A systematic review of the validity of non-invasive sleep-measuring devices in mid-to-late life adults: Future utility for Alzheimer's disease research.

Changes in sleep during mid-to-late life are associated with risk for Alzheimer's disease (AD). Mechanistic understanding of this association necessitates measurement tools able to quantify these sleep changes longitudinally and accurately. We conducted a systematic review with meta-analysis of validity studies of non-invasive sleep-measuring devices published since 2015 that record sleep metrics associated with AD in adults over 40 (mean 52.9, SD 6.1 years). We reviewed 52 studies, including 32 wearable and ten non-wearable single or multi-sensor devices validated against polysomnography (minimum one night). The apnoea hypopnoea index and oxygen desaturation index were accurately measured across devices. Total sleep time and sleep efficiency were significantly overestimated (p < 0.001) by mean 33.2 minutes and 7.6%, respectively. Slow wave sleep duration was inaccurately measured except by a headband device with electroencephalography. There was no significant difference in accuracy between participants with and without sleep disorders. Studies were undermined by high risk of bias from closed-access algorithms and classification thresholds, and incomplete reporting of accuracy data. Only one study investigated slow wave activity, and none investigated sleep spindles. Nonetheless, we have identified devices that could be used in future studies of sleep and AD risk and discuss some of the limitations of available research.

The past, present, and future of sleep measurement in mild cognitive impairment and early dementia-towards a core outcome set: a scoping review.

STUDY OBJECTIVES: Sleep abnormalities emerge early in dementia and may accelerate cognitive decline. Their accurate characterization may facilitate earlier clinical identification of dementia and allow for assessment of sleep intervention efficacy. This scoping review determines how sleep is currently measured and reported in Mild Cognitive Impairment (MCI) and early dementia, as a basis for future core outcome alignment. METHODS: This review follows the PRISMA Guidelines for Scoping Reviews. CINAHL, Embase, Medline, Psychinfo, and British Nursing Index databases were searched from inception-March 12, 2021. Included studies had participants diagnosed with MCI and early dementia and reported on sleep as a key objective/ outcome measure. RESULTS: Nineteen thousand five hundred and ninety-six titles were returned following duplicate removal with 188 studies [N] included in final analysis. Sleep data was reported on 17 139 unique, diagnostically diverse participants (n). "Unspecified MCI" was the most common diagnosis amongst patients with MCI (n = 5003, 60.6%). Despite technological advances, sleep was measured most commonly by validated questionnaires (n = 12 586, N = 131). Fewer participants underwent polysomnography (PSG) (n = 3492, N = 88) and actigraphy (n = 3359, N = 38) with little adoption of non-PSG electroencephalograms (EEG) (n = 74, N = 3). Sleep outcome parameters were reported heterogeneously. 62/165 (37.6%) were described only once in the literature (33/60 (60%) in interventional studies). There was underrepresentation of circadian (n = 725, N = 25) and micro-architectural (n = 360, N = 12) sleep parameters. CONCLUSIONS: Alongside under-researched areas, there is a need for more detailed diagnostic characterization. Due to outcome heterogeneity, we advocate for international consensus on core sleep outcome parameters to support causal inference and comparison of therapeutic sleep interventions.

Association of Sleep Disorders with Nocturia: A Systematic Review and Nominal Group Technique Consensus on Primary Care Assessment and Treatment.

CONTEXT: Sleep disorders affect responsiveness to sensory information and can cause nocturnal polyuria and reduced sleep depth; hence, these are potentially influential in understanding the mechanism of nocturia. OBJECTIVE: To report the systematic review (SR) and expert consensus for primary care management of nocturia in sleep disorders. EVIDENCE ACQUISITION: Four databases were searched from January to April 2020. A total of 1658 titles and abstracts were screened, and 23 studies potentially applicable were included for full-text screening. The nominal group technique (NGT) was used to derive a consensus on recommendations for management using an expert panel with public involvement. EVIDENCE SYNTHESIS: Thirteen studies met the SR inclusion criteria, all of which studied obstructive sleep apnoea (OSA), with ten evaluating the effect of continuous positive airway pressure. The NGT consensus discussed the assessment of OSA with other key sleep disorders, notably insomnia, restless legs syndrome/periodic limb movements of sleep, and parasomnias, including non-rapid eye movement (non-REM) parasomnias and REM sleep behaviour disorder (RBD). The NGT considered that the use of screening questions to reach a clinical diagnosis is a sufficient basis for offering conservative therapy within primary care. Reasons for referral to a sleep clinic are suspected sleep disorder with substantially impaired daytime function despite conservative treatment. Suspected RBD should be referred, and if confirmed, neurology opinion is indicated. Referrals should follow local guidelines. Persisting nocturia is not currently considered an indication for referral to a sleep clinic. CONCLUSIONS: Sleep disorders are potentially highly influential in nocturia, but are often overlooked. PATIENT SUMMARY: People with sleep disorders can experience nocturia due to easy waking or increased bladder filling. We looked at published research, and information was limited to one form of sleep disturbance-obstructive sleep apnoea. We assembled a group of experts, to develop practical approaches for assessing and treating nocturia in the potentially relevant sleep disorders.

