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1.
Cochrane Database Syst Rev ; 10: CD011611, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623633

RESUMO

BACKGROUND: Glutamergic system dysfunction has been implicated in the pathophysiology of bipolar depression. This is an update of the 2015 Cochrane Review for the use of glutamate receptor modulators for depression in bipolar disorder. OBJECTIVES: 1. To assess the effects of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with bipolar disorder. 2. To review the acceptability of ketamine and other glutamate receptor modulators in people with bipolar disorder who are experiencing depressive symptoms. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO all years to July 2020.  We did not apply any restrictions to date, language or publication status. SELECTION CRITERIA: RCTs comparing ketamine or other glutamate receptor modulators with other active psychotropic drugs or saline placebo in adults with bipolar depression. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed trial quality and extracted data. Primary outcomes were response rate and adverse events. Secondary outcomes included remission rate, depression severity change scores, suicidality, cognition, quality of life, and dropout rate. The GRADE framework was used to assess the certainty of the evidence. MAIN RESULTS: Ten studies (647 participants) were included in this review (an additional five studies compared to the 2015 review). There were no additional studies added to the comparisons identified in the 2015 Cochrane review on ketamine, memantine and cytidine versus placebo. However, three new comparisons were found: ketamine versus midazolam, N-acetylcysteine versus placebo, and riluzole versus placebo. The glutamate receptor modulators studied were ketamine (three trials), memantine (two), cytidine (one), N-acetylcysteine (three), and riluzole (one). Eight of these studies were placebo-controlled and two-armed. In seven trials the glutamate receptor modulators had been used as add-on drugs to mood stabilisers. Only one trial compared ketamine with an active comparator, midazolam. The treatment period ranged from a single intravenous administration (all ketamine studies), to repeated administration for riluzole, memantine, cytidine, and N-acetylcysteine (with a follow-up of eight weeks, 8 to 12 weeks, 12 weeks, and 16 to 20 weeks, respectively). Six of the studies included sites in the USA, one in Taiwan, one in Denmark, one in Australia, and in one study the location was unclear. All participants had a primary diagnosis of bipolar disorder and were experiencing an acute bipolar depressive episode, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (IV) or fourth edition text revision (IV-TR). Among all glutamate receptor modulators included in this review, only ketamine appeared to be more efficacious than placebo 24 hours after infusion for response rate (odds ratio (OR) 11.61, 95% confidence interval (CI) 1.25 to 107.74; P = 0.03; participants = 33; studies = 2; I² = 0%, low-certainty evidence). Ketamine seemed to be more effective in reducing depression rating scale scores (MD -11.81, 95% CI -20.01 to -3.61; P = 0.005; participants = 32; studies = 2; I2 = 0%, very low-certainty evidence). There was no evidence of ketamine's efficacy in producing remission over placebo at 24 hours (OR 5.16, 95% CI 0.51 to 52.30; P = 0.72; participants = 33; studies = 2; I2 = 0%, very low-certainty evidence). Evidence on response, remission or depression rating scale scores between ketamine and midazolam was uncertain at 24 hours due to very low-certainty evidence (OR 3.20, 95% CI 0.23 to 45.19). In the one trial assessing ketamine and midazolam, there were no dropouts due to adverse effects or for any reason (very low-certainty evidence). Placebo may have been more effective than N-acetylcysteine in reducing depression rating scale scores at three months, although this was based on very low-certainty evidence (MD 1.28, 95% CI 0.24 to 2.31; participants = 58; studies = 2). Very uncertain evidence found no difference in response at three months (OR 0.82, 95% CI 0.32 to 2.14; participants = 69; studies = 2; very low-certainty evidence). No data were available for remission or acceptability. Extremely limited data were available for riluzole vs placebo, finding only very-low certainty evidence of no difference in dropout rates (OR 2.00, 95% CI 0.31 to 12.84; P = 0.46; participants = 19; studies = 1; I2 = 0%). AUTHORS' CONCLUSIONS: It is difficult to draw reliable conclusions from this review due to the certainty of the evidence being low to very low, and the relatively small amount of data usable for analysis in bipolar disorder, which is considerably less than the information available for unipolar depression. Nevertheless, we found uncertain evidence in favour of a single intravenous dose of ketamine (as add-on therapy to mood stabilisers) over placebo in terms of response rate up to 24 hours, however ketamine did not show any better efficacy for remission in bipolar depression. Even though ketamine has the potential to have a rapid and transient antidepressant effect, the efficacy of a single intravenous dose may be limited. We did not find conclusive evidence on adverse events with ketamine, and there was insufficient evidence to draw meaningful conclusions for the remaining glutamate receptor modulators. However, ketamine's psychotomimetic effects (such as delusions or delirium) may have compromised study blinding in some studies, and so we cannot rule out the potential bias introduced by inadequate blinding procedures. To draw more robust conclusions, further methodologically sound RCTs (with adequate blinding) are needed to explore different modes of administration of ketamine, and to study different methods of sustaining antidepressant response, such as repeated administrations.

