Objective: to evaluate the performance of the 4 ‘A’s Test (4AT) in screening for delirium in older patients. The 4AT is a new test for rapid screening of delirium in routine clinical practice.Design: prospective study of consecutively admitted elderly patients with independent 4AT and reference standard assessments.Setting: an acute geriatrics ward and a department of rehabilitation.Participants: two hundred and thirty-six patients (aged ≥70 years) consecutively admitted over a period of 4 months.Measurements: in each centre, the 4AT was administered by a geriatrician to eligible patients within 24 h of admission. Reference standard delirium diagnosis (DSM-IV-TR criteria) was obtained within 30 min by a different geriatrician who was blind to the 4AT score. The presence of dementia was assessed using the Alzheimer's Questionnaire and the informant section of the Clinical Dementia Rating scale. The main outcome measure was the accuracy of the 4AT in diagnosing delirium.Results: patients were 83.9 ± 6.1 years old, and the majority were women (64%). Delirium was detected in 12.3% (n = 29), dementia in 31.2% (n = 74) and a combination of both in 7.2% (n = 17). The 4AT had a sensitivity of 89.7% and specificity 84.1% for delirium. The areas under the receiver operating characteristic curves for delirium diagnosis were 0.93 in the whole population, 0.92 in patients without dementia and 0.89 in patients with dementia.Conclusions: the 4AT is a sensitive and specific method of screening for delirium in hospitalised older people. Its brevity and simplicity support its use in routine clinical practice.

Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia. However, previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline. Herein, we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline. We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium. The Vantaa 85+ study examined 553 individuals (92% of those eligible) aged ≥85 years at baseline, 3, 5, 8 and 10 years. Brain autopsy was performed in 52%. Fixed and random-effects regression models were used to assess associations between (i) delirium and incident dementia and (ii) decline in Mini-Mental State Examination scores in the whole group. The relationship between dementia and common neuropathological markers (Alzheimer-type, infarcts and Lewy-body) was modelled, stratified by history of delirium. Delirium increased the risk of incident dementia (odds ratio 8.7, 95% confidence interval 2.1–35). Delirium was also associated with worsening dementia severity (odds ratio 3.1, 95% confidence interval 1.5–6.3) as well as deterioration in global function score (odds ratio 2.8, 95% confidence interval 1.4–5.5). In the whole study population, delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year (95% confidence interval 0.11–1.89) than those with no history of delirium. In individuals with dementia and no history of delirium (n = 232), all pathologies were significantly associated with dementia. However, in individuals with delirium and dementia (n = 58), no relationship between dementia and these markers was found. For example, higher Braak stage was associated with dementia when no history of delirium (odds ratio 2.0, 95% confidence interval 1.1–3.5, P = 0.02), but in those with a history of delirium, there was no significant relationship (odds ratio 1.2, 95% confidence interval 0.2–6.7, P = 0.85). This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid, apolipoprotein ε status, presence of infarcts, α-synucleinopathy and neuronal loss in substantia nigra. These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old. However, in this study, the relationship did not appear to be mediated by classical neuropathologies associated with dementia.

Delirium and dementia are two of the most common causes of cognitive impairment in older populations, yet their interrelationship remains poorly understood. Previous studies have documented that dementia is the leading risk factor for delirium; and delirium is an independent risk factor for subsequent dementia. However, a major area of controversy is whether delirium is simply a marker of vulnerability to dementia, whether the impact of delirium is solely related to its precipitating factors, or whether delirium itself can cause permanent neuronal damage and lead to dementia. Ultimately, it is likely that all of these hypotheses are true. Emerging evidence from epidemiological, clinicopathological, neuroimaging, biomarker, and experimental studies provide support for a strong interrelationship and for both shared and distinct pathological mechanisms. Targeting delirium for new preventive and therapeutic approaches may offer the sought-after opportunity for early intervention, preservation of cognitive reserve, and prevention of irreversible cognitive decline in ageing.

