Objectives:To evaluate the efficacy and safety of 18 months of tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP). Methods:In this randomized, double-blind trial, patients received tafamidis 20 mg QD or placebo.Coprimary endpoints were the Neuropathy Impairment Score-Lower Limbs (NIS-LL) responder analysis (Ͻ2-point worsening) and treatment-group difference in the mean change from baseline in Norfolk Quality of Life-Diabetic Neuropathy total score (TQOL) in the intent-to-treat (ITT) population (n ϭ 125). These endpoints were also evaluated in the efficacy-evaluable (EE; n ϭ 87) population. Secondary endpoints, including changes in neurologic function, nutritional status, and TTR stabilization, were analyzed in the ITT population.Results: There was a higher-than-anticipated liver transplantation dropout rate. No differences were observed between the tafamidis and placebo groups for the coprimary endpoints, NIS-LL responder analysis (45.3% vs 29.5% responders; p ϭ 0.068) and change in TQOL (2.0 vs 7.2; p ϭ 0.116) in the ITT population. In the EE population, significantly more tafamidis patients than placebo patients were NIS-LL responders (60.0% vs 38.1%; p ϭ 0.041), and tafamidis patients had better-preserved TQOL (0.1 vs 8.9; p ϭ 0.045). Significant differences in most secondary endpoints favored tafamidis. TTR was stabilized in 98% of tafamidis and 0% of placebo patients (p Ͻ 0.0001). Adverse events were similar between groups. Conclusions:Although the coprimary endpoints were not met in the ITT population, tafamidis was associated with no trend toward more NIS-LL responders and a significant reduction in worsening of most neurologic variables, supporting the hypothesis that preventing TTR dissociation can delay peripheral neurologic impairment. Classification of evidence:This study provides Class II evidence that 20 mg tafamidis QD was associated with no difference in clinical progression in patients with TTR-FAP, as measured by the NIS-LL and the Norfolk QOL-DN score. Secondary outcomes demonstrated a significant delay in peripheral neurologic impairment with tafamidis, which was well tolerated over 18 months. Neurology® 2012;79:785-792 GLOSSARY AE ϭ adverse event; ANCOVA ϭ analysis of covariance; ARR ϭ absolute risk reduction; CI ϭ confidence interval; DPN ϭ diabetic polyneuropathy; EE ϭ efficacy-evaluable; ITT ϭ intent-to-treat; LS Mean ϭ least-squares mean; mBMI ϭ modified body mass index; NIS-LL ϭ Neuropathy Impairment Score-Lower Limbs; NNT ϭ number needed to treat; QOL ϭ quality of life; QOL-DN ϭ Quality of Life-Diabetic Neuropathy Questionnaire; TQOL ϭ total quality of life; TTR-FAP ϭ transthyretin familial amyloid polyneuropathy.

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Dialysis units are at especially high risk of infectious disease transmission, and concern exists about spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dialysis units in Wuhan, China, have reported high coronavirus disease 2019 (COVID-19) prevalence, due in part to unique exposure challenges that limit social distancing efforts, including open bay formats and rotating/multiple nursing assignments. 1,2 This study describes SARS-CoV-2 seroconversion in patients and health care workers in a pediatric dialysis unit.

Background. In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development.Methods. Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic fibrosis, an elevated baseline serum creatinine, or without a serum creatinine concentration obtained after receipt of vancomycin were excluded. Acute kidney injury was defined using adapted pediatric RIFLE criteria as an increase in serum creatinine from baseline of 50% or more. BACKGROUNDVancomycin is commonly used in the pediatric population for empiric or targeted treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections and has been associated with acute kidney injury (AKI) [1].Empiric intravenous (IV) vancomycin in children has traditionally been dosed as 40 mg/kg per day in 4 divided doses to achieve target serum trough concentrations of 5-10 mg/L. Recent evidence and recommendations suggest that such doses are unlikely to achieve the goal serum trough concentrations (10-20 mg/L) that are necessary for the optimal area under the curve (AUC) for plasma concentration relative to the organism minimum inhibitory concentration (MIC) (AUC/MIC) [2][3][4][5].

Background Fibrodysplasia Ossificans Progressiva (FOP; OMIM#135100) is an ultra-rare, severely disabling genetic disease characterized by congenital malformation of the great toes and progressive heterotopic ossification (HO) in muscles, tendons, ligaments, fascia, and aponeuroses often preceded by painful, recurrent soft tissue swelling (flare-ups). The formation of HO leads to progressive disability, severe functional limitations in joint mobility, and to a shortened life-span. In this prospective natural history study, we describe the baseline, cross-sectional disease phenotype of 114 individuals with FOP. Methods All subjects underwent protocol-specified baseline assessments to determine their disease status. Cross-sectional analyses were performed using linear regression in which functional evaluations (Cumulative Analogue Joint Involvement Scale [CAJIS] and the FOP-Physical Function Questionnaire [FOP-PFQ]) and the burden of HO as measured by low-dose whole body CT (volume of HO and number of body regions with HO) were assessed. Results Findings from 114 subjects (age range 4 to 56 years) were evaluated. While subject age was significantly ( p < 0.0001) correlated with increased CAJIS ( r = 0.66) and FOP-PFQ scores ( r = 0.41), the estimated mean increases per year (based on cross-sectional average changes over time) were small (0.47 units and 1.2%, respectively). There was also a significant ( p < 0.0001) correlation between baseline age and HO volume ( r = 0.56), with an estimated mean increase of 25,574 mm 3 /year. There were significant ( p < 0.0001) correlations between the objective assessment of HO volume and clinical assessments of CAJIS ( r = 0.57) and FOP-PFQ ( r = 0.52). Conclusions Based on the cross-sectional analysis of the baseline data, functional and physical disability as assessed by CAJIS and the FOP-PFQ increased over time. Although longitudinal data are not yet available, the cross-sectional analyses suggest that CAJIS and FOP-PFQ are not sensitive to detect substantial progression over a 1- to 2-year period. Future evaluation of longitudinal data will test this hypothesis. The statistically significant correlations between HO volume and the functional endpoints, and the estimated average annual increase in total HO volume, suggest that the formation of new HO will be measurable over the relative short-term course of a clinical trial, and represents an endpoint that is clinically meaningful to patients. Trial registration This study ( NCT02322255 ) was first posted on 23 December, 2014. Electronic supplementary material The online version of this article (10.1186/...

In young adults with onset of chronic kidney disease in childhood, cardiovascular disease is the most common cause of death. The likely reason for increased cardiovascular disease in these patients is high prevalence of traditional and uremia-related cardiovascular disease risk factors during childhood chronic kidney disease. Early markers of cardiomyopathy, such as left ventricular hypertrophy and left ventricular dysfunction and early markers of atherosclerosis, such as increased carotid artery intima-media thickness, carotid arterial wall stiffness and coronary artery calcification are frequently found in this patient population. The purpose of this review is to provide an update of recent advances in the understanding and management of cardiovascular disease risks in this population.

metabolic syndrome is common at time of pediatric kidney transplant, and prevalence rises sharply at one-yr post-transplant. The presence of metabolic syndrome is strongly associated with LVH in these patients.

A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.