2.
Cochrane Database Syst Rev ; 9: CD011612, 2021 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510411

RESUMO

BACKGROUND: Many studies have recently been conducted to assess the antidepressant efficacy of glutamate modification in mood disorders. This is an update of a review first published in 2015 focusing on the use of glutamate receptor modulators in unipolar depression. OBJECTIVES: To assess the effects - and review the acceptability and tolerability - of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with unipolar major depressive disorder. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO all years to July 2020.  We did not apply any restrictions to date, language or publication status. SELECTION CRITERIA: Double- or single-blinded randomised controlled trials (RCTs) comparing ketamine, memantine, esketamine or other glutamate receptor modulators with placebo (pill or saline infusion), other active psychotropic drugs, or electroconvulsive therapy (ECT) in adults with unipolar major depression. DATA COLLECTION AND ANALYSIS: Three review authors independently identified studies, assessed trial quality and extracted data. The primary outcomes were response rate (50% reduction on a standardised rating scale) and adverse events. We decided a priori to measure the efficacy outcomes at different time points and run sensitivity/subgroup analyses. Risk of bias was assessed using the Cochrane tool, and certainty of the evidence was assessed using GRADE. MAIN RESULTS: Thirty-one new studies were identified for inclusion in this updated review. Overall, we included 64 studies (5299 participants) on ketamine (31 trials), esketamine (9), memantine (5), lanicemine (4), D-cycloserine (2), Org26576 (2), riluzole (2), atomoxetine (1), basimglurant (1), citicoline (1), CP-101,606 (1), decoglurant (1), MK-0657 (1), N-acetylcysteine (1), rapastinel (1), and sarcosine (1). Forty-eight studies were placebo-controlled, and 48 were two-arm studies. The majority of trials defined an inclusion criterion for the severity of depressive symptoms at baseline: 29 at least moderate depression; 17 severe depression; and five mild-to-moderate depression. Nineteen studies recruited only patients with treatment-resistant depression, defined as inadequate response to at least two antidepressants. The majority of studies investigating ketamine administered as a single dose, whilst all of the included esketamine studies used a multiple dose regimen (most frequently twice a week for four weeks). Most studies looking at ketamine used intravenous administration, whilst the majority of esketamine trials used intranasal routes. The evidence suggests that ketamine may result in an increase in response and remission compared with placebo at 24 hours odds ratio (OR) 3.94, 95% confidence interval (CI) 1.54 to 10.10; n = 185, studies = 7, very low-certainty evidence). Ketamine may reduce depression rating scale scores over placebo at 24 hours, but the evidence is very uncertain (standardised mean difference (SMD) -0.87, 95% CI -1.26 to -0.48; n = 231, studies = 8, very low-certainty evidence). There was no difference in the number of participants assigned to ketamine or placebo who dropped out for any reason (OR 1.25, 95% CI 0.19 to 8.28; n = 201, studies = 6, very low-certainty evidence). When compared with midazolam, the evidence showed that ketamine increases remission rates at 24 hours (OR 2.21, 95% CI 0.67 to 7.32; n = 122,studies = 2, low-certainty evidence). The evidence is very uncertain about the response efficacy of ketamine at 24 hours in comparison with midazolam, and its ability to reduce depression rating scale scores at the same time point (OR 2.48, 95% CI 1.00 to 6.18; n = 296, studies = 4,very low-certainty evidence). There was no difference in the number of participants who dropped out of studies for any reason between ketamine and placebo (OR 0.33, 95% CI 0.05 to 2.09; n = 72, studies = 1, low-certainty evidence). Esketamine treatment likely results in a large increase in participants achieving remission at 24 hours compared with placebo (OR 2.74, 95% CI 1.71 to 4.40; n = 894, studies = 5, moderate-certainty evidence). Esketamine probably results in decreases in depression rating scale scores at 24 hours compared with placebo (SMD -0.31, 95% CI -0.45 to -0.17; n = 824, studies = 4, moderate-certainty evidence). Our findings show that esketamine increased response rates, although this evidence is uncertain (OR 2.11, 95% CI 1.20 to 3.68; n = 1071, studies = 5, low-certainty evidence). There was no evidence that participants assigned to esketamine treatment dropped out of trials more frequently than those assigned to placebo for any reason (OR 1.58, 95% CI 0.92 to 2.73; n = 773, studies = 4,moderate-certainty evidence). We found very little evidence for the remaining glutamate receptor modulators. We rated the risk of bias as low or unclear for most domains, though lack of detail regarding masking of treatment in the studies reduced our certainty in the effect for all outcomes. AUTHORS' CONCLUSIONS: Our findings show that ketamine and esketamine may be more efficacious than placebo at 24 hours. How these findings translate into clinical practice, however, is not entirely clear. The evidence for use of the remaining glutamate receptor modulators is limited as very few trials were included in the meta-analyses for each comparison and the majority of comparisons included only one study. Long term non-inferiority RCTs comparing repeated ketamine and esketamine, and rigorous real-world monitoring are needed to establish comprehensive data on safety and efficacy.

3.
Trials ; 22(1): 508, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332638

RESUMO

BACKGROUND: Although Alzheimer's disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer's disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer's disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer's disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer's disease. METHODS: The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer's disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values. DISCUSSION: This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer's disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, the next step will be to rapidly progress to a larger study to establish whether levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03489044 . Registered on April 5, 2018.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Animais , Estudos Cross-Over , Método Duplo-Cego , Humanos , Levetiracetam/efeitos adversos , Camundongos , Estudo de Prova de Conceito , Qualidade de Vida
4.
Cochrane Database Syst Rev ; 7: CD011333, 2021 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-34275145

RESUMO

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 accuracy of the informant-based questionnaire IQCODE for the early detection of dementia across a variety of health care settings. 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 detection 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.


Assuntos
Transtornos Cognitivos/diagnóstico , Demência/diagnóstico , Diagnóstico Precoce , Inquéritos Epidemiológicos/normas , Idoso , Estudos de Coortes , Atenção à Saúde , Demência/epidemiologia , Fraturas do Quadril , Humanos , Padrões de Referência , Sensibilidade e Especificidade , Acidente Vascular Cerebral/complicações , Fatores de Tempo
5.
Cochrane Database Syst Rev ; 7: CD010771, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34278564