SummaryBackgroundThe emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the effectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug resistance in treatment-naive individuals with HIV since initiation of rollout in resource-limited settings.MethodsWe did a systematic search for studies and conference abstracts published between January, 2001, and July, 2011, and included additional data from the WHO HIV drug resistance surveillance programme. We assessed the prevalence of drug-resistance mutations in untreated individuals with respect to time since rollout in a series of random-effects meta-regression models.FindingsStudy-level data were available for 26 102 patients from sub-Saharan Africa, Asia, and Latin America. We recorded no difference between chronic and recent infection on the prevalence of one or more drug-resistance mutations for any region. East Africa had the highest estimated rate of increase at 29% per year (95% CI 15 to 45; p=0·0001) since rollout, with an estimated prevalence of HIV-1 drug resistance at 8 years after rollout of 7·4% (4·3 to 12·7). We recorded an annual increase of 14% (0% to 29%; p=0·054) in southern Africa and a non-significant increase of 3% (–0·9 to 16; p=0·618) in west and central Africa. There was no change in resistance over time in Latin America, and because of much country-level heterogeneity the meta-regression analysis was not appropriate for Asia. With respect to class of antiretroviral, there were substantial increases in resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) in east Africa (36% per year [21 to 52]; p<0·0001) and southern Africa (23% per year [7 to 42]; p=0·0049). No increase was noted for the other drug classes in any region.InterpretationOur findings suggest a significant increase in prevalence of drug resistance over time since antiretroviral rollout in regions of sub-Saharan Africa; this rise is driven by NNRTI resistance in studies from east and southern Africa. The findings are of concern and draw attention to the need for enhanced surveillance and drug-resistance prevention efforts by national HIV treatment programmes. Nevertheless, estimated levels, although increasing, are not unexpected in view of the large expansion of antiretroviral treatment coverage seen in low-income and middle-income countries—no changes in antiretroviral treatment guidelines are warranted at the moment.FundingBill & Melinda Gates Foundation and the European Community's Seventh Framework Programme

A life course approach to ageing relies on maintaining participation rates in national birth cohorts and other long-term longitudinal studies. This reduces the risk of selective attrition biasing associations between lifetime risk factors and health outcomes in later life and ensures the studies remain as representative as possible of the original population. We report the participation patterns for a postal questionnaire and home visit at 68–69 years of study members in the MRC National Survey of Health and Development, the oldest and longest-running British birth cohort study. We investigated how participation varied by lifetime and recent contact, health status, previous clinical feedback and study engagement, taking account of prior socioeconomic and cognitive characteristics. Overall participation and home visit participation remained high (94 and 80%, respectively) and there were no gender differences. Participation was higher in those with higher levels of prior contact and lower in those with the poorest health status. Having previously received clinical feedback on actionable blood results was associated with reduced home visit participation but other forms of clinical feedback were not associated with subsequent participation. Activities that fostered study engagement were associated with increased home visit participation. These findings inform strategies to maintain participation in life course studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-016-0217-8) contains supplementary material, which is available to authorized users.

The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.

RAUMATIC BRAIN INJURY (TBI) IS the leading cause of death following blunt trauma, and survivors often sustain severe disability. TBI is responsible for the greatest number of potential years of life lost from any cause and carries the highest burden on loss of quality-adjusted life-years among survivors. 1 The primary injury to the brain occurs at the time of impact; however, subsequent compromise of cerebral perfusion can lead to an ischemic insult that extends the primary injury, creating a secondary brain injury. 2 Current therapy following severe TBI is focused on minimizing secondary injury by supporting systemic perfusion and reducing intracranial pressure Author Affiliations are listed at the end of this article.

Background The aim of this study was to describe outcomes in hospitalised older people with different levels of frailty and COVID-19 infection. Methods We undertook a single centre, retrospective cohort study examining COVID-19 related mortality using Electronic Health Records, for older people (65 and over) with frailty, hospitalised with or without COVID-19 infection. Baseline covariates included demographics, Early Warning Scores, Charlson Comorbidity Indices and frailty (Clinical Frailty Scale, CFS), linked to COVID-19 status. Findings We analysed outcomes on 1,071 patients with COVID-19 test results; 285 (27%) were positive for COVID-19.)The mean age at ED arrival was 79.7 and 49.4% were female. All-cause mortality (by 30 days) rose from 9% (not frail) through to 33% (severely frail) in the COVID negative cohort but was around 60% for all frailty categories in the COVID positive cohort. In adjusted analyses, the hazard ratio for death in those with COVID-19 compared to those without COVID-19 was 7.3, 95% CI: 3.00, 18.0) with age, comorbidities and illness severity making small additional contributions. Interpretation In this study frailty, measured using the Clinical Frailty Scale, appeared to make little incremental contribution to the hazard of dying in older people hospitalised with COVID-19 infection; illness severity and comorbidity had a modest association with the overall adjusted hazard of death, whereas confirmed COVID-19 infection dominated, with a seven-fold hazard for death.