Implications of Cardiovascular Disease for Assessment and Treatment of Nocturia in Primary Care: Systematic Review and Nominal Group Technique Consensus.

CONTEXT: Heart conditions affect salt and water homeostasis as a consequence of the underlying condition, compensatory processes, and therapy, and can result in nocturnal polyuria. These processes need to be identified as part of a full evaluation of nocturia. OBJECTIVE: To conduct a systematic review of nocturia in cardiovascular disease and achieve expert consensus for primary care management. Primary care was defined as a health care setting in which the expertise did not include specialist cardiology. EVIDENCE ACQUISITION: Four databases were searched from January 2000 to April 2020. A total of 3524 titles and abstracts were screened and 27 studies underwent full-text screening. Of these, eight studies were included in the analysis. The nominal group technique (NGT) was used to achieve consensus among an expert panel incorporating public involvement. EVIDENCE SYNTHESIS: Most studies focused on nocturia related to blood pressure (BP), while one investigated leg oedema. Hypertension, particularly overnight blood pressure above normal, corresponds with higher risk of nocturia. NGT identified fluid and salt overload, nondipping hypertension, and some therapeutic interventions as key nocturia contributors. History taking and examination should identify raised jugular venous pressure/ankle swelling, with relevant investigations including measurement of BP, resting electrocardiogram, and B-type natriuretic peptide. Treatment recommends reducing salt (including substitutes), alcohol and caffeine. Heart failure is managed according to local guidance and controlling fluid intake to 1-2 l daily. If there is no fluid retention, reduce or discontinue diuretics or calcium channel blockers and follow up to reassess the condition. The target clinic blood pressure is 140/90 mm Hg. CONCLUSIONS: Cardiovascular disease and its treatment are influential for understanding nocturia. Management aims to identify and treat heart failure and/or hypertension. PATIENT SUMMARY: People with cardiovascular disease can suffer severe sleep disturbance because of a need to pass urine at night due to increased overnight blood pressure or heart failure. Following a detailed evaluation of the published research, a group of experts recommended practical approaches for assessing and treating these issues.

Assessment and Treatment of Nocturia in Endocrine Disease in a Primary Care Setting: Systematic Review and Nominal Group Technique Consensus.

CONTEXT: Salt and water homeostasis is regulated hormonally, so polyuria can result from endocrine disease directly or via secondary effects. These mechanisms are not consistently considered in primary care management of nocturia. OBJECTIVE: To conduct a systematic review (SR) of nocturia in endocrine disease and reach expert consensus for primary care management. EVIDENCE ACQUISITION: Four databases were searched from January 2000 to April 2020. A total of 4382 titles and abstracts were screened, 36 studies underwent full-text screening, and 14 studies were included in the analysis. Expert and public consensus was achieved using the nominal group technique (NGT). EVIDENCE SYNTHESIS: Twelve studies focused on mechanisms of nocturia, while two evaluated treatment options; none of the studies took place in a primary care setting. NGT consensus identified key clinical evaluation themes, including the presence of thirst, a medical background of diabetes mellitus or insipidus, thyroid disease, oestrogen status, medications (fluid loss or xerostomia), and general examination including body mass index. Proposed investigations include a bladder diary, renal and thyroid function, calcium, and glycated haemoglobin. Morning urine osmolarity should be examined in the context of polyuria of >2.5 l/24 h persisting despite fluid advice, with urine concentration >600 mOsm/l after fluid restriction excluding diabetes insipidus. Treatment should involve education, including adjustment of lifestyle and medication where possible. Any underlying endocrine disorder should be managed according to local guidance. Referral to endocrinology is needed if there is hyperthyroidism, hyperparathyroidism, or morning urine osmolarity <600 mOsm/l after overnight fluid avoidance. CONCLUSIONS: Endocrine disease can result in nocturia via varied salt and water regulation pathways. The aim of management is to identify and treat causative factors, but secondary effects can restrict improvements in nocturia. PATIENT SUMMARY: People with altered hormone function can suffer from severe sleep disturbance because of a need to pass urine caused by problems in controlling water and salt levels. An expert panel recommended the best ways to assess and treat these problems on the basis of the rather small amount of up-to-date published research available.