RESUMO

BACKGROUND: The IQCODE (Informant Questionnaire for Cognitive Decline in the Elderly) is a commonly used questionnaire based tool that uses collateral information to assess for cognitive decline and dementia. Brief tools that can be used for dementia "screening" or "triage" may have particular utility in primary care / general practice healthcare settings but only if they have suitable test accuracy. A synthesis of the available data regarding IQCODE accuracy in a primary care setting should help inform cognitive assessment strategies for clinical practice; research and policy. OBJECTIVES: To determine the accuracy of the informant-based questionnaire IQCODE, for detection of dementia in a primary care setting. SEARCH METHODS: A search was performed in the following sources on the 28th of January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS (Ovid SP), ISI Web of Science and Conference Proceedings (ISI Web of Knowledge), CINHAL (EBSCOhost) and LILACs (BIREME). We also searched sources specific to diagnostic test accuracy: MEDION (Universities of Maastricht and Leuven); DARE (York University); HTA Database (Health Technology Assessments Database via The Cochrane Library) and ARIF (Birmingham University). 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 standardized database subject headings such as MeSH terms (in MEDLINE) and other standardized headings (controlled vocabulary) in other databases, as appropriate. SELECTION CRITERIA: We selected those studies performed in primary care settings, which included (not necessarily exclusively) IQCODE to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. For the "primary care" setting, we included those healthcare settings where unselected patients, present for initial, non-specialist assessment of memory or non-memory related symptoms; often with a view to onward referral for more definitive assessment. DATA COLLECTION AND ANALYSIS: We screened all titles generated by electronic database searches and abstracts of all potentially relevant studies were reviewed. Full papers were assessed for eligibility and data extracted by two independent assessors. Quality assessment (risk of bias and applicability) was determined using the QUADAS-2 tool. Reporting quality was determined using the STARDdem extension to the STARD tool. MAIN RESULTS: From 71 papers describing IQCODE test accuracy, we included 1 paper, representing data from 230 individuals (n=16 [7%] with dementia). The paper described those patients consulting a primary care service who self-identified as Japanese-American. Dementia diagnosis was made using Benson & Cummings criteria and the IQCODE was recorded as part of a longer interview with the informant. IQCODE accuracy was assessed at various test thresholds, with a "trade-off" between sensitivity and specificity across these cutpoints. At an IQCODE threshold of 3.2 sensitivity: 100%, specificity: 76%; for IQCODE 3.7 sensitivity: 75%, specificity: 98%. Applying the QUADAS-2 assessments, the study was at high risk of bias in all categories. In particular degree of blinding was unclear and not all participants were included in the final analysis. AUTHORS' CONCLUSIONS: It is not possible to give definitive guidance on the test accuracy of IQCODE for the diagnosis of dementia in a primary care setting based on the single study identified. We are surprised by the lack of research using the IQCODE in primary care as this is, arguably, the most appropriate setting for targeted case finding of those with undiagnosed dementia in order to maximise opportunities to intervene and provide support for the individual and their carers.


Assuntos
Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Família , Amigos , Medicina Geral , Inquéritos Epidemiológicos/normas , Americanos Asiáticos , Humanos , Japão/etnologia , Atenção Primária à Saúde , Sensibilidade e Especificidade , Estados Unidos
6.
Cochrane Database Syst Rev ; 7: CD010772, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34278561

RESUMO

BACKGROUND: The diagnosis of dementia relies on the presence of new-onset cognitive impairment affecting an individual's functioning and activities of daily living. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a questionnaire instrument, completed by a suitable 'informant' who knows the patient well, designed to assess change in functional performance secondary to cognitive change; it is used as a tool for identifying those who may have dementia. In secondary care there are two specific instances where patients may be assessed for the presence of dementia. These are in the general acute hospital setting, where opportunistic screening may be undertaken, or in specialist memory services where individuals have been referred due to perceived cognitive problems. To ensure an instrument is suitable for diagnostic use in these settings, its test accuracy must be established. OBJECTIVES: To determine the accuracy of the informant-based questionnaire IQCODE for detection of dementia in a secondary care setting. SEARCH METHODS: We searched the following sources on the 28th of January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (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 - via the Cochrane Library); HTA Database (Health Technology Assessment Database via the Cochrane Library) and ARIF (Birmingham University). We also checked reference lists of relevant studies and reviews, used searches of known relevant 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 those studies performed in secondary-care settings, which included (not necessarily exclusively) IQCODE to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. For the 'secondary care' setting we included all studies which assessed patients in hospital (e.g. acute unscheduled admissions, referrals to specialist geriatric assessment services etc.) and those referred for specialist 'memory' assessment, typically in psychogeriatric services. DATA COLLECTION AND ANALYSIS: We screened all titles generated by electronic database searches, and reviewed abstracts of all potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool, and reporting quality using the STARD tool. MAIN RESULTS: From 72 papers describing IQCODE test accuracy, we included 13 papers, representing data from 2745 individuals (n = 1413 (51%) with dementia). Pooled analysis of all studies using data presented closest to a cut-off of 3.3 indicated that sensitivity was 0.91 (95% CI 0.86 to 0.94); specificity 0.66 (95% CI 0.56 to 0.75); the positive likelihood ratio was 2.7 (95% CI 2.0 to 3.6) and the negative likelihood ratio was 0.14 (95% CI 0.09 to 0.22). There was a statistically significant difference in test accuracy between the general hospital setting and the specialist memory setting (P = 0.019), suggesting that IQCODE performs better in a 'general' setting. We found no significant differences in the test accuracy of the short (16-item) versus the 26-item IQCODE, or in the language of administration. There was significant heterogeneity in the included studies, including a highly varied prevalence of dementia (10.5% to 87.4%). Across the included papers there was substantial potential for bias, particularly around sampling of included participants and selection criteria, which may limit generalisability. There was also evidence of suboptimal reporting, particularly around disease severity and handling indeterminate results, which are important if considering use in clinical practice. AUTHORS' CONCLUSIONS: The IQCODE can be used to identify older adults in the general hospital setting who are at risk of dementia and require specialist assessment; it is useful specifically for ruling out those without evidence of cognitive decline. The language of administration did not affect test accuracy, which supports the cross-cultural use of the tool. These findings are qualified by the significant heterogeneity, the potential for bias and suboptimal reporting found in the included studies.


