Association of metabolic syndrome with hyperfiltration in a general non-diabetic population – The Renal Iohexol Clearance Survey

Background: Metabolic syndrome (MS) affects approximately one quarter of the world, making it a global epidemic (1). Although MS has been associated with increased risk of rapid decline in the glomerular filtration rate (GFR) (2), only a few studies have investigated the association of MS with abnormally elevated GFR, known as renal hyperfiltration (RHF). Previous studies of MS and RHF were limited by the use of estimated GFR (eGFR) and the results were divergent. Establishing the relationship between MS and RHF is of clinical importance as there are promising treatment options for RHF. Methods: In the Renal Iohexol Clearance Survey (RENIS) we included 1551 subjects from the population based Tromsø survey (2007-2009). The participants were 50-62 years old without known diabetes, cardiovascular disease or kidney disease. The GFR was measured (mGFR) using iohexol clearance. The aim was to investigate the relationship between MS and RHF. The dichotomous variable for RHF was defined as an absolute GFR (ml/min) above the 90th percentile adjusted for gender, age and height (3). Results: MS was associated with increased absolute GFR (ml/min) and RHF (yes/no) independent of age, sex and height (OR 2.44 95% CI; 1.71 – 3.46, p<0.001). All risk factors except for hypertension were independently associated with RHF and increased absolute GFR. The risk of RHF was highest in subjects fulfilling 5 out of 5 criteria (OR 4.06, 95% CI; 1.54-10.67, p=0.005) compared to those fulfilling 0 or 1 criteria. Conversely, MS was not associated with higher estimated GFR based on creatinine, cystatin C or both together. Conclusions: Subjects with MS have a higher absolute GFR and increased risk of RHF compared to subjects without MS. RCTs are needed to explore whether treatment of RHF can prevent accelerated GFR decline and CKD in persons with MS

Major depression mistaken as frontotemporal dementia due to PET scan

Frontotemporal dementia (FTD) is associated with progressive degeneration of the frontal lobes and this leads to changes in language, motor symptoms, behavior and executive functions.1 In an early stage, patients with FTD usually have intact memory functions.2 40% of the cases of FTD are misdiagnosed,3 with delayed diagnosis compared to other dementias.4 Differentiating FTD from other psychiatric disorders poses challenges, given executive impairment is a common symptom across disorders.5 The need for diagnostic tools has led to the increased use of positron emission tomography (PET), which is regarded as the most accurate in-vivo method for investigating brain metabolism.6 We present a case where PET was central to the diagnostic process.publishedVersio

A four-month home-based tDCS study on patients with Alzheimer’s disease

In the present open-label study, our first aim was to study the tolerability and feasibility of long-term treatment with transcranial direct current stimulation (tDCS) and the second aim was to measure whether the treatment led to cognitive improvement. Participants with AD used a tDCS home-treatment kit inducing a low current (2 mA) via two scalp electrodes 30 minutes daily for 4 months. A total of 8 participants were recruited. The treatment technique was manageable for the participants and their spouses, and no troublesome side effects were reported. No significant effects of treatment were found after 4 months

The Association Between Metabolic Syndrome, Hyperfiltration, and Long-Term GFR Decline in the General Population

Introduction: One-quarter of adults worldwide meet the criteria of metabolic syndrome (MetS). MetS increases the risk of diabetes, chronic kidney disease (CKD), and cardiovascular disease. However, the association between MetS, hyperfiltration, and long-term glomerular filtration rate (GFR) decline in the general population is unknown. Methods: In the Renal Iohexol Clearance Survey (RENIS), we investigated 1551 people aged 50 to 63 years; representative of the general population without diabetes, cardiovascular disease, or kidney disease. The GFR was measured using iohexol clearance at baseline and twice during 11 years of follow-up. Hyperfiltration at baseline was defined as an absolute GFR (ml/min) above the 90th percentile adjusted for sex, age, and height, because these variables correlate with nephron number. MetS was defined as increased waist circumference and 2 risk factors among hypertension, hyperglycemia, elevated triglycerides, and low high density lipoprotein (HDL)-cholesterol levels. The GFR decline rate was calculated using linear mixed models. Results: MetS was associated with hyperfiltration at baseline (odds ratio [OR] 2.4; 95% CI: 1.7–3.5, P 2 /yr). Compared to those without MetS, GFR decline was 0.83 (95% CI: 1.13 to 0.53) ml/min per 1.73 m2 /yr in those with MetS and baseline hyperfiltration and 0.15 ( 0.30 to 0.00) in those MetS without hyperfiltration, P ¼ 0.2 for interaction. Conclusions: In the nondiabetic general population, those with MetS had an increased OR of hyperfiltration and steeper long-term GFR decline. Randomized controlled trials are needed to explore whether treatment of hyperfiltration can prevent loss of GFR in persons with MetS

Patients Who Die by Suicide: A Study of Treatment Patterns and Patient Safety Incidents in Norway