Processed EEG from depth of anaesthesia monitors and seizures: A scoping review.

PURPOSE: Processed electroencephalogram (EEG) is used peri-operatively for monitoring depth of anaesthesia. Because these utilise EEG data, attempts have been made to investigate their use in diagnosing and monitoring seizures. This is important as formal EEG monitoring can be hard to obtain in many critical care environments. We undertook a scoping review of the evidence for using processed EEG (pEEG) from depth of anaesthesia monitors for this indication. METHODS: Medline, Psych INFO, and Embase were searched for peer-reviewed journals until 20 March 2021. Data and conclusions taken from the study of pEEG in both critical care and peri-operative settings have been included in a qualitative synthesis about the current evidence for the use of pEEG in the detection and monitoring of seizures. RESULTS: Searches yielded 8 observational studies, 1 randomised trial and 15 case reports in which the use of pEEG in critical care and peri-operative medicine was described. Most concerned the Bispectral Index (BIS) device. The majority of observational studies reported the use of BIS for optimisation of burst suppression in patients with refractory status-epilepticus (RSE), or in the comparison of pEEG data with conventional EEG during epileptic activity. Multiple case reports describe the application of pEEG in the presence of disorders of consciousness as a tool for detection of non-convulsive status-epilepticus, finding variable trends in the pEEG output. CONCLUSIONS: Processed EEG may be helpful in monitoring pharmacologically induced burst suppression. Despite this, its use in the diagnosing or monitoring seizure activity is controversial and currently not evidenced, with numerous confounding variables that requires systematic assessment in future studies.

Bedside teaching: everybody's but nobody's responsibility.

Evidence shows dwindling levels of bedside teaching for medical students in the UK, especially in district general hospitals. Lack of individual responsibility has resulted in disengagement in teaching. Based on a quality improvement project (QIP) at a District General Hospital, we suggest some ways this could be addressed. We suggest here that harnessing support from the medical education lead, incentivizing teaching, allocating student-junior doctor groups to harbor personal responsibility, providing a supportive framework, and educating about barriers to teaching can all be used to develop an effective teaching program.

Support for midlife anxiety diagnosis as an independent risk factor for dementia: a systematic review.

OBJECTIVES: Anxiety is an increasingly recognised predictor of cognitive deterioration in older adults and in those with mild cognitive impairment. Often believed to be a prodromal feature of neurodegenerative disease, anxiety may also be an independent risk factor for dementia, operationally defined here as preceding dementia diagnosis by ≥10 years. DESIGN: A systematic review of the literature on anxiety diagnosis and long-term risk for dementia was performed following published guidelines. SETTING AND PARTICIPANTS: Medline, PsycINFO and Embase were searched for peer-reviewed journals until 8 March 2017. Publications reporting HR/OR for all-cause dementia based on clinical criteria from prospective cohort or case-control studies were selected. Included studies measured clinically significant anxiety in isolation or after controlling for symptoms of depression, and reported a mean interval between anxiety assessment and dementia diagnosis of at least 10 years. Methodological quality assessments were performed using the Newcastle-Ottawa Scale. OUTCOME MEASURE: HR/OR for all-cause dementia. RESULTS: Searches yielded 3510 articles, of which 4 (0.02%) were eligible. The studies had a combined sample size of 29 819, and all studies found a positive association between clinically significant anxiety and future dementia. Due to the heterogeneity between studies, a meta-analysis was not conducted. CONCLUSIONS: Clinically significant anxiety in midlife was associated with an increased risk of dementia over an interval of at least 10 years. These findings indicate that anxiety may be a risk factor for late-life dementia, excluding anxiety that is related to prodromal cognitive decline. With increasing focus on identifying modifiable risk factors for dementia, more high-quality prospective studies are required to clarify whether clinical anxiety is a risk factor for dementia, separate from a prodromal symptom.