Assuntos
Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Inquéritos Epidemiológicos/normas , Procurador , Atenção Secundária à Saúde , Atividades Cotidianas , Adulto , Idoso , Transtornos Cognitivos/diagnóstico , Intervalos de Confiança , Diagnóstico Diferencial , Hospitais , Humanos , Idioma , Pessoa de Meia-Idade , Sensibilidade e Especificidade
7.
Cochrane Database Syst Rev ; 7: CD010079, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34278562

RESUMO

BACKGROUND: Various tools exist for initial assessment of possible dementia with no consensus on the optimal assessment method. Instruments that use collateral sources to assess change in cognitive function over time may have particular utility. The most commonly used informant dementia assessment is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A synthesis of the available data regarding IQCODE accuracy will help inform cognitive assessment strategies for clinical practice, research and policy. OBJECTIVES: Our primary obective was to determine the accuracy of the informant-based questionnaire IQCODE for detection of dementia within community dwelling populations. Our secondary objective was to describe the effect of heterogeneity on the summary estimates. We were particularly interested in the traditional 26-item scale versus the 16-item short form; and language of administration. We explored the effect of varying the threshold IQCODE score used to define 'test positivity'. SEARCH METHODS: We searched the following sources on 28 January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science with Conference Proceedings (ISI Web of Knowledge), LILACS (BIREME). We also searched sources relevant or specific to diagnostic test accuracy: MEDION (Universities of Maastrict and Leuven); DARE (York University); ARIF (Birmingham University). We used sensitive search terms based on MeSH terms and other controlled vocabulary. SELECTION CRITERIA: We selected those studies performed in community settings that used (not necessarily exclusively) the IQCODE to assess for presence of dementia and, where dementia diagnosis was confirmed with clinical assessment. Our intention with limiting the search to a 'community' setting was to include those studies closest to population level assessment. Within our predefined community inclusion criteria, there were relevant papers that fulfilled our definition of community dwelling but represented a selected population, for example stroke survivors. We included these studies but performed sensitivity analyses to assess the effects of these less representative populations on the summary results. DATA COLLECTION AND ANALYSIS: We screened all titles generated by the electronic database searches and abstracts of all potentially relevant studies were reviewed. Full papers were assessed for eligibility and data extracted by two independent assessors. For quality assessment (risk of bias and applicability) we used the QUADAS 2 tool. We included test accuracy data on the IQCODE used at predefined diagnostic thresholds. Where data allowed, we performed meta-analyses to calculate summary values of sensitivity and specificity with corresponding 95% confidence intervals (CIs). We pre-specified analyses to describe the effect of IQCODE format (traditional or short form) and language of administration for the IQCODE. MAIN RESULTS: From 16,144 citations, 71 papers described IQCODE test accuracy. We included 10 papers (11 independent datasets) representing data from 2644 individuals (n = 379 (14%) with dementia). Using IQCODE cut-offs commonly employed in clinical practice (3.3, 3.4, 3.5, 3.6) the sensitivity and specificity of IQCODE for diagnosis of dementia across the studies were generally above 75%. Taking an IQCODE threshold of 3.3 (or closest available) the sensitivity was 0.80 (95% CI 0.75 to 0.85); specificity was 0.84 (95% CI 0.78 to 0.90); positive likelihood ratio was 5.2 (95% CI 3.7 to 7.5) and the negative likelihood ratio was 0.23 (95% CI 0.19 to 0.29). Comparative analysis suggested no significant difference in the test accuracy of the 16 and 26-item IQCODE tests and no significant difference in test accuracy by language of administration. There was little difference in sensitivity across our predefined diagnostic cut-points. There was substantial heterogeneity in the included studies. Sensitivity analyses removing potentially unrepresentative populations in these studies made little difference to the pooled data estimates. The majority of included papers had potential for bias, particularly around participant selection and sampling. The quality of reporting was suboptimal particularly regarding timing of assessments and descriptors of reproducibility and inter-observer variability. AUTHORS' CONCLUSIONS: Published data suggest that if using the IQCODE for community dwelling older adults, the 16 item IQCODE may be preferable to the traditional scale due to lesser test burden and no obvious difference in accuracy. Although IQCODE test accuracy is in a range that many would consider 'reasonable', in the context of community or population settings the use of the IQCODE alone would result in substantial misdiagnosis and false reassurance. Across the included studies there were issues with heterogeneity, several potential biases and suboptimal reporting quality.


Assuntos
Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Inquéritos Epidemiológicos/normas , Vida Independente , Procurador , Idoso , Idoso de 80 Anos ou mais , Viés , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
Qual Life Res ; 30(6): 1641-1652, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33575918

RESUMO

PURPOSE: The aim of this study was to validate the Long-Term Conditions Questionnaire (LTCQ) among patients using memory clinic services in England. LTCQ is a short self-administered measure of 'living well with long-term conditions' that has not been previously tested in patients with cognitive impairment. METHODS: The mixed-methods study included cognitive interviews to test the comprehensibility and content validity of LTCQ from the patient's perspective, followed by a pilot survey to test the measure's internal consistency, construct validity, structural validity, and responsiveness. Participants were recruited through memory clinics following a diagnosis of mild cognitive impairment or dementia. RESULTS: Interview respondents (n = 12) all found LTCQ's content relevant, with only minor formatting modifications required. Among survey respondents (n = 105), most patients (86%) were able to self-report answers to LTCQ. High multimorbidity among the sample was associated with reduced LTCQ and EQ-5D scores. Internal consistency of LTCQ was high (Cronbach's α = 0.93), no floor or ceiling effects were observed, and missing data levels were low. Factor analysis results further supported LTCQ's structural validity, and predicted positive correlation with EQ-5D indicated construct validity. Score changes observed in a four-month follow-up survey (n = 61) are suggestive of LTCQ's responsiveness. CONCLUSION: LTCQ is a valid means of assessing health-related quality of life for people living with cognitive impairment (including dementia) in the early period of support following diagnosis. Owing to high levels of multimorbidity in this patient population, LTCQ offers an advantage over dementia-specific measures in capturing the cumulative impact of all LTCs experienced by the patient.


