Interaction of language, auditory and memory brain networks in auditory verbal hallucinations

Auditory verbal hallucinations (AVH) occur in psychotic disorders, but also as a symptom of other conditions and even in healthy people. Several current theories on the origin of AVH converge, with neuroimaging studies suggesting that the language, auditory and memory/limbic networks are of particular relevance. However, reconciliation of these theories with experimental evidence is missing. We review 50 studies investigating functional (EEG and fMRI) and anatomic (diffusion tensor imaging) connectivity in these networks, and explore the evidence supporting abnormal connectivity in these networks associated with AVH. We distinguish between functional connectivity during an actual hallucination experience (symptom capture) and functional connectivity during either the resting state or a task comparing individuals who hallucinate with those who do not (symptom association studies). Symptom capture studies clearly reveal a pattern of increased coupling among the auditory, language and striatal regions. Anatomical and symptom association functional studies suggest that the interhemispheric connectivity between posterior auditory regions may depend on the phase of illness, with increases in non-psychotic individuals and first episode patients and decreases in chronic patients. Leading hypotheses involving concepts as unstable memories, source monitoring, top-down attention, and hybrid models of hallucinations are supported in part by the published connectivity data, although several caveats and inconsistencies remain. Specifically, possible changes in fronto-temporal connectivity are still under debate. Precise hypotheses concerning the directionality of connections deduced from current theoretical approaches should be tested using experimental approaches that allow for discrimination of competing hypotheses

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Veneuze trombose als eerste signaal van SLE

Venous thrombosis in children is rare. In adolescents it may be the first manifestation of a chronic disease such as systemic lupus erythematosus (SLE). An obese 12-year-old girl visited the Obesity Clinic and mentioned pain in her right calf. Some time before her arrival she spent time in bed with a respiratory infection. Deep vein thrombosis was diagnosed by ultrasonography. Radiography showed an infiltrate, laboratory tests showed elevated inflammatory parameters, and thrombophilia testing showed a Factor V Leiden mutation as well as the presence of lupus anticoagulants. During her stay she developed haematological, immunological and clinical signs of SLE. The cause of venous thrombosis in children is usually multifactorial. Despite the presence of obvious risk factors, it is important to follow adolescents with thrombosis and to be alert for any signs of an underlying systemic diseas

Efficacy and tolerability of a high loading dose (25,000 IU weekly) vitamin D3 supplementation in obese children with vitamin D insufficiency/deficiency

BACKGROUND: The recommended dose of vitamin D supplementation of 400 IU/day might be inadequate to treat obese children with vitamin D insufficiency. Therefore, we tested the efficacy and tolerability of a high loading dose vitamin D3 supplementation of 25,000 IU weekly in multiethnic obese children, 8-18 years of age, with vitamin D insufficiency/deficiency. METHODS: Fasting blood samples were drawn for the assessment of vitamin D. Vitamin D-insufficient/-deficient children (50 nmol/l) was reached in >75% without side effects nor reaching toxic levels. RESULTS: In total, 109 children (mean ± SD age 11.1 ± 3.0, 34.2% boys, 90.8% obese) received vitamin D supplementation. In 84.4% of the children, the vitamin D status improved from insufficiency/deficiency (<50 nmol/l) to sufficiency (≥50 nmol/l). The majority of children that did not reach vitamin D sufficiency reported non-compliance. No side effects were reported, and the highest level reached was far below the threshold for toxicity. CONCLUSION: A high loading dose vitamin D3 supplementation is effective and well-tolerated in our cohort of multiethnic obese children with vitamin D insufficiency/deficiency

Home‐based exergaming to treat gait and balance disorders in patients with Parkinson's disease: A phase II randomized controlled trial

Abstract Background Exergaming has been proposed to improve gait and balance disorders in Parkinson's disease (PD) patients. We aimed to assess the efficacy of a home‐based, tailored, exergaming training system designed for PD patients with dopa‐resistant gait and/or balance disorders in a controlled randomized trial. Methods We recruited PD patients with dopa‐resistant gait and/or balance disorders. Patients were randomly assigned (1:1 ratio) to receive 18 training sessions at home by playing a tailored exergame with full‐body movements using a motion capture system (Active group), or by playing the same game with the computer's keyboard (Control group). The primary endpoint was the between‐group difference in the Stand‐Walk‐Sit Test (SWST) duration change after training. Secondary outcomes included parkinsonian clinical scales, gait recordings, and safety. Results Fifty PD patients were enrolled and randomized. After training, no significant difference in SWST change was found between groups (mean change SWST duration [SD] −3.71 [18.06] s after Active versus −0.71 [3.41] s after Control training, p = 0.61). Some 32% of patients in the Active and 8% in the Control group were considered responders to the training program (e.g., SWST duration change ≥2 s, p = 0.03). The clinical severity of gait and balance disorders also significantly decreased after Active training, with a between‐group difference in favor of the Active training ( p = 0.0082). Home‐based training induced no serious adverse events. Conclusions Home‐based training using a tailored exergame can be performed safely by PD patients and could improve gait and balance disorders. Future research is needed to investigate the potential of exergaming