A longitudinal examination of plasma neurofilament light and total tau for the clinical detection and monitoring of Alzheimer's disease

We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer's disease (AD). A total of 579 participants (238, normal cognition [NC]; 185, mild cognitive impairment [MCI]; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia than MCI (standardized mean difference = 0.55, 95% CI: 0.37–0.73) and NC (standardized mean difference = 0.68, 95% CI: 0.49–0.88), corresponded to Clinical Dementia Rating scores (OR = 1.94, 95% CI: 1.35–2.79]), and correlated with all neuropsychological tests (r's = 0.13–0.42). Longitudinally, NfL did not predict diagnostic conversion but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia than NC with a small effect (standardized mean difference = 0.33, 95% CI: 0.10–0.57) but not MCI. t-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau

Hypnosis for treatment of insomnia in school-age children: a retrospective chart review

BACKGROUND: The purposes of this study are to document psychosocial stressors and medical conditions associated with development of insomnia in school-age children and to report use of hypnosis for this condition. METHODS: A retrospective chart review was performed for 84 children and adolescents with insomnia, excluding those with central or obstructive sleep apnea. All patients were offered and accepted instruction in self-hypnosis for treatment of insomnia, and for other symptoms if it was felt that these were amenable to therapy with hypnosis. Seventy-five patients returned for follow-up after the first hypnosis session. Their mean age was 12 years (range, 7–17). When insomnia did not resolve after the first instruction session, patients were offered the opportunity to use hypnosis to gain insight into the cause. RESULTS: Younger children were more likely to report that the insomnia was related to fears. Two or fewer hypnosis sessions were provided to 68% of the patients. Of the 70 patients reporting a delay in sleep onset of more than 30 minutes, 90% reported a reduction in sleep onset time following hypnosis. Of the 21 patients reporting nighttime awakenings more than once a week, 52% reported resolution of the awakenings and 38% reported improvement. Somatic complaints amenable to hypnosis were reported by 41%, including chest pain, dyspnea, functional abdominal pain, habit cough, headaches, and vocal cord dysfunction. Among these patients, 87% reported improvement or resolution of the somatic complaints following hypnosis. CONCLUSION: Use of hypnosis appears to facilitate efficient therapy for insomnia in school-age children

Controlling behavior, power relations within intimate relationships and intimate partner physical and sexual violence against women in Nigeria

<p>Abstract</p> <p>Background</p> <p>Controlling behavior is more common and can be equally or more threatening than physical or sexual violence. This study sought to determine the role of husband/partner controlling behavior and power relations within intimate relationships in the lifetime risk of physical and sexual violence in Nigeria.</p> <p>Methods</p> <p>This study used secondary data from a cross-sectional nationally-representative survey collected by face-to-face interviews from women aged 15 - 49 years in the 2008 Nigeria Demographic and Health Survey. Utilizing a stratified two-stage cluster sample design, data was collected frrm 19 216 eligible with the DHS domestic violence module, which is based on the Conflict Tactics Scale (CTS). Multivariate logistic regression analysis was used to determine the role of husband/partner controlling behavior in the risk of ever experiencing physical and sexual violence among 2877 women aged 15 - 49 years who were currently or formerly married or cohabiting with a male partner.</p> <p>Results</p> <p>Women who reported controlling behavior by husband/partner had a higher likelihood of experiencing physical violence (RR = 3.04; 95% CI: 2.50 - 3.69), and women resident in rural areas and working in low status occupations had increased likelihood of experiencing physical IPV. Controlling behavior by husband/partner was associated with higher likelihood of experiencing physical violence (RR = 4.01; 95% CI: 2.54 - 6.34). In addition, women who justified wife beating and earned more than their husband/partner were at higher likelihood of experiencing physical and sexual violence. In contrast, women who had decision-making autonomy had lower likelihood of experiencing physical and sexual violence.</p> <p>Conclusion</p> <p>Controlling behavior by husband/partner significantly increases the likelihood of physical and sexual IPV, thus acting as a precursor to violence. Findings emphasize the need to adopt a proactive integrated approach to controlling behavior and intimate partner violence within the society.</p

Study protocol: a randomized controlled trial of a computer-based depression and substance abuse intervention for people attending residential substance abuse treatment