Assuntos
Disfunção Cognitiva/psicologia , Demência/psicologia , Nível de Saúde , Psicometria/métodos , Qualidade de Vida/psicologia , Inglaterra , Humanos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Multimorbidade , Projetos Piloto , Reprodutibilidade dos Testes , Autorrelato , Inquéritos e Questionários , Reino Unido
9.
BJPsych Open ; 7(1): e9, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33283696

RESUMO

BACKGROUND: Ketamine has recently received considerable attention regarding its antidepressant and anti-suicidal effects. Trials have generally focused on short-term effects of single intravenous infusions. Research on patient experiences is lacking. AIMS: To investigate the experiences over time of individuals receiving ketamine treatment in a routine clinic, including impacts on mood and suicidality. METHOD: Twelve fee-paying patients with treatment-resistant depression (6 females, 6 males, age 21-70 years; 11 reporting suicidality and 6 reporting self-harm) who were assessed as eligible for ketamine treatment participated in up to three semi-structured interviews: before treatment started, a few weeks into treatment and ≥2 months later. Data were analysed thematically. RESULTS: Most participants hoped that ketamine would provide respite from their depression. Nearly all experienced improvement in mood following initial treatments, ranging from negligible to dramatic, and eight reported a reduction in suicidality. Improvements were transitory for most participants, although two experienced sustained consistent benefit and two had sustained but limited improvement. Some participants described hopelessness when treatment stopped working, paralleled by increased suicidal ideation for three participants. The transient nature and cost of treatment were problematic. Eleven participants experienced side-effects, which were significant for two participants. Suggestions for improving treatment included closer monitoring and adjunctive psychological therapy. CONCLUSIONS: Ketamine treatment was generally experienced as effective in improving mood and reducing suicidal ideation in the short term, but the lack of longer-term benefit was challenging for participants, as was treatment cost. Informed consent procedures should refer to the possibilities of relapse and associated increased hopelessness and suicidality.

10.
Health Qual Life Outcomes ; 18(1): 279, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795317

RESUMO

PURPOSE: The aim of this work was to develop a mapping algorithm for estimating EuroQoL 5 Dimension (EQ-5D) utilities from responses to the Long-Term Conditions Questionnaire (LTCQ), thus increasing LTCQ's potential as a comprehensive outcome measure for evaluating integrated care initiatives. METHODS: We combined data from three studies to give a total sample of 1334 responses. In each of the three datasets, we randomly selected 75% of the sample and combined the selected random samples to generate the estimation dataset, which consisted of 1001 patients. The unselected 25% observations from each dataset were combined to generate an internal validation dataset of 333 patients. We used direct mapping models by regressing responses to the LTCQ-8 directly onto EQ-5D-5L and EQ-5D-3L utilities as well as response (or indirect) mapping to predict the response level that patients selected for each of the five EQ-5D-5L domains. Several models were proposed and compared on mean squared error and mean absolute error. RESULTS: A two-part model with OLS was the best performing based on the mean squared error (0.038) and mean absolute error (0.147) when estimating the EQ-5D-5L utilities. A multinomial response mapping model using LTCQ-8 responses was used to predict EQ-5D-5L responses levels. CONCLUSIONS: This study provides a mapping algorithm for estimating EQ-5D utilities from LTCQ responses. The results from this study can help broaden the applicability of the LTCQ by producing utility values for use in economic analyses.


Assuntos
Qualidade de Vida , Inquéritos e Questionários/normas , Adulto , Doença Crônica/psicologia , Doença Crônica/terapia , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Psychopharmacol ; 34(9): 931-937, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32522058

RESUMO

BACKGROUND: In the UK, medical cannabis was approved in November 2018, leading many patients to believe that the medicine would now be available on the NHS. Yet, to date, there have been only 12 NHS prescriptions and less than 60 prescriptions in total. In marked contrast, a recent patient survey by the Centre for Medical Cannabis (Couch, 2020) found 1.4 m people are using illicit cannabis for medical problems. AIMS: Such a mismatch between demand and supply is rare in medicine. This article outlines some of the current controversies about medical cannabis that underpin this disparity, beginning by contrasting current medical evidence from research studies with patient-reported outcomes. OUTCOMES: Although definite scientific evidence is scarce for most conditions, there is significant patient demand for access to medical cannabis. This disparity poses a challenge for prescribers, and there are many concerns of physicians when deciding if, and how, to prescribe medical cannabis which still need to be addressed. Potential solutions are outlined as to how the medical profession and regulators could respond to the strong demand from patients and families for access to medical cannabis to treat chronic illnesses when there is often a limited scientific evidence base on whether and how to use it in many of these conditions. CONCLUSIONS: There is a need to maximise both clinical research and patient benefit, in a safe, cautious and ethical manner, so that those patients for whom cannabis is shown to be effective can access it. We hope our discussion and outlines for future progress offer a contribution to this process.

12.
J Affect Disord ; 266: 615-620, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32056935

RESUMO

BACKGROUND: Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive Ketamine Side Effect Tool (KSET) to capture acute and longer-term side effects associated with repeated ketamine treatments. METHODS: Informed by systematic review data and clinical research, we drafted a list of the most commonly reported side effects. Face and content validation were obtained via feedback from collaborators with expertise in psychiatry and anaesthetics, clinical trial piloting and a modified Delphi Technique involving ten international experts. RESULTS: The final version consisted of four forms that collect information at time points: screening, baseline, immediately after a single treatment, and longer-term follow-up. Instructions were developed to guide users and promote consistent utilisation. LIMITATIONS: Further evaluation of feasibility, construct validity and reliability is required, and is planned across multiple international sites. CONCLUSIONS: The structured Ketamine Side Effect Tool (KSET) was developed, with confirmation of content and face validity via a Delphi consensus process. This tool is timely, given the paucity of data regarding ketamine's safety, tolerability and abuse potential over the longer term, and its recent adoption internationally as a clinical treatment for depression. Although based on data from depression studies, the KSET has potential applicability for ketamine (or derivatives) used in other medical disorders, including chronic pain. We recommend its utilisation for both research and clinical scenarios, including data registries.


Assuntos
Dor Crônica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ketamina , Humanos , Ketamina/efeitos adversos , Reprodutibilidade dos Testes
13.
Am J Geriatr Psychiatry ; 28(2): 121-141, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31734084

RESUMO

BACKGROUND: Elderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment. METHODS: This phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Analyses included a preplanned analysis by age (65-74 versus ≥75 years) and post-hoc analyses including age at depression onset. RESULTS: For the primary endpoint, the median-unbiased estimate of the treatment difference (95% CI) was -3.6 (-7.20, 0.07); weighted combination test using MMRM analyses z = 1.89, two-sided p = 0.059. Adjusted mean (95% CI) difference for change in MADRS score between treatment groups was -4.9 (-8.96, -0.89; t = -2.4, df = 127; two-sided nominal p = 0.017) for patients 65 to 74 years versus -0.4 (-10.38, 9.50; t = -0.09, two-sided nominal p = 0.930) for those ≥75 years, and -6.1 (-10.33, -1.81; t = -2.8, df = 127; two-sided nominal p = 0.006) for patients with depression onset <55 years and 3.1 (-4.51, 10.80; t = 0.8, two-sided nominal p = 0.407) for those ≥55 years. Patients who rolled over into the long-term open-label study showed continued improvement with esketamine following 4 additional treatment weeks. CONCLUSIONS: Esketamine/antidepressant did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen for younger patients (65-74 years) and patients with earlier onset of depression (<55 years).