Underlying patterns and factors behind suicides of patients in treatment are still unclear and there is a pressing need for more studies to address this knowledge gap. We analysed 278 cases of suicide reported to The Norwegian System of Patient Injury Compensation, drawing on anonymised data, i.e., age group, gender, diagnostic category, type of treatment provided, inpatient vs. outpatient status, type of treatment facility, and expert assessments of medical errors. The data originated from compensation claim forms, expert assessments, and medical records. Chi-square tests for independence, multinominal logistic regression, and Bayes factors for independence were used to analyse whether the age group, gender, diagnostic category, inpatient/outpatient status, type of institution, and type of treatment received by patients that had died by suicide were associated with different types of medical errors. Patients who received medication tended to be proportionally more exposed to an insufficient level of observation. Those who received medication and psychotherapy tended to be proportionally more exposed to inadequate treatment, including inadequate medication. Inpatients were more likely to be exposed to inappropriate diagnostics and inadequate treatment and follow up while outpatients to insufficient level of observation and inadequate suicide risk assessment. We conclude that the patients who had received medication as their main treatment tended to have been insufficiently observed, while patients who had received psychotherapy and medication tended to have been provided insufficient treatment, including inadequate medication. These observations may be used as learning points for the suicide prevention of patients in treatment in Norwegian psychiatric services

Døgnvariasjoner for innleggelser ved akuttpsykiatriske enheter

Akuttpsykiatriske enheter gir øyeblikkelig hjelp til pasienter med særlig vanskelige og kompliserte tilstander med behov utover det som kan ivaretas i kommunehelsetjenesten eller ved distriktspsykiatriske senter (DPS). Flere studier har de siste årene sett på antallet innleggelser og hyppigheten av tvangsbruk i akuttpsykiatriske enheter i Norge (Bjerke et al., 2019; Tøgersen et al., 2015; Wynn, 2018). Bjerke, Gjelstad og Ruud viser at antallet tvangsinnleggelser holdt seg stabilt i perioden 2010 til 2017 (Bjerke et al., 2019). Videre er det funnet at den gjennomsnittlige liggetiden i psykisk helsevern er redusert med 30 % i perioden fra 2009 til 2018 (Statistisk sentralbyrå, 2019). Noen studier har også sett på tidspunkt for innleggelser i akuttpsykiatrien, det vil si når på døgnet pasienter blir lagt inn. Dette har imidlertid ikke blitt undersøkt de siste 10 årene og etter at samhandlingsreformen trådte i kraft (St.meld. nr. 47, 2008). Innleggelser ved akuttpsykiatriske enheter viser noe ulike mønstre. En norsk multisenterstudie fra 2006 der 19 akuttpsykiatriske enheter deltok, viste at gjennomsnittlig 48 % av innleggelsene i akuttpsykiatrien fant sted på dagtid, mens 42 % på kveldstid og 10 % på natt (Gråwe, Hatling & Ruud, 2006). En annen norsk studie fant at 24 % av pasientene ble innlagt mellom klokken (kl.) 16:00 og 22:00, mens 19 % ble lagt inn mellom kl. 22:00 og kl. 08:00, og øvrige innleggelser fant sted på dagtid (Deraas et al., 2006). Videre viste en undersøkelse av 1323 psykiatriske akuttinnleggelser på Lovisenberg Sykehus at 52 % av innleggelsene fant sted på dagtid, altså mellom klokken 08:00 og 16:00 (Berg, 2007). Det ble funnet at 39 % ble innlagt mellom klokken 16:00 og 01:00 og 9 % i tidsrommet 01:00–08:00. Forskjellene mellom tidspunktene var imidlertid ikke signifikante. Hensikten med den nåværende studien er å undersøke hvordan innleggelser i akuttpsykiatriske enheter fordeler seg over døgnet. Vi forventet å finne at flertallet av innleggelsene skjedde på dagtid

Transcranial direct current stimulation as a memory enhancer in patients with Alzheimer’s disease: a randomized, placebo-controlled trial

Background: The purpose of this study was to assess the efficacy of transcranial direct current stimulation (tDCS) on verbal memory function in patients with Alzheimer’s disease. Methods: We conducted a randomized, placebo-controlled clinical trial in which tDCS was applied in six 30-minute sessions for 10 days. tDCS was delivered to the left temporal cortex with 2-mA intensity. A total of 25 patients with Alzheimer’s disease were enrolled in the study. All of the patients were diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association criteria. Twelve patients received active stimulation, and thirteen patients received placebo stimulation. The primary outcome measure was the change in two parallel versions of the California Verbal Learning Test–Second Edition, a standardized neuropsychological memory test normalized by age and gender. The secondary outcome measures were the Mini Mental State Examination, clock-drawing test, and Trail Making Test A and B. Results: Changes in the California Verbal Learning Test–Second Edition scores were not significantly different between the active and placebo stimulation groups for immediate recall (p = 0.270), delayed recall (p = 0.052), or recognition (p = 0.089). There were nonsignificant differences in score changes on the Mini Mental State Examination (p = 0.799), clock-drawing test (p = 0.378), and Trail Making Test A (p = 0.288) and B (p = 0.093). Adverse effects were not observed. Conclusions: Compared with placebo stimulation, active tDCS stimulation in this clinical trial did not significantly improve verbal memory function in Alzheimer’s disease. This study differs from previous studies in terms of the stimulation protocol, trial design, and application of standardized neuropsychological memory assessment. Trial registration: ClinicalTrials.gov identifier NCT02518412. Registered on 10 August 2015