Background: A large proportion of people attending residential alcohol and other substance abuse treatment have a co-occurring mental illness. Empirical evidence suggests that it is important to treat both the substance abuse problem and co-occurring mental illness concurrently and in an integrated fashion. However, the majority of residential alcohol and other substance abuse services do not address mental illness in a systematic way. It is likely that computer delivered interventions could improve the ability of substance abuse services to address co-occurring mental illness. This protocol describes a study in which we will assess the effectiveness of adding a computer delivered depression and substance abuse intervention for people who are attending residential alcohol and other substance abuse treatment. Methods/Design. Participants will be recruited from residential rehabilitation programs operated by the Australian Salvation Army. All participants who satisfy the diagnostic criteria for an alcohol or other substance dependence disorder will be asked to participate in the study. After completion of a baseline assessment, participants will be randomly assigned to either a computer delivered substance abuse and depression intervention (treatment condition) or to a computer-delivered typing tutorial (active control condition). All participants will continue to complete The Salvation Army residential program, a predominantly 12-step based treatment facility. Randomisation will be stratified by gender (Male, Female), length of time the participant has been in the program at the commencement of the study (4 weeks or less, 4 weeks or more), and use of anti-depressant medication (currently prescribed medication, not prescribed medication). Participants in both conditions will complete computer sessions twice per week, over a five-week period. Research staff blind to treatment allocation will complete the assessments at baseline, and then 3, 6, 9, and 12 months post intervention. Participants will also complete weekly self-report measures during the treatment period. Discussion. This study will provide comprehensive data on the effect of introducing a computer delivered, cognitive behavioral therapy based co-morbidity treatment program within a residential substance abuse setting. If shown to be effective, this intervention can be disseminated within other residential substance abuse programs. Trial registration. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000618954

Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. The prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) pathway is a key mammalian oxygen sensing pathway and is frequently perturbed by pathological states including infection and inflammation. We discovered a significant upregulation of hypoxia regulated gene transcripts in patients with chronic hepatitis B (CHB) in the absence of liver cirrhosis. We used state-of-the-art in vitro and in vivo HBV infection models to evaluate a role for HBV infection and the viral regulatory protein HBx to drive HIF-signalling. HBx had no significant impact on HIF expression or associated transcriptional activity under normoxic or hypoxic conditions. Furthermore, we found no evidence of hypoxia gene expression in HBV de novo infection, HBV infected human liver chimeric mice or transgenic mice with integrated HBV genome. Collectively, our data show clear evidence of hypoxia gene induction in CHB that is not recapitulated in existing models for acute HBV infection, suggesting a role for inflammatory mediators in promoting hypoxia gene expression

Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis

Previous reports indicate an association between autism spectrum disorders (ASD) and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder.We reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC) dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32%) and unusual patterns of regression (40%). Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64%) and complex III (20%). Two patients had rare mtDNA mutations of likely pathogenicity.Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism

Methods for the guideline-based development of quality indicators--a systematic review

<p>Abstract</p> <p>Background</p> <p>Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development.</p> <p>Methods</p> <p>We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables.</p> <p>Results</p> <p>From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement.</p> <p>Conclusions</p> <p>Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork.</p

Safe approaches for camptothecin delivery: Structural analogues and nanomedicines

[EN] Twenty-(S)-camptothecin is a strongly cytotoxic molecule with excellent antitumor activity over a wide spectrum of human cancers. However, the direct formulation is limited by its poor water solubility, low plasmatic stability and severe toxicity, which currently limits its clinical use. As a consequence, two strategies have been developed in order to achieve safe and efficient delivery of camptothecin to target cells: structural analogues and nanomedicines. In this review, we summarize recent advances in the design, synthesis and development of camptothecin molecular derivatives and supramolecular vehicles, following a systematic classification according to structure-activity relationships (structural analogues) or chemical nature (nanomedicines). A series of organic, inorganic and hybrid materials are presented as nanoplatforms to overcome camptothecin restrictions in administration, biodistribution, pharmacokinetics and toxicity. Nanocarriers which respond to a variety of stimuli endogenously (e.g., pH, redox potential, enzyme activity) or exogenously (e.g., magnetic field, light, temperature, ultrasound) seem the best positioned therapeutic materials for optimal spatial and temporal control over drug release. The main goal of this review is to be used as a source of relevant literature for others interested in the field of camptothecin-based therapeutics. To this end, final remarks on the most important formulations currently under clinical trial are provided. (C) 2016 Elsevier B.V. All rights reserved.Financial support of the Spanish Ministry of Economy and Competitiveness (projects MAT2012-39290-C02-02 and SEV-2012-0267) is gratefully acknowledged. Dr. E.M. Rivero thanks the Cursol Foundation for a post-doctoral scholarship.Botella Asuncion, P.; Rivero-Buceta, EM. (2017). Safe approaches for camptothecin delivery: Structural analogues and nanomedicines. Journal of Controlled Release. 247:28-54. https://doi.org/10.1016/j.jconrel.2016.12.023S285424