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Administração Oral , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Ketamina/administração & dosagem , Masculino , Sprays Nasais , Resultado do Tratamento
14.
JAMA Neurol ; 77(2): 164-174, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31738372

RESUMO

Importance: There are no disease-modifying treatments for Alzheimer disease (AD), the most common cause of dementia. Minocycline is anti-inflammatory, protects against the toxic effects of ß-amyloid in vitro and in animal models of AD, and is a credible repurposed treatment candidate. Objective: To determine whether 24 months of minocycline treatment can modify cognitive and functional decline in patients with mild AD. Design, Setting, and Participants: Participants were recruited into a double-blind randomized clinical trial from May 23, 2014, to April 14, 2016, with 24 months of treatment and follow-up. This multicenter study in England and Scotland involved 32 National Health Service memory clinics within secondary specialist services for people with dementia. From 886 screened patients, 554 patients with a diagnosis of mild AD (Standardised Mini-Mental State Examination [sMMSE] score ≥24) were randomized. Interventions: Participants were randomly allocated 1:1:1 in a semifactorial design to receive minocycline (400 mg/d or 200 mg/d) or placebo for 24 months. Main Outcomes and Measures: Primary outcome measures were decrease in sMMSE score and Bristol Activities of Daily Living Scale (BADLS), analyzed by intention-to-treat repeated-measures regression. Results: Of 544 eligible participants (241 women and 303 men), the mean (SD) age was 74.3 (8.2) years, and the mean (SD) sMMSE score was 26.4 (1.9). Fewer participants completed 400-mg minocycline hydrochloride treatment (28.8% [53 of 184]) than 200-mg minocycline treatment (61.9% [112 of 181]) or placebo (63.7% [114 of 179]; P < .001), mainly because of gastrointestinal symptoms (42 in the 400-mg group, 15 in the 200-mg group, and 10 in the placebo group; P < .001), dermatologic adverse effects (10 in the 400-mg group, 5 in the 200-mg group, and 1 in the placebo group; P = .02), and dizziness (14 in the 400-mg group, 3 in the 200-mg group, and 1 in the placebo group; P = .01). Assessment rates were lower in the 400-mg group: 68.4% (119 of 174 expected) for sMMSE at 24 months compared with 81.8% (144 of 176) for the 200-mg group and 83.8% (140 of 167) for the placebo group. Decrease in sMMSE scores over 24 months in the combined minocycline group was similar to that in the placebo group (4.1 vs 4.3 points). The combined minocycline group had mean sMMSE scores 0.1 points higher than the placebo group (95% CI, -1.1 to 1.2; P = .90). The decrease in mean sMMSE scores was less in the 400-mg group than in the 200-mg group (3.3 vs 4.7 points; treatment effect = 1.2; 95% CI, -0.1 to 2.5; P = .08). Worsening of BADLS scores over 24 months was similar in all groups: 5.7 in the 400-mg group, 6.6 in the 200-mg group, and 6.2 in the placebo groups (treatment effect for minocycline vs placebo = -0.53; 95% CI, -2.4 to 1.3; P = .57; treatment effect for 400 mg vs 200 mg of minocycline = -0.31; 95% CI, -0.2 to 1.8; P = .77). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Conclusions and Relevance: Minocycline did not delay the progress of cognitive or functional impairment in people with mild AD during a 2-year period. This study also found that 400 mg of minocycline is poorly tolerated in this population. Trial Registration: isrctn.org Identifier: ISRCTN16105064.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Minociclina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Minociclina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Resultado do Tratamento
16.
BJPsych Open ; 5(5): e62, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31530293

RESUMO

BACKGROUND: Only one-third of patients with major depressive disorder achieve remission. One new and promising treatment, ketamine, may prove challenging to implement because of its abuse potential. Although clinicians' views have been sought, we need patients' views before large scale roll-out is considered. AIMS: To explore patients' and carers' views to inform policy and practical decisions about the clinical use of ketamine. METHOD: We carried out a mixed-methods study using data from 44 participants in 21 focus groups in three sessions and an online survey with patients, carers and advocates during a consultation day. Focus groups explored participant's views about ketamine as a form of treatment and the best way for ketamine to be prescribed and monitored. The qualitative data were analysed by two patient-researchers using an exploratory framework analysis and was supplemented by a survey. RESULTS: The ten themes generated were monitoring, information, effect on daily life, side-effects, recreational use, effectiveness, appropriate support, cost, stigma and therapy. Participants wanted better evidence on the safety of ketamine after long-term use and felt that monitoring was required. Collecting this information would provide evidence for ketamine's safe use and administration. There were, however, concerns about the misuse of this information. Practical issues of access were important: repeated travelling to clinics and a lack of sufficiently informed medical staff were key barriers. CONCLUSIONS: Clinicians have some similar and some different views to those of patients, carers and advocates, which need to be considered in any future roll-out of ketamine. DECLARATION OF INTEREST: R.M. has had UK National Institute for Health Research grant funding to study ketamine, is participating in trials of esketamine, runs a clinic that provides ketamine treatment, and has consulted for Johnson & Johnson and Eleusis.

17.
Alzheimers Dement (N Y) ; 5: 420-430, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31517029

RESUMO

Introduction: The objective of this study was to define current assistive technology and telecare (ATT) practice for people with dementia living at home. Methods: This is a randomized controlled trial (N = 495) of ATT assessment and ATT installation intervention, compared with control (restricted ATT package). ATT assessment and installation data were collected. Qualitative work identified value networks delivering ATT, established an ATT assessment standard. Results: ATT was delivered by public and not-for-profit telecare networks. ATT assessments showed 52% fidelity to the ATT assessment standard. Areas of assessment most frequently leading to identifying ATT need were daily activities (93%), memory (89%), and problem-solving (83%). ATT needs and recommendations were weakly correlated (τ = 0.242; P < .000), with ATT recommendations and installations moderately correlated (τ = -0.470; P < .000). Half (53%) of recommended technology was not installed. Safety concerns motivated 38% of installations. Discussion: Assessment recommendations were routinely disregarded at the point of installation. ATT was commonly recommended for safety and seldom for supporting leisure.