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the early diagnosis of dementia across a variety of healthcare settings

Background: The Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) is a structured interview based on informant responses that is used to assess for possible dementia. IQCODE has been used for retrospective or contemporaneous assessment of cognitive decline. There is considerable interest in tests that may identify those at future risk of developing dementia. Assessing a population free of dementia for the prospective development of dementia is an approach often used in studies of dementia biomarkers. In theory, questionnaire-based assessments, such as IQCODE, could be used in a similar way, assessing for dementia that is diagnosed on a later (delayed) assessment. Objectives: To determine the diagnostic accuracy of IQCODE in a population free from dementia for the delayed diagnosis of dementia (test accuracy with delayed verification study design). Search methods: We searched these sources on 16 January 2016: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE Ovid SP, Embase Ovid SP, PsycINFO Ovid SP, BIOSIS Previews on Thomson Reuters Web of Science, Web of Science Core Collection (includes Conference Proceedings Citation Index) on Thomson Reuters Web of Science, CINAHL EBSCOhost, and LILACS BIREME. We also searched sources specific to diagnostic test accuracy: MEDION (Universities of Maastricht and Leuven); DARE (Database of Abstracts of Reviews of Effects, in the Cochrane Library); HTA Database (Health Technology Assessment Database, in the Cochrane Library), and ARIF (Birmingham University). We checked reference lists of included studies and reviews, used searches of included studies in PubMed to track related articles, and contacted research groups conducting work on IQCODE for dementia diagnosis to try to find additional studies. We developed a sensitive search strategy; search terms were designed to cover key concepts using several different approaches run in parallel, and included terms relating to cognitive tests, cognitive screening, and dementia. We used standardised database subject headings, such as MeSH terms (in MEDLINE) and other standardised headings (controlled vocabulary) in other databases, as appropriate. Selection criteria: We selected studies that included a population free from dementia at baseline, who were assessed with the IQCODE and subsequently assessed for the development of dementia over time. The implication was that at the time of testing, the individual had a cognitive problem sufficient to result in an abnormal IQCODE score (defined by the study authors), but not yet meeting dementia diagnostic criteria. Data collection and analysis: We screened all titles generated by the electronic database searches, and reviewed abstracts of all potentially relevant studies. Two assessors independently checked the full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool, and reported quality using the STARDdem tool. Main results: From 85 papers describing IQCODE, we included three papers, representing data from 626 individuals. Of this total, 22% (N = 135/626) were excluded because of prevalent dementia. There was substantial attrition; 47% (N = 295) of the study population received reference standard assessment at first follow-up (three to six months) and 28% (N = 174) received reference standard assessment at final follow-up (one to three years). Prevalence of dementia ranged from 12% to 26% at first follow-up and 16% to 35% at final follow-up. The three studies were considered to be too heterogenous to combine, so we did not perform meta-analyses to describe summary estimates of interest. Included patients were poststroke (two papers) and hip fracture (one paper). The IQCODE was used at three thresholds of positivity (higher than 3.0, higher than 3.12 and higher than 3.3) to predict those at risk of a future diagnosis of dementia. Using a cut-off of 3.0, IQCODE had a sensitivity of 0.75 (95%CI 0.51 to 0.91) and a specificity of 0.46 (95%CI 0.34 to 0.59) at one year following stroke. Using a cut-off of 3.12, the IQCODE had a sensitivity of 0.80 (95%CI 0.44 to 0.97) and specificity of 0.53 (95C%CI 0.41 to 0.65) for the clinical diagnosis of dementia at six months after hip fracture. Using a cut-off of 3.3, the IQCODE had a sensitivity of 0.84 (95%CI 0.68 to 0.94) and a specificity of 0.87 (95%CI 0.76 to 0.94) for the clinical diagnosis of dementia at one year after stroke. In generaI, the IQCODE was sensitive for identification of those who would develop dementia, but lacked specificity. Methods for both excluding prevalent dementia at baseline and assessing for the development of dementia were varied, and had the potential to introduce bias. Authors' conclusions: Included studies were heterogenous, recruited from specialist settings, and had potential biases. The studies identified did not allow us to make specific recommendations on the use of the IQCODE for the future diagnosis of dementia in clinical practice. The included studies highlighted the challenges of delayed verification dementia research, with issues around prevalent dementia assessment, loss to follow-up over time, and test non-completion potentially limiting the studies. Future research should recognise these issues and have explicit protocols for dealing with them