70 to 79 years (OR, 1.36 [95% CI, 1.06-1.74]), when compared with persons aged 80-89 years.
We found that more than one-half of incident CDIs in this population were identified in the outpatient setting. Patients with outpatient-identified CDI were younger with fewer comorbidities, although they frequently had previous exposure to healthcare. These data suggest that practitioners should be aware of CDI and obtain appropriate diagnostic testing on outpatients with CDI symptoms.
Infect Control Hosp Epidemiol 2012;33(10):1031-1038
Biodiversity is the variability among living organisms, from genes to the biosphere. The value of biodiversity is multifold, from preserving the integrity of the biosphere as a whole, to providing food and medicines, to spiritual and aesthetic well-being.
One of the major drivers of biodiversity loss in Europe is atmospheric deposition of reactive nitrogen (Nr).
This chapter focuses on Nr impacts on European plant species diversity; in particular, the number and abundance of different species in a given area, and the presence of characteristic species of sensitive ecosystems.
We summarise both the scientific and the policy aspects of Nr impacts on diversity and identify, using a range of evidence, the most vulnerable ecosystems and regions in Europe.
Key findings/state of knowledge
Reactive nitrogen impacts vegetation diversity through direct foliar damage, eutrophication, acidification, and susceptibility to secondary stress.
Species and communities most sensitive to chronically elevated Nr deposition are those that are adapted to low nutrient levels, or are poorly buffered against acidification. Grassland, heathland, peatland, forest, and arctic/montane ecosystems are recognised as vulnerable habitats in Europe; other habitats may be vulnerable but are still poorly studied.
It is not yet clear if different wet-deposited forms of Nr (e.g. nitrate, NO3− versus ammonium, NH4+) have different effects on biodiversity. However, gaseous ammonia (NH3) can be particularly harmful to vegetation, especially lower plants, through direct foliar damage.
Fructose consumption in the USA has increased over the past three decades. During this time, obesity, insulin resistance and the metabolic syndrome have also increased in prevalence. While diets high in fructose have been shown to promote insulin resistance and increase TAG concentrations in animals, there are insufficient data available regarding the long-term metabolic effects of fructose consumption in humans. The objective of the present study was to investigate the metabolic effects of 10-week consumption of fructose-sweetened beverages in human subjects under energy-balanced conditions in a controlled research setting. Following a 4-week weight-maintaining complex carbohydrate diet, seven overweight or obese (BMI 26·8–33·3 kg/m2) postmenopausal women were fed an isoenergetic intervention diet, which included a fructose-sweetened beverage with each meal, for 10 weeks. The intervention diet provided 15 % of energy from protein, 30 % from fat and 55 % from carbohydrate (30 % complex carbohydrate, 25 % fructose). Fasting and postprandial glucose, insulin, TAG and apoB concentrations were measured. Fructose consumption increased fasting glucose concentrations and decreased meal-associated glucose and insulin responses (P = 0·0002, P = 0·007 and P = 0·013, respectively). Moreover, after 10 weeks of fructose consumption, 14 h postprandial TAG profiles were significantly increased, with the area under the curve at 10 weeks being 141 % higher than at baseline (P = 0·04). Fructose also increased fasting apoB concentrations by 19 % (P = 0·043 v. baseline). In summary, consumption of fructose-sweetened beverages increased postprandial TAG and fasting apoB concentrations, and the present results suggest that long-term consumption of diets high in fructose could lead to an increased risk of CVD.