18.
BMJ Open ; 9(8): e029108, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420388

RESUMO

OBJECTIVE: It is recognised that ketamine treatment can reduce suicidal ideation (SI) in people with depression, at least in the short term. However, information is lacking on patients' perspectives on such effects. Studying these can contribute to greater understanding of the mechanisms underlying impact of ketamine treatment on SI. The aim of this study was to investigate patients' reports of the impact of treatment on their SI, the duration of effects and possible mechanisms. DESIGN AND SETTING: This qualitative study consisted of semi-structured interviews with patients who had received ketamine treatment for depression. Interview data were analysed thematically. PARTICIPANTS: Fourteen patients (8 females, 6 males, aged 24-64 years) who had received treatment with ketamine for treatment-resistant depression, and had SI at the initiation of treatment. Two participants also had a diagnosis of bipolar type 1 and two of emotionally unstable personality disorder. Eight had a history of self-harm. RESULTS: SI reduced following ketamine treatment in 12 out of 14 participants for periods of a few hours following a single treatment to up to three years with ongoing treatment. Reduction of SI was variable in terms of extent and duration, and re-emergence of suicidal thoughts often occurred when treatment ceased. Participants' accounts indicated that reduced SI was associated with improved mood and reduced anxiety, as were clarity of thought, focus and concentration, and ability to function. Participants reported experiencing some or all of these effects in various orders of occurrence. CONCLUSION: Generally, ketamine treatment was experienced as effective in reducing SI, although duration of effects varied considerably. Patients' perspectives indicated similarities in the mechanisms of reduction in SI, but some differences in their manifestation, particularly in relation to chronology. Experiences of this cohort suggest that reduced anxiety and improvement in ability to think and function were important mechanisms alongside, or in some cases independently of, improvement in mood. Further studies of patients' experiences are required to gain enhanced understanding of the variability of effects of ketamine on SI and functionality.


Assuntos
Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Ideação Suicida , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Comportamento Autodestrutivo , Reino Unido
19.
Cochrane Database Syst Rev ; 3: CD011121, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30828783

RESUMO

BACKGROUND: Dementia assessment often involves initial screening, using a brief tool, followed by more detailed assessment where required. The AD-8 is a short questionnaire, completed by a suitable 'informant' who knows the person well. AD-8 is designed to assess change in functional performance secondary to cognitive change. OBJECTIVES: To determine the diagnostic accuracy of the informant-based AD-8 questionnaire, in detection of all-cause (undifferentiated) dementia in adults. Where data were available, we described the following: the diagnostic accuracy of the AD-8 at various predefined threshold scores; the diagnostic accuracy of the AD-8 for each healthcare setting and the effects of heterogeneity on the reported diagnostic accuracy of the AD-8. SEARCH METHODS: We searched the following sources on 27 May 2014, with an update to 7 June 2018: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost) and LILACS (BIREME). We checked reference lists of relevant studies and reviews, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on the AD-8 to try to find additional studies. We developed a sensitive search strategy and used standardised database subject headings as appropriate. Foreign language publications were translated. SELECTION CRITERIA: We selected those studies which included the AD-8 to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. We only included those studies where the AD-8 was used as an informant assessment. We made no exclusions in relation to healthcare setting, language of AD-8 or the AD-8 score used to define a 'test positive' case. DATA COLLECTION AND ANALYSIS: We screened all titles generated by electronic database searches, and reviewed abstracts of potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We extracted data into two-by-two tables to allow calculation of accuracy metrics for individual studies. We then created summary estimates of sensitivity, specificity and likelihood ratios using the bivariate approach and plotting results in receiver operating characteristic (ROC) space. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool. MAIN RESULTS: From 36 papers describing AD-8 test accuracy, we included 10 papers. We utilised data from nine papers with 4045 individuals, 1107 of whom (27%) had a clinical diagnosis of dementia. Pooled analysis of seven studies, using an AD-8 informant cut-off score of two, indicated that sensitivity was 0.92 (95% confidence interval (CI) 0.86 to 0.96); specificity was 0.64 (95% CI 0.39 to 0.82); the positive likelihood ratio was 2.53 (95% CI 1.38 to 4.64); and the negative likelihood ratio was 0.12 (95% CI 0.07 to 0.21). Pooled analysis of five studies, using an AD-8 informant cut-off score of three, indicated that sensitivity was 0.91 (95% CI 0.80 to 0.96); specificity was 0.76 (95% CI 0.57 to 0.89); the positive likelihood ratio was 3.86 (95% CI 2.03 to 7.34); and the negative likelihood ratio was 0.12 (95% CI 0.06 to 0.24).Four studies were conducted in community settings; four were in secondary care (one in the acute hospital); and one study was in primary care. The AD-8 has a higher relative sensitivity (1.11, 95% CI 1.02 to 1.21), but lower relative specificity (0.51, 95% CI 0.23 to 1.09) in secondary care compared to community care settings.There was heterogeneity across the included studies. Dementia prevalence rate varied from 12% to 90% of included participants. The tool was also used in various different languages. Among all the included studies there was evidence of risk of bias. Issues included the selection of participants, conduct of index test, and flow of assessment procedures. AUTHORS' CONCLUSIONS: The high sensitivity of the AD-8 suggests it can be used to identify adults who may benefit from further specialist assessment and diagnosis, but is not a diagnostic test in itself. This pattern of high sensitivity and lower specificity is often suited to a screening test. Test accuracy varies by setting, however data in primary care and acute hospital settings are limited. This review identified significant heterogeneity and risk of bias, which may affect the validity of its summary findings.