Routine use of patient reported outcome measures (PROMs) for improving treatment of common mental health disorders in adults.

BACKGROUND: Routine outcome monitoring of common mental health disorders (CMHDs), using patient reported outcome measures (PROMs), has been promoted across primary care, psychological therapy and multidisciplinary mental health care settings, but is likely to be costly, given the high prevalence of CMHDs. There has been no systematic review of the use of PROMs in routine outcome monitoring of CMHDs across these three settings. OBJECTIVES: To assess the effects of routine measurement and feedback of the results of PROMs during the management of CMHDs in 1) improving the outcome of CMHDs; and 2) in changing the management of CMHDs. SEARCH METHODS: We searched the Cochrane Depression Anxiety and Neurosis group specialised controlled trials register (CCDANCTR-Studies and CCDANCTR-References), the Oxford University PROMS Bibliography (2002-5), Ovid PsycINFO, Web of Science, The Cochrane Library, and International trial registries, initially to 30 May 2014, and updated to 18 May 2015. SELECTION CRITERIA: We selected cluster and individually randomised controlled trials (RCTs) including participants with CMHDs aged 18 years and over, in which the results of PROMs were fed back to treating clinicians, or both clinicians and patients. We excluded RCTs in child and adolescent treatment settings, and those in which more than 10% of participants had diagnoses of eating disorders, psychoses, substance use disorders, learning disorders or dementia. DATA COLLECTION AND ANALYSIS: At least two authors independently identified eligible trials, assessed trial quality, and extracted data. We conducted meta-analysis across studies, pooling outcome measures which were sufficiently similar to each other to justify pooling. MAIN RESULTS: We included 17 studies involving 8787 participants: nine in multidisciplinary mental health care, six in psychological therapy settings, and two in primary care. Pooling of outcome data to provide a summary estimate of effect across studies was possible only for those studies using the compound Outcome Questionnaire (OQ-45) or Outcome Rating System (ORS) PROMs, which were all conducted in multidisciplinary mental health care or psychological therapy settings, because both primary care studies identified used single symptom outcome measures, which were not directly comparable to the OQ-45 or ORS.Meta-analysis of 12 studies including 3696 participants using these PROMs found no evidence of a difference in outcome in terms of symptoms, between feedback and no-feedback groups (standardised mean difference (SMD) -0.07, 95% confidence interval (CI) -0.16 to 0.01; P value = 0.10). The evidence for this comparison was graded as low quality however, as all included studies were considered at high risk of bias, in most cases due to inadequate blinding of assessors and significant attrition at follow-up.Quality of life was reported in only two studies, social functioning in one, and costs in none. Information on adverse events (thoughts of self-harm or suicide) was collected in one study, but differences between arms were not reported.It was not possible to pool data on changes in drug treatment or referrals as only two studies reported these. Meta-analysis of seven studies including 2608 participants found no evidence of a difference in management of CMHDs between feedback and no-feedback groups, in terms of the number of treatment sessions received (mean difference (MD) -0.02 sessions, 95% CI -0.42 to 0.39; P value = 0.93). However, the evidence for this comparison was also graded as low quality. AUTHORS' CONCLUSIONS: We found insufficient evidence to support the use of routine outcome monitoring using PROMs in the treatment of CMHDs, in terms of improving patient outcomes or in improving management. The findings are subject to considerable uncertainty however, due to the high risk of bias in the large majority of trials meeting the inclusion criteria, which means further research is very likely to have an important impact on the estimate of effect and is likely to change the estimate. More research of better quality is therefore required, particularly in primary care where most CMHDs are treated.Future research should address issues of blinding of assessors and attrition, and measure a range of relevant symptom outcomes, as well as possible harmful effects of monitoring, health-related quality of life, social functioning, and costs. Studies should include people treated with drugs as well as psychological therapies, and should follow them up for longer than six months.

Safety assessment of genetically modified plants with deliberately altered composition.

The development and marketing of 'novel' genetically modified (GM) crops in which composition has been deliberately altered poses a challenge to the European Union (EU)'s risk assessment processes, which are based on the concept of substantial equivalence with a non-GM comparator. This article gives some examples of these novel GM crops and summarizes the conclusions of a report that was commissioned by the European Food Safety Authority on how the EU's risk assessment processes could be adapted to enable their safety to be assessed.