Assuntos
Demência/diagnóstico , Questionário de Saúde do Paciente , Procurador , Idoso , Humanos , Sensibilidade e Especificidade
20.
Cochrane Database Syst Rev ; 3: CD003154, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30891742

RESUMO

BACKGROUND: Memantine is a moderate affinity uncompetitive antagonist of glutamate NMDA receptors. It is licensed for use in moderate and severe Alzheimer's disease (AD); in the USA, it is also widely used off-label for mild AD. OBJECTIVES: To determine efficacy and safety of memantine for people with dementia. To assess whether memantine adds benefit for people already taking cholinesterase inhibitors (ChEIs). SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register of trials (http://www.medicine.ox.ac.uk/alois/) up to 25 March 2018. We examined clinical trials registries, press releases and posters of memantine manufacturers; and the web sites of the FDA, EMEA and NICE. We contacted authors and companies for missing information. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomised trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: We pooled and analysed data from four clinical domains across different aetiologies and severities of dementia and for AD with agitation. We assessed the impact of study duration, severity and concomitant use of ChEIs. Consequently, we restricted analyses to the licensed dose (20 mg/day or 28 mg extended release) and data at six to seven months duration of follow-up, and analysed separately results for mild and moderate-to-severe AD.We transformed results for efficacy outcomes into the difference in points on particular outcome scales. MAIN RESULTS: Across all types of dementia, data were available from almost 10,000 participants in 44 included trials, most of which were at low or unclear risk of bias. For nearly half the studies, relevant data were obtained from unpublished sources. The majority of trials (29 in 7885 participants) were conducted in people with AD.1. Moderate-to-severe AD (with or without concomitant ChEIs). High-certainty evidence from up to 14 studies in around 3700 participants consistently shows a small clinical benefit for memantine versus placebo: clinical global rating (CGR): 0.21 CIBIC+ points (95% confidence interval (CI) 0.14 to 0.30); cognitive function (CF): 3.11 Severe Impairment Battery (SIB) points (95% CI 2.42 to 3.92); performance on activities of daily living (ADL): 1.09 ADL19 points (95% CI 0.62 to 1.64); and behaviour and mood (BM): 1.84 Neuropsychiatric Inventory (NPI) points (95% CI 1.05 to 2.76). There may be no difference in the number of people discontinuing memantine compared to placebo: risk ratio (RR) 0.93 (95% CI 0.83 to 1.04) corresponding to 13 fewer people per 1000 (95% CI 31 fewer to 7 more). Although there is moderate-certainty evidence that fewer people taking memantine experience agitation as an adverse event: RR 0.81 (95% CI 0.66 to 0.99) (25 fewer people per 1000, 95% CI 1 to 44 fewer), there is also moderate-certainty evidence, from three additional studies, suggesting that memantine is not beneficial as a treatment for agitation (e.g. Cohen Mansfield Agitation Inventory: clinical benefit of 0.50 CMAI points, 95% CI -3.71 to 4.71) .The presence of concomitant ChEI does not impact on the difference between memantine and placebo, with the possible exceptions of the BM outcome (larger effect in people taking ChEIs) and the CF outcome (smaller effect).2. Mild AD (Mini Mental State Examination (MMSE) 20 to 23): mainly moderate-certainty evidence based on post-hoc subgroups from up to four studies in around 600 participants suggests there is probably no difference between memantine and placebo for CF: 0.21 ADAS-Cog points (95% CI -0.95 to 1.38); performance on ADL: -0.07 ADL 23 points (95% CI -1.80 to 1.66); and BM: -0.29 NPI points (95% CI -2.16 to 1.58). There is less certainty in the CGR evidence, which also suggests there may be no difference: 0.09 CIBIC+ points (95% CI -0.12 to 0.30). Memantine (compared with placebo) may increase the numbers of people discontinuing treatment because of adverse events (RR 2.12, 95% CI 1.03 to 4.39).3. Mild-to-moderate vascular dementia. Moderate- and low-certainty evidence from two studies in around 750 participants indicates there is probably a small clinical benefit for CF: 2.15 ADAS-Cog points (95% CI 1.05 to 3.25); there may be a small clinical benefit for BM: 0.47 NOSGER disturbing behaviour points (95% CI 0.07 to 0.87); there is probably no difference in CGR: 0.03 CIBIC+ points (95% CI -0.28 to 0.34); and there may be no difference in ADL: 0.11 NOSGER II self-care subscale points (95% CI -0.35 to 0.54) or in the numbers of people discontinuing treatment: RR 1.05 (95% CI 0.83 to 1.34).There is limited, mainly low- or very low-certainty efficacy evidence for other types of dementia (Parkinson's disease and dementia Lewy bodies (for which CGR may show a small clinical benefit; four studies in 319 people); frontotemporal dementia (two studies in 133 people); and AIDS-related Dementia Complex (one study in 140 people)).There is high-certainty evidence showing no difference between memantine and placebo in the proportion experiencing at least one adverse event: RR 1.03 (95% CI 1.00 to 1.06); the RR does not differ between aetiologies or severities of dementia. Combining available data from all trials, there is moderate-certainty evidence that memantine is 1.6 times more likely than placebo to result in dizziness (6.1% versus 3.9%), low-certainty evidence of a 1.3-fold increased risk of headache (5.5% versus 4.3%), but high-certainty evidence of no difference in falls. AUTHORS' CONCLUSIONS: We found important differences in the efficacy of memantine in mild AD compared to that in moderate-to-severe AD. There is a small clinical benefit of memantine in people with moderate-to-severe AD, which occurs irrespective of whether they are also taking a ChEI, but no benefit in people with mild AD.Clinical heterogeneity in AD makes it unlikely that any single drug will have a large effect size, and means that the optimal drug treatment may involve multiple drugs, each having an effect size that may be less than the minimum clinically important difference.A definitive long-duration trial in mild AD is needed to establish whether starting memantine earlier would be beneficial over the long term and safe: at present the evidence is against this, despite it being common practice. A long-duration trial in moderate-to-severe AD is needed to establish whether the benefit persists beyond six months.


Assuntos
Demência/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Memantina/uso terapêutico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Acatisia Induzida por Medicamentos/etiologia , Doença de Alzheimer/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Humanos , Memantina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Suspensão de Tratamento
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